NCBI Conserved Domain Search

Pleckstrin homology domain;

Pssm-ID: 465218 Cd Length: 143 Bit Score: 293.53 E-value: 9.00e-92

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1433 VQCEGLSEQLVFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQIIKPLGSSGTDKVFSPKSNLQYKMYKTP 1512
Cdd:pfam16652    1 VQCEGLSEQLVFNSLTNCLGPRKLLHSGKLYKVKSNKELVGFLFNDFLLLTQPVKPLSSAGTDKLFSSKSNIQYKMYKTP 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1513 IFLNEVLVKLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKKKRE 1575
Cdd:pfam16652   81 IFLNEVMVKLPTDPSSSEPTFQLSHIDRVYTLKAESPNERTAWVKKIKEASELYIETEKKKRE 143

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 271.57 E-value: 2.93e-84

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1575 EKAYLVRSQRATGIGRLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCI 1654
Cdd:cd08375      1 EKAYLARSQRASGIGRLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCI 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1655 TVFERDQFSPDDFLGRTEIRVADIKKD-QGSKGPVTKCLLLHEVPTGEIVVRLDLQ 1709
Cdd:cd08375     81 TVFDRDFFSPDDFLGRTEIRVADILKEtKESKGPITKRLLLHEVPTGEVVVKLDLQ 136

Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in endo- and exocytosis, actin cytoskeleton rearrangement and signal transduction. There are two human ITSN genes: ITSN1 and ITSN2. They share significant sequence identity and a similar domain structure having both short and long isoforms produced by alternative splicing. The short isoform (ITSN-S) consists of two Eps15 homology domains (EH1 and EH2), a coiled-coil region (CCR) and five Src homology 3 domains (SH3A-E). The EH domains bind to Asn-Pro-Phe motifs and are implicated in endocytosis and vesicle transport. The SH3 domains bind to proline-rich sequences and are commonly found in proteins implicated in cell signalling pathways, cytoskeletal organization and membrane traffic. The long isoform (ITSN-L) contains three additional C-terminal domains, a Dbl homology domain (DH), a Pleckstrin homology domain (PH) and a C2 domain. The tandem DH-PH domains are present in all Dbl family of GEFs. ITSN acts specifically on Cdc42 through its DH domain with no portion of the PH domain making contact with Cdc42. This is in contrast to Dbs which requires the PH domain for full catalytic activity. The ITSN PH domain binds phosphoinositides. C2 domains are usually involved in Ca2+-dependent and Ca2+-independent phospholipid binding. There are more than 30 proteins that interact with ITSNs. ITSN-S is present in mammals, frogs, flies and nematodes, while ITSN-L is present only in vertebrates. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 270084 Cd Length: 132 Bit Score: 271.25 E-value: 3.10e-84

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1441 QLVFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQIIKPLGSSGTDKVFSPKSNLQYKMYKTPIFLNEVLV 1520
Cdd:cd13264      1 QLIFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQPIKPLGSSGNDFVFDNKANIQYKMYKTPIFLNEVLV 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1521 KLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKK 1572
Cdd:cd13264     81 KLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKK 132

Intersectin and clathrin adaptor AP2 binding region; INTAP is a natively unstructured region of intersectin 1 proteins, lying between the first pair of SH3 domains, that binds to the clathrin adaptor AP2. This binding forms an intersectin-AP2 complex that functions as an important regulator of clathrin-mediated SV recycling in synapses.

Pssm-ID: 435467 Cd Length: 115 Bit Score: 240.17 E-value: 1.48e-73

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  800 KIPESEVPASIKP-AEAAPAPKVSVHETT-TSLGTAASTECTTTANNWADFSSTWPANTNEKPETDNWDAWAAQPSLTVP 877
Cdd:pfam16617    1 KIPESEVPASVKPaADSTAAPKVALRETPtTPLAPPTSSESSTASNNWADFSSTWPTNSSEKAETDNWDAWAAQPSLTVP 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2024344592  878 SAGQLRQRSAFTPATVTGSSPSPVLGQGEKVEGLQ 912
Cdd:pfam16617   81 SAGQLRQRSAFTPATVTGSSPSPVLGQGEKVEGLQ 115

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

Pssm-ID: 238091 [Multi-domain] Cd Length: 181 Bit Score: 179.42 E-value: 2.19e-51

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1231 RQGYIHELIVTEENYVNDLQLVTEIFQKPLMESEL-LTEKEVAMIFVNWKELIMCNIKLLKALRVRKKMSGekMPVKMIG 1309
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1310 DILTAQLPHMQPYIRFCSCQLNGAALIQQKTDEVPEFKEFVKRLamDPRCKGMPLSSFLLKPMQRVTRYPLIIKNIIENT 1389
Cdd:cd00160     79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKA--ESECGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156

                          170       180
                   ....*....|....*....|....*
gi 2024344592 1390 PENHPDHSHLKHALEKAEELCSQVN 1414
Cdd:cd00160    157 PDGHEDREDLKKALEAIKEVASQVN 181

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

Pssm-ID: 459876 [Multi-domain] Cd Length: 176 Bit Score: 174.41 E-value: 9.18e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1235 IHELIVTEENYVNDLQLVTEIFQKPLMESELLTEKEVAMIFVNWKELIMCNIKLLkaLRVRKKmsgEKMPVKMIGDILTA 1314
Cdd:pfam00621    2 IKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLK---EWISIQRIGDIFLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1315 QLPHMQPYIRFCSCQLNGAALIQQKTDEVPEFKEFVKRLAMDPRCKGMPLSSFLLKPMQRVTRYPLIIKNIIENTPENHP 1394
Cdd:pfam00621   77 FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156

                          170       180
                   ....*....|....*....|
gi 2024344592 1395 DHSHLKHALEKAEELCSQVN 1414
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

Pssm-ID: 214619 [Multi-domain] Cd Length: 180 Bit Score: 172.87 E-value: 4.41e-49

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  1235 IHELIVTEENYVNDLQLVTEIFQKPLMESE-LLTEKEVAMIFVNWKELIMCNIKLLKALRVRKKMSGekMPVKMIGDILT 1313
Cdd:smart00325    2 LKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWD--DSVERIGDVFL 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  1314 AQLPHMQPYIRFCSCQLNGAALIQQKTDEvPEFKEFVKRLAMDPRCKGMPLSSFLLKPMQRVTRYPLIIKNIIENTPENH 1393
Cdd:smart00325   80 KLEEFFKIYSEYCSNHPDALELLKKLKKN-PRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158

                           170       180
                    ....*....|....*....|..
gi 2024344592  1394 PDHSHLKHALEKAEELCSQVNE 1415
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 157.82 E-value: 5.25e-45

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592   213 EWAVPQSSRLKYRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLATIWNLSDIDQDGKLTAEEFILAMHLIDVAMSGQ 292
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80

                            90
                    ....*....|....*.
gi 2024344592   293 PLPPVLPPEYIPPSFR 308
Cdd:smart00027   81 PIPASLPPSLIPPSKR 96

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 137.41 E-value: 7.67e-38

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592    14 IWAITVEERAKHDQQFHSLKPT-SGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQLEFSIAMKLIKLKLQGY 92
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNqDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80

                            90
                    ....*....|....
gi 2024344592    93 QLPSALPPVMKQPP 106
Cdd:smart00027   81 PIPASLPPSLIPPS 94

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212926 Cd Length: 65 Bit Score: 130.24 E-value: 9.83e-36

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1069 KKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQ--GKKRQIGWFPANYVKLLSP 1131
Cdd:cd11993      1 KKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQarGKKRQIGWFPANYVKLLSP 65

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 128.58 E-value: 2.77e-35

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVkrewvDESQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11987      1 YYRALYPFEARSHDEITIQPGDIVMV-----DESQTGEPGWLGGELKGKTGWFPANYAEK 55

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 123.91 E-value: 1.04e-33

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1151 CQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11995      1 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGLFPSNYVKL 54

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 122.78 E-value: 2.26e-33

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11991      1 EYVAMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 120.52 E-value: 1.92e-32

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQ--GKKRQIGWFPANYVKL 1128
Cdd:cd11839      1 IAQVIAPFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQarGKKRQIGWFPANYVKL 58

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 115.20 E-value: 9.89e-31

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11838      1 EYIALYPYESNEPGDLTFNAGDVILVTKKDGEWWTGTIGDRTGIFPSNYVRP 52

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 115.21 E-value: 1.04e-30

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11840      1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVEP 53

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 115.20 E-value: 1.39e-30

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11989      1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 52

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 112.45 E-value: 9.80e-30

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVkrewvDESQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11836      1 KYRALYAFEARNPDEISFQPGDIIQV-----DESQVAEPGWLAGELKGKTGWFPANYVEK 55

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 110.07 E-value: 8.15e-29

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1151 CQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11996      1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 54

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 109.38 E-value: 1.42e-28

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQ-GQKGWFPKSYVKL 963
Cdd:cd11837      1 TATALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELEgGEEGWFPKSYVKE 53

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 105.12 E-value: 3.78e-27

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11990      1 KAQALCSWTAKKDNHLNFSKNDIITVLEQQENWWFGEVHGGRGWFPKSYVKL 52

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 102.30 E-value: 6.17e-26

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  224 YRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLATIWNLSDIDQDGKLTAEEFILAMHLIDVAMS 290
Cdd:cd00052      1 YDQIFRSLDPDGDGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 101.14 E-value: 1.51e-25

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592   26 DQQFHSLKPT-SGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQLEFSIAMKLIKLKLQ 90
Cdd:cd00052      2 DQIFRSLDPDgDGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 99.31 E-value: 4.07e-25

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd11992      1 EYIALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVR 51

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 97.69 E-value: 2.06e-24

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQ--GKKRQIGWFPANYVKLL 1129
Cdd:cd11994      1 IAQVTTAYVASGVEQLSLSPGQLILILKKNSSGWWLGELQarGKKRQKGWFPASHVKLL 59

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 97.77 E-value: 6.50e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHI--TKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDD 1666
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKkkTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                           90
                   ....*....|....*..
gi 2024344592 1667 FLGRTEIRVADIKKDQG 1683
Cdd:pfam00168   81 FIGEVRIPLSELDSGEG 97

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 97.17 E-value: 9.02e-24

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  1590 RLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHI---TKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDD 1666
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEkkkTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                            90       100
                    ....*....|....*....|
gi 2024344592  1667 FLGRTEIRVADIKKDQGSKG 1686
Cdd:smart00239   81 FIGQVTIPLSDLLLGGRHEK 100

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 94.44 E-value: 1.05e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1591 LMVNIVEGIELKPCRSHGKSNPYCEVTMGS-QCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDDFLG 1669
Cdd:cd00030      1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFLG 80

                           90
                   ....*....|....*
gi 2024344592 1670 RTEIRVADIKKDQGS 1684
Cdd:cd00030     81 EVEIPLSELLDSGKE 95

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 89.13 E-value: 1.53e-21

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  1149 SVCQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPSNYVK 1203
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 86.46 E-value: 1.52e-20

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  739 IVYYRALYPFESRSHDEITIQPGDIVMVkrewvDESQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11988      1 LVNYRALYPFEARNHDEMSFNAGDIIQV-----DEKTVGEPGWLYGSFQGNFGWFPCNYVEK 57

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 85.21 E-value: 3.93e-20

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPSNY 1201
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNgGREGLFPANY 51

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];

Pssm-ID: 227709 [Multi-domain] Cd Length: 1175 Bit Score: 97.65 E-value: 5.05e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1220 LLDMLTPTERKRQGYIHELIVTEENYVNDLQLVTEIFQKPLMESELLTE----KEVAMIFVNWKELIMCNIKLLKALRVR 1295
Cdd:COG5422    474 VWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPEnarrNFIKHVFANINEIYAVNSKLLKALTNR 553

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1296 KKMSGekmPVKMIGDILTAQLPHMQPYIRFCSCQLNGAALIQQKTDEVPEFKEFVKRLAMDPRCKGMPLSSFLLKPMQRV 1375
Cdd:COG5422    554 QCLSP---IVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRL 630

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1376 TRYPLIIKNIIENTPENHPDHSHLKHALEKAEELCSQVNEGVREKENsdRLEWIQahvqcegLSEQLVFNSVTNCLG--- 1452
Cdd:COG5422    631 ARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAEN--RGDLFH-------LNQQLLFKPEYVNLGlnd 701

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1453 -PRKFLHSGKLY---KAKSNKELYG----FLFNDFLLLTQiIKPLGSSGTDKVFSPKSNLQYkMYKTPIFLNEVLVKLPT 1524
Cdd:COG5422    702 eYRKIIFKGVLKrkaKSKTDGSLRGdiqfFLLDNMLLFCK-AKAVNKWRQHKVFQRPIPLEL-LFISPDEDSPDRAEYLK 779

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1525 D-PSGD--EPIFHISHIDRVY-------------TLRAESINERTAWVQKIK 1560
Cdd:COG5422    780 PaPSADvlDPAYNTKPPKNAYgfelygngqryqiTLYAETHAGRDTWLEHIK 831

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 95.77 E-value: 1.61e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQAL----LEQQRKEQERL-AQLERAEQERKERERQEQERKRQLElekQLEKQRELERQREEERRKEIERREAAK 437
Cdd:COG1196    221 ELKELEAELlllkLRELEAELEELeAELEELEAELEELEAELAELEAELE---ELRLELEELELELEEAQAEEYELLAEL 297

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  438 RELERQRQLewERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRE 517
Cdd:COG1196    298 ARLEQDIAR--LEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELA 375

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  518 LRIAEithlqqqlqesqqmlgklipEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQ 597
Cdd:COG1196    376 EAEEE--------------------LEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEE 435

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  598 EIDIFNNQLKELREihnrQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQ 674
Cdd:COG1196    436 EEEEEEEALEEAAE----EEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGFLE 508

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 83.06 E-value: 2.35e-19

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11805      1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYVQ 52

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 92.69 E-value: 1.36e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  342 EKKLPVTfedkkRENFERGNL---ELEKRRQALlEQQR---------KEQERLAQLERAEQERKERERQEQERKRQL-EL 408
Cdd:COG1196    178 ERKLEAT-----EENLERLEDilgELERQLEPL-ERQAekaeryrelKEELKELEAELLLLKLRELEAELEELEAELeEL 251

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  409 EKQLEKQRelerqreeerrkeierreAAKRELERQRQLEweRNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKK 488
Cdd:COG1196    252 EAELEELE------------------AELAELEAELEEL--RLELEELELELEEAQAEEYELLAELARLEQDIARLEERR 311

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  489 NQLEGKLQdircRLSTQRQEIEstnksrelriAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQnslhrdslltik 568
Cdd:COG1196    312 RELEERLE----ELEEELAELE----------EELEELEEELEELEEELEEAEEELEEAEAELAEAEE------------ 365

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  569 rALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKEL-REIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQ 647
Cdd:COG1196    366 -ALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELeEAEEALLERLERLEEELEELEEALAELEEEEEEEEEAL 444

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  648 RRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQEPVKPAVQAPwsNAGKA 727
Cdd:COG1196    445 EEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGFLEGVKAALLLA--GLRGL 522

                          410
                   ....*....|....*...
gi 2024344592  728 PLTISAQEDVKIVYYRAL 745
Cdd:COG1196    523 AGAVAVLIGVEAAYEAAL 540

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 80.47 E-value: 1.81e-18

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11875      5 LFDYEAENEDELTLREGDIVTILSKDceDKGWWKGELNGKRGVFPDNFVEP 55

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 91.54 E-value: 3.49e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRqALLE---------QQRKEQERlaQLERAEQ--ERKERERQEQERkrQLE-LEKQLEKqrelerqreeerrkeier 432
Cdd:COG1196    155 EERR-AIIEeaagiskykERKEEAER--KLEATEEnlERLEDILGELER--QLEpLERQAEK------------------ 211

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  433 reAAK-RELerqrQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIES 511
Cdd:COG1196    212 --AERyREL----KEELKELEAELLLLKLRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEE 285

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  512 TNKSRELRIAEITHLqqqlqesqqmLGKLIPEKQLLNDQLKQVQQNslhRDSLLTIKRALEAKELARQQLRDQLDEVEKE 591
Cdd:COG1196    286 AQAEEYELLAELARL----------EQDIARLEERRRELEERLEEL---EEELAELEEELEELEEELEELEEELEEAEEE 352

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  592 TRSKLQEIDIFNNQLKEL-REIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEpqwq 670
Cdd:COG1196    353 LEEAEAELAEAEEALLEAeAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEE---- 428

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|.
gi 2024344592  671 kkNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:COG1196    429 --ALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAE 467

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 78.52 E-value: 8.80e-18

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11826      2 VVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYV 51

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 78.15 E-value: 1.26e-17

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11823      6 YSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYV 51

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 77.31 E-value: 2.30e-17

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11766      5 KFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYV 51

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 88.19 E-value: 3.89e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  347 VTFEDKKREN--FERGNlELEKrrqalLEQQRKEQERLA------------QLERAEQERKERERQEQERKRQL-ELEKQ 411
Cdd:TIGR02168  661 ITGGSAKTNSsiLERRR-EIEE-----LEEKIEELEEKIaelekalaelrkELEELEEELEQLRKELEELSRQIsALRKD 734

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  412 LEK-QRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQ 490
Cdd:TIGR02168  735 LARlEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKALREALDELRAELTL 814

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  491 LEGKLQDIRCRLSTQRQEIESTNKS---RELRIAEITHLQQQLQESQQMLGKLIPE-----KQLLNDQLKQVQQNSLHRD 562
Cdd:TIGR02168  815 LNEEAANLRERLESLERRIAATERRledLEEQIEELSEDIESLAAEIEELEELIEEleselEALLNERASLEEALALLRS 894

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  563 SLLTIKRALEAKELARQQLRDQLDEV-EKETRSKLQEIDIfnnqlkELREIHNRQQLQKQKNLEAERLKQKEQERKTELE 641
Cdd:TIGR02168  895 ELEELSEELRELESKRSELRRELEELrEKLAQLELRLEGL------EVRIDNLQERLSEEYSLTLEEAEALENKIEDDEE 968

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  642 KQKEAQRRIQdRDKQRLDRVQQE--EEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQ 707
Cdd:TIGR02168  969 EARRRLKRLE-NKIKELGPVNLAaiEEYEELKERYDFLTAQKEDLTEAKETLEEAIEEIDREARERFK 1035

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 78.10 E-value: 8.64e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1606 SHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQfSPDDFLGRTEIRVADIKKdqgsK 1685
Cdd:cd08391     24 VKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDP-DKDDFLGRLSIDLGSVEK----K 98

                           90       100
                   ....*....|....*....|.
gi 2024344592 1686 GPVTKCLLLHEVPTGEIVVRL 1706
Cdd:cd08391     99 GFIDEWLPLEDVKSGRLHLKL 119

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 75.63 E-value: 9.83e-17

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11950      1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 52

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 75.58 E-value: 1.16e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1150 VCQVigMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd12142      1 YCRV--LFDYNPVAPDELALKKGDVIEVISKetEDEGWWEGELNGRRGFFPDNFV 53

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 75.04 E-value: 1.49e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVKE 53

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 74.77 E-value: 1.84e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDG---DWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11842      3 VALYDFAGEQPGDLAFQKGDIITILKKSDsqnDWWTGRIGGREGIFPANYVEL 55

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 74.49 E-value: 2.15e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11949      2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 52

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 74.68 E-value: 2.28e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1151 CQVIgmYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11874      2 CKVL--FSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 53

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 74.60 E-value: 2.31e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVklTTD 1207
Cdd:cd11964      2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFV--TAD 55

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 74.32 E-value: 2.68e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKE-DPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11804      3 VAKHDFKATAEDELSFKKGSILKVLNMEdDPNWYKAELDGKEGLIPKNYI 52

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 73.59 E-value: 4.69e-16

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPD----WWKGEVNGQVGLFPS 1199
Cdd:cd11762      5 LYDYEAQSDEELSFPEGAIIRILRKDDNGvddgWWEGEFNGRVGVFPS 52

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 84.81 E-value: 4.78e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEK----------RRQALL--EQQRK--------EQERLAQLERAEQERK--ERERQEQERKRQLE 407
Cdd:PTZ00121  1240 EEAKKAEEERNNEEIRKfeearmahfaRRQAAIkaEEARKadelkkaeEKKKADEAKKAEEKKKadEAKKKAEEAKKADE 1319

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  408 LEKQLEKQRELERQREEERRKEIERREAAKRELERQRQlEWERNRRQELLNQRNREQEDIVVLKAKKKTLEF-ELEALND 486
Cdd:PTZ00121  1320 AKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAAD-EAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKkKADEAKK 1398

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  487 KKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLT 566
Cdd:PTZ00121  1399 KAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKK 1478

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  567 IKRALEAKELAR--QQLRDQLDEVEK--ETRSKLQEIDIFNNQLK--ELREIHNRQQLQKQKNLE----------AERLK 630
Cdd:PTZ00121  1479 AEEAKKADEAKKkaEEAKKKADEAKKaaEAKKKADEAKKAEEAKKadEAKKAEEAKKADEAKKAEekkkadelkkAEELK 1558

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  631 QKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQ-----EIQEKPSKL 705
Cdd:PTZ00121  1559 KAEEKKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEElkkaeEEKKKVEQL 1638

                          410
                   ....*....|...
gi 2024344592  706 FQPHQEPVKPAVQ 718
Cdd:PTZ00121  1639 KKKEAEEKKKAEE 1651

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 73.49 E-value: 5.50e-16

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11772      5 LYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYV 51

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 72.96 E-value: 7.47e-16

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592   998 SGEEYVAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGD-KTGVFPSNYVR 1051
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKsDDGWWKGRLGRgKEGLFPSNYVE 56

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 83.65 E-value: 1.12e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLElEKRRQALLEQQRKEQERLAQLERAEQERKERE---RQEQERKRQLELEKQLEKQRELERQREEER 426
Cdd:PTZ00121  1415 AAKKKADEAKKKAE-EKKKADEAKKKAEEAKKADEAKKKAEEAKKAEeakKKAEEAKKADEAKKKAEEAKKADEAKKKAE 1493

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  427 RKEIERREAAKRELERQRQLEW---ERNRRQELLN--QRNREQEDIVVLKAKKKTLEF----ELEALNDKKNQLEGKLQD 497
Cdd:PTZ00121  1494 EAKKKADEAKKAAEAKKKADEAkkaEEAKKADEAKkaEEAKKADEAKKAEEKKKADELkkaeELKKAEEKKKAEEAKKAE 1573

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  498 IRCRLSTQRQEIesTNKSRELRIAEITHLQQQlqesqqmlgklipEKQLLNDQLKQVQQNSLHRDSLltiKRALEAKELA 577
Cdd:PTZ00121  1574 EDKNMALRKAEE--AKKAEEARIEEVMKLYEE-------------EKKMKAEEAKKAEEAKIKAEEL---KKAEEEKKKV 1635

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  578 RQQLRDQLDEVEK--ETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDK 655
Cdd:PTZ00121  1636 EQLKKKEAEEKKKaeELKKAEEENKIKAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKEAEEAKKAEELKKKEAEEK 1715

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  656 QRLDRVQQEEEPQWQK-----KNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:PTZ00121  1716 KKAEELKKAEEENKIKaeeakKEAEEDKKKAEEAKKDEEEKKKIAHLKKEEEKKAEEIRKE 1776

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 80.35 E-value: 1.13e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  362 LELEKRRQALLEQQRKEQERLAQLER----AEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAK 437
Cdd:pfam13868   28 IAEKKRIKAEEKEEERRLDEMMEEEReralEEEEEKEEERKEERKRYRQELEEQIEEREQKRQEEYEEKLQEREQMDEIV 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  438 RELERQRQLEWERNRRQELLNQrnREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIrcRLSTQRQEIESTNKSRE 517
Cdd:pfam13868  108 ERIQEEDQAEAEEKLEKQRQLR--EEIDEFNEEQAEWKELEKEEEREEDERILEYLKEKAE--REEEREAEREEIEEEKE 183

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  518 LRIAEITHlqqqlqesqqmlgklipekqllndQLKQVQQNSLHRDSLLtIKRALEAKElaRQQLRDQLDEVEKETRsklQ 597
Cdd:pfam13868  184 REIARLRA------------------------QQEKAQDEKAERDELR-AKLYQEEQE--RKERQKEREEAEKKAR---Q 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  598 EIDIFNNQLKELREIHNRQQLQKQKN-LEAERL--KQKEQERKTELEKQKEAQRR----------IQDRDKQRLDRVQQE 664
Cdd:pfam13868  234 RQELQQAREEQIELKERRLAEEAEREeEEFERMlrKQAEDEEIEQEEAEKRRMKRlehrrelekqIEEREEQRAAEREEE 313

                          330       340
                   ....*....|....*....|....
gi 2024344592  665 EEPQWQKKNQEDDKQKREEIIKKK 688
Cdd:pfam13868  314 LEEGERLREEEAERRERIEEERQK 337

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 71.88 E-value: 1.71e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:pfam14604    2 LYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 71.47 E-value: 2.28e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPS 1199
Cdd:pfam00018    3 LYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKgGKEGLIPS 47

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 71.47 E-value: 2.73e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1151 CQVIgmYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd12057      2 CKVL--FPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRRGVFPDNFVKL 55

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 71.03 E-value: 3.59e-15

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592   909 EGLQAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQ-GQKGWFPKSYVK 962
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDdGWWKGRLGrGKEGLFPSNYVE 56

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Pssm-ID: 289529 Cd Length: 104 Bit Score: 72.79 E-value: 3.86e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  223 KYRQLFNSHdKTMSGHLTGPQARTILMQSSLPQAQLATIWNLSDIDQDGKLTAEEFILAMHLIDVAMSG--QPLPPVLPP 300
Cdd:pfam12763   11 KYWEIFSGL-KPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLIFDLVNGniADVPDELPD 89


                   ....*.
gi 2024344592  301 EYIPPS 306
Cdd:pfam12763   90 WLVPGS 95

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 81.73 E-value: 4.45e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  351 DKKRENFERGNLELEKRRQAL---LEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERR 427
Cdd:PTZ00121  1363 EEKAEAAEKKKEEAKKKADAAkkkAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAKKKAEE 1442

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  428 KEIERReaAKRELERQRQLE-----WERNRRQELLNQRNREQEDivVLKAKKKTLEFELEALNDKKNQLEGKLQDiRCRL 502
Cdd:PTZ00121  1443 AKKADE--AKKKAEEAKKAEeakkkAEEAKKADEAKKKAEEAKK--ADEAKKKAEEAKKKADEAKKAAEAKKKAD-EAKK 1517

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  503 STQRQEIESTNKSRELRIAEitHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAK--ELARQQ 580
Cdd:PTZ00121  1518 AEEAKKADEAKKAEEAKKAD--EAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKAEEAKkaEEARIE 1595

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  581 LRDQLDEVEKETRS----KLQEIDIFNNQLKELREIhnRQQLQKQKNLEAERLKQKEQERKTELEK--QKEAQRRIQDRD 654
Cdd:PTZ00121  1596 EVMKLYEEEKKMKAeeakKAEEAKIKAEELKKAEEE--KKKVEQLKKKEAEEKKKAEELKKAEEENkiKAAEEAKKAEED 1673

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  655 KQRLDRVQQEEEpqwQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQEPVKPAVQA 719
Cdd:PTZ00121  1674 KKKAEEAKKAEE---DEKKAAEALKKEAEEAKKAEELKKKEAEEKKKAEELKKAEEENKIKAEEA 1735

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 70.23 E-value: 8.23e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE-VNGQVGLFPSNYV 1202
Cdd:cd11812      2 VVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSlVNGQQGYFPANYV 52

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 69.80 E-value: 9.30e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11820      2 KVRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFVT 53

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Pssm-ID: 289529 Cd Length: 104 Bit Score: 71.64 E-value: 9.63e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592   21 ERAKHDQQFHSLKPTSGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQLEFSIAMKLIKLKLQGYQ--LPSAL 98
Cdd:pfam12763    8 EIKKYWEIFSGLKPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLIFDLVNGNIadVPDEL 87


                   .
gi 2024344592   99 P 99
Cdd:pfam12763   88 P 88

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 69.83 E-value: 9.71e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11951      6 YDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGFFPRNYV 51

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 70.05 E-value: 9.91e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQ-VGLFPSNYVK 1203
Cdd:cd11825      5 LYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKkQKWFPANYVE 53

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 70.05 E-value: 9.92e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVklTTDM 1208
Cdd:cd11963      3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGLFPSNFV--TTDL 57

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 68.99 E-value: 2.02e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDP--DWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSqnDWWTGRIGGREGIFPANYVEL 55

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 68.60 E-value: 2.42e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1151 CQVIgmYDYTAQNDDELAFNKGQIINVLnKEDPD-WWKGEVNGQVGLFPSNYV 1202
Cdd:cd11827      2 CKAL--YAYDAQDTDELSFNEGDIIEIL-KEDPSgWWTGRLRGKEGLFPGNYV 51

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 68.72 E-value: 2.73e-14

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  1070 KPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRqiGWFPANYVK 1127
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKE--GLFPSNYVE 56

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 68.26 E-value: 2.88e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGD-KTGVFPSNY 1049
Cdd:cd00174      2 ARALYDYEAQDDDELSFKKGDIITVLEKdDDGWWEGELNGgREGLFPANY 51

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 68.60 E-value: 3.17e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11959      3 VALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYGLFPANYVEL 53

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 67.95 E-value: 4.33e-14

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592   738 KIVYYRALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELK-GKTGWFPANYAE 799
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEK-------SDDGWWKGRLGrGKEGLFPSNYVE 56

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 67.87 E-value: 5.22e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRqiGWFPANY 1125
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGGRE--GLFPANY 51

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 67.78 E-value: 5.39e-14

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11824      5 LYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLEK 53

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 77.79 E-value: 5.90e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  347 VTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQER-----KRQLELEKQLEKQRELERq 421
Cdd:TIGR02168  234 LEELREELEELQEELKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKElyalaNEISRLEQQKQILRERLA- 312

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  422 reeerrkeierreAAKRELER-QRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRC 500
Cdd:TIGR02168  313 -------------NLERQLEElEAQLEELESKLDELAEELAELEEKLEELKEELESLEAELEELEAELEELESRLEELEE 379

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  501 RLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDsLLTIKRALEAKELARQQ 580
Cdd:TIGR02168  380 QLETLRSKVAQLELQIASLNNEIERLEARLERLEDRRERLQQEIEELLKKLEEAELKELQAE-LEELEEELEELQEELER 458

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  581 LRDQLDEVEKETRSKLQEIDIFNNQLKELR-EIHNRQQLQKQKNLEAERLKQKEQERK 637
Cdd:TIGR02168  459 LEEALEELREELEEAEQALDAAERELAQLQaRLDSLERLQENLEGFSEGVKALLKNQS 516

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 67.28 E-value: 7.38e-14

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11803      6 LYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGFFPVNYV 52

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 67.29 E-value: 7.77e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11873      2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 67.16 E-value: 8.46e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11961      2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGLFPSNYVEL 53

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 75.93 E-value: 1.34e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  362 LELEKRRQALLEQQRKEQ-ERLAQlERAEQERKERERqEQERKRQLElEKQLEKQrelerqreeERRKEIERREAAKREL 440
Cdd:pfam17380  275 LHIVQHQKAVSERQQQEKfEKMEQ-ERLRQEKEEKAR-EVERRRKLE-EAEKARQ---------AEMDRQAAIYAEQERM 342

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  441 ERQRQLEWERNRRQEllnqRNREQEDIvvlkaKKKTLEFELEALND-KKNQLEGKLQDIRCrlstqRQEIEStnkSRELR 519
Cdd:pfam17380  343 AMERERELERIRQEE----RKRELERI-----RQEEIAMEISRMRElERLQMERQQKNERV-----RQELEA---ARKVK 405

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  520 IAEithlqqqlqesqQMLGKLIPEKQLLNDQLKQVQQNSLHRDSlltikRALEaKELARQQLRDQLDEVEKEtrsklQEI 599
Cdd:pfam17380  406 ILE------------EERQRKIQQQKVEMEQIRAEQEEARQREV-----RRLE-EERAREMERVRLEEQERQ-----QQV 462

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  600 DIFNNQLKELReihnRQQLQKQKnlEAERLKQKEQERKTELEKQKEAQRR--IQDRDKQRLDRVQQEEEpqwQKKNQEDD 677
Cdd:pfam17380  463 ERLRQQEEERK----RKKLELEK--EKRDRKRAEEQRRKILEKELEERKQamIEEERKRKLLEKEMEER---QKAIYEEE 533

                          330       340
                   ....*....|....*....|....
gi 2024344592  678 KQKREEIIKKKESEDKGKQEIQEK 701
Cdd:pfam17380  534 RRREAEEERRKQQEMEERRRIQEQ 557

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 66.79 E-value: 1.43e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1150 VCQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11956      1 EVEAVACFDYTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMRGLIPHKYISV 55

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 66.55 E-value: 1.45e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVT-KKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11772      2 FRALYDYEAQHPDELSFEEGDLLYISdKSDPNWWKATCGGKTGLIPSNYV 51

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 175990 [Multi-domain] Cd Length: 128 Bit Score: 68.99 E-value: 1.62e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIEL--KPCRSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDD 1666
Cdd:cd04024      1 GVLRVHVVEAKDLaaKDRSGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1667 FLGRTEIRVADIKKDqGSKGPVTKCLLLHEVPT-------GEIVVRLDL 1708
Cdd:cd04024     81 YLGEFDIALEEVFAD-GKTGQSDKWITLKSTRPgktsvvsGEIHLQFSW 128

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 66.19 E-value: 1.69e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11826      3 VALYDYTADKDDELSFQEGDIIYVTKKNDDgWYEGVLNGVTGLFPGNYV 51

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 66.50 E-value: 1.69e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11805      4 ALYDFNPQEPGELEFRRGDIITVLDSsDPDWWKGELRGRVGIFPANYV 51

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 66.18 E-value: 1.81e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11877      4 AKFNFEGTNEDELSFDKGDIITVTQVvEGGWWEGTLNGKTGWFPSNYVKE 53

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 69.28 E-value: 1.87e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1588 IGRLMVNIVEGIELKPCRSHGkSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQdVLCITVFERDQFSPDDF 1667
Cdd:cd04038      1 LGLLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMA-PLKLEVFDKDTFSKDDS 78


                   ....*.
gi 2024344592 1668 LGRTEI 1673
Cdd:cd04038     79 MGEAEI 84

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 66.07 E-value: 2.05e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12052      6 FDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRGLFPDNFVR 52

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 65.88 E-value: 2.22e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILV---TKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11841      4 ALYSFEGQQPCDLSFQAGDRITVltrTDSQFDWWEGRLRGRVGIFPANYV 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 66.18 E-value: 2.24e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQ---VGLFPSNY 1201
Cdd:cd11821      5 LYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGDpsrRGVFPVSF 53

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 65.95 E-value: 2.32e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQ-GQKGWFPKSY 960
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDgWWEGELNgGREGLFPANY 51

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 65.90 E-value: 2.40e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11840      3 IALFPYTAQNEDELSFQKGDIInVLSKDDPDWWRGELNGQTGLFPSNYV 51

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 65.68 E-value: 2.44e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNY 1201
Cdd:cd11845      1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARhlSTGKEGYIPSNY 52

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 75.56 E-value: 3.23e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERE-RQEQERKRQLELEKQLEKQRELERQREEERrk 428
Cdd:PTZ00121  1480 EEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEaKKAEEAKKADEAKKAEEKKKADELKKAEEL-- 1557

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  429 eierreaakRELERQRQLEwERNRRQELLNQRNREQEdiVVLKAKKKTLEFELEALNDKKnqlegklqdiRCRLSTQRQE 508
Cdd:PTZ00121  1558 ---------KKAEEKKKAE-EAKKAEEDKNMALRKAE--EAKKAEEARIEEVMKLYEEEK----------KMKAEEAKKA 1615

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  509 IESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAK--ELARQQLRDQLD 586
Cdd:PTZ00121  1616 EEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKAEEAKkaEEDEKKAAEALK 1695

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  587 EVEKETRsKLQEIdifnnQLKELREIHNRQQLQKQKnlEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEE 666
Cdd:PTZ00121  1696 KEAEEAK-KAEEL-----KKKEAEEKKKAEELKKAE--EENKIKAEEAKKEAEEDKKKAEEAKKDEEEKKKIAHLKKEEE 1767

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 2024344592  667 pqwqkKNQEDDKQKREEIIKK--KESEDKGKQEIQEKPSKLF 706
Cdd:PTZ00121  1768 -----KKAEEIRKEKEAVIEEelDEEDEKRRMEVDKKIKDIF 1804

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 65.41 E-value: 3.87e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPSNYVKL 1204
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAkGQKGLFPANYVEL 54

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 65.44 E-value: 3.95e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11823      3 KALYSYTANREDELSLQPGDIIEVHEK-------QDDGWWLGELNGKKGIFPATYVE 52

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 65.44 E-value: 4.04e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11781      3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGIFPASYVEI 53

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 75.18 E-value: 4.38e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  349 FEDKKREnfERGNLElEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQreeerrk 428
Cdd:PTZ00121  1100 AEEAKKT--ETGKAE-EARKAEEAKKKAEDARKAEEARKAEDARKAEEARKAEDAKRVEIARKAEDARKAEEA------- 1169

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  429 eierreaakRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTlEFELEALNDKKNQLEGKLQDIRcRLSTQRQE 508
Cdd:PTZ00121  1170 ---------RKAEDAKKAEAARKAEEVRKAEELRKAEDARKAEAARKA-EEERKAEEARKAEDAKKAEAVK-KAEEAKKD 1238

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  509 IESTNKSRELRIAEITHLQQQLQESQQMLGKLIP--EKQLLNDQLKQVQQNSLHRDSLLT--IKRALEAKELARQQLR-D 583
Cdd:PTZ00121  1239 AEEAKKAEEERNNEEIRKFEEARMAHFARRQAAIkaEEARKADELKKAEEKKKADEAKKAeeKKKADEAKKKAEEAKKaD 1318

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  584 QLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKeaqrriQDRDKQRLDRVQQ 663
Cdd:PTZ00121  1319 EAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAKKK------ADAAKKKAEEKKK 1392

                          330       340       350
                   ....*....|....*....|....*....|....*...
gi 2024344592  664 EEEpqwQKKNQEDDKQKREEiIKKKESEDKGKQEIQEK 701
Cdd:PTZ00121  1393 ADE---AKKKAEEDKKKADE-LKKAAAAKKKADEAKKK 1426

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 65.23 E-value: 4.72e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKE-----DPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11876      5 LFDYDARGEDELTLRRGQPVEVLSKDaavsgDEGWWTGKIGDKVGIFPSNYV 56

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 65.09 E-value: 4.80e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12061      6 FNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVR 52

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 65.03 E-value: 5.05e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYVKL 1128
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGK---TGWFPSNYVKE 53

Caldesmon;

Pssm-ID: 460421 [Multi-domain] Cd Length: 495 Bit Score: 73.36 E-value: 6.17e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  386 ERAEQERKERERQEQERKRQLE--------LEKQLEKQRELERQREEERRKEIERREAA------KRELERQRQLEWERN 451
Cdd:pfam02029    5 EEAARERRRRAREERRRQKEEEepsgqvteSVEPNEHNSYEEDSELKPSGQGGLDEEEAfldrtaKREERRQKRLQEALE 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  452 RRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKL----------QDIRCRLSTQRQEIESTNKSRELRIA 521
Cdd:pfam02029   85 RQKEFDPTIADEKESVAERKENNEEEENSSWEKEEKRDSRLGRYkeeeteirekEYQENKWSTEVRQAEEEGEEEEDKSE 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  522 EITHL-QQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRD----SLLTIKRALEAKELARQQLRDQLDEVEKETRSKL 596
Cdd:pfam02029  165 EAEEVpTENFAKEEVKDEKIKKEKKVKYESKVFLDQKRGHPEvksqNGEEEVTKLKVTTKRRQGGLSQSQEREEEAEVFL 244

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  597 QEidifNNQLKELreihnRQQLQKQKNLEAERLKQKEQERKTELE---KQKEAQRRIQDRDKQRldRVQQEEEPqwQKKN 673
Cdd:pfam02029  245 EA----EQKLEEL-----RRRRQEKESEEFEKLRQKQQEAELELEelkKKREERRKLLEEEEQR--RKQEEAER--KLRE 311

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....
gi 2024344592  674 QEDDKQKREEIIK---------KKESEDKGKQEiqEKPSKLFQP 708
Cdd:pfam02029  312 EEEKRRMKEEIERrraeaaekrQKLPEDSSSEG--KKPFKCFSP 353

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 64.92 E-value: 6.25e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1150 VCQVIGmyDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:pfam07653    1 YGRVIF--DYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVEE 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 64.75 E-value: 6.47e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYV 1202
Cdd:cd11843      2 VRALYDYEGQESDELSFKAGDILTKLEEEDEQgWCKGRLDGRVGLYPANYV 52

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 66.82 E-value: 7.06e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1591 LMVNIVEGIELKPCRSHGKSNPYCEVTM-GSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDDFLG 1669
Cdd:cd04040      1 LTVDVISAENLPSADRNGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKDDLLG 80


                   ....*....
gi 2024344592 1670 RTEIRVADI 1678
Cdd:cd04040     81 SAYIDLSDL 89

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 73.62 E-value: 7.12e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERgnLELEKRRQALlEQQRKEQERLAQLERAEQERK-----------ERERQEQERKRQLELEKQLEKQREL 418
Cdd:pfam17380  286 ERQQQEKFEK--MEQERLRQEK-EEKAREVERRRKLEEAEKARQaemdrqaaiyaEQERMAMERERELERIRQEERKREL 362

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  419 ERQREEERRKeierreaakrELERQRQLEWERNRRQElLNQRNREQedivvLKAKKKTLEFELEALNDKKNQLEgKLQDI 498
Cdd:pfam17380  363 ERIRQEEIAM----------EISRMRELERLQMERQQ-KNERVRQE-----LEAARKVKILEEERQRKIQQQKV-EMEQI 425

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  499 RCRLSTQRQ-EIESTNKSRELRIAEITHLQQqlqesqqmlgklipEKQLLNDQLKqvQQNSLHRDSLLTIKRALEAKELA 577
Cdd:pfam17380  426 RAEQEEARQrEVRRLEEERAREMERVRLEEQ--------------ERQQQVERLR--QQEEERKRKKLELEKEKRDRKRA 489

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  578 RQQLRDQLDEVEKETRSKLQEidifnnqLKELREIHNRQQLQKQKNL-EAERLKQKEQERKTELE----KQKEAQRRIQD 652
Cdd:pfam17380  490 EEQRRKILEKELEERKQAMIE-------EERKRKLLEKEMEERQKAIyEEERRREAEEERRKQQEmeerRRIQEQMRKAT 562

                          330       340       350
                   ....*....|....*....|....*....|
gi 2024344592  653 RDKQRLDRVQQEEEPQWQKKNQEDDKQKRE 682
Cdd:pfam17380  563 EERSRLEAMEREREMMRQIVESEKARAEYE 592

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 64.47 E-value: 7.71e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1150 VCQViGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKLT 1205
Cdd:cd12073      1 ICAV-ALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVELL 55

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 64.31 E-value: 8.41e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDpDWWKGEV-NGQVGLFPSNYVKL 1204
Cdd:cd11837      1 TATALYPWRAKKENHLSFAKGDIITVLEQQE-MWWFGELeGGEEGWFPKSYVKE 53

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 64.34 E-value: 9.35e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDP--DWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11841      1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRLRGRVGIFPANYVS 54

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 72.88 E-value: 1.04e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  340 QLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL-ELEKQLEKQREL 418
Cdd:COG4717    106 ELEAELEELREELEKLEKLLQLLPLYQELEALEAELAELPERLEELEERLEELRELEEELEELEAELaELQEELEELLEQ 185

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  419 ERQREEERRKEierreaAKRELERQRQlewernRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGK---- 494
Cdd:COG4717    186 LSLATEEELQD------LAEELEELQQ------RLAELEEELEEAQEELEELEEELEQLENELEAAALEERLKEARllll 253

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  495 LQDIRCRLSTQRQEIESTnksrELRIAEIThlQQQLQESQQMLGKLIPEKQLLNDQLKQVQ----QNSLHRDSLLTIKRA 570
Cdd:COG4717    254 IAAALLALLGLGGSLLSL----ILTIAGVL--FLVLGLLALLFLLLAREKASLGKEAEELQalpaLEELEEEELEELLAA 327

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  571 LEAK-ELARQQLRDQLDEVEkETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAE-----RLKQKEQERKTElEKQK 644
Cdd:COG4717    328 LGLPpDLSPEELLELLDRIE-ELQELLREAEELEEELQLEELEQEIAALLAEAGVEDEeelraALEQAEEYQELK-EELE 405

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  645 EAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEdDKQKREEIIKKKESEDKGKQEIQEK 701
Cdd:COG4717    406 ELEEQLEELLGELEELLEALDEEELEEELEE-LEEELEELEEELEELREELAELEAE 461

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 64.26 E-value: 1.18e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11972      4 KVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVE 55

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 71.72 E-value: 1.26e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  450 RNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKsrelRIAEIthlqqq 529
Cdd:COG4942     26 EAELEQLQQEIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAELAELEK----EIAEL------ 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  530 lqesqqmLGKLIPEKQLLNDQLKQVQQNSLHrDSLLTIKRALEAKELARQQlrDQLDEVEKETRSKLQEIdifNNQLKEL 609
Cdd:COG4942     96 -------RAELEAQKEELAELLRALYRLGRQ-PPLALLLSPEDFLDAVRRL--QYLKYLAPARREQAEEL---RADLAEL 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  610 REIhnRQQLQKQKNlEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDrvQQEEEPQWQKKNQEDDKQKREEIIKKKE 689
Cdd:COG4942    163 AAL--RAELEAERA-ELEALLAELEEERAALEALKAERQKLLARLEKELA--ELAAELAELQQEAEELEALIARLEAEAA 237


                   ....
gi 2024344592  690 SEDK 693
Cdd:COG4942    238 AAAE 241

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 63.89 E-value: 1.39e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11971      1 KVVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVE 52

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 63.83 E-value: 1.45e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1151 CQVigMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12054      3 CKV--LFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVK 53

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 73.17 E-value: 1.54e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  359 RGNLElekRRQALLEQQRKEQERL-AQLERAEqerKERERQEQERKRQLELEKQ--LEKQRELerqreeerrkeierrea 435
Cdd:TIGR02168  185 RENLD---RLEDILNELERQLKSLeRQAEKAE---RYKELKAELRELELALLVLrlEELREEL----------------- 241

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  436 akrelerqRQLEWERNRRQEllnQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKS 515
Cdd:TIGR02168  242 --------EELQEELKEAEE---ELEELTAELQELEEKLEELRLEVSELEEEIEELQKELYALANEISRLEQQKQILRER 310

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  516 RELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNS-LHRDSLLTIKRALEAKELARQQLRDQLDEVEKETRS 594
Cdd:TIGR02168  311 LANLERQLEELEAQLEELESKLDELAEELAELEEKLEELKEELeSLEAELEELEAELEELESRLEELEEQLETLRSKVAQ 390

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  595 KLQEIDIFNNQLKELREihnrQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQ 674
Cdd:TIGR02168  391 LELQIASLNNEIERLEA----RLERLEDRRERLQQEIEELLKKLEEAELKELQAELEELEEELEELQEELERLEEALEEL 466

                          330       340       350
                   ....*....|....*....|....*....|..
gi 2024344592  675 eddkqkREEIIKKKESEDKGKQEIQEKPSKLF 706
Cdd:TIGR02168  467 ------REELEEAEQALDAAERELAQLQARLD 492

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 63.80 E-value: 1.57e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11894      2 VKALYDYEGQTDDELSFPEGAIIRILNKENQDddgFWEGEFNGRIGVFPSVLVE 55

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 63.52 E-value: 1.60e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11823      1 RCKALYSYTANREDELSLQPGDIIEVHEKQdDGWWLGELNGKKGIFPATYV 51

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 63.89 E-value: 1.65e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKE-DPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11946      2 EAIAKYDFKATADDELSFKRGDILKVLNEEcDQNWYKAELNGKDGFIPKNYIEM 55

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 72.79 E-value: 1.67e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  349 FEDKKRENFErgnlELEKRRQALLEQQRKEQERLAQLERAEQER--KERERQEQERKRQLEL-EKQLEKQRELERQREEE 425
Cdd:TIGR02169  168 FDRKKEKALE----ELEEVEENIERLDLIIDEKRQQLERLRRERekAERYQALLKEKREYEGyELLKEKEALERQKEAIE 243

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  426 RRKEIERREAAKRELERQrQLEWERNRRQELLNQRNRE------------QEDIVVLKAKKKTLEFELEALNDKKNQLEG 493
Cdd:TIGR02169  244 RQLASLEEELEKLTEEIS-ELEKRLEEIEQLLEELNKKikdlgeeeqlrvKEKIGELEAEIASLERSIAEKERELEDAEE 322

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  494 KLQDIRCRLSTQRQEIESTnkSRELRiaeithlqQQLQESQQMLGKLIPEKQLLNDQLKQVQQ----NSLHRDSLLTIKR 569
Cdd:TIGR02169  323 RLAKLEAEIDKLLAEIEEL--EREIE--------EERKRRDKLTEEYAELKEELEDLRAELEEvdkeFAETRDELKDYRE 392

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  570 ALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNrqQLQKQKNLEAERLKQKEQERKTELEKQKEAQRR 649
Cdd:TIGR02169  393 KLEKLKREINELKRELDRLQEELQRLSEELADLNAAIAGIEAKIN--ELEEEKEDKALEIKKQEWKLEQLAADLSKYEQE 470

                          330
                   ....*....|....*
gi 2024344592  650 IQDRdKQRLDRVQQE 664
Cdd:TIGR02169  471 LYDL-KEEYDRVEKE 484

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 63.69 E-value: 1.80e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd12056      7 LFHYEGTNEDELDFKEGEIILIISKDtgEPGWWKGELNGKEGVFPDNFVSQ 57

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 65.78 E-value: 1.89e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLeQDVLCITVFERDQFSPDDFL 1668
Cdd:cd08377      1 GFLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDI-HDVLEVTVYDEDKDKKPEFL 79

                           90
                   ....*....|.
gi 2024344592 1669 GRTEIRVADIK 1679
Cdd:cd08377     80 GKVAIPLLSIK 90

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 72.48 E-value: 2.28e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEKRRQAL--LEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERR 427
Cdd:PTZ00121  1455 EAKKAEEAKKKAEEAKKADEAKkkAEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAK 1534

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  428 KEIERREAA-KRELERQRQLEwERNRRQEL--LNQRNREQEDIVVLKAKKKtlefELEALNDKKNQLEGKLQDIRCRLST 504
Cdd:PTZ00121  1535 KADEAKKAEeKKKADELKKAE-ELKKAEEKkkAEEAKKAEEDKNMALRKAE----EAKKAEEARIEEVMKLYEEEKKMKA 1609

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  505 Q--RQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKElARQQLR 582
Cdd:PTZ00121  1610 EeaKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKAEEAKK-AEEDEK 1688

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  583 DQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERK---TELEKQKEAQRRIQDRDKQ--- 656
Cdd:PTZ00121  1689 KAAEALKKEAEEAKKAEELKKKEAEEKKKAEELKKAEEENKIKAEEAKKEAEEDKkkaEEAKKDEEEKKKIAHLKKEeek 1768

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....
gi 2024344592  657 RLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQE 700
Cdd:PTZ00121  1769 KAEEIRKEKEAVIEEELDEEDEKRRMEVDKKIKDIFDNFANIIE 1812

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 72.10 E-value: 3.65e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERgnlELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLE---KQRELERQREEER 426
Cdd:PTZ00121  1149 EDAKRVEIAR---KAEDARKAEEARKAEDAKKAEAARKAEEVRKAEELRKAEDARKAEAARKAEeerKAEEARKAEDAKK 1225

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  427 RKEIERREAAKRELERQRQLEWERNRRQELLNQRNREQE---DIVVLKAKKKTLEFELEALNDKKNQLEGKlqdircRLS 503
Cdd:PTZ00121  1226 AEAVKKAEEAKKDAEEAKKAEEERNNEEIRKFEEARMAHfarRQAAIKAEEARKADELKKAEEKKKADEAK------KAE 1299

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  504 TQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSlHRDSLLTIKRALEAKELARQQLRD 583
Cdd:PTZ00121  1300 EKKKADEAKKKAEEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEA-AADEAEAAEEKAEAAEKKKEEAKK 1378

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  584 QLDEVEK--ETRSKLQEIDIFNNQLKELREIHNRQQLQKQKnleAERLKQKEQERKT--ELEKQKEAQRRIQDRDKQRLD 659
Cdd:PTZ00121  1379 KADAAKKkaEEKKKADEAKKKAEEDKKKADELKKAAAAKKK---ADEAKKKAEEKKKadEAKKKAEEAKKADEAKKKAEE 1455

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  660 RVQQEEEPQ--WQKKNQEDDKQKREEiiKKKESEDKGKQEIQEKPSKLFQPHQEPVKPAVQA 719
Cdd:PTZ00121  1456 AKKAEEAKKkaEEAKKADEAKKKAEE--AKKADEAKKKAEEAKKKADEAKKAAEAKKKADEA 1515

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 71.51 E-value: 4.20e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEKRRQALLEQQRkEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKE 429
Cdd:COG1196    397 ELAAQLEELEEAEEALLERLERLEEEL-EELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALL 475

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  430 IERREAAKRELERQRQLEWERN-------------RRQELLNQRNREQEDIVVLKAKKKTLEFELEALndkknqLEGKLQ 496
Cdd:COG1196    476 EAALAELLEELAEAAARLLLLLeaeadyegflegvKAALLLAGLRGLAGAVAVLIGVEAAYEAALEAA------LAAALQ 549

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  497 DIRCRLSTQRQEIESTNKSRELRIAEI----THLQQQLQESQQMLGKLIPE--------------KQLLNDQLKQVQQNS 558
Cdd:COG1196    550 NIVVEDDEVAAAAIEYLKAAKAGRATFlpldKIRARAALAAALARGAIGAAvdlvasdlreadarYYVLGDTLLGRTLVA 629

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  559 LHRDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKT 638
Cdd:COG1196    630 ARLEAALRRAVTLAGRLREVTLEGEGGSAGGSLTGGSRRELLAALLEAEAELEELAERLAEEELELEEALLAEEEEEREL 709

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  639 ELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQE 700
Cdd:COG1196    710 AEAEEERLEEELEEEALEEQLEAEREELLEELLEEEELLEEEALEELPEPPDLEELERELER 771

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 62.48 E-value: 4.29e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKE-----DPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd12059      5 VFDYEASAEDELTLRRGDRVEVLSKDsavsgDEGWWTGKINDRVGIFPSNYV 56

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 71.24 E-value: 4.67e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLeQQRKEQERLAQLERAeqeRKERERQEQERKRQLEL-EKQLEKQrelerqreeerrkeierreAAKRELERQ 443
Cdd:TIGR02168  172 ERRKETER-KLERTRENLDRLEDI---LNELERQLKSLERQAEKaERYKELK-------------------AELRELELA 228

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  444 ---RQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIEstnksrelri 520
Cdd:TIGR02168  229 llvLRLEELREELEELQEELKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKELYALANEIS---------- 298

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  521 aeithlqqqlqesqqmlgKLIPEKQLLNDQLKQVQQNslhrdsLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEID 600
Cdd:TIGR02168  299 ------------------RLEQQKQILRERLANLERQ------LEELEAQLEELESKLDELAEELAELEEKLEELKEELE 354

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  601 IFNNQLKELREihnrqqlqKQKNLEaerlkqkeqERKTELEKQKEAQRR-----IQDRDKQRLDRVQQEEEPQWQKKNQE 675
Cdd:TIGR02168  355 SLEAELEELEA--------ELEELE---------SRLEELEEQLETLRSkvaqlELQIASLNNEIERLEARLERLEDRRE 417

                          330       340       350
                   ....*....|....*....|....*....|
gi 2024344592  676 DDKQKREEIIKKKESEDkgKQEIQEKPSKL 705
Cdd:TIGR02168  418 RLQQEIEELLKKLEEAE--LKELQAELEEL 445

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 70.92 E-value: 4.84e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  374 QQRKEQERLAQLERAEQERKE-RERQEQERKRQLELEK-QLEKQRELerqreeerrkeierreaakRELERQRQLEWERN 451
Cdd:pfam17380  263 QTMTENEFLNQLLHIVQHQKAvSERQQQEKFEKMEQERlRQEKEEKA-------------------REVERRRKLEEAEK 323

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  452 RRQELLNQRNR---EQEDIvvlkAKKKTLEFELEALNDKKNQLEgklqdiRCRLSTQRQEIEstnKSRELRiaeithlqq 528
Cdd:pfam17380  324 ARQAEMDRQAAiyaEQERM----AMERERELERIRQEERKRELE------RIRQEEIAMEIS---RMRELE--------- 381

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  529 qlqesqqmlgKLIPEKQLLNDQLKQvQQNSLHRDSLLTIKRALEAKELARQ--QLRDQLDEVEKETRSKLQEidifnnql 606
Cdd:pfam17380  382 ----------RLQMERQQKNERVRQ-ELEAARKVKILEEERQRKIQQQKVEmeQIRAEQEEARQREVRRLEE-------- 442

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  607 KELREIHNRQQLQKQKNLEAERLKQKEQER---KTELEKQKEAQRRIQDrdkQRLDRVQQEEEPQWQKKNQEDDKQK--- 680
Cdd:pfam17380  443 ERAREMERVRLEEQERQQQVERLRQQEEERkrkKLELEKEKRDRKRAEE---QRRKILEKELEERKQAMIEEERKRKlle 519

                          330       340       350
                   ....*....|....*....|....*....|..
gi 2024344592  681 -----------REEIIKKKESEDKGKQEIQEK 701
Cdd:pfam17380  520 kemeerqkaiyEEERRREAEEERRKQQEMEER 551

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 62.13 E-value: 4.88e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12046      1 QVVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGKIGIFPSAFVE 52

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 62.33 E-value: 5.08e-12

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12060      8 FNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVR 54

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 62.05 E-value: 5.82e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVlNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11838      3 IALYPYESNEPGDLTFNAGDVILV-TKKDGEWWTGTIGDRTGIFPSNYVRP 52

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 61.99 E-value: 6.01e-12

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11786      4 ALYNYEGKEPGDLSFKKGDIILLRKRiDENWYHGECNGKQGFFPASYV 51

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 61.86 E-value: 6.50e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELKGKTGWFPANYAE 799
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEE-------SEDGWWEGINTGRTGLVPANYVE 49

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 70.87 E-value: 7.16e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  375 QRKEQERLAQL-ERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKeierreaakreleRQRQLEWERNRR 453
Cdd:TIGR02169  669 SRSEPAELQRLrERLEGLKRELSSLQSELRRIENRLDELSQELSDASRKIGEIEK-------------EIEQLEQEEEKL 735

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  454 QELLNQRNRE----QEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQR--------QEIESTNKSRELRIA 521
Cdd:TIGR02169  736 KERLEELEEDlsslEQEIENVKSELKELEARIEELEEDLHKLEEALNDLEARLSHSRipeiqaelSKLEEEVSRIEARLR 815

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  522 EITHLQQQLQESQQMLGKLIPEKQLLNDQLKQvQQNSLHR--DSLLTIKRALEA----KELARQQLRDQLDEVEKEtRSK 595
Cdd:TIGR02169  816 EIEQKLNRLTLEKEYLEKEIQELQEQRIDLKE-QIKSIEKeiENLNGKKEELEEeleeLEAALRDLESRLGDLKKE-RDE 893

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  596 LQeidifnnqlKELREIHNRQQlqkQKNLEAERLKQKEQERKTELEKQkeaqrriQDRDKQRLDRVQQEEEPQWQKKNQE 675
Cdd:TIGR02169  894 LE---------AQLRELERKIE---ELEAQIEKKRKRLSELKAKLEAL-------EEELSEIEDPKGEDEEIPEEELSLE 954

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 2024344592  676 DDKQKREEI--------------IKKKESEDKGKQEIQEKPSKLF 706
Cdd:TIGR02169  955 DVQAELQRVeeeiralepvnmlaIQEYEEVLKRLDELKEKRAKLE 999

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 61.76 E-value: 7.72e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKD----GD--WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11876      2 WTALFDYDARGEDELTLRRGQPVEVLSKDaavsGDegWWTGKIGDKVGIFPSNYV 56

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 61.56 E-value: 7.79e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGE-VNGQVGLFPSNYVKL 1204
Cdd:cd11767      2 VVALYPFTGENDEELSFEKGERLEIIEKpeDDPDWWKARnALGTTGLVPRNYVEV 56

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 61.58 E-value: 8.64e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWK-GEVNGQVGLFPSNYVKL 1204
Cdd:cd11904      3 VQALYPFSSSNDEELNFEKGEVMDVIEKpeNDPEWWKcRKANGQVGLVPKNYVTV 57

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 61.55 E-value: 9.13e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1151 CQVigMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12055      2 CQV--AFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIK 52

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 61.71 E-value: 9.46e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKD----GD--WWTGTLGDKTGVFPSNYVR 1051
Cdd:cd12059      2 WTAVFDYEASAEDELTLRRGDRVEVLSKDsavsGDegWWTGKINDRVGIFPSNYVT 57

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 61.49 E-value: 9.67e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKE-DPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11830      3 KARYDFCARDMRELSLKEGDVVKIYNKKgQQGWWRGEINGRIGWFPSTYVE 53

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 61.26 E-value: 1.18e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11809      3 TAQFDYTGRSERELSFKKGDSLTLYRQVSDDWWRGQLNGQDGLVPHKYITL 53

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 69.71 E-value: 1.24e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  343 KKLPVTFEDKKRENFER-GNL--------ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLE 413
Cdd:PRK03918   234 EELKEEIEELEKELESLeGSKrkleekirELEERIEELKKEIEELEEKVKELKELKEKAEEYIKLSEFYEEYLDELREIE 313

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  414 KQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKA------KKKT------LEFEL 481
Cdd:PRK03918   314 KRLSRLEEEINGIEERIKELEEKEERLEELKKKLKELEKRLEELEERHELYEEAKAKKEelerlkKRLTgltpekLEKEL 393

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  482 EALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKS-RELRIA---------EIT--HLQQQLQESQQMLGKLIPEKQLLND 549
Cdd:PRK03918   394 EELEKAKEEIEEEISKITARIGELKKEIKELKKAiEELKKAkgkcpvcgrELTeeHRKELLEEYTAELKRIEKELKEIEE 473

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  550 QLKQVQQNSLHRDSLLTIKRALeakeLARQQLRDQLDEVEKETRS-KLQEIDIFNNQLKELREIHNRQQlQKQKNL--EA 626
Cdd:PRK03918   474 KERKLRKELRELEKVLKKESEL----IKLKELAEQLKELEEKLKKyNLEELEKKAEEYEKLKEKLIKLK-GEIKSLkkEL 548

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  627 ERLKQKEQERKTELEKQKEAQRRIQDRDKQ----------RLDRVQQEEEPQWQK----KNQEDDKQKREEIIKKKESE- 691
Cdd:PRK03918   549 EKLEELKKKLAELEKKLDELEEELAELLKEleelgfesveELEERLKELEPFYNEylelKDAEKELEREEKELKKLEEEl 628

                          410
                   ....*....|....
gi 2024344592  692 DKGKQEIQEKPSKL 705
Cdd:PRK03918   629 DKAFEELAETEKRL 642

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 60.94 E-value: 1.29e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGEL-KGKTGWFPANY 797
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEK-------DDDGWWEGELnGGREGLFPANY 51

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 70.00 E-value: 1.30e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKErERQEQERKRQLELEKQLEKQRELERQREEERRKE 429
Cdd:pfam02463  207 KKALEYYQLKEKLELEEEYLLYLDYLKLNEERIDLLQELLRDEQE-EIESSKQEIEKEEEKLAQVLKENKEEEKEKKLQE 285

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  430 IERREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVvlKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEI 509
Cdd:pfam02463  286 EELKLLAKEEEELKSELLKLERRKVDDEEKLKESEKEKK--KAEKELKKEKEEIEELEKELKELEIKREAEEEEEEELEK 363

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  510 ESTNKSRELRIAEITHLQqqlqesqqmlgklipEKQLLNDQLKQVQQNslHRDSLLTIKRALEAKELARQQLRDQLDevE 589
Cdd:pfam02463  364 LQEKLEQLEEELLAKKKL---------------ESERLSSAAKLKEEE--LELKSEEEKEAQLLLELARQLEDLLKE--E 424

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  590 KETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQdrdKQRLDRVQQEEEPQW 669
Cdd:pfam02463  425 KKEELEILEEEEESIELKQGKLTEEKEELEKQELKLLKDELELKKSEDLLKETQLVKLQEQL---ELLLSRQKLEERSQK 501

                          330       340       350
                   ....*....|....*....|....*....|...
gi 2024344592  670 QKKNQEDDKQKREEIIKKKESEDKGKQEIQEKP 702
Cdd:pfam02463  502 ESKARSGLKVLLALIKDGVGGRIISAHGRLGDL 534

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 61.16 E-value: 1.36e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11882      1 RARALYACKAEDESELSFEPGQIItNVQPSDEPGWLEGTLNGRTGLIPENYVEF 54

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 61.16 E-value: 1.38e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1151 CQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGL-FPSNYVK 1203
Cdd:cd11970      4 CAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 57

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 69.58 E-value: 1.57e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLE--LEKQLEKQRELERQReeerr 427
Cdd:COG1196    307 LEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEeaLLEAEAELAEAEEEL----- 381

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  428 keierREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQ 507
Cdd:COG1196    382 -----EELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEE 456

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  508 EIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQ-NSLHRDSLLTIKRALEAKELARQQLRDQLD 586
Cdd:COG1196    457 EEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGfLEGVKAALLLAGLRGLAGAVAVLIGVEAAY 536

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  587 EVEKETRSKLQEIDIFNNQLKELREIhnrqqlqkqknleAERLKQKEQERKTELEKQKEAQRRIQDRDKQRL 658
Cdd:COG1196    537 EAALEAALAAALQNIVVEDDEVAAAA-------------IEYLKAAKAGRATFLPLDKIRARAALAAALARG 595

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 60.62 E-value: 1.66e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVG-LFPSNYVK 1203
Cdd:cd11969      2 VKALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGDYGGKVQhYFPSNYVE 53

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 60.49 E-value: 1.80e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV-NGQVGLFPSNYVKL 1204
Cdd:cd11960      5 LYDYQAADDTEISFDPGDIITDIEQIDEGWWRGTGpDGTYGLFPANYVEL 54

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 60.73 E-value: 1.91e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11976      6 YDFCARDRSELSLKEGDIIKILNKKGQQgWWRGEIYGRVGWFPANYVE 53

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 60.59 E-value: 1.98e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLnKEDP--DWWKGEVNGQVGLFPSNY 1201
Cdd:cd11778      2 VEALYDYEAQGDDEISIRVGDRIAVI-RGDDgsGWTYGEINGVKGLFPTSY 51

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 68.89 E-value: 2.16e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  343 KKLPVTFEDKKRENFERGNlELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKrqlELEKQLEKQRELERQR 422
Cdd:TIGR04523  345 SQLKKELTNSESENSEKQR-ELEEKQNEIEKLKKENQSYKQEIKNLESQINDLESKIQNQE---KLNQQKDEQIKKLQQE 420

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  423 eeerrkeierreaaKRELERQRQlewernrrqELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRL 502
Cdd:TIGR04523  421 --------------KELLEKEIE---------RLKETIIKNNSEIKDLTNQDSVKELIIKNLDNTRESLETQLKVLSRSI 477

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  503 STQRQEIESTNKSRELRIAEIThlqqqlqesqqmlgKLIPEKQLLNDQLKQVQQNSlhrdslltikraleakelarQQLR 582
Cdd:TIGR04523  478 NKIKQNLEQKQKELKSKEKELK--------------KLNEEKKELEEKVKDLTKKI--------------------SSLK 523

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  583 DQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQ 662
Cdd:TIGR04523  524 EKIEKLESEKKEKESKISDLEDELNKDDFELKKENLEKEIDEKNKEIEELKQTQKSLKKKQEEKQELIDQKEKEKKDLIK 603

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  663 QEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQEPVKPAVqAPWSN 723
Cdd:TIGR04523  604 EIEEKEKKISSLEKELEKAKKENEKLSSIIKNIKSKKNKLKQEVKQIKETIKEIR-NKWPE 663

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 60.38 E-value: 2.23e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIInVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11991      1 EYVAMYTYESNEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 60.47 E-value: 2.23e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd12061      4 AKFNFQQTNEDELSFSKGDVIHVTRvEEGGWWEGTHNGRTGWFPSNYVR 52

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.

Pssm-ID: 464768 [Multi-domain] Cd Length: 374 Bit Score: 67.75 E-value: 2.23e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  373 EQQRKEQERLAQLERAEQERKERERQEQ-ERKRQLELEKQLE------KQRELERQREEERRKEIERREAAKRELERQRQ 445
Cdd:pfam15558   20 EQRMRELQQQAALAWEELRRRDQKRQETlERERRLLLQQSQEqwqaekEQRKARLGREERRRADRREKQVIEKESRWREQ 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  446 LEWERNRRQELLnQRNREQEdivvlKAKKKTLEFEL----EALNDKKNQLEGKLQDI--RCRLSTQRQEIESTNKSRELR 519
Cdd:pfam15558  100 AEDQENQRQEKL-ERARQEA-----EQRKQCQEQRLkekeEELQALREQNSLQLQERleEACHKRQLKEREEQKKVQENN 173

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  520 IAEithlqqqlqesqqmlgklipekqLLNDQLKQVQQNSLHRDSLLTIKRALEAKELARQQLRDQLdeVEKETRsKLQEi 599
Cdd:pfam15558  174 LSE-----------------------LLNHQARKVLVDCQAKAEELLRRLSLEQSLQRSQENYEQL--VEERHR-ELRE- 226

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  600 difnnqlKELREihnRQQLQKQKnleaERLKQKEQERKTELEK-QKEAQRRIQD---------RDKQRLDRVQQEEEPQW 669
Cdd:pfam15558  227 -------KAQKE---EEQFQRAK----WRAEEKEEERQEHKEAlAELADRKIQQarqvahktvQDKAQRARELNLEREKN 292

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592  670 QKKN----QEDDKQKREEI---IKKKE--SED--KGKQEIQEKPSKL 705
Cdd:pfam15558  293 HHILklkvEKEEKCHREGIkeaIKKKEqrSEQisREKEATLEEARKT 339

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 60.34 E-value: 2.32e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKE-----DPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd12058      5 LYDYEASGEDELSLRRGDVVEVLSQDaavsgDDGWWAGKIRHRLGIFPANYV 56

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];

Pssm-ID: 443091 [Multi-domain] Cd Length: 379 Bit Score: 67.55 E-value: 2.43e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  459 QRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKsrELRIAEithlqqqlqesqqmlg 538
Cdd:COG3883     17 QIQAKQKELSELQAELEAAQAELDALQAELEELNEEYNELQAELEALQAEIDKLQA--EIAEAE---------------- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  539 KLIPEKQ-LLNDQLKQVQQNSLHRDSLLTIkraLEAKELArqQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIhnRQQ 617
Cdd:COG3883     79 AEIEERReELGERARALYRSGGSVSYLDVL---LGSESFS--DFLDRLSALSKIADADADLLEELKADKAELEAK--KAE 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  618 LQKQKNlEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQeeepqwQKKNQEDDKQKREEIIKKKESEDKGKQE 697
Cdd:COG3883    152 LEAKLA-ELEALKAELEAAKAELEAQQAEQEALLAQLSAEEAAAEA------QLAELEAELAAAEAAAAAAAAAAAAAAA 224

                          250       260
                   ....*....|....*....|....*...
gi 2024344592  698 IQEKPSKLFQPHQEPVKPAVQAPWSNAG 725
Cdd:COG3883    225 AAAAAAAAAAAAAAAAAAAASAAGAGAA 252

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 60.02 E-value: 2.56e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVkrewvdeSQTGEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11877      2 VRAKFNFEGTNEDELSFDKGDIITV-------TQVVEGGWWEGTLNGKTGWFPSNYVK 52

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 59.74 E-value: 3.27e-11

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gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11840      1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDpDWWRGELNGQTGLFPSNYVEP 53

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 59.75 E-value: 3.86e-11

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gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWK-------GEVNGQVGLFPSNY 1201
Cdd:cd11773      5 LYDYEPQTEDELTIQEDDILYLLEKSDDDWWKvklkvnsSDDDEPVGLVPATY 57

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 59.42 E-value: 4.85e-11

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gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE-VNGQVGLFPSNYVKL 1204
Cdd:cd11962      6 YDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTnSKGESGLFPSNYVEL 54

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 59.29 E-value: 5.32e-11

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gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMV-KREwvdesqTGEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11875      1 KARVLFDYEAENEDELTLREGDIVTIlSKD------CEDKGWWKGELNGKRGVFPDNFVE 54

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 59.19 E-value: 5.74e-11

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                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11856      5 IADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLE 52

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 58.97 E-value: 5.99e-11

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gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKD-GDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11827      4 ALYAYDAQDTDELSFNEGDIIEILKEDpSGWWTGRLRGKEGLFPGNYV 51

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 59.22 E-value: 6.46e-11

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gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQV-----GLFPSNY 1201
Cdd:cd11883      2 VVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSgkvkrGWFPSNY 55

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 59.26 E-value: 6.51e-11

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gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGE-VNGQVGLFPSNYV 1202
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDgWLEGRnSRGEVGLFPSSYV 53

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 59.28 E-value: 6.68e-11

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gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11901      8 FNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYV 53

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 58.91 E-value: 7.34e-11

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gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11786      5 LYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQGFFPASYVQ 52

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 58.94 E-value: 7.55e-11

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gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11806      2 YVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHL 51

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 58.64 E-value: 7.55e-11

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gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNY 1201
Cdd:cd11817      2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 58.86 E-value: 7.66e-11

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gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEgGWWEGTLNGKTGWFPSNYVKE 53

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 58.81 E-value: 7.73e-11

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gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd11985      2 YVALYKFLPQENNDLPLQPGDRVMVVDdSNEDWWKGKSGDRVGFFPANFVQ 52

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 61.21 E-value: 8.43e-11

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gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTM-----GSQCHITKTMQDTLNPKWNSNCQFFIK--DLEQDVLCITVFERDQ 1661
Cdd:cd08384     13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYLkpdagKKSKHKTQVKKKTLNPEFNEEFFYDIKhsDLAKKTLEITVWDKDI 92


                   ....*...
gi 2024344592 1662 FSPDDFLG 1669
Cdd:cd08384     93 GKSNDYIG 100

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 58.82 E-value: 8.57e-11

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gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG-EVNGQVGLFPSNYVK 1203
Cdd:cd11768      1 IVVALYDFQPIEPGDLPLEKGEEYVVLDDSNEHWWRArDKNGNEGYIPSNYVT 53

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 58.55 E-value: 9.07e-11

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gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11828      2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVRL 53

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 58.83 E-value: 9.17e-11

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gi 2024344592 1157 YDYTAQNDD-ELAFNKGQIINVLNKEDP-----DWWKGEV-NGQVGLFPSNYV 1202
Cdd:cd11771      6 YDFTPENPEmELSLKKGDIVAVLSKTDPlgrdsEWWKGRTrDGRIGWFPSNYV 58

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 58.51 E-value: 1.02e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV-----NGQVGLFPSNYV 1202
Cdd:cd11887      4 VKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEYvdsngNTKEGIFPKNFV 58

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 58.63 E-value: 1.07e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwvdesQTGEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd12142      1 YCRVLFDYNPVAPDELALKKGDVIEVISK-----ETEDEGWWEGELNGRRGFFPDNFVM 54

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 58.28 E-value: 1.16e-10

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                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILV-TKKDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd12046      3 VALFSYEASQPEDLEFQKGDVILVlSKVNEDWLEGQCKGKIGIFPSAFVE 52

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 58.26 E-value: 1.19e-10

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                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNY 1201
Cdd:cd11818      5 LYDFTGENEDELSFKAGDIITELESIDEEWMSGELRGKSGIFPKNF 50

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212708 [Multi-domain] Cd Length: 52 Bit Score: 58.25 E-value: 1.31e-10

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDW-WKGEVNGQVGLFPSNYV 1202
Cdd:cd11774      1 QAKALYDYDKQTEEELSFNEGDTLDVYDDSDSDWiLVGFNGTQFGFVPANYI 52

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 58.12 E-value: 1.31e-10

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                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1079 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd11823      7 SYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKK---GIFPATYV 51

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 58.05 E-value: 1.34e-10

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYV 1126
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNG---QVGWFPSNYV 51

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 58.29 E-value: 1.36e-10

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKE-DPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11948      1 EAVALYSFQATESDELPFQKGDILKILNMEdDQNWYKAELQGREGYIPKNYIKV 54

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 58.14 E-value: 1.41e-10

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gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVL--NKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11836      5 LYAFEARNPDEISFQPGDIIQVDesQVAEPGWLAGELKGKTGWFPANYV 53

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 58.09 E-value: 1.49e-10

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gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11902      7 FAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIGWFPSNYV 52

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 58.06 E-value: 1.51e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRQI--GWFPANY 1125
Cdd:cd11883      1 VVVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKVkrGWFPSNY 55

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 57.86 E-value: 1.59e-10

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd12142      3 RVLFDYNPVAPDELALKKGDVIEVISKETEdeGWWEGELNGRR---GFFPDNFV 53

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 57.87 E-value: 1.80e-10

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gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNY 1049
Cdd:cd11817      3 VALYDFTGETEEDLSFQRGDRILVTEHlDAEWSRGRLNGREGIFPRAF 50

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 57.51 E-value: 2.11e-10

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                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11833      2 YVALYKFKPQENEDLEMRPGDKITLLDdSNEDWWKGKIEDRVGFFPANFV 51

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 57.42 E-value: 2.39e-10

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gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11816      6 FDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 57.33 E-value: 2.41e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVKL 1204
Cdd:cd11789      1 RYRAMYDYAAADDDEVSFQEGDVIINVEIIDDGWMEGTVqrTGQSGMLPANYVEL 55

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212742 [Multi-domain] Cd Length: 53 Bit Score: 57.49 E-value: 2.45e-10

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                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11808      2 VVALYDYQEKSPREVSMKKGDILTLLNSSNKDWWKVEVNDRQGFVPAAYVK 52

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 57.50 E-value: 2.60e-10

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                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKEDpDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11947      4 GKFDFTASGEDELSFKKGDVLKILSSDD-IWFKAELNGEEGYVPKNFV 50

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 57.30 E-value: 2.84e-10

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKKDG-DWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11996      2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDpDWWQGEINGVTGLFPSNYVKM 54

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 57.28 E-value: 2.85e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSsDGWWRGECNGQVGWFPSNYV 51

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 56.84 E-value: 3.49e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVKLL 1129
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRV---GLVPSTAVEEI 54

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 56.93 E-value: 4.42e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd12060      6 ARFNFKQTNEDELSVCKGDIIYVTRvEEGGWWEGTLNGKTGWFPSNYVR 54

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 56.56 E-value: 4.71e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11920      6 VYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYVE 53

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 56.62 E-value: 4.86e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11807      2 VVYALFDYEAENGDELSFREGDELTVLRKGDDDeteWWWARLNDKEGYVPRNLLGL 57

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 63.63 E-value: 4.99e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  435 AAKRELER-QRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIestn 513
Cdd:COG4942     31 QLQQEIAElEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAELAELEKEIAELRAELEAQKEEL---- 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  514 kSRELRIAEithlqqqlqesqqMLGKLIPEKQLLNdqlkqvQQNSLHRDSLLT-IKRALEAKELARQQLRDQLDEVEKET 592
Cdd:COG4942    107 -AELLRALY-------------RLGRQPPLALLLS------PEDFLDAVRRLQyLKYLAPARREQAEELRADLAELAALR 166

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  593 RSKLQEIDIFNNQLKELREIHNR-QQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQdrdkQRLDRVQQEEEPQ 668
Cdd:COG4942    167 AELEAERAELEALLAELEEERAAlEALKAERQKLLARLEKELAELAAELAELQQEAEELE----ALIARLEAEAAAA 239

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 56.54 E-value: 5.01e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVkrewvdeSQTGEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11772      2 FRALYDYEAQHPDELSFEEGDLLYI-------SDKSDPNWWKATCGGKTGLIPSNYVE 52

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 56.53 E-value: 5.01e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVmvkrewVDESQTGEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11882      3 RALYACKAEDESELSFEPGQII------TNVQPSDEPGWLEGTLNGRTGLIPENYVE 53

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 56.51 E-value: 5.23e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd11873      1 EVIVEFDYDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 56.27 E-value: 5.57e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwvDESqtgepGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11827      3 KALYAYDAQDTDELSFNEGDIIEILKE--DPS-----GWWTGRLRGKEGLFPGNYVEK 53

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 56.57 E-value: 5.60e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11978      4 IARYDFCARDMRELSLLKGDVVKIYTKMSTNgWWRGEVNGRVGWFPSTYVE 54

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 56.25 E-value: 5.64e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVL---EQQDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd11841      1 EVTALYSFEGQQPCDLSFQAGDRITVLtrtDSQFDWWEGRLRGRVGIFPANYVS 54

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 56.35 E-value: 5.91e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11813      1 RAKALLDFERHDDDELGFRKNDIITIISQKDeHCWVGELNGLRGWFPAKFVEL 53

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 56.20 E-value: 6.03e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11823      3 KALYSYTANREDELSLQPGDIIEVHEKQDDgWWLGELNGKKGIFPATYV 51

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 56.20 E-value: 6.96e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKDGD---WWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11875      4 VLFDYEAENEDELTLREGDIVTILSKDCEdkgWWKGELNGKRGVFPDNFVEP 55

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 55.99 E-value: 7.20e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11961      4 ALYDYDAAEDNELSFFENDKIInIEFVDDDWWLGECHGSRGLFPSNYVEL 53

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 55.98 E-value: 7.59e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGE-VQGQKGWFPKSYV 961
Cdd:cd11812      4 ALYDYTANRSDELTIHRGDIIRVLYKdNDNWWFGSlVNGQQGYFPANYV 52

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 56.11 E-value: 8.23e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKrewvdeSQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11976      3 KARYDFCARDRSELSLKEGDIIKIL------NKKGQQGWWRGEIYGRVGWFPANYVEE 54

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 55.67 E-value: 8.37e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQ-GQKGWFP 957
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSeDGWWKGRNKgGKEGLIP 46

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 56.04 E-value: 8.62e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11815      5 LHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYRGKCKNTTGIFPANHVK 52

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 55.74 E-value: 8.69e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd11873      4 VEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKR---GMFPDNFVK 52

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 63.93 E-value: 8.88e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  341 LEKKLpvtfEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLEraeQERKERERQEQERK----------RQLELEK 410
Cdd:PRK03918   377 LKKRL----TGLTPEKLEKELEELEKAKEEIEEEISKITARIGELK---KEIKELKKAIEELKkakgkcpvcgRELTEEH 449

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  411 QLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRN---------REQEDIVVLKAKKKTLEFEL 481
Cdd:PRK03918   450 RKELLEEYTAELKRIEKELKEIEEKERKLRKELRELEKVLKKESELIKLKElaeqlkeleEKLKKYNLEELEKKAEEYEK 529

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  482 eaLNDKKNQLEGKLQDIRCRLS------TQRQEIESTNKSRELRIAEITHLQQQLQESQQMLgklipekqlLNDQLKQVQ 555
Cdd:PRK03918   530 --LKEKLIKLKGEIKSLKKELEkleelkKKLAELEKKLDELEEELAELLKELEELGFESVEE---------LEERLKELE 598

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  556 qnSLHRD--SLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKN--LEAERLKQ 631
Cdd:PRK03918   599 --PFYNEylELKDAEKELEREEKELKKLEEELDKAFEELAETEKRLEELRKELEELEKKYSEEEYEELREeyLELSRELA 676

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  632 KEQERKTELEKQK-EAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIK-KKESEDKGKQEIQEKPSKLF 706
Cdd:PRK03918   677 GLRAELEELEKRReEIKKTLEKLKEELEEREKAKKELEKLEKALERVEELREKVKKyKALLKERALSKVGEIASEIF 753

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212939 [Multi-domain] Cd Length: 56 Bit Score: 55.83 E-value: 9.33e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1202
Cdd:cd12006      4 VALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARslTTGETGYIPSNYV 54

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 57.65 E-value: 9.64e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1593 VNI--VEGIELKPCRSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDDFLGR 1670
Cdd:cd08376      2 VTIvlVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDEFIGR 81

                           90
                   ....*....|..
gi 2024344592 1671 TEIRVADIKKDQ 1682
Cdd:cd08376     82 CEIDLSALPREQ 93

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 55.78 E-value: 1.00e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEV-QGQKGWFPKSYVKL 963
Cdd:cd11819      1 RAKALYDYQAAEDNEISFVEGDIITQIEQIDEgWWLGVNaKGQKGLFPANYVEL 54

Coiled-coil domain-containing protein 158; CCDC158 is a family of proteins found in eukaryotes. The function is not known.

Pssm-ID: 464943 [Multi-domain] Cd Length: 1112 Bit Score: 63.60 E-value: 1.11e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  368 RQALLEQQRKEQErlAQLER---AEQERKERERQEQERKR------QLELEKQLEKQRELERQREEERRKEIERREAAKR 438
Cdd:pfam15921  109 RQSVIDLQTKLQE--MQMERdamADIRRRESQSQEDLRNQlqntvhELEAAKCLKEDMLEDSNTQIEQLRKMMLSHEGVL 186

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  439 ELERQRQLEWERNRRQELLNQRN-----------------REQE-DIVVLKAKKKTLEFELEAL-NDKKNQLEGKLQdir 499
Cdd:pfam15921  187 QEIRSILVDFEEASGKKIYEHDSmstmhfrslgsaiskilRELDtEISYLKGRIFPVEDQLEALkSESQNKIELLLQ--- 263

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  500 crlstQRQE-IESTNKSRELRIAEITHLQQQLQEsqqmlgklipEKQLLNDQLKQVQQNSLHRDSLLTikRALEAKELAR 578
Cdd:pfam15921  264 -----QHQDrIEQLISEHEVEITGLTEKASSARS----------QANSIQSQLEIIQEQARNQNSMYM--RQLSDLESTV 326

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  579 QQLRDQLDEVEKETRSKLQEID----IFNNQLKELREihNRQQL-QKQKNL--EAERLKQKEQERKTELEKQKEAQRRIQ 651
Cdd:pfam15921  327 SQLRSELREAKRMYEDKIEELEkqlvLANSELTEART--ERDQFsQESGNLddQLQKLLADLHKREKELSLEKEQNKRLW 404

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  652 DRDKQR---LDRVQQEEEpqwqKKNQEddKQKREEIIKKKESEDKGKQEIQ 699
Cdd:pfam15921  405 DRDTGNsitIDHLRRELD----DRNME--VQRLEALLKAMKSECQGQMERQ 449

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 55.33 E-value: 1.13e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 962
Cdd:cd11805      1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPdWWKGELRGRVGIFPANYVQ 52

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212930 [Multi-domain] Cd Length: 56 Bit Score: 55.74 E-value: 1.15e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEV-NGQVGLFPSNYVK 1203
Cdd:cd11997      3 RVRALYDYTGQEADELSFKAGEELLKIGEEDEQgWCKGRLlSGRIGLYPANYVE 56

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212709 [Multi-domain] Cd Length: 57 Bit Score: 55.79 E-value: 1.15e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDP-DWWKGE--VNGQVGLFPSNYVKL 1204
Cdd:cd11775      6 LYDFDAQSDDELTVKEGDVVYILDDKKSkDWWMVEnvSTGKEGVVPASYIEI 57

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212942 [Multi-domain] Cd Length: 54 Bit Score: 55.59 E-value: 1.18e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLnKEDPDWW--KGEVNGQVGLFPSNYV 1202
Cdd:cd12009      2 VIAQYDFVPSNERDLQLKKGEKLQVL-KSDGEWWlaKSLTTGKEGYIPSNYV 52

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 55.59 E-value: 1.23e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11833      3 VALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIEDRVGFFPANFV 51

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 55.43 E-value: 1.24e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQGKKrqiGWFPANYVKL 1128
Cdd:cd11875      2 ARVLFDYEAENEDELTLREGDIVTILSKDCEdkGWWKGELNGKR---GVFPDNFVEP 55

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 63.45 E-value: 1.24e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  325 DQRLPEEPALEEEQQQLEKKLPVTFEDKKRENFER--GNLELEKRRQALLEQQRKE-----QERLAQLERAEQERKERER 397
Cdd:TIGR00618  256 LKKQQLLKQLRARIEELRAQEAVLEETQERINRARkaAPLAAHIKAVTQIEQQAQRihtelQSKMRSRAKLLMKRAAHVK 335

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  398 QEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTL 477
Cdd:TIGR00618  336 QQSSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHTLQQQKTTLTQKLQSLCKELDILQREQATIDTR 415

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  478 EFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGklipEKQLLNDQLKQVQQN 557
Cdd:TIGR00618  416 TSAFRDLQGQLAHAKKQQELQQRYAELCAAAITCTAQCEKLEKIHLQESAQSLKEREQQLQ----TKEQIHLQETRKKAV 491

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  558 SLHRDSLL-TIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIhnRQQLQKQKNlEAERLKQKEQER 636
Cdd:TIGR00618  492 VLARLLELqEEPCPLCGSCIHPNPARQDIDNPGPLTRRMQRGEQTYAQLETSEEDV--YHQLTSERK-QRASLKEQMQEI 568

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  637 KTELekQKEAQRRiqDRDKQRLDRVQQEEE--PQWQKKNQEDDKQKREE--IIKKKESEDKGKQEI 698
Cdd:TIGR00618  569 QQSF--SILTQCD--NRSKEDIPNLQNITVrlQDLTEKLSEAEDMLACEqhALLRKLQPEQDLQDV 630

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 55.42 E-value: 1.32e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1202
Cdd:cd11793      1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGErlRDGERGWFPSSYT 53

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 55.28 E-value: 1.38e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGD-MILVTKKDGDWW------TGtlgdKTGVFPSNY 1049
Cdd:cd11845      2 YVALYDYEARTDDDLSFKKGDrLQILDDSDGDWWlarhlsTG----KEGYIPSNY 52

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 55.11 E-value: 1.44e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11838      3 IALYPYESNEPGDLTFNAGDVILVTKKDGEWWTGTIGDRTGIFPSNYVRP 52

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 54.90 E-value: 1.49e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVT-KKDGDWWTGTL-GDKTGVFPS 1047
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLeKSEDGWWKGRNkGGKEGLIPS 47

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 57.73 E-value: 1.51e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1590 RLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFI---KDLEQDVLCITVF-ERDQFSPD 1665
Cdd:cd04022      1 KLVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVsdpSRLSNLVLEVYVYnDRRSGRRR 80


                   ....*...
gi 2024344592 1666 DFLGRTEI 1673
Cdd:cd04022     81 SFLGRVRI 88

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 57.64 E-value: 1.53e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTM---GSQCHI--TKTMQDTLNPKWNsncQFFI------KDLEQDVLCITVF 1657
Cdd:cd04031     16 SQLIVTVLQARDLPPRDDGSLRNPYVKVYLlpdRSEKSKrrTKTVKKTLNPEWN---QTFEysnvrrETLKERTLEVTVW 92

                           90       100
                   ....*....|....*....|
gi 2024344592 1658 ERDQFSPDDFLGRTEIRVAD 1677
Cdd:cd04031     93 DYDRDGENDFLGEVVIDLAD 112

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 55.23 E-value: 1.55e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 962
Cdd:cd11949      2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPnWWKGACHGQTGMFPRNYVT 52

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 62.28 E-value: 1.67e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  355 ENFERGNLELEKRRQALLEQQRKEQErlaQLERAEQERKERERQEQERKRQLELEKQlekQRELERQREEERRKEIERRE 434
Cdd:pfam15709  341 ERAEMRRLEVERKRREQEEQRRLQQE---QLERAEKMREELELEQQRRFEEIRLRKQ---RLEEERQRQEEEERKQRLQL 414

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  435 AAKRELERQRQLEWERnRRQELlnQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIE 510
Cdd:pfam15709  415 QAAQERARQQQEEFRR-KLQEL--QRKKQQEEAERAEAEKQRQKELEMQLAEEQKRLMEMAEEERLEYQRQKQEAE 487

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 55.22 E-value: 1.71e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwvdesQTGEPGWLGGELKGKTGWFPANYA 798
Cdd:cd12056      3 YCKALFHYEGTNEDELDFKEGEIILIISK-----DTGEPGWWKGELNGKEGVFPDNFV 55

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 56.40 E-value: 1.84e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  1456 FLHSGKLYKAKSN-----KELYGFLFNDFLLLtqiikplgssgtdkvFSPKSNLQYKMYKTPIFLNEVLVKLPTDPSGDE 1530
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLFNSTLLY---------------YKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSK 65

                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 2024344592  1531 P--IFHISHIDR-VYTLRAESINERTAWVQKIKAAS 1563
Cdd:smart00233   66 KphCFEIKTSDRkTLLLQAESEEEREKWVEALRKAI 101

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 54.54 E-value: 1.92e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVK 962
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEEsEDGWWEGINTGRTGLVPANYVE 49

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 54.91 E-value: 2.11e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKLI 964
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKdNDGWWEGETGGRVGLVPSTAVEEI 54

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 56.93 E-value: 2.27e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1612 PYCEVTM-GSQCHITKTMQDTLNPKWNSNCQFFIKDleQDVLCITVFERDQFSPDD--FLGRTEIRVADIkkdQGSKGPV 1688
Cdd:cd08382     23 PFAVITVdGGQTHSTDVAKKTLDPKWNEHFDLTVGP--SSIITIQVFDQKKFKKKDqgFLGCVRIRANAV---LPLKDTG 97

                           90       100
                   ....*....|....*....|....*
gi 2024344592 1689 TKCLLLH-------EVPTGEIVVRL 1706
Cdd:cd08382     98 YQRLDLRklkksdnLSVRGKIVVSL 122

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 54.66 E-value: 2.27e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1159 YTAQNDDELAFNKGQIINVLNKEDpDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11990      8 WTAKKDNHLNFSKNDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKL 52

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 54.54 E-value: 2.32e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEEsEDGWWEGINTGRTGLVPANYVE 49

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 54.85 E-value: 2.45e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12053      1 EYIVEYDYDAVHEDELTIRVGEIIrNVKKLEEEGWLEGELNGRRGMFPDNFVK 53

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212703 [Multi-domain] Cd Length: 57 Bit Score: 54.62 E-value: 2.48e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLN-KEDPDWWKGE-VNGQVGLFPSNYVK 1203
Cdd:cd11769      3 ECIAKYNFNGASEEDLPFKKGDILTIVAvTKDPNWYKAKnKDGREGMIPANYVQ 56

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 54.63 E-value: 2.48e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGD-KTGVFPSNYVRL 1052
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDIITqIEQIDEGWWLGVNAKgQKGLFPANYVEL 54

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 54.63 E-value: 2.51e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGGELKGKTGWFPANYAE 799
Cdd:cd11826      3 VALYDYTADKDDELSFQEGDIIYVTKKNDD-------GWYEGVLNGVTGLFPGNYVE 52

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 54.64 E-value: 2.67e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVL--EQQDMWWFGE--VQGQKGWFPKSYVK 962
Cdd:cd11779      2 RVKALYPHAAGGETQLSFEEGDVITLLgpEPRDGWHYGEneRSGRRGWFPIAYTE 56

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 54.61 E-value: 2.69e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVKL 1204
Cdd:cd11916      6 ALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSrrTKQFGTFPGNYVKL 57

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 54.25 E-value: 2.77e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKeDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11992      1 EYIALYPYSSSEPGDLTFNEGEEILVTQK-DGEWWTGSIEDRTGIFPSNYVR 51

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 54.57 E-value: 2.95e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11964      5 AIYDFEAAEDNELTFKAGDIItILDDSDPNWWKGETPQGTGLFPSNFV 52

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

Pssm-ID: 274303 [Multi-domain] Cd Length: 346 Bit Score: 60.63 E-value: 2.95e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  573 AKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIH-NRQQLQKQKNLEAERLKQKEQERKTELEKQKEA----- 646
Cdd:TIGR02794   47 AVAQQANRIQQQKKPAAKKEQERQKKLEQQAEEAEKQRAAEqARQKELEQRAAAEKAAKQAEQAAKQAEEKQKQAeeaka 126

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  647 -------QRRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEK 701
Cdd:TIGR02794  127 kqaaeakAKAEAEAERKAKEEAAKQAEEEAKAKAAAEAKKKAEEAKKKAEAEAKAKAEAEAK 188

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 54.29 E-value: 3.43e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 962
Cdd:cd11786      2 AKALYNYEGKEPGDLSFKKGDIILLRKRIDEnWYHGECNGKQGFFPASYVQ 52

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 54.19 E-value: 3.62e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11995      2 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPdWWKGELNGQVGLFPSNYVKL 54

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 54.19 E-value: 3.80e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11995      2 QVIGMYDYTAQNDDELAFSKGQIInVLNKEDPDWWKGELNGQVGLFPSNYVKL 54

Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) proteins; The MPP/p55 subfamily of MAGUK (membrane-associated guanylate kinase) proteins includes at least eight vertebrate members (MPP1-7 and CASK), four Drosophila proteins (Stardust, Varicose, CASK and Skiff), and other similar proteins; they all contain one each of the core of three domains characteristic of MAGUK proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, most members except for MPP1 contain N-terminal L27 domains and some also contain a Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. CASK has an additional calmodulin-dependent kinase (CaMK)-like domain at the N-terminus. Members of this subfamily are scaffolding proteins that play important roles in regulating and establishing cell polarity, cell adhesion, and synaptic targeting and transmission, among others. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212796 Cd Length: 61 Bit Score: 54.12 E-value: 3.83e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1156 MYDYTAQNDDE-------LAFNKGQIINVLNKEDPDWWK----GEVNGQVGLFPS 1199
Cdd:cd11862      5 LFDYDPEEDPLipckeagLSFKKGDILQIVNQDDPNWWQarkvGDPNGRAGLIPS 59

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 53.96 E-value: 3.86e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1075 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYVKL 1128
Cdd:cd11840      1 QVIAlfPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNG---QTGLFPSNYVEP 53

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 53.88 E-value: 3.88e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKL 963
Cdd:cd11781      2 ARALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYeGEHNGRVGIFPASYVEI 53

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 275424 Cd Length: 124 Bit Score: 56.12 E-value: 3.96e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1454 RKFLHSGKLYKAkSNKEL---YGFLFNDFLLLTqiiKPLGSSGTDKVFS--PKSNLQYKMYKTPIFLNEvlvklptdpsg 1528
Cdd:cd13389     12 RKLIKEGELMKV-SRKEMqprYFFLFNDCLLYT---TPVQSSGMLKLNNelPLSGMKVKLPEDEEYSNE----------- 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1529 depiFHISHIDRVYTLRAESINERTAWVQKIKAAselyIETEKKKR 1574
Cdd:cd13389     77 ----FQIISTKRSFTLIASSEEERDEWVKALSRA----IEEHTKKQ 114

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 54.07 E-value: 4.19e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLE-QQDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11961      2 AKALYDYDAAEDNELSFFENDKIINIEfVDDDWWLGECHGSRGLFPSNYVEL 53

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 54.07 E-value: 4.26e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11870      1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDGRVGIFPKCFVV 52

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 53.91 E-value: 4.46e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKED----PDWWKGEVNGQVGLFPSNY 1201
Cdd:cd11800      1 YYYALYTFEARSPGELSVTEGQVVTVLEKHDlkgnPEWWLVEDRGKQGYVPSNY 54

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 53.84 E-value: 4.54e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG--EVNGQVGLFPSNYVK 1203
Cdd:cd11780      5 LYSYTPQNEDELELREGDIVYVMEKCDDGWFVGtsERTGLFGTFPGNYVA 54

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 53.79 E-value: 4.58e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKE----DPDWWKGEVNGQ-VGLFPSNYVKL 1204
Cdd:cd11864      3 RAEYDFVAESEDELSFRAGDKLRLAPKElqprVRGWLLATVDGQkIGLVPANYVKI 58

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212781 [Multi-domain] Cd Length: 58 Bit Score: 54.10 E-value: 4.66e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTGTLGDK------TGVFPSNYV 1050
Cdd:cd11847      2 YKALWDFKARGDEELSFQAGDQFRIAERSGDWWTALKLDRaggvvaQGFVPNNYL 56

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 53.62 E-value: 4.71e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11820      5 ALYDFEAAEDNELTFKAGEIITVLDdSDPNWWKGSNHRGEGLFPANFV 52

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 53.89 E-value: 4.83e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGD-----KTGVFPSNYV 1050
Cdd:cd11887      5 KALYPYESDHEDDLNFDVGQLITVTEEeDADWYFGEYVDsngntKEGIFPKNFV 58

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 61.52 E-value: 5.24e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  341 LEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQ-----ERLAQLERAEQERkeRERQEQERKRQLELEKQLEKQ 415
Cdd:TIGR00618  175 LDQYTQLALMEFAKKKSLHGKAELLTLRSQLLTLCTPCMpdtyhERKQVLEKELKHL--REALQQTQQSHAYLTQKREAQ 252

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  416 relerqreeerrkeierreaaKRELERQRQLEWERNRRQELLNQrnreqedIVVLKAKKKTLEFELEALndkknqlegKL 495
Cdd:TIGR00618  253 ---------------------EEQLKKQQLLKQLRARIEELRAQ-------EAVLEETQERINRARKAA---------PL 295

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  496 QDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKE 575
Cdd:TIGR00618  296 AAHIKAVTQIEQQAQRIHTELQSKMRSRAKLLMKRAAHVKQQSSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQH 375

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  576 LARQQLR---DQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEK--QKEAQRRI 650
Cdd:TIGR00618  376 TLTQHIHtlqQQKTTLTQKLQSLCKELDILQREQATIDTRTSAFRDLQGQLAHAKKQQELQQRYAELCAAaiTCTAQCEK 455

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  651 Q-DRDKQRLDRVQQEEEPQWQKKNQEDDKQKReeiikKKESEDKGKQEIQEKPSKLFQPHQEPVKPAVQA 719
Cdd:TIGR00618  456 LeKIHLQESAQSLKEREQQLQTKEQIHLQETR-----KKAVVLARLLELQEEPCPLCGSCIHPNPARQDI 520

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 53.54 E-value: 5.39e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELKGKTGWFPANYAEKI 801
Cdd:cd12061      3 RAKFNFQQTNEDELSFSKGDVIHVTRV-------EEGGWWEGTHNGRTGWFPSNYVREI 54

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 53.47 E-value: 5.51e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTL---GdKTGVFPSNYVRL 1052
Cdd:cd11789      2 YRAMYDYAAADDDEVSFQEGDVIInVEIIDDGWMEGTVqrtG-QSGMLPANYVEL 55

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 53.42 E-value: 5.62e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11803      3 CRALYDFEPENEGELGFKEGDIItLTNQIDENWYEGMVNGQSGFFPVNYV 52

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 53.29 E-value: 6.15e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2024344592 1086 EQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd11829     15 QGLSFEAGELIRVLQAPDGGWWEGEKDGLR---GWFPASYV 52

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 61.21 E-value: 6.19e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  349 FEDKKRENFERGNLELEKRRQALleQQRKEQERLAQ---LERAEQERKE----RERQEQERKRQLELEKQLEKQRELERQ 421
Cdd:PRK02224   304 LDDADAEAVEARREELEDRDEEL--RDRLEECRVAAqahNEEAESLREDaddlEERAEELREEAAELESELEEAREAVED 381

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  422 REEERRKEIERREAAKRELE-RQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEfelEALNDKKNQLE-GKL---- 495
Cdd:PRK02224   382 RREEIEELEEEIEELRERFGdAPVDLGNAEDFLEELREERDELREREAELEATLRTAR---ERVEEAEALLEaGKCpecg 458

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  496 QDIR-----CRLSTQRQEIESTnksrELRIAEITHLQQQLQESQQMLGKLIP-EKQLlnDQLKQVQQNSlhrDSLLTIKR 569
Cdd:PRK02224   459 QPVEgsphvETIEEDRERVEEL----EAELEDLEEEVEEVEERLERAEDLVEaEDRI--ERLEERREDL---EELIAERR 529

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  570 A-LEAKELARQQLRDQLDEVEKETRSK--------------LQEIDIFNNQLKELRE--------------IHN------ 614
Cdd:PRK02224   530 EtIEEKRERAEELRERAAELEAEAEEKreaaaeaeeeaeeaREEVAELNSKLAELKErieslerirtllaaIADaedeie 609

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  615 -----RQQLQKQKNLEAERLKQKeQERKTELEKQKEAQRRIQDR-DKQRLDRVQQEEEPQW-QKKNQEDDKQKR----EE 683
Cdd:PRK02224   610 rlrekREALAELNDERRERLAEK-RERKRELEAEFDEARIEEAReDKERAEEYLEQVEEKLdELREERDDLQAEigavEN 688

                          410       420
                   ....*....|....*....|....*...
gi 2024344592  684 IIKKKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:PRK02224   689 ELEELEELRERREALENRVEALEALYDE 716

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212940 [Multi-domain] Cd Length: 58 Bit Score: 53.50 E-value: 6.64e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1202
Cdd:cd12007      4 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsiATGKNGYIPSNYV 54

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 53.18 E-value: 6.93e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPdWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11989      1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 52

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 53.13 E-value: 7.19e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQDM---WWFGEVQGQKGWFPKSYV 961
Cdd:cd11836      3 RALYAFEARNPDEISFQPGDIIQVDESQVAepgWLAGELKGKTGWFPANYV 53

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 53.42 E-value: 7.54e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 964
Cdd:cd11803      2 CCRALYDFEPENEGELGFKEGDIITLTNQIDENWYeGMVNGQSGFFPVNYVEVL 55

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 53.11 E-value: 8.29e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGGE--LKGKTGWFPANYAE 799
Cdd:cd11793      4 CVHAYTAQQPDELTLEEGDVVNVLRKMPD-------GWYEGErlRDGERGWFPSSYTE 54

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 53.09 E-value: 8.33e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQ---VGLFPSNYVKL 1204
Cdd:cd11965      1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHI 56

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 270065 Cd Length: 128 Bit Score: 55.36 E-value: 8.55e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1457 LHSGKLYKAKSNK--ELYGFLFNDFLLLTQIIKPLG-SSGTDKVFS---------PKSNLQYKMYKTPIFLNEVLVK--L 1522
Cdd:cd13245      3 LHEGPLTLIESGKtlDVYLFLFDDMLLITKMKKNLKkKKSSDSENSmpsleltplIKEGGSYTVYKQPIPLDRLCLHdvD 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1523 PTDPS--GDEPIFHISHIDR------VYTLRAESINERTAWVQKIK 1560
Cdd:cd13245     83 PNEATanGLKHAFVLVHLNRyqqvigVYTLQASSENTKQTWMSKLR 128

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212980 Cd Length: 53 Bit Score: 52.90 E-value: 8.73e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd12047      1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDGRIGIFPKCFA 51

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 59.43 E-value: 8.75e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  614 NRQQLQKQKNLEAERLKQKEQERKTE--LEKQKEAQRRIQDRDKQRLDRvQQEEEPQWQKKNQEDDKQKREEIIKKKESE 691
Cdd:PRK09510    65 NRQQQQQKSAKRAEEQRKKKEQQQAEelQQKQAAEQERLKQLEKERLAA-QEQKKQAEEAAKQAALKQKQAEEAAAKAAA 143

                           90
                   ....*....|.
gi 2024344592  692 D-KGKQEIQEK 701
Cdd:PRK09510   144 AaKAKAEAEAK 154

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 53.00 E-value: 9.10e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11928      5 ALYSYEGKEPGDLKFNKGDIIILRRKvDENWYHGELNGCHGFLPASYIQC 54

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 52.74 E-value: 9.16e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2024344592 1158 DYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11796      7 DLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRRGIFPEGFV 51

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 52.77 E-value: 9.28e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11828      2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKdWWWGSIRDEEGWFPASFVRL 53

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 53.10 E-value: 1.01e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILV-TKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11963      6 ALYDFEAVEDNELTFKHGEIIIVlDDSDANWWKGENHRGVGLFPSNFV 53

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 52.99 E-value: 1.01e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11986      2 FVALYRFKALEKDDLDFHPGERITVIDdSNEEWWRGKIGEKTGYFPMNFI 51

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 53.02 E-value: 1.01e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11929      6 LCNYRGHNPGDLKFNKGDVILLRRQLDENWYLGEINGVSGIFPASSVEV 54

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 52.73 E-value: 1.04e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAE 799
Cdd:cd11781      3 RALYPFKAQSAKELSLKKGDIIYIRRQ-IDKN------WYEGEHNGRVGIFPASYVE 52

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 52.92 E-value: 1.11e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd11949      4 ALFDFDPQEDGELGFRRGDFIeVMDNSDPNWWKGACHGQTGMFPRNYVT 52

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 53.09 E-value: 1.16e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1000 EEYVAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11972      3 EKVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDgWYEGVMNGVTGLFPGNYV 54

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 52.42 E-value: 1.26e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMV-KREwvdesqtgEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11840      3 IALFPYTAQNEDELSFQKGDIINVlSKD--------DPDWWRGELNGQTGLFPSNYVE 52

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 52.59 E-value: 1.31e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIV-MVKREWVDesqtgePGWLGGELKGKTGWFPANYAE 799
Cdd:cd12057      1 YCKVLFPYEAQNEDELTIKEGDIVtLISKDCID------AGWWEGELNGRRGVFPDNFVK 54

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 52.78 E-value: 1.33e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKDGD-----WWTGTLGDKTGVFPS 1047
Cdd:cd11762      4 ALYDYEAQSDEELSFPEGAIIRILRKDDNgvddgWWEGEFNGRVGVFPS 52

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 52.42 E-value: 1.36e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMvKREWVDESqtgepGWLGGELKGKTGWFPANYAE 799
Cdd:cd11843      3 RALYDYEGQESDELSFKAGDILT-KLEEEDEQ-----GWCKGRLDGRVGLYPANYVE 53

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 55.43 E-value: 1.37e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLEQQRKEQERLAQLERAEQERKE-RERQEQERKRQLELEKQLEKQRELERQREEERrkeierreaAKRELERQ 443
Cdd:pfam05672   18 EKRRQAREQREREEQERLEKEEEERLRKEElRRRAEEERARREEEARRLEEERRREEEERQRK---------AEEEAEER 88

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  444 RQLEWERNRRQELLNQRN--REQEDivvlkAKKKTLEFELEALNDKKNQLEGK 494
Cdd:pfam05672   89 EQREQEEQERLQKQKEEAeaKAREE-----AERQRQEREKIMQQEEQERLERK 136

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 52.52 E-value: 1.40e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKD-GD--WWTGTLGDKTGVFPSNYV 1050
Cdd:cd12056      6 ALFHYEGTNEDELDFKEGEIILIISKDtGEpgWWKGELNGKEGVFPDNFV 55

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 52.64 E-value: 1.41e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREwvDESQTGEPGWLGGELKGKTGWFPANY 797
Cdd:cd12058      2 WTALYDYEASGEDELSLRRGDVVEVLSQ--DAAVSGDDGWWAGKIRHRLGIFPANY 55

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 52.29 E-value: 1.45e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11996      2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDPdWWQGEINGVTGLFPSNYVKM 54

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 52.43 E-value: 1.48e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11866      4 GLWDCSGNEPDELSFKRGDLIYIISKEydSFGWWVGELNGKVGLVPKDYL 53

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 52.42 E-value: 1.53e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11959      2 AVALYDYQAADDDEISFDPDDIITNIEMIDEgWWRGVCRGKYGLFPANYVEL 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 52.26 E-value: 1.60e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEV-NGQVGLFPSNYVK 1203
Cdd:cd11998      2 RVRALYDYDGQEQDELSFKAGDELTKLEDEDEQgWCKGRLdSGQVGLYPANYVE 55

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 52.38 E-value: 1.61e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1079 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd12061      7 NFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRT---GWFPSNYVR 52

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 52.31 E-value: 1.62e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1079 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd12060      9 NFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKT---GWFPSNYVR 54

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212789 [Multi-domain] Cd Length: 55 Bit Score: 52.42 E-value: 1.63e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1155 GMYDYTAQNDD--ELAFNKGQIINVLNKEDpDWWKGEV-NGQVGLFPSNYVKL 1204
Cdd:cd11855      4 ALYPYDASPDDpnELSFEKGEILEVSDTSG-KWWQARKsNGETGICPSNYLQL 55

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 59.74 E-value: 1.65e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  347 VTFEDKKRENFERGNLELEKRRQALL--EQQRKEQERLAQLERAEQERKERERQ-------EQERKRQL-ELEKQLEKQR 416
Cdd:pfam05483  405 VELEELKKILAEDEKLLDEKKQFEKIaeELKGKEQELIFLLQAREKEIHDLEIQltaiktsEEHYLKEVeDLKTELEKEK 484

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  417 ELERQREEErrkeierreAAKRELERQRQLEWERNRRQELLNQrnreQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQ 496
Cdd:pfam05483  485 LKNIELTAH---------CDKLLLENKELTQEASDMTLELKKH----QEDIINCKKQEERMLKQIENLEEKEMNLRDELE 551

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  497 DIRCRLSTQRQEIE-STNKSRElriaeitHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKE 575
Cdd:pfam05483  552 SVREEFIQKGDEVKcKLDKSEE-------NARSIEYEVLKKEKQMKILENKCNNLKKQIENKNKNIEELHQENKALKKKG 624

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  576 LARQQlrdQLDEVEKETRSKLQEIDIFNNQLKELreIHNRQQLQKQKNLEAERLKQKEQERKTELEK----QKEAQRRIQ 651
Cdd:pfam05483  625 SAENK---QLNAYEIKVNKLELELASAKQKFEEI--IDNYQKEIEDKKISEEKLLEEVEKAKAIADEavklQKEIDKRCQ 699

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  652 ----------DRDKQRLDRVQQEEEPQ---WQKKNQEDDKQK----------REEIIK-------KKESEDKGKQEIQEK 701
Cdd:pfam05483  700 hkiaemvalmEKHKHQYDKIIEERDSElglYKNKEQEQSSAKaaleielsniKAELLSlkkqleiEKEEKEKLKMEAKEN 779


                   ....
gi 2024344592  702 PSKL 705
Cdd:pfam05483  780 TAIL 783

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 52.33 E-value: 1.67e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQK-GWFPKSYVK 962
Cdd:cd11825      2 VKALYDYRAQRPDELSFCKHAIITNVEKEDgGWWRGDYGGKKqKWFPANYVE 53

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 59.60 E-value: 1.72e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  403 KRQLELEK----QLEKQRELERQREEerrkeierreaaKRELERQRQLEW----ERNRRQELLNQRNREQEDIVVLKAKK 474
Cdd:pfam02463  153 ERRLEIEEeaagSRLKRKKKEALKKL------------IEETENLAELIIdleeLKLQELKLKEQAKKALEYYQLKEKLE 220

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  475 KTLEFELeaLNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQV 554
Cdd:pfam02463  221 LEEEYLL--YLDYLKLNEERIDLLQELLRDEQEEIESSKQEIEKEEEKLAQVLKENKEEEKEKKLQEEELKLLAKEEEEL 298

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  555 QQNSLHRDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAER-----L 629
Cdd:pfam02463  299 KSELLKLERRKVDDEEKLKESEKEKKKAEKELKKEKEEIEELEKELKELEIKREAEEEEEEELEKLQEKLEQLEeellaK 378

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  630 KQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEpqwqkkNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPH 709
Cdd:pfam02463  379 KKLESERLSSAAKLKEEELELKSEEEKEAQLLLELAR------QLEDLLKEEKKEELEILEEEEESIELKQGKLTEEKEE 452


                   ..
gi 2024344592  710 QE 711
Cdd:pfam02463  453 LE 454

Second Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212945 Cd Length: 62 Bit Score: 52.29 E-value: 1.73e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592 1154 IGMYDYTAQ----NDD----ELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12012      3 VALFDYDPLtmspNPDaaeeELPFKEGQLIKVYGDKDADgFYLGEINGRRGLVPCNMVS 61

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 52.33 E-value: 1.81e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREWVDEsqtgepGWLGGE-LKGKTGWFPANYAE 799
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGD------GWLEGRnSRGEVGLFPSSYVE 54

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 52.26 E-value: 1.82e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAE 799
Cdd:cd11803      3 CRALYDFEPENEGELGFKEGDIITLTNQ-IDEN------WYEGMVNGQSGFFPVNYVE 53

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212836 [Multi-domain] Cd Length: 59 Bit Score: 52.37 E-value: 1.88e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGE-VNGQVGLFPSNYV 1202
Cdd:cd11903      6 LYPFSSVTEEELNFEKGETMEVIEKpeNDPEWWKCKnSRGQVGLVPKNYV 55

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 59.42 E-value: 1.88e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKR---ENFERGNLELEKRRQALLEQQ----RKEQErLAQLERA-EQERKERERQEQE-RKRQL----ELEKQLEKqr 416
Cdd:pfam01576  291 EKQRRdlgEELEALKTELEDTLDTTAAQQelrsKREQE-VTELKKAlEEETRSHEAQLQEmRQKHTqaleELTEQLEQ-- 367

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  417 elerqreeerrkeierREAAKRELERQRQ-LEWERNRRQE---LLNQRNREQEDivvlkaKKKTLEFELEALNDKKNQLE 492
Cdd:pfam01576  368 ----------------AKRNKANLEKAKQaLESENAELQAelrTLQQAKQDSEH------KRKKLEGQLQELQARLSESE 425

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  493 GKLQDIRCRLSTQRQEIESTNKSreLRIAEithlqqqlqesqqmlGKLIP--------EKQLLNDQlKQVQQNSLHRDSL 564
Cdd:pfam01576  426 RQRAELAEKLSKLQSELESVSSL--LNEAE---------------GKNIKlskdvsslESQLQDTQ-ELLQEETRQKLNL 487

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  565 LTIKRALEAKelaRQQLRDQLDEVEKETRSKLQEIDIFNNQLKELRE--------IHNRQQLQKQKNLEAERLKQKEQER 636
Cdd:pfam01576  488 STRLRQLEDE---RNSLQEQLEEEEEAKRNVERQLSTLQAQLSDMKKkleedagtLEALEEGKKRLQRELEALTQQLEEK 564

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  637 KTELEKQKEAQRRIQdrdkQRLDRVQQEEEPQWQKKNQEDDKQKR-------EEIIKKK--ESEDKGKQEIQEKPSK 704
Cdd:pfam01576  565 AAAYDKLEKTKNRLQ----QELDDLLVDLDHQRQLVSNLEKKQKKfdqmlaeEKAISARyaEERDRAEAEAREKETR 637

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 52.13 E-value: 1.90e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGD-KTGVFPSNYV 1050
Cdd:cd11812      3 VALYDYTANRSDELTIHRGDIIRVLYKDNDnWWFGSLVNgQQGYFPANYV 52

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 52.21 E-value: 1.93e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1005 MYTYESSEQGDLTFQQGDMILVTKK---DGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd12057      5 LFPYEAQNEDELTIKEGDIVTLISKdciDAGWWEGELNGRRGVFPDNFVKL 55

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212942 [Multi-domain] Cd Length: 54 Bit Score: 52.13 E-value: 2.00e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGDWW------TGtlgdKTGVFPSNYV 1050
Cdd:cd12009      2 VIAQYDFVPSNERDLQLKKGEKLQVLKSDGEWWlaksltTG----KEGYIPSNYV 52

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 52.01 E-value: 2.06e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKK--DGdWWTGT--LGDKTGVFPSNYV 1050
Cdd:cd11783      2 YVALYPYKPQKPDELELRKGEMYTVTEKcqDG-WFKGTslRTGQSGVFPGNYV 53

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 52.12 E-value: 2.06e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1158 DYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11813      7 DFERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRGWFPAKFVEL 53

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 54.19 E-value: 2.18e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1609 KSNPYCEV---TMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFsPDDFLGRTEIRVADIKKDQgsk 1685
Cdd:cd04036     20 TPDCYVELwlpTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDDHLGTVLFDVSKLKLGE--- 95

                           90       100
                   ....*....|....*....|....*
gi 2024344592 1686 gPVTKCLLLHEVPTGEIVVRLDLQL 1710
Cdd:cd04036     96 -KVRVTFSLNPQGKEELEVEFLLEL 119

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212828 Cd Length: 58 Bit Score: 51.89 E-value: 2.32e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKE----DPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11895      4 ALYSYTGQSPEELSFPEGALIRLLPRAqdgvDDGFWRGEFGGRVGVFPSLLVE 56

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 51.90 E-value: 2.36e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEV-----QGQKGWFPKSY 960
Cdd:cd11883      3 VALYDFTPKSKNQLSFKAGDIIYVLNKDPSgWWDGVIisssgKVKRGWFPSNY 55

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 51.73 E-value: 2.51e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwvdesQTGEpGWLGGELKGKTGWFPANY 797
Cdd:cd11778      1 YVEALYDYEAQGDDEISIRVGDRIAVIRG-----DDGS-GWTYGEINGVKGLFPTSY 51

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 51.87 E-value: 2.52e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11927      5 ALYNYEGKEPGDLKFSKGDIIILRRQvDENWYHGEVNGIHGFFPTNFVQI 54

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 51.94 E-value: 2.63e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPD-----WWKG--EVNGQVGLFPSNYVK 1203
Cdd:cd11790      9 HDYTAEDTDELTFEKGDVILVIPFDDPEeqdegWLMGvkESTGCRGVFPENFTE 62

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 51.85 E-value: 2.64e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11952      3 VYALWDYSAEFPDELSFKEGDMVTVLRKdgEGTDWWWASLCGREGYVPRNYFGL 56

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 51.56 E-value: 2.77e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKE---DPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11884      2 VVAVRAYITRDQTLLSFHKGDVIKLLPKEgplDPGWLFGTLDGRSGAFPKEYV 54

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 54.28 E-value: 2.85e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1591 LMVNIVEGIELKPCRSHGKSNPYCEVTM-------GSQCHITKTMQDTLNPKWnsNCQFFIK-DLEQDVLCITVFERDQF 1662
Cdd:cd04033      2 LRVKVLAGIDLAKKDIFGASDPYVKISLydpdgngEIDSVQTKTIKKTLNPKW--NEEFFFRvNPREHRLLFEVFDENRL 79

                           90       100
                   ....*....|....*....|....*....
gi 2024344592 1663 SPDDFLGRTEIRVADIK-KDQGSKGPVTK 1690
Cdd:cd04033     80 TRDDFLGQVEVPLNNLPtETPGNERRYTF 108

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 53.82 E-value: 2.97e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1590 RLMVNIVEGIELKPCRSHGKSNPYCEVTM-GSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLcITVFERDQFSPDDFL 1668
Cdd:cd04042      1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYgGKTVYKSKTIYKNLNPVWDEKFTLPIEDVTQPLY-IKVFDYDRGLTDDFM 79

                           90
                   ....*....|....
gi 2024344592 1669 GRTEIRVADIKKDQ 1682
Cdd:cd04042     80 GSAFVDLSTLELNK 93

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 51.55 E-value: 2.99e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd11826      4 ALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVT---GLFPGNYV 51

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 51.54 E-value: 3.04e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKRewvdesqTGEPGWLGGELKGKTGWFPANYAEKI 801
Cdd:cd12060      5 KARFNFKQTNEDELSVCKGDIIYVTR-------VEEGGWWEGTLNGKTGWFPSNYVREI 56

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 51.48 E-value: 3.08e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKD----GD--WWTGTLGDKTGVFPSNYV 1050
Cdd:cd12058      2 WTALYDYEASGEDELSLRRGDVVEVLSQDaavsGDdgWWAGKIRHRLGIFPANYV 56

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 51.56 E-value: 3.10e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1079 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRqiGWFPANYVK 1127
Cdd:cd11825      7 DYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKKQ--KWFPANYVE 53

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 51.43 E-value: 3.43e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd12052      1 EAIVEFDYKAQHEDELTITVGDIITkIKKDDGGWWEGEIKGRRGLFPDNFVR 52

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 51.22 E-value: 3.66e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11974      6 LWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFVRL 54

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 51.46 E-value: 3.69e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11928      6 LYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCHGFLPASYIQC 54

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212725 [Multi-domain] Cd Length: 59 Bit Score: 51.53 E-value: 3.71e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWVDESQTgepGWLGG--ELKGKTGWFPANYAEK 800
Cdd:cd11791      2 LRVLYPYTPQEEDELELVPGDYIYVSPEELDSSSD---GWVEGtsWLTGCSGLLPENYTEK 59

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 51.20 E-value: 3.73e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11782      6 YNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQ 52

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176064 [Multi-domain] Cd Length: 126 Bit Score: 53.61 E-value: 3.74e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1593 VNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDL-----EQDVLCITVFERDQFSPDDF 1667
Cdd:cd08682      3 VTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSFELPGLlsgngNRATLQLTVMHRNLLGLDKF 82

                           90
                   ....*....|....*...
gi 2024344592 1668 LGRTEIRVADIKKDQGSK 1685
Cdd:cd08682     83 LGQVSIPLNDLDEDKGRR 100

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 51.19 E-value: 3.74e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11844      5 LYDNVAESPDELAFRRGDILTVLEQNTAGlegWWLCSLRGRQGIAPGNRLKL 56

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 51.16 E-value: 3.78e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE-VNGQVGLFPSNYVKL 1204
Cdd:cd11770      2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAEnSKGNRGLVPKTYLKV 54

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 58.39 E-value: 3.81e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  366 KRRQALLEQQRKE-QERLAQLERAEQERKERERQEQERKRQLE-LEKQLEKQrelerqreeerrkeiERREAAKRELERQ 443
Cdd:COG4913    609 RAKLAALEAELAElEEELAEAEERLEALEAELDALQERREALQrLAEYSWDE---------------IDVASAEREIAEL 673

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  444 RQlewernRRQELLnqrnREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQdircRLSTQRQEIEstnksRELRIAEI 523
Cdd:COG4913    674 EA------ELERLD----ASSDDLAALEEQLEELEAELEELEEELDELKGEIG----RLEKELEQAE-----EELDELQD 734

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  524 THLQQQLQESQQMLGKLIPE-KQLLNDQLKQVQQNSLHRDslltIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIF 602
Cdd:COG4913    735 RLEAAEDLARLELRALLEERfAAALGDAVERELRENLEER----IDALRARLNRAEEELERAMRAFNREWPAETADLDAD 810

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  603 NNQLKELREIHNRqqlqkqknLEAERLKQKEQ---ERKTELEKQ---------KEAQRRIQDR 653
Cdd:COG4913    811 LESLPEYLALLDR--------LEEDGLPEYEErfkELLNENSIEfvadllsklRRAIREIKER 865

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 51.05 E-value: 4.15e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM---WWFGEVQGQKGWFPKSYVKLI 964
Cdd:cd12057      1 YCKVLFPYEAQNEDELTIKEGDIVTLISKDCIdagWWEGELNGRRGVFPDNFVKLL 56

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212692 [Multi-domain] Cd Length: 55 Bit Score: 51.21 E-value: 4.30e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE-VNGQVGLFPSNYV 1202
Cdd:cd11758      3 VRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNARnSEGKTGMIPVPYV 53

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 50.95 E-value: 4.36e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYV 961
Cdd:cd11951      2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDpNWWRGRISGRVGFFPRNYV 51

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 51.13 E-value: 4.53e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1075 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYVKL 1128
Cdd:cd11996      2 QVIAmyDYTANNEDELSFSKGQLINVLNKDDPDWWQGEING---VTGLFPSNYVKM 54

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 50.98 E-value: 4.63e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLnKEDPDWWKGE--VNGQVGLFPSNYV 1202
Cdd:cd12005      1 LVVALYSYEPSHDGDLGFEKGEKLRIL-EQSGEWWKAQslTTGQEGFIPFNFV 52

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 50.79 E-value: 4.64e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11874      4 VLFSYTPQNEDELELKVGDTIEVLGEVEEgWWEGKLNGKVGVFPSNFVKE 53

Second or C-terminal Src homology 3 domain of NADPH oxidase (Nox) Organizing protein 1; Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1 is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. NoxO1 contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of NoxO1. The tandem SH3 domains of NoxO1 interact with the PRR of p22phox, which also complexes with Nox1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212957 Cd Length: 53 Bit Score: 50.80 E-value: 4.67e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1159 YTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd12024      8 YEAQKEDELSVPAGVVVEVLQKSDNGWWLIRYNGRAGYVPSMYLQP 53

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 51.10 E-value: 5.05e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11927      5 ALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNGIHGFFPTNFVQI 54

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 51.12 E-value: 5.09e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11919      7 FDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIEL 54

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 50.94 E-value: 5.10e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVmVKREWVDESqtgepgWLGGELKGKTGWFPANY 797
Cdd:cd11818      3 RALYDFTGENEDELSFKAGDII-TELESIDEE------WMSGELRGKSGIFPKNF 50

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212977 Cd Length: 53 Bit Score: 51.01 E-value: 5.25e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKEDP--DWWKGEVNGQVGLFPSNYV 1202
Cdd:cd12044      4 GLWDCFGDNPDELSFQRGDLIYILSKEYNmyGWWVGELNGIVGIVPKDYL 53

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212932 [Multi-domain] Cd Length: 56 Bit Score: 50.71 E-value: 5.47e-08

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gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEVN-GQVGLFPSNYV 1202
Cdd:cd11999      3 RVRAVYDYTGQEPDELSFKAGEELLKVEDEDEQgWCKGVTDgGAVGLYPANYV 55

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 50.78 E-value: 5.53e-08

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gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11977      4 VARYNFAARDMRELSLREGDVVRIYSRigGDQGWWKGETNGRIGWFPSTYVE 55

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 50.88 E-value: 5.72e-08

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                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11827      1 QCKALYAYDAQDTDELSFNEGDIIEILkEDPSGWWTGRLRGKEGLFPGNYV 51

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 50.78 E-value: 5.84e-08

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                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVmVKREWVDEsqtgepGWLGGELK--GKTGWFPANYAEK 800
Cdd:cd11789      2 YRAMYDYAAADDDEVSFQEGDVI-INVEIIDD------GWMEGTVQrtGQSGMLPANYVEL 55

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 50.28 E-value: 5.86e-08

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                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRqiGWFPA 1123
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGKE--GLIPS 47

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 50.40 E-value: 6.06e-08

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                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11826      4 ALYDYTADKDDELSFQEGDIIYVTkKNDDGWYEGVLNGVTGLFPGNYV 51

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 50.58 E-value: 6.12e-08

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gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD--MWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11948      1 EAVALYSFQATESDELPFQKGDILKILNMEDdqNWYKAELQGREGYIPKNYIKV 54

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 50.50 E-value: 6.16e-08

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIITILKKsdsQNDWWTGRIGGREGIFPANYVEL 55

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 50.71 E-value: 6.27e-08

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gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKrewvdeSQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11830      4 ARYDFCARDMRELSLKEGDVVKIY------NKKGQQGWWRGEINGRIGWFPSTYVEE 54

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 50.47 E-value: 6.28e-08

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gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYVKL 1204
Cdd:cd11783      2 YVALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTslRTGQSGVFPGNYVQP 55

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 50.71 E-value: 6.34e-08

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gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd11856      4 AIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKE---GWVPASYLE 52

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 50.59 E-value: 6.41e-08

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gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILV-TKKDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd11950      4 ALYDFEALEDDELGFNSGDVIEVlDSSNPSWWKGRLHGKLGLFPANYVA 52

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 50.64 E-value: 6.42e-08

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gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd11988      5 RALYPFEARNHDEMSFNAGDIIQVDEKtvgEPGWLYGSFQGNFGWFPCNYVE 56

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 50.34 E-value: 6.46e-08

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gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDgWWRGECNGQVGWFPSNYV 51

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 50.42 E-value: 6.96e-08

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gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYV 1126
Cdd:cd11901      4 AYVKFNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNG---QVGWFPSNYV 53

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 50.41 E-value: 7.01e-08

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gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGE-LQGKKRqiGWFPANYV 1126
Cdd:cd11793      2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGErLRDGER--GWFPSSYT 53

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 50.49 E-value: 7.14e-08

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gi 2024344592  744 ALYPFESRSHDEITIQPGDIVmVKREWVDEsqtgepGWLGGELKGKTGWFPANYAE 799
Cdd:cd11959      4 ALYDYQAADDDEISFDPDDII-TNIEMIDE------GWWRGVCRGKYGLFPANYVE 52

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 50.40 E-value: 7.26e-08

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gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKED---PDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11954      3 VYALWDYEAQNADELSFQEGDAITILRRKDdseTEWWWARLNDKEGYVPKNLLGL 57

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 50.54 E-value: 7.30e-08

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gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 962
Cdd:cd11820      2 KVRALYDFEAAEDNELTFKAGEIITVLDDSDPnWWKGSNHRGEGLFPANFVT 53

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 50.33 E-value: 7.54e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYV 961
Cdd:cd11964      2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDpNWWKGETPQGTGLFPSNFV 52

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 50.28 E-value: 7.56e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVkrewVDESqtgEPGWLGGELK-GKTGWFPA 795
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIV----LEKS---EDGWWKGRNKgGKEGLIPS 47

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 50.54 E-value: 7.68e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwvDESQTGEPGWLGGELKGKTGWFPANY 797
Cdd:cd12059      1 VWTAVFDYEASAEDELTLRRGDRVEVLSK--DSAVSGDEGWWTGKINDRVGIFPSNY 55

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 50.34 E-value: 7.68e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1075 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYVKL 1128
Cdd:cd11995      2 QVIGmyDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNG---QVGLFPSNYVKL 54

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 50.41 E-value: 8.10e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKRewVDESqtgepGWLGGELKGK-----TGWFPANYAEK 800
Cdd:cd11839      3 QVIAPFTATAENQLSLAVGQLVLVRK--KSPS-----GWWEGELQARgkkrqIGWFPANYVKL 58

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 50.34 E-value: 8.17e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVmvkrewVDESQTgEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11873      2 VIVEFDYDAEEPDELTLKVGDII------TNVKKM-EEGWWEGTLNGKRGMFPDNFVKV 53

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 50.43 E-value: 8.48e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDG---DWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11836      2 YRALYAFEARNPDEISFQPGDIIQVDESQVaepGWLAGELKGKTGWFPANYV 53

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175991 [Multi-domain] Cd Length: 123 Bit Score: 52.49 E-value: 8.62e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1590 RLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDDFLG 1669
Cdd:cd04025      1 RLRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDFLG 80

                           90
                   ....*....|....*..
gi 2024344592 1670 RTEIRVADIKKDQGSKG 1686
Cdd:cd04025     81 KVVFSIQTLQQAKQEEG 97

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 57.23 E-value: 8.65e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  450 RNRRQELLNQRNREqedivvlkaKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQq 529
Cdd:COG4913    597 RIRSRYVLGFDNRA---------KLAALEAELAELEEELAEAEERLEALEAELDALQERREALQRLAEYSWDEIDVASA- 666

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  530 lqesqqmlgklipEKQL--LNDQLKQVQQNSlhrDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLK 607
Cdd:COG4913    667 -------------EREIaeLEAELERLDASS---DDLAALEEQLEELEAELEELEEELDELKGEIGRLEKELEQAEEELD 730

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  608 ELREIHN----------RQQLQKQknLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQW 669
Cdd:COG4913    731 ELQDRLEaaedlarlelRALLEER--FAAALGDAVERELRENLEERIDALRARLNRAEEELERAMRAFNREW 800

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 57.39 E-value: 8.69e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  435 AAKRELERQRQ--------LEWERNRRQELlnQRNREQ-EDIVVLKAKKKtlEFELEALNDKKNQLEGKLQDIRCRLSTQ 505
Cdd:TIGR02169  174 KALEELEEVEEnierldliIDEKRQQLERL--RREREKaERYQALLKEKR--EYEGYELLKEKEALERQKEAIERQLASL 249

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  506 RQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQL----------------------LNDQLK----QVQQNSL 559
Cdd:TIGR02169  250 EEELEKLTEEISELEKRLEEIEQLLEELNKKIKDLGEEEQLrvkekigeleaeiaslersiaeKERELEdaeeRLAKLEA 329

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  560 HRDSLLT----IKRALEAKELARQQLRDQLDEVEKE---TRSKLQEID----IFNNQLKELRE-----IHNRQQLQKQKN 623
Cdd:TIGR02169  330 EIDKLLAeieeLEREIEEERKRRDKLTEEYAELKEEledLRAELEEVDkefaETRDELKDYREkleklKREINELKRELD 409

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  624 LEAERLKQKEQER---KTELEKQKEAQRRIQDRDKQRLDRVQQEEepqWQ-KKNQEDDKQKREEIIKKKESEDKGKQEIQ 699
Cdd:TIGR02169  410 RLQEELQRLSEELadlNAAIAGIEAKINELEEEKEDKALEIKKQE---WKlEQLAADLSKYEQELYDLKEEYDRVEKELS 486


                   ....*.
gi 2024344592  700 EKPSKL 705
Cdd:TIGR02169  487 KLQREL 492

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212769 [Multi-domain] Cd Length: 54 Bit Score: 50.14 E-value: 9.25e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1159 YTAQNDDELAFNKGQIINVLN---KEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11835      8 YTAQAPDELSLEVGDIVSVIDmppPEESTWWRGKKGFQVGFFPSECV 54

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 50.11 E-value: 9.33e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd11827      2 CKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKE---GLFPGNYV 51

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 50.07 E-value: 1.00e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1007 TYESSEqgdLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11828     10 TMDPEE---LGFKAGDVIEVLDmSDKDWWWGSIRDEEGWFPASFVRL 53

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 49.90 E-value: 1.01e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKD-GDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDnDGWWEGETGGRVGLVPSTAVEE 53

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 49.92 E-value: 1.05e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRT---GLVPANYVE 49

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 50.19 E-value: 1.08e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-----WWFGEVQGQKGWFPKSYVK 962
Cdd:cd12141      4 AVYTFKARSPNELSVSANQRVRILEFSDLtgnkeWWLAEANGQKGYVPSNYIR 56

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 49.98 E-value: 1.08e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMI--LVTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11882      3 RALYACKAEDESELSFEPGQIItnVQPSDEPGWLEGTLNGRTGLIPENYVEF 54

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 49.95 E-value: 1.10e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11985      3 VALYKFLPQENNDLPLQPGDRVMVVDDSNEDWWKGKSGDRVGFFPANFVQ 52

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 49.90 E-value: 1.12e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKN--PGGWWEGELQGKKrqiGWFPANYVKLL 1129
Cdd:cd12057      3 KVLFPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRR---GVFPDNFVKLL 56

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 50.07 E-value: 1.15e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 962
Cdd:cd12061      3 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGgWWEGTHNGRTGWFPSNYVR 52

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 49.83 E-value: 1.17e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd12073      3 AVALYDYQGEGDDEISFDPQETITDIEMVDEgWWKGTCHGHRGLFPANYVEL 54

Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full length form of the previously-identified tumor supressor, p53-binding protein 2 (p53BP2). ASPP2 activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). It plays a central role in regulating apoptosis and cell growth; ASPP2-deficient mice show postnatal death. Downregulated expression of ASPP2 is frequently found in breast tumors, lung cancer, and diffuse large B-cell lymphoma where it is correlated with a poor clinical outcome. ASPP2 contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP2 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212886 [Multi-domain] Cd Length: 57 Bit Score: 49.95 E-value: 1.18e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11953      3 VYALWDYEGESDDELSFKEGDCMTILRREDEDeteWWWARLNDKEGYVPRNLLGL 57

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 56.90 E-value: 1.19e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  342 EKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQL--EKQRELE 419
Cdd:pfam02463  453 LEKQELKLLKDELELKKSEDLLKETQLVKLQEQLELLLSRQKLEERSQKESKARSGLKVLLALIKDGVGGRiiSAHGRLG 532

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  420 RQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLE----FELEALNDKKNQLEGKL 495
Cdd:pfam02463  533 DLGVAVENYKVAISTAVIVEVSATADEVEERQKLVRALTELPLGARKLRLLIPKLKLPLksiaVLEIDPILNLAQLDKAT 612

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  496 QDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKE 575
Cdd:pfam02463  613 LEADEDDKRAKVVEGILKDTELTKLKESAKAKESGLRKGVSLEEGLAEKSEVKASLSELTKELLEIQELQEKAESELAKE 692

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  576 LARQQLRDQldeveKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQdrdK 655
Cdd:pfam02463  693 EILRRQLEI-----KKKEQREKEELKKLKLEAEELLADRVQEAQDKINEELKLLKQKIDEEEEEEEKSRLKKEEKE---E 764

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  656 QRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:pfam02463  765 EKSELSLKEKELAEEREKTEKLKVEEEKEEKLKAQEEELRALEEELKEEAELLEEE 820

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 50.00 E-value: 1.22e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVKL 1204
Cdd:cd11935      6 MYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGTVqrTGRTGMLPANYIEF 56

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 57.00 E-value: 1.27e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  351 DKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERA------EQERKERERQEQERKRQLELEKQLEKQRElerqree 424
Cdd:TIGR02169  750 EQEIENVKSELKELEARIEELEEDLHKLEEALNDLEARlshsriPEIQAELSKLEEEVSRIEARLREIEQKLN------- 822

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  425 errkeierreaaKRELERQrQLEWERN----RRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDirc 500
Cdd:TIGR02169  823 ------------RLTLEKE-YLEKEIQelqeQRIDLKEQIKSIEKEIENLNGKKEELEEELEELEAALRDLESRLGD--- 886

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  501 rLSTQRQEIESTNKSRELRIAEIthlQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNslhrdslltIKRALE--AKELAR 578
Cdd:TIGR02169  887 -LKKERDELEAQLRELERKIEEL---EAQIEKKRKRLSELKAKLEALEEELSEIEDP---------KGEDEEipEEELSL 953

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  579 QQLRDQLDEVEKETRS-------KLQEIDIFNNQLKELREihnrqqlqKQKNLEAERlkQKEQERKTELEKQK 644
Cdd:TIGR02169  954 EDVQAELQRVEEEIRAlepvnmlAIQEYEEVLKRLDELKE--------KRAKLEEER--KAILERIEEYEKKK 1016

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 49.78 E-value: 1.28e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1202
Cdd:cd11784      3 VALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLslVTGRVGIFPSNYV 53

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 49.82 E-value: 1.31e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVK 962
Cdd:cd11950      1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNpSWWKGRLHGKLGLFPANYVA 52

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 49.87 E-value: 1.37e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11988      7 LYPFEARNHDEMSFNAGDIIQVDEKTvgEPGWLYGSFQGNFGWFPCNYVE 56

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 49.89 E-value: 1.42e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd12003      6 LYDNAAESPEELSFRRGDVLMVLKREHGSlpgWWLCSLHGQQGIAPANRLRL 57

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 49.62 E-value: 1.43e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYV 1126
Cdd:cd11902      3 AFVKFAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNG---QIGWFPSNYV 52

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 51.90 E-value: 1.45e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1590 RLMVNIVEGIELKPCRSHGKSNPYCevtmgsQCHI-----------TKTMQDTLNPKWNSNCQFF---IKDLEQDVLCIT 1655
Cdd:cd04035     16 ALHCTIIRAKGLKAMDANGLSDPYV------KLNLlpgaskatklrTKTVHKTRNPEFNETLTYYgitEEDIQRKTLRLL 89

                           90       100
                   ....*....|....*....|....*..
gi 2024344592 1656 VFERDQFSpDDFLGRTEIRVADIKKDQ 1682
Cdd:cd04035     90 VLDEDRFG-NDFLGETRIPLKKLKPNQ 115

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 49.61 E-value: 1.46e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  998 SGEEYVAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTL---GDkTGVFPSNYV 1050
Cdd:cd11934      1 GGKRYRAVYDYNAADEDEVSFQDGDTIVnVQQIDDGWMYGTVertGD-TGMLPANYV 56

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 49.51 E-value: 1.46e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd12052      8 YKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRR---GLFPDNFVR 52

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 56.31 E-value: 1.51e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  544 KQLLNDQLKQVQQNslhRDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKN 623
Cdd:COG4717     66 PELNLKELKELEEE---LKEAEEKEEEYAELQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQELEALEAELA 142

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  624 LEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQ-EDDKQKREEIIKKKESEDKGKQEIQEKP 702
Cdd:COG4717    143 ELPERLEELEERLEELRELEEELEELEAELAELQEELEELLEQLSLATEEElQDLAEELEELQQRLAELEEELEEAQEEL 222


                   ...
gi 2024344592  703 SKL 705
Cdd:COG4717    223 EEL 225

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 49.25 E-value: 1.58e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYVKL 1128
Cdd:cd11874      2 CKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGK---VGVFPSNFVKE 53

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212874 Cd Length: 57 Bit Score: 49.52 E-value: 1.62e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKED----PDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11941      1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDkkgsPEWSLVEVNGQRGYVPSSYL 55

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 56.23 E-value: 1.63e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  352 KKRENFERGNLELEKRRQALLEQQRKEQERLAQLERA-EQERKERERQEQERKRQLELEKQLEKqRELERQREEERRKei 430
Cdd:PRK03918   186 KRTENIEELIKEKEKELEEVLREINEISSELPELREElEKLEKEVKELEELKEEIEELEKELES-LEGSKRKLEEKIR-- 262

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  431 erreaakrELERQRQlewERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQdircRLSTQRQEIE 510
Cdd:PRK03918   263 --------ELEERIE---ELKKEIEELEEKVKELKELKEKAEEYIKLSEFYEEYLDELREIEKRLS----RLEEEINGIE 327

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  511 STNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQL-KQVQQNSLHRD----SLLTIKRALEAKELARQQLRDQL 585
Cdd:PRK03918   328 ERIKELEEKEERLEELKKKLKELEKRLEELEERHELYEEAKaKKEELERLKKRltglTPEKLEKELEELEKAKEEIEEEI 407

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  586 DEVEKETRSKLQEIDIFNNQLKEL-----------REI--HNRQQLQKQ-----KNLEAERLKQKEQERK-----TELEK 642
Cdd:PRK03918   408 SKITARIGELKKEIKELKKAIEELkkakgkcpvcgRELteEHRKELLEEytaelKRIEKELKEIEEKERKlrkelRELEK 487

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  643 QKEAQRRIQdRDKQRLDRVQQEEEpQWQKKNQEDDKQKREEIIKKKESEDKGKQEI 698
Cdd:PRK03918   488 VLKKESELI-KLKELAEQLKELEE-KLKKYNLEELEKKAEEYEKLKEKLIKLKGEI 541

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 49.28 E-value: 1.67e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKN--PGGWWEGELQGKkrqIGWFPANYV 1126
Cdd:cd11836      3 RALYAFEARNPDEISFQPGDIIQVDESQvaEPGWLAGELKGK---TGWFPANYV 53

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 55.58 E-value: 1.70e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  573 AKELARQQlRDQLDEVEKETRSKLQEidifNNQLKELREIHNRQQlQKQKNLEAERLKQKEQerktelEKQKEAQRRiQD 652
Cdd:PRK09510    61 VEQYNRQQ-QQQKSAKRAEEQRKKKE----QQQAEELQQKQAAEQ-ERLKQLEKERLAAQEQ------KKQAEEAAK-QA 127

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  653 RDKQRldrvQQEEEPQWQK---KNQEDDKQKREEIIKKKESEDKGKQEIQEKPSK 704
Cdd:PRK09510   128 ALKQK----QAEEAAAKAAaaaKAKAEAEAKRAAAAAKKAAAEAKKKAEAEAAKK 178

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 49.39 E-value: 1.74e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQ---DMWWFGEVQGQKGWFPKSYV 961
Cdd:cd12142      3 RVLFDYNPVAPDELALKKGDVIEVISKEtedEGWWEGELNGRRGFFPDNFV 53

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 56.34 E-value: 1.75e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  341 LEKKLPVTfEDKK----------RENFERgnlELEKRRQALLEQQRKEQERLAQLE-RAEQERKERErQEQERKRQLELE 409
Cdd:pfam01576  704 LEDELQAT-EDAKlrlevnmqalKAQFER---DLQARDEQGEEKRRQLVKQVRELEaELEDERKQRA-QAVAAKKKLELD 778

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  410 -KQLEKQRELERQREEERRKEIERREAAKRELerQRQLEWERNRRQELLNQ-RNRE-------------QEDIVVLKAKK 474
Cdd:pfam01576  779 lKELEAQIDAANKGREEAVKQLKKLQAQMKDL--QRELEEARASRDEILAQsKESEkklknleaellqlQEDLAASERAR 856

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  475 KTLEFELEALNDK-KNQLEGK--LQDIRCRLSTQRQEIESTNKSRELRIaeithlqqqlqesqqmlgklipekQLLNDQL 551
Cdd:pfam01576  857 RQAQQERDELADEiASGASGKsaLQDEKRRLEARIAQLEEELEEEQSNT------------------------ELLNDRL 912

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  552 KQVQQNSLHRDSLLTIKRALEAK-ELARQQLRDQldevEKETRSKLQEID-IFNNQLKELREIHNRQQLQKQKNLEAER- 628
Cdd:pfam01576  913 RKSTLQVEQLTTELAAERSTSQKsESARQQLERQ----NKELKAKLQEMEgTVKSKFKSSIAALEAKIAQLEEQLEQESr 988

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  629 --------LKQKEQERKtELEKQKEAQRRIQDRDKQRLD----RVQQ------EEEPQWQKKNQEDDKQKRE 682
Cdd:pfam01576  989 erqaanklVRRTEKKLK-EVLLQVEDERRHADQYKDQAEkgnsRMKQlkrqleEAEEEASRANAARRKLQRE 1059

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 49.57 E-value: 1.79e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQV---GLFPSNYV 1202
Cdd:cd11966      1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPtrrGAFPVSFV 54

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 49.20 E-value: 1.83e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILV-TKKDGDWWTGTLGD-----KTGVFPSNY 1049
Cdd:cd11883      3 VALYDFTPKSKNQLSFKAGDIIYVlNKDPSGWWDGVIISssgkvKRGWFPSNY 55

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 49.28 E-value: 1.85e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAE 799
Cdd:cd11786      1 CAKALYNYEGKEPGDLSFKKGDIILLRKR-IDEN------WYHGECNGKQGFFPASYVQ 52

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 49.43 E-value: 1.95e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVT--KKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11948      1 EAVALYSFQATESDELPFQKGDILKILnmEDDQNWYKAELQGREGYIPKNYIKV 54

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 56.20 E-value: 1.96e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  341 LEKKLPVTFEDKKRENFERGNLElEKRRQA--LLEQQRKEQERLAQLERA-----------EQERKE-RERQEQERKRQL 406
Cdd:PRK02224   211 LESELAELDEEIERYEEQREQAR-ETRDEAdeVLEEHEERREELETLEAEiedlretiaetEREREElAEEVRDLRERLE 289

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  407 ELEKQLEKQRELERQREEERRKEIERREA-AKRELERQRQLEWERNRRQELLNQRNREQEDIVVL--KAKKK-----TLE 478
Cdd:PRK02224   290 ELEEERDDLLAEAGLDDADAEAVEARREElEDRDEELRDRLEECRVAAQAHNEEAESLREDADDLeeRAEELreeaaELE 369

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  479 FELE----ALNDKKNQ---LEGKLQDIRCRLS---TQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLN 548
Cdd:PRK02224   370 SELEeareAVEDRREEieeLEEEIEELRERFGdapVDLGNAEDFLEELREERDELREREAELEATLRTARERVEEAEALL 449

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  549 DQLK-----QVQQNSLHRDSLLTIKRALEAKELARQQLRDQLDEVEK--ETRSKLQEIDIFNNQLKELREIHNRQQLQKQ 621
Cdd:PRK02224   450 EAGKcpecgQPVEGSPHVETIEEDRERVEELEAELEDLEEEVEEVEErlERAEDLVEAEDRIERLEERREDLEELIAERR 529

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....
gi 2024344592  622 KNLEAERLKQKE-QERKTELEKQKEAQRRIQDRDKQRLDRVQQE 664
Cdd:PRK02224   530 ETIEEKRERAEElRERAAELEAEAEEKREAAAEAEEEAEEAREE 573

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 54.53 E-value: 2.06e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  383 AQLERAEQERKE-RERQEQERKRQLELEKQLEKqrelerqreeerrkeierrEAAKRELERQrQLEWERNRRQELLNQRN 461
Cdd:COG1340      8 SSLEELEEKIEElREEIEELKEKRDELNEELKE-------------------LAEKRDELNA-QVKELREEAQELREKRD 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  462 REQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCR---LSTQRQEIE-----------STNKSREL--RIAEIth 525
Cdd:COG1340     68 ELNEKVKELKEERDELNEKLNELREELDELRKELAELNKAggsIDKLRKEIErlewrqqtevlSPEEEKELveKIKEL-- 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  526 lqqqlqesqqmlgklipeKQLLNDQLKQVQQNslhrDSLLTIKRALEakelarqQLRDQLDEVEKETRSKLQEIDIFNNQ 605
Cdd:COG1340    146 ------------------EKELEKAKKALEKN----EKLKELRAELK-------ELRKEAEEIHKKIKELAEEAQELHEE 196

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  606 LKELREihNRQQLQKqknlEAERLKQKEQERKTEL----EKQKEAQRRIQDRDKQrLDRVQQEEEPQWQKKNQEDDKQKR 681
Cdd:COG1340    197 MIELYK--EADELRK----EADELHKEIVEAQEKAdelhEEIIELQKELRELRKE-LKKLRKKQRALKREKEKEELEEKA 269


                   ....*.
gi 2024344592  682 EEIIKK 687
Cdd:COG1340    270 EEIFEK 275

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 54.92 E-value: 2.09e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  376 RKEQERLAQLERAEQE---RKERERQEQERKRQLELEKQLEKQRelerqreeerrkeierreAAKRELERQRQLEWERNR 452
Cdd:pfam13868    2 RENSDELRELNSKLLAakcNKERDAQIAEKKRIKAEEKEEERRL------------------DEMMEEERERALEEEEEK 63

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  453 RQELLNQRNREQEDIvvlkakKKTLEfelEALNDKKNQLEGKLQDIRCRLSTQRQEIEstnksRELRIAEithlqqqlqe 532
Cdd:pfam13868   64 EEERKEERKRYRQEL------EEQIE---EREQKRQEEYEEKLQEREQMDEIVERIQE-----EDQAEAE---------- 119

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  533 sqqmlgklipekqllndqLKQVQQNSLHRDslltIKRALEAKELARQQLRDQLDEVEKETrsklqeidifnnqLKELREI 612
Cdd:pfam13868  120 ------------------EKLEKQRQLREE----IDEFNEEQAEWKELEKEEEREEDERI-------------LEYLKEK 164

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  613 HNRQQLQKQKNLEAERLKQKEQERKteLEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQK-----------R 681
Cdd:pfam13868  165 AEREEEREAEREEIEEEKEREIARL--RAQQEKAQDEKAERDELRAKLYQEEQERKERQKEREEAEKKarqrqelqqarE 242

                          330       340       350
                   ....*....|....*....|....*....|
gi 2024344592  682 EEIIKKKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:pfam13868  243 EQIELKERRLAEEAEREEEEFERMLRKQAE 272

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 49.03 E-value: 2.10e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQDM--WWFGEVQGQKGWFPKSY 960
Cdd:cd11778      3 EALYDYEAQGDDEISIRVGDRIAVIRGDDGsgWTYGEINGVKGLFPTSY 51

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 49.17 E-value: 2.18e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd11856      1 SYVAIADYEAQGDDEISLQEGEVVEVLEKnDSGWWYVRKGDKEGWVPASYLE 52

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212839 [Multi-domain] Cd Length: 55 Bit Score: 49.05 E-value: 2.21e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG-EVNGQVGLFPSNYV 1202
Cdd:cd11906      3 VVALYDYTPMNAQDLQLRKGEEYVILEESNLPWWRArDKNGREGYIPSNYV 53

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 48.93 E-value: 2.22e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd11806      4 AIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCC---GYIPASHL 51

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 48.91 E-value: 2.31e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11974      3 AEALWDHVTMDDQELAFKAGDVIRVLEASNKdWWWGRNEDREAWFPASFVRL 54

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 49.06 E-value: 2.33e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd12073      4 VALYDYQGEGDDEISFDPQETITdIEMVDEGWWKGTCHGHRGLFPANYVEL 54

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 48.85 E-value: 2.34e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGElqGKKRQIGWFPANYVKL 1128
Cdd:cd11819      2 AKALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGV--NAKGQKGLFPANYVEL 54

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212941 [Multi-domain] Cd Length: 56 Bit Score: 48.95 E-value: 2.40e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1202
Cdd:cd12008      3 VALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHslTTGQTGYIPSNYV 53

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 48.91 E-value: 2.44e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKDGD----WWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11807      5 ALFDYEAENGDELSFREGDELTVLRKGDDdeteWWWARLNDKEGYVPRNLLGL 57

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 48.74 E-value: 2.54e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKEDP--DWWKGEVNGQVGLFPSNYV 1202
Cdd:cd12045      4 GLWDCTGDQPDELSFKRGDTIYILSKEYNrfGWWVGEMKGTIGLVPKAYI 53

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 48.79 E-value: 2.60e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVkrewvdeSQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11856      2 YVAIADYEAQGDDEISLQEGEVVEV-------LEKNDSGWWYVRKGDKEGWVPASYLEP 53

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 48.89 E-value: 2.93e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVL--EQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11875      1 KARVLFDYEAENEDELTLREGDIVTILskDCEDKgWWKGELNGKRGVFPDNFVEP 55

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 49.05 E-value: 2.94e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKREwvDESQTGEPGWLGGELKGKTGWFPANY 797
Cdd:cd11876      4 ALFDYDARGEDELTLRRGQPVEVLSK--DAAVSGDEGWWTGKIGDKVGIFPSNY 55

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 48.94 E-value: 2.95e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1149 SVCQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11975      3 SIVSAEAVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDEEGWFPASFVRL 58

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212940 [Multi-domain] Cd Length: 58 Bit Score: 48.88 E-value: 2.97e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWW------TGtlgdKTGVFPSNYVRLKD 1054
Cdd:cd12007      3 FVALYDYEARTTEDLSFKKGERFqIINNTEGDWWearsiaTG----KNGYIPSNYVAPAD 58

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 48.87 E-value: 2.98e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKrewvdeSQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11978      5 ARYDFCARDMRELSLLKGDVVKIY------TKMSTNGWWRGEVNGRVGWFPSTYVEE 55

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 48.52 E-value: 2.99e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEKgEDGWWTVERNGQKGLVPGTYLEK 53

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 48.79 E-value: 3.21e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1080 YTATGPEQLTLAPGQLI-LIRKKNPGGWWEGELQGKkrqIGWFPANYVK 1127
Cdd:cd11976      8 FCARDRSELSLKEGDIIkILNKKGQQGWWRGEIYGR---VGWFPANYVE 53

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 54.52 E-value: 3.22e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLEQQRKEQER---LAQLERAEQERKERERQ-EQERKRQLELEKQL-EKQRELERQREEERRKEIERREAAKRE 439
Cdd:COG4372     31 EQLRKALFELDKLQEELeqlREELEQAREELEQLEEElEQARSELEQLEEELeELNEQLQAAQAELAQAQEELESLQEEA 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  440 LERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQdircRLSTQRQEIESTNKSREL- 518
Cdd:COG4372    111 EELQEELEELQKERQDLEQQRKQLEAQIAELQSEIAEREEELKELEEQLESLQEELA----ALEQELQALSEAEAEQALd 186

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  519 RIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQE 598
Cdd:COG4372    187 ELLKEANRNAEKEEELAEAEKLIESLPRELAEELLEAKDSLEAKLGLALSALLDALELEEDKEELLEEVILKEIEELELA 266

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  599 IDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEDDK 678
Cdd:COG4372    267 ILVEKDTEEEELEIAALELEALEEAALELKLLALLLNLAALSLIGALEDALLAALLELAKKLELALAILLAELADLLQLL 346

                          330       340
                   ....*....|....*....|
gi 2024344592  679 QKREEIIKKKESEDKGKQEI 698
Cdd:COG4372    347 LVGLLDNDVLELLSKGAEAG 366

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 51.60 E-value: 3.24e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592 1623 HITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDqfspDDFLGRTEIRVADIKKD 1681
Cdd:cd08676     91 KVTEVKPQTLNPVWNETFRFEVEDVSNDQLHLDIWDHD----DDFLGCVNIPLKDLPSC 145

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 48.54 E-value: 3.31e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQGkkrQIGWFPANYVK 1127
Cdd:cd11841      1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRLRG---RVGIFPANYVS 54

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 48.63 E-value: 3.35e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSY 960
Cdd:cd11818      1 KARALYDFTGENEDELSFKAGDIITELESIDEEWMsGELRGKSGIFPKNF 50

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 48.83 E-value: 3.53e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKG-WFPKSYVKLIS 965
Cdd:cd11970      7 KALFDYKAQREDELTFTKNAIIQNVEKQEgGWWRGDYGGKKQlWFPSNYVEEIS 60

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 48.38 E-value: 3.62e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11928      4 KALYSYEGKEPGDLKFNKGDIIILRRKVDeNWYHGELNGCHGFLPASYIQC 54

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212939 [Multi-domain] Cd Length: 56 Bit Score: 48.51 E-value: 3.85e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTG---TLGDkTGVFPSNYV 1050
Cdd:cd12006      3 FVALYDYEARTEDDLSFHKGEKFqILNSSEGDWWEArslTTGE-TGYIPSNYV 54

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 48.18 E-value: 3.96e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKrewvdeSQTGEpgWLGGELKGKTGWFPANYAEK 800
Cdd:cd11838      1 EYIALYPYESNEPGDLTFNAGDVILVT------KKDGE--WWTGTIGDRTGIFPSNYVRP 52

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 48.39 E-value: 4.02e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKrEWVDesqtgePGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11805      3 QALYDFNPQEPGELEFRRGDIITVL-DSSD------PDWWKGELRGRVGIFPANYVQP 53

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 48.16 E-value: 4.21e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQ-GQKGWFPKSYVKL 963
Cdd:cd11960      2 ARALYDYQAADDTEISFDPGDIITDIEQIDEgWWRGTGPdGTYGLFPANYVEL 54

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 50.66 E-value: 4.36e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHI-----TKTMQDTLNPKWnsNCQFFIK----DLEQDVLCITVFER 1659
Cdd:cd00276     14 ERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKlkkkkTSVKKGTLNPVF--NEAFSFDvpaeQLEEVSLVITVVDK 91

                           90
                   ....*....|....
gi 2024344592 1660 DQFSPDDFLGRTEI 1673
Cdd:cd00276     92 DSVGRNEVIGQVVL 105

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 48.30 E-value: 4.43e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRQigWFPANYVK 1127
Cdd:cd11969      8 YRAKRSDELSFCKGALIHNVSKETGGWWKGDYGGKVQH--YFPSNYVE 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 48.08 E-value: 4.48e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQ---KGWFPKSY 960
Cdd:cd11821      2 VRALYDCQADNDDELTFSEGEIIVVTGEEDdEWWEGHIEGDpsrRGVFPVSF 53

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 54.94 E-value: 4.53e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKE 429
Cdd:COG1196    426 LEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEG 505

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  430 IERREAAKRELERQRQL--------EWE-------RNRRQELLNQRNREQED-----IVVLKAKKKTLEFELEALNDKKN 489
Cdd:COG1196    506 FLEGVKAALLLAGLRGLagavavliGVEaayeaalEAALAAALQNIVVEDDEvaaaaIEYLKAAKAGRATFLPLDKIRAR 585

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  490 QLEGKLQDIRCRL-------------STQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQ 556
Cdd:COG1196    586 AALAAALARGAIGaavdlvasdlreaDARYYVLGDTLLGRTLVAARLEAALRRAVTLAGRLREVTLEGEGGSAGGSLTGG 665

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  557 NSLHRDSLLTIKRALEAkELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQER 636
Cdd:COG1196    666 SRRELLAALLEAEAELE-ELAERLAEEELELEEALLAEEEEERELAEAEEERLEEELEEEALEEQLEAEREELLEELLEE 744

                          330       340       350
                   ....*....|....*....|....*....|....*
gi 2024344592  637 KTELEKQ-----------KEAQRRIQDRdKQRLDR 660
Cdd:COG1196    745 EELLEEEaleelpeppdlEELERELERL-EREIEA 778

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 48.40 E-value: 4.53e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11929      2 RAKALCNYRGHNPGDLKFNKGDVILLRRQLDEnWYLGEINGVSGIFPASSVEV 54

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 48.28 E-value: 4.63e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  743 RALYPFESRSHDE-ITIQPGDIVMVkrewvdeSQTGEPGWLGGELKGKTGWFPANY 797
Cdd:cd11829      3 RTLYAFTGEQHQQgLSFEAGELIRV-------LQAPDGGWWEGEKDGLRGWFPASY 51

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 48.45 E-value: 4.68e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVmVKREWVDEsqtgepGWLGG--ELKGKTGWFPANYAEKI 801
Cdd:cd11934      5 YRAVYDYNAADEDEVSFQDGDTI-VNVQQIDD------GWMYGtvERTGDTGMLPANYVEAI 59

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 48.14 E-value: 4.82e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-----WWFGEVQGQKGWFPKSY 960
Cdd:cd11800      4 ALYTFEARSPGELSVTEGQVVTVLEKHDLkgnpeWWLVEDRGKQGYVPSNY 54

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176009 [Multi-domain] Cd Length: 124 Bit Score: 50.25 E-value: 4.83e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1588 IGRLMVNIVEGIELKPCRSHGKS-NPYCEVTMGSQCHI--TKTMQDTLNPKWNSNcQFFIKDLEQDVLCITVFERDQFSP 1664
Cdd:cd04044      1 IGVLAVTIKSARGLKGSDIIGGTvDPYVTFSISNRRELarTKVKKDTSNPVWNET-KYILVNSLTEPLNLTVYDFNDKRK 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1665 DDFLGRTEIRVADIkKDQGSKGPVTKCLLLHEVPTGEIvvRLDLQLF 1711
Cdd:cd04044     80 DKLIGTAEFDLSSL-LQNPEQENLTKNLLRNGKPVGEL--NYDLRFF 123

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 48.13 E-value: 4.95e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592 1148 PSVCQVIgmYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKG-EVNGQVGLFPSNYVKL 1204
Cdd:cd11761      1 PVTCKVL--YSYEAQRPDELTITEGEELEVIEDGDGDgWVKArNKSGEVGYVPENYLQF 57

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 48.02 E-value: 5.03e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQ--QDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd11976      2 AKARYDFCARDRSELSLKEGDIIKILNKkgQQGWWRGEIYGRVGWFPANYVE 53

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 49.91 E-value: 5.05e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1608 GKSNPYCEVTMGSQ-CHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFErDQFSPDDFLGRTEIRVADI 1678
Cdd:cd04052     11 GLLSPYAELYLNGKlVYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKD-DRDRHDPVLGSVSISLNDL 81

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 48.10 E-value: 5.08e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGE--VQGQKGWFPKSYV 961
Cdd:cd11793      1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKmPDGWYEGErlRDGERGWFPSSYT 53

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176006 [Multi-domain] Cd Length: 111 Bit Score: 49.95 E-value: 5.15e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1608 GKSNPYCEVTM---GSQCHITKTMQDTLNPKWNSNCqfFIKDLEQDV-----LCITVFERDQFSPDDFLGRTEIRVADIK 1679
Cdd:cd04041     21 GSSDPYVTASFakfGKPLYSTRIIRKDLNPVWEETW--FVLVTPDEVkagerLSCRLWDSDRFTADDRLGRVEIDLKELI 98


                   ..
gi 2024344592 1680 KD 1681
Cdd:cd04041     99 ED 100

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 48.00 E-value: 5.34e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAEKI 801
Cdd:cd11921      4 RLKFDFQAQSPKELTLQKGDIVYIHKE-VDKN------WLEGEHHGRVGIFPANYVEVL 55

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 47.88 E-value: 5.45e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTK-KDGDWWTGTL-GDKT-GVFPSNYV 1050
Cdd:cd11889      4 AVYSWAGETEGDLGFLEGDLIEVLSiGDGSWWSGKLrRNGAeGIFPSNFV 53

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212941 [Multi-domain] Cd Length: 56 Bit Score: 48.18 E-value: 5.63e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTG---TLGdKTGVFPSNYV 1050
Cdd:cd12008      2 FVALYDYESRTETDLSFKKGERLqIVNNTEGDWWLAhslTTG-QTGYIPSNYV 53

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 47.88 E-value: 5.70e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKED----PDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12141      5 VYTFKARSPNELSVSANQRVRILEFSDltgnKEWWLAEANGQKGYVPSNYIR 56

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 47.98 E-value: 5.82e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11986      3 VALYRFKALEKDDLDFHPGERITVIDDSNEEWWRGKIGEKTGYFPMNFI 51

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 47.70 E-value: 5.83e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd11992      4 ALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVR 51

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 48.07 E-value: 6.09e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVK 1203
Cdd:cd11934      7 AVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGTVerTGDTGMLPANYVE 57

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 47.87 E-value: 6.21e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11951      4 AQYDFSAEDPSQLSFRRGDIIEVLDCpDPNWWRGRISGRVGFFPRNYV 51

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212721 [Multi-domain] Cd Length: 53 Bit Score: 47.71 E-value: 6.23e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESS---EQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNY 1049
Cdd:cd11787      4 ALYDFEMKdedEKDCLTFKKGDVITVIRRvDENWAEGRLGDKIGIFPISF 53

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 54.01 E-value: 6.25e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  571 LEAKELArQQLRDqldEVEKETRSKLQEIDIFNNQLKELREIHNRQ-QLQKQKNLEAERLKQKEQERKTELEKQKEAQRR 649
Cdd:PRK12704    60 LEAKEEI-HKLRN---EFEKELRERRNELQKLEKRLLQKEENLDRKlELLEKREEELEKKEKELEQKQQELEKKEEELEE 135

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  650 IQDRDKQRLDRV---QQEEEPQWQKKNQEDdkQKREEIIKK-KESEDKGKQEIQEK 701
Cdd:PRK12704   136 LIEEQLQELERIsglTAEEAKEILLEKVEE--EARHEAAVLiKEIEEEAKEEADKK 189

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 47.96 E-value: 6.39e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQ---GQKGWFPKSYVKL 963
Cdd:cd11872      4 AIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGFSLrnkSLKGIFPKSYVHI 55

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 47.73 E-value: 6.53e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVK 962
Cdd:cd11782      1 EARAKYNFNADTGVELSFRKGDVITLTRRVDENWYeGRIGGRQGIFPVSYVQ 52

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 47.71 E-value: 6.57e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD----WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11884      3 VAVRAYITRDQTLLSFHKGDVIKLLPKEGPldpgWLFGTLDGRSGAFPKEYV 54

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 47.71 E-value: 6.72e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDK-TGVFPSNYV 1050
Cdd:cd11825      4 ALYDYRAQRPDELSFCKHAIITnVEKEDGGWWRGDYGGKkQKWFPANYV 52

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 47.78 E-value: 6.74e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDKT-GVFPSNYVRL 1052
Cdd:cd11960      4 ALYDYQAADDTEISFDPGDIITdIEQIDEGWWRGTGPDGTyGLFPANYVEL 54

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 47.85 E-value: 6.76e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVkrewVDESqtgEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11820      4 RALYDFEAAEDNELTFKAGEIITV----LDDS---DPNWWKGSNHRGEGLFPANFVTA 54

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 47.66 E-value: 7.19e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  743 RALYPFESRSHD-EITIQPGDIVMVKREwvdESQTGEP-GWLGGELK-GKTGWFPANYAE 799
Cdd:cd11771      3 RALYDFTPENPEmELSLKKGDIVAVLSK---TDPLGRDsEWWKGRTRdGRIGWFPSNYVE 59

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 47.72 E-value: 7.21e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYVKL 963
Cdd:cd11839      2 AQVIAPFTATAENQLSLAVGQLVLVRKKSPSgWWEGELQArgkkrQIGWFPANYVKL 58

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 48.09 E-value: 7.27e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKrEWVDESQTGEpGWLGG--ELKGKTGWFPANYAEKI 801
Cdd:cd11790      6 RATHDYTAEDTDELTFEKGDVILVI-PFDDPEEQDE-GWLMGvkESTGCRGVFPENFTERI 64

Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of central nervous system tissues. srGAP2 is expressed in zones of neuronal differentiation. It plays a role in the regeneration of neurons and axons. srGAP3, also called MEGAP (MEntal disorder associated GTPase-Activating Protein), is a Rho GAP with activity towards Rac1 and Cdc42. It impacts cell migration by regulating actin and microtubule cytoskeletal dynamics. The association between srGAP3 haploinsufficiency and mental retardation is under debate. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212888 [Multi-domain] Cd Length: 53 Bit Score: 47.63 E-value: 7.41e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11955      1 EAIAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRHNGIDGLVPHQYI 51

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 47.67 E-value: 7.45e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11991      4 AMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 47.53 E-value: 7.53e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDKTG-VFPSNYV 1050
Cdd:cd11969      4 ALYDYRAKRSDELSFCKGALIHnVSKETGGWWKGDYGGKVQhYFPSNYV 52

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 54.29 E-value: 7.57e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  450 RNRRQELLNQRNREQEDivvlkakkktlefeLEALNDKKNQLEGKLQdircRLSTQRqeiESTNKSRELRiAEITHLqqq 529
Cdd:TIGR02168  171 KERRKETERKLERTREN--------------LDRLEDILNELERQLK----SLERQA---EKAERYKELK-AELREL--- 225

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  530 lqesqqmlgklipEKQLLNDQLKQvqqnslHRDSLLTIKRALEAKELARQQLRDQLDEVEketrSKLQEIDIFNNQLKEl 609
Cdd:TIGR02168  226 -------------ELALLVLRLEE------LREELEELQEELKEAEEELEELTAELQELE----EKLEELRLEVSELEE- 281

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  610 rEIHNRQQLQKQKNLEAERLKQKEQ---ERKTELEKQKEAQRRIQDRDKQRLDRvQQEEEPQWQKKnQEDDKQKREEIIK 686
Cdd:TIGR02168  282 -EIEELQKELYALANEISRLEQQKQilrERLANLERQLEELEAQLEELESKLDE-LAEELAELEEK-LEELKEELESLEA 358

                          250       260
                   ....*....|....*....|....*
gi 2024344592  687 KKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:TIGR02168  359 ELEELEAELEELESRLEELEEQLET 383

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 47.51 E-value: 7.63e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592  914 QALYPWRAKKDNH-LNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYV 961
Cdd:cd11829      3 RTLYAFTGEQHQQgLSFEAGELIRVLQAPDgGWWEGEKDGLRGWFPASYV 52

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 47.61 E-value: 8.07e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11921      7 FDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGRVGIFPANYVEV 54

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 53.80 E-value: 8.74e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  571 LEAKELARQQLRDQ-----LDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKE 645
Cdd:pfam15709  328 REQEKASRDRLRAEraemrRLEVERKRREQEEQRRLQQEQLERAEKMREELELEQQRRFEEIRLRKQRLEEERQRQEEEE 407

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  646 AQRRIQDRDKQRLDRVQQEEepqWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEK 701
Cdd:pfam15709  408 RKQRLQLQAAQERARQQQEE---FRRKLQELQRKKQQEEAERAEAEKQRQKELEMQ 460

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 47.33 E-value: 8.87e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12076      6 IYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYLK 53

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 53.87 E-value: 8.98e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  437 KRELERQR-QLEWERNRRQELL----NQRNREQEDIVVLKAKK---KTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQE 508
Cdd:TIGR04523  168 KEELENELnLLEKEKLNIQKNIdkikNKLLKLELLLSNLKKKIqknKSLESQISELKKQNNQLKDNIEKKQQEINEKTTE 247

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  509 IESTNKSRELRIAEITHLQQQLQESQQ---MLGKLIPEkqlLNDQLKQVQ------QNSLHRDSLLTIKRALEAKELARQ 579
Cdd:TIGR04523  248 ISNTQTQLNQLKDEQNKIKKQLSEKQKeleQNNKKIKE---LEKQLNQLKseisdlNNQKEQDWNKELKSELKNQEKKLE 324

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  580 QLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQ-KQKNLEAERLKQKEQERKTELEKQKEaqrRIQDRDKQRL 658
Cdd:TIGR04523  325 EIQNQISQNNKIISQLNEQISQLKKELTNSESENSEKQRElEEKQNEIEKLKKENQSYKQEIKNLES---QINDLESKIQ 401

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 2024344592  659 DRVQQEEEPQWQKKNQEDDKQKREEIIKK-KESEDKGKQEIQE 700
Cdd:TIGR04523  402 NQEKLNQQKDEQIKKLQQEKELLEKEIERlKETIIKNNSEIKD 444

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 47.52 E-value: 9.02e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVmVKREWVDEsqtgepGWLGGELKGKTGWFPANYAE 799
Cdd:cd12073      5 ALYDYQGEGDDEISFDPQETI-TDIEMVDE------GWWKGTCHGHRGLFPANYVE 53

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 47.31 E-value: 9.53e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN--GQVGLFPSNYVK 1203
Cdd:cd11933      7 MYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGTVQrtGKTGMLPANYVE 56

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212998 [Multi-domain] Cd Length: 54 Bit Score: 47.29 E-value: 9.70e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIvmvkreWVDESQTGEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd12065      3 KAVYPCEAEHSSELSFEVGAI------FEDVTLSREPGWLEGTLNGKRGLIPENYVE 53

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 47.32 E-value: 9.83e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVkrewVDESQTGEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11884      1 YVVAVRAYITRDQTLLSFHKGDVIKL----LPKEGPLDPGWLFGTLDGRSGAFPKEYVQ 55

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212933 Cd Length: 57 Bit Score: 47.18 E-value: 9.85e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd12000      6 LYDNKADCSDELAFRRGDILTVLEQNVPGsegWWKCLLHGRQGLAPANRLQL 57

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 47.14 E-value: 1.03e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILV-TKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11870      3 VALHRYEAQGPEDLGFREGDTIDVlSEVNEAWLEGHSDGRVGIFPKCFV 51

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 47.33 E-value: 1.04e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd12076      5 VIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKE---GWAPASYLK 53

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 47.31 E-value: 1.04e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVmVKREWVDEsqtgepGWLGGEL-KGKTGWFPANYAE 799
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDII-TQIEQIDE------GWWLGVNaKGQKGLFPANYVE 53

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212840 [Multi-domain] Cd Length: 55 Bit Score: 47.26 E-value: 1.07e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPSNYV 1202
Cdd:cd11907      2 QVKALYDFLPREPSNLALKRAEEYLILEQYDPHWWKARDRyGNEGLIPSNYV 53

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 47.32 E-value: 1.10e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK----DGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11954      5 ALWDYEAQNADELSFQEGDAITILRRkddsETEWWWARLNDKEGYVPKNLLGL 57

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 47.37 E-value: 1.10e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwvdESQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11800      1 YYYALYTFEARSPGELSVTEGQVVTVLEK---HDLKGNPEWWLVEDRGKQGYVPSNYLAK 57

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 47.24 E-value: 1.12e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQ--QDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd11830      2 AKARYDFCARDMRELSLKEGDVVKIYNKkgQQGWWRGEINGRIGWFPSTYVE 53

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 46.96 E-value: 1.14e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11782      1 EARAKYNFNADTGVELSFRKGDVITLTRRvDENWYEGRIGGRQGIFPVSYV 51

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 46.98 E-value: 1.18e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTGTL-GDKTGVFPSNYVRL 1052
Cdd:cd11837      2 ATALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELeGGEEGWFPKSYVKE 53

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 47.07 E-value: 1.19e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12016      2 KYITTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKEGWAPATYLK 53

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 53.57 E-value: 1.24e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLEQQRKEQERLAQLERAEQERKERERQ-EQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQ 443
Cdd:pfam05483  239 EKQVSLLLIQITEKENKMKDLTFLLEESRDKANQlEEKTKLQDENLKELIEKKDHLTKELEDIKMSLQRSMSTQKALEED 318

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  444 RQ--------LEWERNRRQELLNqRNREQEDIVVLKAKKKTLEFElEALNDKKNQLEG---KLQDIRCRLSTQRQEIEST 512
Cdd:pfam05483  319 LQiatkticqLTEEKEAQMEELN-KAKAAHSFVVTEFEATTCSLE-ELLRTEQQRLEKnedQLKIITMELQKKSSELEEM 396

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  513 NKSRELRIAEITHLQQQLQesqqmlgklipEKQLLNDQLKQVQQnslhrdslltIKRALEAKElarQQLRDQLDEVEKET 592
Cdd:pfam05483  397 TKFKNNKEVELEELKKILA-----------EDEKLLDEKKQFEK----------IAEELKGKE---QELIFLLQAREKEI 452

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  593 RSKLQEIDIFNNQ----LKELREIHNRQQLQKQKN-----------LEAERLKQKEQERKTELEKQKEAQRRIQDRDKQR 657
Cdd:pfam05483  453 HDLEIQLTAIKTSeehyLKEVEDLKTELEKEKLKNieltahcdkllLENKELTQEASDMTLELKKHQEDIINCKKQEERM 532

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  658 LDRVQQEEEPQWQKKNQ-----EDDKQKREEI-IKKKESEDKGKQEIQEKPSKLFQ 707
Cdd:pfam05483  533 LKQIENLEEKEMNLRDElesvrEEFIQKGDEVkCKLDKSEENARSIEYEVLKKEKQ 588

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 47.31 E-value: 1.24e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVmVKREWVDEsqtgepGWLGGELK--GKTGWFPANYAEKI 801
Cdd:cd11935      3 YRAMYDYSAQDEDEVSFRDGDYI-VNVQPIDE------GWMYGTVQrtGRTGMLPANYIEFV 57

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 47.01 E-value: 1.27e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11809      1 EATAQFDYTGRSERELSFKKGDSLtLYRQVSDDWWRGQLNGQDGLVPHKYITL 53

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 46.87 E-value: 1.32e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVkrewVDESqtgEPGWLGGELKGKTGWFPANY 797
Cdd:cd11964      4 RAIYDFEAAEDNELTFKAGDIITI----LDDS---DPNWWKGETPQGTGLFPSNF 51

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 47.01 E-value: 1.33e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLI-LIRKKNPG---GWWEGELQGKkrqIGWFPA 1123
Cdd:cd11762      1 LVRALYDYEAQSDEELSFPEGAIIrILRKDDNGvddGWWEGEFNGR---VGVFPS 52

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 46.94 E-value: 1.35e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYV 961
Cdd:cd11963      3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDAnWWKGENHRGVGLFPSNFV 53

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 46.92 E-value: 1.35e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd11987      8 FEARSHDEITIQPGDIVMVDESQTGepGWLGGELKGKT---GWFPANYAE 54

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 46.72 E-value: 1.47e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1075 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYVK 1127
Cdd:cd12046      1 QVVAlfSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGK---IGIFPSAFVE 52

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 49.18 E-value: 1.52e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTM-----GSQCHITKTMQDTLNPKWNSncQFFIKDLEQDV---LCITVFERD 1660
Cdd:cd04026     13 NKLTVEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNE--TFTFDLKPADKdrrLSIEVWDWD 90

                           90       100
                   ....*....|....*....|..
gi 2024344592 1661 QFSPDDFLGRTEIRVADIKKDQ 1682
Cdd:cd04026     91 RTTRNDFMGSLSFGVSELIKMP 112

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 46.95 E-value: 1.54e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQD---MWW-FGEVQGQKGWFPKSYVKL 963
Cdd:cd11904      4 QALYPFSSSNDEELNFEKGEVMDVIEKPEndpEWWkCRKANGQVGLVPKNYVTV 57

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 46.81 E-value: 1.54e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNpGGWWEGELQGKKRQIGWFPANYVKL 1128
Cdd:cd11872      4 AIYNFQGDGEHQLSLQVGDTVQILEEC-EGWYRGFSLRNKSLKGIFPKSYVHI 55

Src Homology 3 domain of the p85 regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212710 Cd Length: 72 Bit Score: 47.12 E-value: 1.56e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKR--------EWVDESQTGEPGWLGG--ELKGKTGWFPANYAE 799
Cdd:cd11776      3 YRALYDYEKERDEDIILKTGDVLVVENpellalgvPDGKETVPKPEGWLEGknERTGERGDFPGTYVE 70

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 53.43 E-value: 1.58e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLEQQRKEQE---RLAQLERAEQERKERERQEQERKRQlELEKQLEKQRELERqreeerrkeierreaAKRE 439
Cdd:TIGR00618  553 SERKQRASLKEQMQEIQQsfsILTQCDNRSKEDIPNLQNITVRLQD-LTEKLSEAEDMLAC---------------EQHA 616

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  440 LERQrqLEWERNRRQELLNQRNREQEdivvLKAKKKTLEFELEALNDkknqlegklQDIRCRLSTQRQEIESTNKSRELR 519
Cdd:TIGR00618  617 LLRK--LQPEQDLQDVRLHLQQCSQE----LALKLTALHALQLTLTQ---------ERVREHALSIRVLPKELLASRQLA 681

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  520 IAEITHLQQQLQESQQMlgklIPEKQ-LLNDQLKQVQQNSLHRD----SLLTIKRALEAKELARQQLRDQLDEvEKETRS 594
Cdd:TIGR00618  682 LQKMQSEKEQLTYWKEM----LAQCQtLLRELETHIEEYDREFNeienASSSLGSDLAAREDALNQSLKELMH-QARTVL 756

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  595 KLQEIDIFNNQLKELREIhnrQQLQKQKNLEAE-RLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQ--WQK 671
Cdd:TIGR00618  757 KARTEAHFNNNEEVTAAL---QTGAELSHLAAEiQFFNRLREEDTHLLKTLEAEIGQEIPSDEDILNLQCETLVQeeEQF 833

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|.
gi 2024344592  672 KNQ-EDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:TIGR00618  834 LSRlEEKSATLGEITHQLLKYEECSKQLAQLTQEQAKIIQL 874

First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The first SH3 domain of Nck proteins preferentially binds the PxxDY sequence, which is present in the CD3e cytoplasmic tail. This binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212699 [Multi-domain] Cd Length: 51 Bit Score: 46.64 E-value: 1.59e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPdWWKGE-VNGQVGLFPSNYV 1202
Cdd:cd11765      2 VVAKYDYTAQGDQELSIKKNEKLTLLDDSKH-WWKVQnSSNQTGYVPSNYV 51

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 46.71 E-value: 1.61e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11947      1 EARGKFDFTASGEDELSFKKGDVLKILSSDDIWFKAELNGEEGYVPKNFV 50

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 46.74 E-value: 1.62e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1156 MYDYTA-QNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11829      5 LYAFTGeQHQQGLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 52

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 46.48 E-value: 1.64e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11927      3 AKALYNYEGKEPGDLKFSKGDIIILRRQVDEnWYHGEVNGIHGFFPTNFVQI 54

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 46.56 E-value: 1.65e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVkrewvdeSQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd12076      3 YTVIYPYTARDQDEINLEKGAVVEV-------IQKNLEGWWKIRYQGKEGWAPASYLKK 54

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176063 [Multi-domain] Cd Length: 118 Bit Score: 48.40 E-value: 1.70e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITKT-MQDTLNPKWNSNCQFFIKDLEQDVLCITVFErDQFSPDDF 1667
Cdd:cd08681      1 GTLVVVVLKARNLPNKRKLDKQDPYCVLRIGGVTKKTKTdFRGGQHPEWDEELRFEITEDKKPILKVAVFD-DDKRKPDL 79

                           90
                   ....*....|...
gi 2024344592 1668 LGRTEIrvaDIKK 1680
Cdd:cd08681     80 IGDTEV---DLSP 89

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 46.69 E-value: 1.71e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1005 MYTYESSEQGDLTFQQGDMILVTKK---DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd12142      5 LFDYNPVAPDELALKKGDVIEVISKeteDEGWWEGELNGRRGFFPDNFV 53

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 53.30 E-value: 1.71e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLEQQRKEQERLAQLERAEQER---------KERERQEQERKRQLE--------LEKQLEKQRELERQREEE 425
Cdd:pfam12128  358 NLEERLKALTGKHQDVTAKYNRRRSKIKEQnnrdiagikDKLAKIREARDRQLAvaeddlqaLESELREQLEAGKLEFNE 437

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  426 RRKEIERR-----------EAAKRELERQRQLEWERNRRQELLNQRNREQEDivvlkakkktLEFELEALNDKKNQLEGK 494
Cdd:pfam12128  438 EEYRLKSRlgelklrlnqaTATPELLLQLENFDERIERAREEQEAANAEVER----------LQSELRQARKRRDQASEA 507

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  495 LQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQES-QQMLGKLIPEKQL----------------------LNDQL 551
Cdd:pfam12128  508 LRQASRRLEERQSALDELELQLFPQAGTLLHFLRKEAPDwEQSIGKVISPELLhrtdldpevwdgsvggelnlygVKLDL 587

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  552 KQVQQNSLHrDSLLTIKRALEAKELARQQLRDQLDEVEKE---TRSKLQEID---------IFNNQLKELREIHNRQQLQ 619
Cdd:pfam12128  588 KRIDVPEWA-ASEEELRERLDKAEEALQSAREKQAAAEEQlvqANGELEKASreetfartaLKNARLDLRRLFDEKQSEK 666

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  620 KQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQE 675
Cdd:pfam12128  667 DKKNKALAERKDSANERLNSLEAQLKQLDKKHQAWLEEQKEQKREARTEKQAYWQV 722

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 46.50 E-value: 1.81e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  913 AQALYPWRAKKD-NHLNFNKNDVITVLEQQDM------WWFGEVQ-GQKGWFPKSYV 961
Cdd:cd11771      2 CRALYDFTPENPeMELSLKKGDIVAVLSKTDPlgrdseWWKGRTRdGRIGWFPSNYV 58

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 46.49 E-value: 1.83e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG--EVNGQVGLFPSNYV 1202
Cdd:cd11918      7 VYQYRPQNEDELELREGDRVDVMQQCDDGWFVGvsRRTQKFGTFPGNYV 55

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 46.47 E-value: 1.83e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPG-----GWWEGELQgkkRQIGWFPANYV 1126
Cdd:cd12058      4 ALYDYEASGEDELSLRRGDVVEVLSQDAAvsgddGWWAGKIR---HRLGIFPANYV 56

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212847 [Multi-domain] Cd Length: 59 Bit Score: 46.73 E-value: 1.88e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2024344592  927 LNFNKNDVITVL--EQQDMWWFGEVQG--QKGWFPKSYVK 962
Cdd:cd11914     18 LRFNRGDIITVLvpEARNGWLYGKLEGssRQGWFPEAYVK 57

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212997 Cd Length: 56 Bit Score: 46.65 E-value: 1.93e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd12064      5 ALYACKAEHDSELSFTAGTVFdNVHPSQEPGWLEGTLNGKTGLIPENYVEF 55

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 46.36 E-value: 1.99e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592 1072 EIAQVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQGKKrqiGWFPANYVKL 1128
Cdd:cd12056      2 EYCKALFHYEGTNEDELDFKEGEIILIISKDTGepGWWKGELNGKE---GVFPDNFVSQ 57

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 52.76 E-value: 2.11e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  368 RQAL-LEQQRKEQERLAQLERAEQERKER-----ERQEQERKRQLELEKQLEKQrelerqreeerrkeierreaakreLE 441
Cdd:PRK03918   152 RQILgLDDYENAYKNLGEVIKEIKRRIERlekfiKRTENIEELIKEKEKELEEV------------------------LR 207

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  442 RQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTnKSRELRIA 521
Cdd:PRK03918   208 EINEISSELPELREELEKLEKEVKELEELKEEIEELEKELESLEGSKRKLEEKIRELEERIEELKKEIEEL-EEKVKELK 286

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  522 EITHLQQQLQesqqmlgKLIPEKQLLNDQLKQVQQN-SLHRDSLLTIKRALEAKELARQQLRdQLDEVEKETRSKLQEID 600
Cdd:PRK03918   287 ELKEKAEEYI-------KLSEFYEEYLDELREIEKRlSRLEEEINGIEERIKELEEKEERLE-ELKKKLKELEKRLEELE 358

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  601 IFNNQLKELREIHNR-QQLQKQ-KNLEAERLKQKEQE---RKTELEKQ-KEAQRRIQDRDKQRLDRVQQEEEPQWQKK-- 672
Cdd:PRK03918   359 ERHELYEEAKAKKEElERLKKRlTGLTPEKLEKELEElekAKEEIEEEiSKITARIGELKKEIKELKKAIEELKKAKGkc 438

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|
gi 2024344592  673 ---NQEDDKQKREEIIKKKESE----DKGKQEIQEKPSKL 705
Cdd:PRK03918   439 pvcGRELTEEHRKELLEEYTAElkriEKELKEIEEKERKL 478

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 52.66 E-value: 2.18e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  364 LEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLE----LEKQLEKQRE---------------------- 417
Cdd:TIGR00618  227 ELKHLREALQQTQQSHAYLTQKREAQEEQLKKQQLLKQLRARIEelraQEAVLEETQErinrarkaaplaahikavtqie 306

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  418 -----------LERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALND 486
Cdd:TIGR00618  307 qqaqrihtelqSKMRSRAKLLMKRAAHVKQQSSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHTLQQ 386

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  487 KKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLT 566
Cdd:TIGR00618  387 QKTTLTQKLQSLCKELDILQREQATIDTRTSAFRDLQGQLAHAKKQQELQQRYAELCAAAITCTAQCEKLEKIHLQESAQ 466

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  567 IKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKElREIHNRQQLQKQKNLEAE--RLKQKEQERK---TELE 641
Cdd:TIGR00618  467 SLKEREQQLQTKEQIHLQETRKKAVVLARLLELQEEPCPLCG-SCIHPNPARQDIDNPGPLtrRMQRGEQTYAqleTSEE 545

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  642 K---QKEAQRRIQDRDKQRLDRVQQEEEP---QWQKKNQEDDKQKREEIIKKKESEDKGKQEIQ 699
Cdd:TIGR00618  546 DvyhQLTSERKQRASLKEQMQEIQQSFSIltqCDNRSKEDIPNLQNITVRLQDLTEKLSEAEDM 609

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 46.17 E-value: 2.21e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVmvkrEWVDESqtgEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11874      3 KVLFSYTPQNEDELELKVGDTI----EVLGEV---EEGWWEGKLNGKVGVFPSNFVK 52

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 46.15 E-value: 2.22e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTL---GDKTGVFPSNY 1049
Cdd:cd11821      4 ALYDCQADNDDELTFSEGEIIVVTGEeDDEWWEGHIegdPSRRGVFPVSF 53

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 46.34 E-value: 2.32e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVkrewVDESqtgEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11833      1 TYVALYKFKPQENEDLEMRPGDKITL----LDDS---NEDWWKGKIEDRVGFFPANFVQR 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 46.10 E-value: 2.39e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  740 VYYRALYPFESRSHDEITIQPGDiVMVKREWVDESqtgepGWLGGEL-KGKTGWFPANYAE 799
Cdd:cd11998      1 VRVRALYDYDGQEQDELSFKAGD-ELTKLEDEDEQ-----GWCKGRLdSGQVGLYPANYVE 55

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 46.20 E-value: 2.41e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYVK 1127
Cdd:cd11786      2 AKALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGK---QGFFPASYVQ 52

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 46.26 E-value: 2.44e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11959      3 VALYDYQAADDDEISFDPDDIITnIEMIDEGWWRGVCRGKYGLFPANYVEL 53

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 46.15 E-value: 2.49e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  742 YRALYPFESRSHDEITIQPGDiVMVKREWVDEsqtgepGWLGGELK--GKTGWFPANYAEKI 801
Cdd:cd11933      4 FRAMYDYRAADDDEVSFKDGD-TIVNVQTIDE------GWMYGTVQrtGKTGMLPANYVEAI 58

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 45.97 E-value: 2.66e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVkrewVDESqtgEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11950      3 RALYDFEALEDDELGFNSGDVIEV----LDSS---NPSWWKGRLHGKLGLFPANYVA 52

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 50.31 E-value: 2.68e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  450 RNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEithlqqq 529
Cdd:COG1579     23 EHRLKELPAELAELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEARIKKYEEQLGNVRNNKEYEALQ------- 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  530 lqesqqmlgklipeKQLlnDQLKQvqQNSLHRDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKEL 609
Cdd:COG1579     96 --------------KEI--ESLKR--RISDLEDEILELMERIEELEEELAELEAELAELEAELEEKKAELDEELAELEAE 157

                          170       180
                   ....*....|....*....|....*...
gi 2024344592  610 REIHNRQQLQKQKNLEAERLKQKEQERK 637
Cdd:COG1579    158 LEELEAEREELAAKIPPELLALYERIRK 185

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); MPP1, also called 55 kDa erythrocyte membrane protein (p55), is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C. MPP1 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains the three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213013 Cd Length: 62 Bit Score: 46.10 E-value: 2.76e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1155 GMYDYTAQNDD-------ELAFNKGQIINVLNKEDPDWWKGEVNGQ----VGLFPS 1199
Cdd:cd12080      4 AQFDYDPKKDNlipckeaGLKFQTGDIIQIINKDDSNWWQGRVEGSgeesAGLIPS 59

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 52.48 E-value: 2.85e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  353 KRENFERGNLELEKRRQ-------ALLEQQRKEQE----------RLA----QLERAEQERKERERQEQERKRQLELEKQ 411
Cdd:pfam01576   20 RQQKAESELKELEKKHQqlceeknALQEQLQAETElcaeaeemraRLAarkqELEEILHELESRLEEEEERSQQLQNEKK 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  412 LEKQRELerqreeerrkeierreaakrELErqRQLEWERNRRQELlnqrnreQEDIVVLKAKKKTLEFELEALNDKKNql 491
Cdd:pfam01576  100 KMQQHIQ--------------------DLE--EQLDEEEAARQKL-------QLEKVTTEAKIKKLEEDILLLEDQNS-- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  492 egklqdircRLSTQRqeiestnKSRELRIAEITHLQQQLQESQQMLGKLIPEKQL----LNDQLKQVQQNslhRDSLLTI 567
Cdd:pfam01576  149 ---------KLSKER-------KLLEERISEFTSNLAEEEEKAKSLSKLKNKHEAmisdLEERLKKEEKG---RQELEKA 209

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  568 KRALEAK------ELARQQ-----LRDQLDEVEKETRSKLQEID----IFNNQLKELREIHNrQQLQKQKNLEAERL-KQ 631
Cdd:pfam01576  210 KRKLEGEstdlqeQIAELQaqiaeLRAQLAKKEEELQAALARLEeetaQKNNALKKIRELEA-QISELQEDLESERAaRN 288

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  632 KEQERKTELEKQKEAQR-RIQDR-----DKQRLdRVQQEEEPQWQKKNQEDDKQKRE 682
Cdd:pfam01576  289 KAEKQRRDLGEELEALKtELEDTldttaAQQEL-RSKREQEVTELKKALEEETRSHE 344

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 47.56 E-value: 2.95e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1605 RSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQ 1661
Cdd:cd04050     16 KSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKT 72

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 46.17 E-value: 2.99e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11971      3 VAIYDYSKDKDDELSFMEGAIIYVIKKNDDgWYEGVCNGVTGLFPGNYV 51

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 46.14 E-value: 3.05e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTGT--LGDKTGVFPSNYV 1050
Cdd:cd12004      3 VALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARslTTKKEGFIPSNYV 52

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 45.79 E-value: 3.05e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd12076      5 VIYPYTARDQDEINLEKGAVVEVIQKNlEGWWKIRYQGKEGWAPASYLK 53

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 45.99 E-value: 3.15e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILV-TKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11956      3 EAVACFDYTGRTAQELSFKRGDVLLLhSKASSDWWRGEHNGMRGLIPHKYISV 55

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).

Pssm-ID: 129694 [Multi-domain] Cd Length: 1311 Bit Score: 52.36 E-value: 3.17e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  369 QALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKqLEKQRELERQREEERRKEIERREAAKRELERQRQLEW 448
Cdd:TIGR00606  690 EAELQEFISDLQSKLRLAPDKLKSTESELKKKEKRRDEMLGL-APGRQSIIDLKEKEIPELRNKLQKVNRDIQRLKNDIE 768

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  449 ERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRiaeithlqq 528
Cdd:TIGR00606  769 EQETLLGTIMPEEESAKVCLTDVTIMERFQMELKDVERKIAQQAAKLQGSDLDRTVQQVNQEKQEKQHELD--------- 839

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  529 qlqesqQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKE 608
Cdd:TIGR00606  840 ------TVVSKIELNRKLIQDQQEQIQHLKSKTNELKSEKLQIGTNLQRRQQFEEQLVELSTEVQSLIREIKDAKEQDSP 913

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  609 LREIHNRQQLQKQ-----KNLEAERLKQKEQERKTELEK----QKEAQRRIQD-RDKQRLDR--------VQQEEEPQWQ 670
Cdd:TIGR00606  914 LETFLEKDQQEKEelissKETSNKKAQDKVNDIKEKVKNihgyMKDIENKIQDgKDDYLKQKetelntvnAQLEECEKHQ 993

                          330       340
                   ....*....|....*....|.
gi 2024344592  671 KKNQEDDKQKREEIIKKKESE 691
Cdd:TIGR00606  994 EKINEDMRLMRQDIDTQKIQE 1014

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212998 [Multi-domain] Cd Length: 54 Bit Score: 45.75 E-value: 3.28e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1156 MYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd12065      5 VYPCEAEHSSELSFEVGAIFeDVTLSREPGWLEGTLNGKRGLIPENYVEI 54

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 45.76 E-value: 3.29e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGG--ELKGKTGWFPANYAEK 800
Cdd:cd11780      2 YRALYSYTPQNEDELELREGDIVYVMEKCDD-------GWFVGtsERTGLFGTFPGNYVAR 55

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 51.96 E-value: 3.30e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  364 LEKRRQAL--LEQQ--RKEQ----ERLAQLE------RAEQERKERER-QEQERKRQLE--LEKQLEKQrelerQREEER 426
Cdd:PRK02224   182 LSDQRGSLdqLKAQieEKEEkdlhERLNGLEselaelDEEIERYEEQReQARETRDEADevLEEHEERR-----EELETL 256

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  427 RKEIERREAAKRELERQR-----QLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCR 501
Cdd:PRK02224   257 EAEIEDLRETIAETEREReelaeEVRDLRERLEELEEERDDLLAEAGLDDADAEAVEARREELEDRDEELRDRLEECRVA 336

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  502 LSTQRQEIESTNKS---RELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQL-KQVQQNslhRDSLLTIKRALEAKELA 577
Cdd:PRK02224   337 AQAHNEEAESLREDaddLEERAEELREEAAELESELEEAREAVEDRREEIEELeEEIEEL---RERFGDAPVDLGNAEDF 413

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  578 RQQLRDQLDEV---EKETRSKLQEIDIFNNQLKELREIHN--------------------RQQLQKqknLEAERLKQKEQ 634
Cdd:PRK02224   414 LEELREERDELrerEAELEATLRTARERVEEAEALLEAGKcpecgqpvegsphvetieedRERVEE---LEAELEDLEEE 490

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  635 -----ERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEpqwQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKL 705
Cdd:PRK02224   491 veeveERLERAEDLVEAEDRIERLEERREDLEELIAE---RRETIEEKRERAEELRERAAELEAEAEEKREAAAEA 563

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 52.45 E-value: 3.40e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  349 FEDKKRENFERGNLELEKRRQAllEQQRKEQERLAQLE-----------RAEQERKERE----RQEQERKRQlELEKQLE 413
Cdd:PTZ00121  1601 YEEEKKMKAEEAKKAEEAKIKA--EELKKAEEEKKKVEqlkkkeaeekkKAEELKKAEEenkiKAAEEAKKA-EEDKKKA 1677

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  414 KQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLnQRNREQEDIVVLKAKKKTLEfelealnDKKNQLEG 493
Cdd:PTZ00121  1678 EEAKKAEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKKKAEEL-KKAEEENKIKAEEAKKEAEE-------DKKKAEEA 1749

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  494 KLQDircrlsTQRQEIESTNKSRELRIAEITHLQQQlqesqqmlgkLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEA 573
Cdd:PTZ00121  1750 KKDE------EEKKKIAHLKKEEEKKAEEIRKEKEA----------VIEEELDEEDEKRRMEVDKKIKDIFDNFANIIEG 1813

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  574 KELARQQLRDQLDEVEKETRsklQEIDIFNNQLKELREIhnrQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDR 653
Cdd:PTZ00121  1814 GKEGNLVINDSKEMEDSAIK---EVADSKNMQLEEADAF---EKHKFNKNNENGEDGNKEADFNKEKDLKEDDEEEIEEA 1887

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  654 DK-QRLDRVQQEEEP---QWQKKNQE--DDKQKREEIIKKkeSEDKGKQEI 698
Cdd:PTZ00121  1888 DEiEKIDKDDIEREIpnnNMAGKNNDiiDDKLDKDEYIKR--DAEETREEI 1936

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 45.58 E-value: 3.49e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG-EVNGQVGLFPSNYV 1202
Cdd:cd11905      3 VVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWWKArDKYGKEGYIPSNYV 53

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 45.48 E-value: 3.59e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11816      3 VARFDFEGEQEDELSFSEGDVITLKEYVGEeWAKGELNGKIGIFPLNFV 51

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 45.70 E-value: 3.67e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1080 YTATGPEQLTLAPGQLILI-RKKNPGGWWEGELQGKkrqIGWFPANYVK 1127
Cdd:cd11830      8 FCARDMRELSLKEGDVVKIyNKKGQQGWWRGEINGR---IGWFPSTYVE 53

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 45.70 E-value: 3.85e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11929      5 ALCNYRGHNPGDLKFNKGDVILLRRQlDENWYLGEINGVSGIFPASSVEV 54

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 45.56 E-value: 3.99e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11869      5 LFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRGATGIFPLSFVKI 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 45.50 E-value: 4.02e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPS 1199
Cdd:cd11832      1 YFIAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFPS 48

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 45.37 E-value: 4.03e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYV 961
Cdd:cd11772      4 ALYDYEAQHPDELSFEEGDLLYISDKSDPnWWKATCGGKTGLIPSNYV 51

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 45.58 E-value: 4.08e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPG-----GWWEGELQGKkrqIGWFPANYV 1126
Cdd:cd11876      8 YDARGEDELTLRRGQPVEVLSKDAAvsgdeGWWTGKIGDK---VGIFPSNYV 56

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 45.38 E-value: 4.12e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592  917 YPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11902      7 FAYVAEREDELSLVKGSRVTVMEKcSDGWWRGSYNGQIGWFPSNYV 52

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 45.40 E-value: 4.13e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKD--GDWWTG-TLGDKTGVFPSNYV 1050
Cdd:cd11763      4 ALYDFDSQPSGELSLRAGEVLTITRQDvgDGWLEGrNSRGEVGLFPSSYV 53

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212785 Cd Length: 62 Bit Score: 45.77 E-value: 4.14e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1153 VIGMYDY----TAQNDD---ELAFNKGQIINVLNKEDPD-WWKGEVNG-QVGLFPSNYVK 1203
Cdd:cd11851      2 MVALYDYnpetMSPNDDpeeELSFHAGDVVRVYGPMDEDgFYYGELEGgRKGLVPSNFVQ 61

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 45.30 E-value: 4.25e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAE 799
Cdd:cd11928      2 CGKALYSYEGKEPGDLKFNKGDIIILRRK-VDEN------WYHGELNGCHGFLPASYIQ 53

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 45.33 E-value: 4.34e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11766      2 AVVKFNYEAQREDELSLRKGDRVLVLEKSSD-------GWWRGECNGQVGWFPSNYVTE 53

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 45.32 E-value: 4.36e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVkrewVDESQTgepGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11985      2 YVALYKFLPQENNDLPLQPGDRVMV----VDDSNE---DWWKGKSGDRVGFFPANFVQR 53

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 51.99 E-value: 4.37e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERA------EQERKErerqEQERKRQLELEKQLEKqrelerqre 423
Cdd:TIGR02169  271 EQLLEELNKKIKDLGEEEQLRVKEKIGELEAEIASLERSiaekerELEDAE----ERLAKLEAEIDKLLAE--------- 337

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  424 eerrkeierREAAKRELERQR----QLEWE-RNRRQELLNQRNREQE---DIVVLKAKKKTLEFELEALNDKKNQLEG-- 493
Cdd:TIGR02169  338 ---------IEELEREIEEERkrrdKLTEEyAELKEELEDLRAELEEvdkEFAETRDELKDYREKLEKLKREINELKRel 408

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  494 -KLQDIRCRLSTQRQEIESTNKSRELRIAEithlqqqlqesqqmlgkLIPEKQLLNDQLKQVQQNslhrdsLLTIKRALE 572
Cdd:TIGR02169  409 dRLQEELQRLSEELADLNAAIAGIEAKINE-----------------LEEEKEDKALEIKKQEWK------LEQLAADLS 465

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 2024344592  573 AKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELRE 611
Cdd:TIGR02169  466 KYEQELYDLKEEYDRVEKELSKLQRELAEAEAQARASEE 504

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 51.06 E-value: 4.40e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  352 KKRENFERGNLELEKRRQALLEQQRKEQER--LAQLERAEQERKERERQEQERKRQLE-LEKQLEK-QRELErqreeerr 427
Cdd:COG4372      5 GEKVGKARLSLFGLRPKTGILIAALSEQLRkaLFELDKLQEELEQLREELEQAREELEqLEEELEQaRSELE-------- 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  428 keierreAAKREL-ERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQR 506
Cdd:COG4372     77 -------QLEEELeELNEQLQAAQAELAQAQEELESLQEEAEELQEELEELQKERQDLEQQRKQLEAQIAELQSEIAERE 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  507 QEIESTNKSRELRIAEIThlQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKELARQQLRDQLD 586
Cdd:COG4372    150 EELKELEEQLESLQEELA--ALEQELQALSEAEAEQALDELLKEANRNAEKEEELAEAEKLIESLPRELAEELLEAKDSL 227

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  587 EVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEE 666
Cdd:COG4372    228 EAKLGLALSALLDALELEEDKEELLEEVILKEIEELELAILVEKDTEEEELEIAALELEALEEAALELKLLALLLNLAAL 307


                   ....*...
gi 2024344592  667 PQWQKKNQ 674
Cdd:COG4372    308 SLIGALED 315

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 45.18 E-value: 4.45e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYV 1202
Cdd:cd11889      5 VYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLrrNGAEGIFPSNFV 53

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 51.89 E-value: 4.47e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQaLLEQQRKEQERLAQLERA---EQERKERERQEQERKRQLELEKQLEKQrelerqreeERRKEIERREAAKRE 439
Cdd:TIGR00618  585 DIPNLQN-ITVRLQDLTEKLSEAEDMlacEQHALLRKLQPEQDLQDVRLHLQQCSQ---------ELALKLTALHALQLT 654

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  440 LERQRQLE-WERNRRQELLNQRNREQEdIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRcRLSTQRQEIESTNKSR-- 516
Cdd:TIGR00618  655 LTQERVREhALSIRVLPKELLASRQLA-LQKMQSEKEQLTYWKEMLAQCQTLLRELETHIE-EYDREFNEIENASSSLgs 732

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  517 ELRIAEITHLQQQLQESQQMLGKLipeKQLLNDQLKQVQQN--SLHRDSLLT-IKRALEAKELARQQLRDQLDEVEKETR 593
Cdd:TIGR00618  733 DLAAREDALNQSLKELMHQARTVL---KARTEAHFNNNEEVtaALQTGAELShLAAEIQFFNRLREEDTHLLKTLEAEIG 809

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  594 SKLQEidifNNQLKELREIHNRQQLQKQKNLEAErLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEpqWQKKN 673
Cdd:TIGR00618  810 QEIPS----DEDILNLQCETLVQEEEQFLSRLEE-KSATLGEITHQLLKYEECSKQLAQLTQEQAKIIQLSDK--LNGIN 882

                          330
                   ....*....|....*...
gi 2024344592  674 QEDDkQKREEIIKKKESE 691
Cdd:TIGR00618  883 QIKI-QFDGDALIKFLHE 899

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212721 [Multi-domain] Cd Length: 53 Bit Score: 45.40 E-value: 4.52e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1152 QVIGMYDYTAQNDDE---LAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNY 1201
Cdd:cd11787      1 QCKALYDFEMKDEDEkdcLTFKKGDVITVIRRVDENWAEGRLGDKIGIFPISF 53

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 46.16 E-value: 4.56e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11973     20 AEALWDHVTMDDQELGFKAGDVIEVMDATNKeWWWGRVLDSEGWFPASFVRL 71

Mitotic checkpoint protein; This family consists of several eukaryotic mitotic checkpoint (Mitotic arrest deficient or MAD) proteins. The mitotic spindle checkpoint monitors proper attachment of the bipolar spindle to the kinetochores of aligned sister chromatids and causes a cell cycle arrest in prometaphase when failures occur. Multiple components of the mitotic spindle checkpoint have been identified in yeast and higher eukaryotes. In S.cerevisiae, the existence of a Mad1-dependent complex containing Mad2, Mad3, Bub3 and Cdc20 has been demonstrated.

Pssm-ID: 461677 [Multi-domain] Cd Length: 660 Bit Score: 51.67 E-value: 4.61e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  351 DKKRENFE--RGNLELEKRRQALLEQQRKEQERLAQLE-RAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERR 427
Cdd:pfam05557   17 EKKQMELEhkRARIELEKKASALKRQLDRESDRNQELQkRIRLLEKREAEAEEALREQAELNRLKKKYLEALNKKLNEKE 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  428 KEIERREAAKREL-----ERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQL---EGKLQDIR 499
Cdd:pfam05557   97 SQLADAREVISCLknelsELRRQIQRAELELQSTNSELEELQERLDLLKAKASEAEQLRQNLEKQQSSLaeaEQRIKELE 176

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  500 CRLSTQRQ--EIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQL----KQVQQNSLHRDSLLTIKRALEA 573
Cdd:pfam05557  177 FEIQSQEQdsEIVKNSKSELARIPELEKELERLREHNKHLNENIENKLLLKEEVedlkRKLEREEKYREEAATLELEKEK 256

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  574 KELARQQ-----------------LRDQLDEVEKETRSKLQEIDIFNNQLKELREihNRQQLQKQKnleAERLKQKEQER 636
Cdd:pfam05557  257 LEQELQSwvklaqdtglnlrspedLSRRIEQLQQREIVLKEENSSLTSSARQLEK--ARRELEQEL---AQYLKKIEDLN 331

                          330
                   ....*....|....*..
gi 2024344592  637 KtELEKQKEAQRRIQDR 653
Cdd:pfam05557  332 K-KLKRHKALVRRLQRR 347

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 45.18 E-value: 4.67e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11869      4 ALFDFTGNSKLELNFKAGDVIfLLSRVNKDWLEGTVRGATGIFPLSFVKI 53

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212980 Cd Length: 53 Bit Score: 45.19 E-value: 4.82e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd12047      3 VAQHDYSAQGPEDLEFSQGDTIdILSEVNQEWLEGHCDGRIGIFPKCFA 51

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 45.41 E-value: 4.84e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYV 961
Cdd:cd11887      6 ALYPYESDHEDDLNFDVGQLITVTEEEDAdWYFGEYVDsngntKEGIFPKNFV 58

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 45.53 E-value: 4.86e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPG-----GWWEGELQGKkrqIGWFPANYV 1126
Cdd:cd12059      8 YEASAEDELTLRRGDRVEVLSKDSAvsgdeGWWTGKINDR---VGIFPSNYV 56

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 51.65 E-value: 4.94e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  344 KLPVTFEDKKRENFERGNLEL-EKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERK-----------RQLELEKQ 411
Cdd:pfam05483   94 KVSIEAELKQKENKLQENRKIiEAQRKAIQELQFENEKVSLKLEEEIQENKDLIKENNATRhlcnllketcaRSAEKTKK 173

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  412 LEKQRELERQREEERRKEIERREAAKRELERQRQ---------LEWERNRRQELLNQRNRE---QEDIVVL--------K 471
Cdd:pfam05483  174 YEYEREETRQVYMDLNNNIEKMILAFEELRVQAEnarlemhfkLKEDHEKIQHLEEEYKKEindKEKQVSLlliqitekE 253

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  472 AKKKTLEFELEALNDKKNQLEGK---------------------LQDIR------------------------CRLSTQR 506
Cdd:pfam05483  254 NKMKDLTFLLEESRDKANQLEEKtklqdenlkeliekkdhltkeLEDIKmslqrsmstqkaleedlqiatktiCQLTEEK 333

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  507 Q-EIESTNKSRELRIAEITHLQQQLQESQQMlgkLIPEKQLL---NDQLK------QVQQNSLHRDSLLTIKRALEAKEL 576
Cdd:pfam05483  334 EaQMEELNKAKAAHSFVVTEFEATTCSLEEL---LRTEQQRLeknEDQLKiitmelQKKSSELEEMTKFKNNKEVELEEL 410

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  577 AR-----QQLRDQLDEVEK---ETRSKLQEIdIFNNQLKElREIHNRQ-QLQKQKNLEAERLKQKEqERKTELEKQKEAQ 647
Cdd:pfam05483  411 KKilaedEKLLDEKKQFEKiaeELKGKEQEL-IFLLQARE-KEIHDLEiQLTAIKTSEEHYLKEVE-DLKTELEKEKLKN 487

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  648 RRI-QDRDKQRLDR---VQQEEEPQWQKKNQEDD----KQKREEIIKK----KESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:pfam05483  488 IELtAHCDKLLLENkelTQEASDMTLELKKHQEDiincKKQEERMLKQienlEEKEMNLRDELESVREEFIQKGDE 563

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 45.78 E-value: 4.98e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11973     22 ALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFVRL 71

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 45.37 E-value: 5.41e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQ--VGLFPSNYVK 1203
Cdd:cd11917     10 LYNYMPRNEDELELREGDVIDVMEKCDDGWFVGTSRRTkfFGTFPGNYVK 59

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 45.19 E-value: 5.55e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKRewvdesQTGEPGWLGGELKGKTGWFPANY 797
Cdd:cd11812      4 ALYDYTANRSDELTIHRGDIIRVLY------KDNDNWWFGSLVNGQQGYFPANY 51

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 275388 [Multi-domain] Cd Length: 92 Bit Score: 46.38 E-value: 5.62e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1458 HSGKLYK-----AKSNKELYGFLFNDFLLLTQiikplgsSGTDKVFSPKsnlqykmykTPIFLNEVLVKLPTDPSGDEPI 1532
Cdd:cd00821      1 KEGYLLKrggggLKSWKKRWFVLFEGVLLYYK-------SKKDSSYKPK---------GSIPLSGILEVEEVSPKERPHC 64

                           90       100
                   ....*....|....*....|....*...
gi 2024344592 1533 FHISH-IDRVYTLRAESINERTAWVQKI 1559
Cdd:cd00821     65 FELVTpDGRTYYLQADSEEERQEWLKAL 92

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 45.00 E-value: 5.62e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  911 LQAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 964
Cdd:cd11920      1 LPARAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYeGEHHGRVGIFPISYVEKL 55

recombination and DNA strand exchange inhibitor protein; Reviewed

Pssm-ID: 234750 [Multi-domain] Cd Length: 782 Bit Score: 51.37 E-value: 5.62e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  579 QQLRDQLDEVEKETRSKLQEIDIFNNQLKElreihnrqQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIqdrdkQRL 658
Cdd:PRK00409   526 EELERELEQKAEEAEALLKEAEKLKEELEE--------KKEKLQEEEDKLLEEAEKEAQQAIKEAKKEADEI-----IKE 592

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  659 DRVQQEEEPQWQKKNQEDDKQKR-EEIIKKKESedkgKQEIQEKPSKLFQPHQEpVK 714
Cdd:PRK00409   593 LRQLQKGGYASVKAHELIEARKRlNKANEKKEK----KKKKQKEKQEELKVGDE-VK 644

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 45.10 E-value: 5.72e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMIL-VTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11843      4 ALYDYEGQESDELSFKAGDILTkLEEEDEQgWCKGRLDGRVGLYPANYV 52

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 44.93 E-value: 5.73e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKDGD--WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11976      4 ARYDFCARDRSELSLKEGDIIKILNKKGQqgWWRGEIYGRVGWFPANYV 52

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 45.18 E-value: 5.99e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd12046      1 QVVALFSYEASQPEDLEFQKGDVILVLSKvNEDWLEGQCKGKIGIFPSAFVE 52

Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442439 [Multi-domain] Cd Length: 687 Bit Score: 51.17 E-value: 6.02e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  443 QRQLEwerNRRQELLNQRN-----REQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRE 517
Cdd:COG3206    181 EEQLP---ELRKELEEAEAaleefRQKNGLVDLSEEAKLLLQQLSELESQLAEARAELAEAEARLAALRAQLGSGPDALP 257

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  518 LRIAEithlqqqlqesqqmlgkliPEKQLLNDQLKQVQQNslhRDSLLT--------IKRALEAKELARQQLRDQLDEVE 589
Cdd:COG3206    258 ELLQS-------------------PVIQQLRAQLAELEAE---LAELSArytpnhpdVIALRAQIAALRAQLQQEAQRIL 315

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  590 KETRSklqEIDIFNNQLKELreihnRQQLQKQKNlEAERLKQKEQERkTELEKQKEAQRRIQDRDKQRLDRVQQEEE 666
Cdd:COG3206    316 ASLEA---ELEALQAREASL-----QAQLAQLEA-RLAELPELEAEL-RRLEREVEVARELYESLLQRLEEARLAEA 382

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 44.97 E-value: 6.20e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREwvdesqtgEPGWLGGELKGKTGWFPANY 797
Cdd:cd11991      2 YVAMYTYESNEQGDLTFQQGDVILVTKK--------DGDWWTGTVGDKTGVFPSNY 49

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 45.36 E-value: 6.25e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRQigWFPANYVK 1127
Cdd:cd11970     12 YKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQL--WFPSNYVE 57

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 44.71 E-value: 7.07e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKrEWVDESqtgepgWLGGELKGKTGWFPANY 797
Cdd:cd11816      3 VARFDFEGEQEDELSFSEGDVITLK-EYVGEE------WAKGELNGKIGIFPLNF 50

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 45.00 E-value: 7.31e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKREWvdesqTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11977      5 ARYNFAARDMRELSLREGDVVRIYSRI-----GGDQGWWKGETNGRIGWFPSTYVEE 56

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 44.78 E-value: 7.31e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSY 960
Cdd:cd11817      2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAeWSRGRLNGREGIFPRAF 50

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 44.99 E-value: 7.53e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKK---DGDWWTGTLGDKTGVFPSNY 1049
Cdd:cd11987      2 YRALYPFEARSHDEITIQPGDIVMVDESqtgEPGWLGGELKGKTGWFPANY 52

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 44.70 E-value: 7.61e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQ-----DMWWFGEVQGQKGWFP 957
Cdd:cd11762      2 VRALYDYEAQSDEELSFPEGAIIRILRKDdngvdDGWWEGEFNGRVGVFP 51

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 44.62 E-value: 7.70e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2024344592 1159 YTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11982      9 YQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFPSDCV 52

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 44.99 E-value: 7.73e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  911 LQAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 962
Cdd:cd12060      2 LVVKARFNFKQTNEDELSVCKGDIIYVTRVEEGgWWEGTLNGKTGWFPSNYVR 54

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 44.41 E-value: 8.24e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPG-GWWEGELQGKKrqiGWFPANY 1125
Cdd:cd11778      3 EALYDYEAQGDDEISIRVGDRIAVIRGDDGsGWTYGEINGVK---GLFPTSY 51

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 44.60 E-value: 8.35e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLG--DKTGVFPSNYV 1050
Cdd:cd11780      2 YRALYSYTPQNEDELELREGDIVYVMEKCDDgWFVGTSErtGLFGTFPGNYV 53

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 44.79 E-value: 8.37e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGE-VQGQKGWFPKSYVKL 963
Cdd:cd11962      2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEdWWMGTnSKGESGLFPSNYVEL 54

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 44.60 E-value: 8.42e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1079 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd11772      7 DYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKT---GLIPSNYV 51

Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212946 Cd Length: 61 Bit Score: 44.68 E-value: 9.34e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1152 QVIGMYDYTAQ----NDD---ELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12013      1 RMVALFDYDPResspNVDaevELSFRAGDIITVFGEMDEDgFYYGELNGQRGLVPSNFLE 60

Guanylate-binding protein, C-terminal domain; Transcription of the anti-viral guanylate-binding protein (GBP) is induced by interferon-gamma during macrophage induction. This family contains GBP1 and GPB2, both GTPases capable of binding GTP, GDP and GMP.

Pssm-ID: 460721 [Multi-domain] Cd Length: 297 Bit Score: 49.59 E-value: 9.61e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  618 LQKQKNL-EAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLD---RVQQEEEPQWQKKNQEDDKQKREEII-----KKK 688
Cdd:pfam02841  193 LQTDQALtAKEKAIEAERAKAEAAEAEQELLREKQKEEEQMMEaqeRSYQEHVKQLIEKMEAEREQLLAEQErmlehKLQ 272

                           90
                   ....*....|....*..
gi 2024344592  689 ESEDKGKQEIQEKPSKL 705
Cdd:pfam02841  273 EQEELLKEGFKTEAESL 289

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 47.70 E-value: 9.71e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTM-----GSQCHITKTMQDTLNPKWN---SNCQFFIKDLEQDVLCITVFERD 1660
Cdd:cd04020     27 GELHVWVKEAKNLPALKSGGTSDSFVKCYLlpdksKKSKQKTPVVKKSVNPVWNhtfVYDGVSPEDLSQACLELTVWDHD 106


                   ....*....
gi 2024344592 1661 QFSPDDFLG 1669
Cdd:cd04020    107 KLSSNDFLG 115

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 50.54 E-value: 9.85e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  341 LEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL-ELEKQLE--KQRE 417
Cdd:COG4717    107 LEAELEELREELEKLEKLLQLLPLYQELEALEAELAELPERLEELEERLEELRELEEELEELEAELaELQEELEelLEQL 186

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  418 LERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLE-----------FELEALND 486
Cdd:COG4717    187 SLATEEELQDLAEELEELQQRLAELEEELEEAQEELEELEEELEQLENELEAAALEERLKEarlllliaaalLALLGLGG 266

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  487 --------------------------------KKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQ 534
Cdd:COG4717    267 sllsliltiagvlflvlgllallflllarekaSLGKEAEELQALPALEELEEEELEELLAALGLPPDLSPEELLELLDRI 346

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  535 QMLGKLIPEKQLLNDQLkQVQQNSLHRDSLLT-------------IKRALEAKELAR----------------------- 578
Cdd:COG4717    347 EELQELLREAEELEEEL-QLEELEQEIAALLAeagvedeeelraaLEQAEEYQELKEeleeleeqleellgeleelleal 425

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  579 ---------QQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQER---KTELEKQKEA 646
Cdd:COG4717    426 deeeleeelEELEEELEELEEELEELREELAELEAELEQLEEDGELAELLQELEELKAELRELAEEWaalKLALELLEEA 505

                          410
                   ....*....|....*...
gi 2024344592  647 QRRIQDRdkqRLDRVQQE 664
Cdd:COG4717    506 REEYREE---RLPPVLER 520

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 44.40 E-value: 1.02e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGD-KTGVFPSNYVRL 1052
Cdd:cd11962      3 VVLYDYEKDEDNEIELVEGEIVTnIEMVDEDWWMGTNSKgESGLFPSNYVEL 54

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 50.44 E-value: 1.04e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  352 KKRENFERGNLELEKRRQAL----------LEQQRKEQERL-AQLERAEqerKERERQEQERKRQLE--LEKQLEKQREL 418
Cdd:TIGR02168  365 AELEELESRLEELEEQLETLrskvaqlelqIASLNNEIERLeARLERLE---DRRERLQQEIEELLKklEEAELKELQAE 441

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  419 ERQREEERRKEIERREAAKRELERQR-QLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEAL-NDKKNQ------ 490
Cdd:TIGR02168  442 LEELEEELEELQEELERLEEALEELReELEEAEQALDAAERELAQLQARLDSLERLQENLEGFSEGVkALLKNQsglsgi 521

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  491 ---------------------LEGKLQDIRCR-LSTQRQEIESTNKSRELRIA------------EITHLQQQLQESQQM 536
Cdd:TIGR02168  522 lgvlselisvdegyeaaieaaLGGRLQAVVVEnLNAAKKAIAFLKQNELGRVTflpldsikgteiQGNDREILKNIEGFL 601

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  537 LGKLIPEKQ------LLNDQLKQV-----------QQNSLHRDSLL------------TIKRALEAKELARQQLRDQLDE 587
Cdd:TIGR02168  602 GVAKDLVKFdpklrkALSYLLGGVlvvddldnaleLAKKLRPGYRIvtldgdlvrpggVITGGSAKTNSSILERRREIEE 681

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  588 VEKETRSKLQEIDIFNNQLKELREIHNR------------QQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDK 655
Cdd:TIGR02168  682 LEEKIEELEEKIAELEKALAELRKELEEleeeleqlrkelEELSRQISALRKDLARLEAEVEQLEERIAQLSKELTELEA 761

                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  656 QRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESE-DKGKQEIQEKPSKLFQ 707
Cdd:TIGR02168  762 EIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEElKALREALDELRAELTL 814

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).

Pssm-ID: 129694 [Multi-domain] Cd Length: 1311 Bit Score: 50.43 E-value: 1.06e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  489 NQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPE----KQLLNDQLKQVQQNSLHRDSL 564
Cdd:TIGR00606  694 QEFISDLQSKLRLAPDKLKSTESELKKKEKRRDEMLGLAPGRQSIIDLKEKEIPElrnkLQKVNRDIQRLKNDIEEQETL 773

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  565 L-TIKRALEAKELAR------QQLRDQLDEVEK---ETRSKLQEIDIFN-----NQLKE---------LREIHNRQQLQK 620
Cdd:TIGR00606  774 LgTIMPEEESAKVCLtdvtimERFQMELKDVERkiaQQAAKLQGSDLDRtvqqvNQEKQekqheldtvVSKIELNRKLIQ 853

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  621 QKNLEAERLKQKEQERKTE-LEKQKEAQRR--IQDRDKQRLDRVQQEEEPQWQKKNQ--------EDDKQKREEIIKKKE 689
Cdd:TIGR00606  854 DQQEQIQHLKSKTNELKSEkLQIGTNLQRRqqFEEQLVELSTEVQSLIREIKDAKEQdspletflEKDQQEKEELISSKE 933

                          250       260
                   ....*....|....*....|.
gi 2024344592  690 SEDKGKQ-EIQEKPSKLFQPH 709
Cdd:TIGR00606  934 TSNKKAQdKVNDIKEKVKNIH 954

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 44.16 E-value: 1.07e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 962
Cdd:cd11856      4 AIADYEAQGDDEISLQEGEVVEVLEKNDSgWWYVRKGDKEGWVPASYLE 52

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 44.37 E-value: 1.13e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592  917 YPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd12016      7 QAYKAENEDEIGFETGVVVEVIQKNlDGWWKIRYQGKEGWAPATYLK 53

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 46.77 E-value: 1.13e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592 1608 GKSNPYCEVTMGSQCHITKTMQDTLNPKWNsncQFFI----------KDLEQD--VLCITVFERDQFSPDDFLGRTEIR 1674
Cdd:cd04017     20 GLSDPFARVSFLNQSQETEVIKETLSPTWD---QTLIfdevelygspEEIAQNppLVVVELFDQDSVGKDEFLGRSVAK 95

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 46.39 E-value: 1.14e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1593 VNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITK--TMQDTLNPKWNSNCQFFIKdLEQD-VLCITVFERDQFSPDDFLG 1669
Cdd:cd04037      4 VYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRdnYIPNTLNPVFGKMFELEAT-LPGNsILKISVMDYDLLGSDDLIG 82


                   ....
gi 2024344592 1670 RTEI 1673
Cdd:cd04037     83 ETVI 86

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 49.95 E-value: 1.15e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  352 KKRENFERGNLELEKRRQALLEQQRKEQERLAQLE--------RAEQERKERERQEQERKRQLELEKQLEKQrelerqre 423
Cdd:pfam15709  393 KQRLEEERQRQEEEERKQRLQLQAAQERARQQQEEfrrklqelQRKKQQEEAERAEAEKQRQKELEMQLAEE-------- 464

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2024344592  424 eerrKEIERREAAKRELERQRQ-LEWERNRRQELLNQRNREQE 465
Cdd:pfam15709  465 ----QKRLMEMAEEERLEYQRQkQEAEEKARLEAEERRQKEEE 503

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212847 [Multi-domain] Cd Length: 59 Bit Score: 44.42 E-value: 1.16e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1075 QVIASYTATG-PEQLTLAPGQLILIRKKNP-GGWWEGELQGKKRQiGWFPANYVKLL 1129
Cdd:cd11914      4 RAIVSHPAGSnPTLLRFNRGDIITVLVPEArNGWLYGKLEGSSRQ-GWFPEAYVKAL 59

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 44.19 E-value: 1.18e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYV 1202
Cdd:cd11926      3 VAIYPYTPRKEDELELRKGEMFLVFERCQDGWFKGTSmhTSKIGVFPGNYV 53

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176024 [Multi-domain] Cd Length: 121 Bit Score: 46.15 E-value: 1.19e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1590 RLMVNIVEGIELKPCrshgKSNPYCEVTMGSQCHITKTMQDTLNPKWNsncQFFI--KD-LEQDVLCITVFERDqFSPDD 1666
Cdd:cd08378      1 YLYVRVVKARGLPAN----SNDPVVEVKLGNYKGSTKAIERTSNPEWN---QVFAfsKDrLQGSTLEVSVWDKD-KAKDD 72

                           90
                   ....*....|..
gi 2024344592 1667 FLGRTEIRVADI 1678
Cdd:cd08378     73 FLGGVCFDLSEV 84

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 44.01 E-value: 1.20e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDKTGVFPSNY 1049
Cdd:cd11818      4 ALYDFTGENEDELSFKAGDIITeLESIDEEWMSGELRGKSGIFPKNF 50

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, also called Insulin Receptor Tyrosine Kinase Substrate (IRTKS); BAIAP2L1 or IRTKS is widely expressed, serves as a substrate for the insulin receptor, and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. IRTKS mediates the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRTKS has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212846 Cd Length: 58 Bit Score: 44.14 E-value: 1.23e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2024344592  927 LNFNKNDVITVL--EQQDMWWFGE--VQGQKGWFPKSYVKL 963
Cdd:cd11913     18 LSFAQGDVITLLipEEKDGWLYGEhdTTKARGWFPSSYTRP 58

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 49.95 E-value: 1.23e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  551 LKQVQQNSLHRDSLLT---IKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIhnrqQLQKQKnLEAE 627
Cdd:pfam15709  325 LEKREQEKASRDRLRAeraEMRRLEVERKRREQEEQRRLQQEQLERAEKMREELELEQQRRFEEI----RLRKQR-LEEE 399

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  628 RLKQKEQERKTELEKQKEAQRRIQD-----RDKQRLDRVQQEEEPqwQKKNQEDDKQKREEII----------------- 685
Cdd:pfam15709  400 RQRQEEEERKQRLQLQAAQERARQQqeefrRKLQELQRKKQQEEA--ERAEAEKQRQKELEMQlaeeqkrlmemaeeerl 477

                          170       180
                   ....*....|....*....|...
gi 2024344592  686 ----KKKESEDKGKQEIQEKPSK 704
Cdd:pfam15709  478 eyqrQKQEAEEKARLEAEERRQK 500

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 44.09 E-value: 1.24e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd11815      3 VVLHDFPAEHSDDLSLNSGEIVyLLEKIDTEWYRGKCKNTTGIFPANHVK 52

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 44.22 E-value: 1.27e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11987      4 ALYPFEARSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 54

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 49.52 E-value: 1.27e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  386 ERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEierREAAKRELERQRQlewERNRRQELLNQRNReqe 465
Cdd:COG4372      3 RLGEKVGKARLSLFGLRPKTGILIAALSEQLRKALFELDKLQEE---LEQLREELEQARE---ELEQLEEELEQARS--- 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  466 divvlkakkktlefELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEIThlqqqlqesqqmlgKLIPEKQ 545
Cdd:COG4372     74 --------------ELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELE--------------ELQKERQ 125

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  546 LLNDQLKQVQQNslhrdslltiKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLE 625
Cdd:COG4372    126 DLEQQRKQLEAQ----------IAELQSEIAEREEELKELEEQLESLQEELAALEQELQALSEAEAEQALDELLKEANRN 195

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  626 AERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSK 704
Cdd:COG4372    196 AEKEEELAEAEKLIESLPRELAEELLEAKDSLEAKLGLALSALLDALELEEDKEELLEEVILKEIEELELAILVEKDTE 274

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 44.23 E-value: 1.29e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAEKI 801
Cdd:cd11920      4 RAVYDFKAQTSKELSFKKGDTVYILRK-IDQN------WYEGEHHGRVGIFPISYVEKL 55

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 43.89 E-value: 1.37e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1075 QVIASY--TATGPEQLTLAPGQLILIRKKNPGgWWEGELQGKkrQIGWFPANYVKL 1128
Cdd:cd11837      1 TATALYpwRAKKENHLSFAKGDIITVLEQQEM-WWFGELEGG--EEGWFPKSYVKE 53

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 44.25 E-value: 1.37e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1007 TYESSEQGDLTFQQGDMILVTKKDGD-WWTGTL---GDK--TGVFPSNYVRL 1052
Cdd:cd11839      7 PFTATAENQLSLAVGQLVLVRKKSPSgWWEGELqarGKKrqIGWFPANYVKL 58

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 43.84 E-value: 1.40e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDM--ILVTKKDGdWWTG--TLGDKtGVFPSNYVRL 1052
Cdd:cd11770      1 LYEALSDFQAEQEGDLSFKKGEVlrIISKRADG-WWLAenSKGNR-GLVPKTYLKV 54

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 44.24 E-value: 1.40e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLI-LIRKKNPGGWWEGELQGKKRQiGWFPANYVK 1127
Cdd:cd11779      4 KALYPHAAGGETQLSFEEGDVItLLGPEPRDGWHYGENERSGRR-GWFPIAYTE 56

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212999 Cd Length: 55 Bit Score: 43.90 E-value: 1.41e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd12066      1 QAKAMYSCKAEHSHELSFPQGAIFsNVYPSVEPGWLKATYEGKTGLVPENYV 52

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.

Pssm-ID: 431111 [Multi-domain] Cd Length: 766 Bit Score: 49.82 E-value: 1.43e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  460 RNREQEDIVVLKAKKKTLEFeleaLNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRElRIAEITHLQqqlqesqqmlgk 539
Cdd:pfam10174  351 RLRLEEKESFLNKKTKQLQD----LTEEKSTLAGEIRDLKDMLDVKERKINVLQKKIE-NLQEQLRDK------------ 413

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  540 lipEKQL--LNDQLKQVQQNSLHRDSLL-TIKRALEAKELARQQLRDQLDeveKETRSKLQEIDIFNNQLKELREIHNRQ 616
Cdd:pfam10174  414 ---DKQLagLKERVKSLQTDSSNTDTALtTLEEALSEKERIIERLKEQRE---REDRERLEELESLKKENKDLKEKVSAL 487

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  617 QLQKQ---------------------------KNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRL-DRVQQEEEpQ 668
Cdd:pfam10174  488 QPELTekesslidlkehasslassglkkdsklKSLEIAVEQKKEECSKLENQLKKAHNAEEAVRTNPEInDRIRLLEQ-E 566

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  669 WQKKNQEDDKQKRE-----EIIKKKESEDKGK-QEIQEKPSKLFQPHQEPVKPAVQ 718
Cdd:pfam10174  567 VARYKEESGKAQAEverllGILREVENEKNDKdKKIAELESLTLRQMKEQNKKVAN 622

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 49.78 E-value: 1.48e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  601 IFNNQLKELREihNRQQLQKQKNLEAERLKQ-KEQERKTELEKQK-EAQRRIQDRDK--QRLD-RVQQEEEPQwqKKNQE 675
Cdd:PRK12704    28 IAEAKIKEAEE--EAKRILEEAKKEAEAIKKeALLEAKEEIHKLRnEFEKELRERRNelQKLEkRLLQKEENL--DRKLE 103

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2024344592  676 DDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:PRK12704   104 LLEKREEELEKKEKELEQKQQELEKKEEELEELIEE 139

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 43.83 E-value: 1.50e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLnKEDPDWWKGE--VNGQVGLFPSNYV 1202
Cdd:cd12004      2 VVALYPYDGIHEDDLSFKKGEKLKVI-EEHGEWWKARslTTKKEGFIPSNYV 52

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 43.87 E-value: 1.53e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  911 LQAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11901      2 LPAYVKFNYTAEREDELSLVKGTKVIVMEKcSDGWWRGSYNGQVGWFPSNYV 53

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212736 [Multi-domain] Cd Length: 52 Bit Score: 43.82 E-value: 1.55e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM---WWFGEVQGQKGWFPKSY 960
Cdd:cd11802      1 KARVLYDYDAEDSTELSLLADEVITVYELPGMdedYMMGERGSQRGKVPVAY 52

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 43.79 E-value: 1.57e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVIT-VLEQQDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd11873      4 VEFDYDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVK 52

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 43.87 E-value: 1.58e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYVKL 1128
Cdd:cd11781      2 ARALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNG---RVGIFPASYVEI 53

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212829 [Multi-domain] Cd Length: 55 Bit Score: 43.80 E-value: 1.61e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  743 RALYPFESRSHDEITIQPGDivmvkrEWVDESQTGEPGWLGGE-LKGKTGWFPANYAE 799
Cdd:cd11896      3 RALYSFQSENKEEINIQENE------ELVIFSENSLDGWLQGQnSRGETGLFPASYVE 54

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 43.76 E-value: 1.64e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKDG---DWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11952      5 ALWDYSAEFPDELSFKEGDMVTVLRKDGegtDWWWASLCGREGYVPRNYFGL 56

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 46.10 E-value: 1.66e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1593 VNIVEGIELKPCRSHGKSNPYceVTM-----GSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDDF 1667
Cdd:cd04043      5 IRIVRAENLKADSSNGLSDPY--VTLvdtngKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHDL 82


                   ....*..
gi 2024344592 1668 LGRTEIR 1674
Cdd:cd04043     83 CGRASLK 89

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 43.86 E-value: 1.75e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQ--DMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd11978      3 AIARYDFCARDMRELSLLKGDVVKIYTKMstNGWWRGEVNGRVGWFPSTYVE 54

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 43.93 E-value: 1.77e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  911 LQAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11975      5 VSAEAVWDHVTMANRELAFKAGDVIKVLDASNKdWWWGQIDDEEGWFPASFVRL 58

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 43.61 E-value: 1.77e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGGELK--GKTGWFPANYAEK 800
Cdd:cd11785      2 YRVIVPYPPQSEAELELKEGDIVFVHKKRED-------GWFKGTLQrtGKTGLFPGSFVES 55

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 43.80 E-value: 1.83e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1005 MYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd12054      6 LFEYVPQNEDELELKVGDIIDINEEvEEGWWSGTLNGKSGLFPSNFVK 53

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 43.84 E-value: 1.88e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  999 GEEYVAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTL--GDKTGVFPSNYV 1050
Cdd:cd11933      1 GKSFRAMYDYRAADDDEVSFKDGDTIVnVQTIDEGWMYGTVqrTGKTGMLPANYV 55

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 43.80 E-value: 1.94e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1075 QVIASYTATG--PEQLTLAPGQLI-LIRKKNpGGWWEGELQGKKRQiGWFPANYVKL 1128
Cdd:cd11924      2 EAVAQYTFKGdlEVELSFRKGEHIcLIRKVN-ENWYEGRITGTGRQ-GIFPASYVQV 56

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 49.53 E-value: 1.95e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELE---------KQLEKQrelerqreeerrkeierREA 435
Cdd:COG4913    287 QRRLELLEAELEELRAELARLEAELERLEARLDALREELDELEAQirgnggdrlEQLERE-----------------IER 349

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  436 AKRELERQRQlewERNRRQELLNQ-------------RNREQedivvLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRL 502
Cdd:COG4913    350 LERELEERER---RRARLEALLAAlglplpasaeefaALRAE-----AAALLEALEEELEALEEALAEAEAALRDLRREL 421


                   ....*....
gi 2024344592  503 STQRQEIES 511
Cdd:COG4913    422 RELEAEIAS 430

Src Homology 3 domain of the p85alpha regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85alpha interacts with activated FGFR3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212843 Cd Length: 75 Bit Score: 44.12 E-value: 1.98e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWV--------DESQTGEPGWLGG--ELKGKTGWFPANYAEKI 801
Cdd:cd11910      4 YRALYDYKKEREEDIDLHLGDILTVNKGSLlalgfsegQEARPEEIGWLNGynETTGERGDFPGTYVEYI 73

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 43.80 E-value: 1.98e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAEKI 801
Cdd:cd11919      4 RAKFDFKAQTLKELPLQKGDIVYIYKQ-IDQN------WYEGEHHGRVGIFPRSYIELL 55

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 43.54 E-value: 2.01e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVmvkrewVDESQTGEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11960      3 RALYDYQAADDTEISFDPGDII------TDIEQIDEGWWRGTGPDGTYGLFPANYVE 53

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 43.78 E-value: 2.01e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQ------DMWWFGEVQGQKGWFPKSYV 961
Cdd:cd12058      4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsgdDGWWAGKIRHRLGIFPANYV 56

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. ITK is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, ITK plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, ITK is crucial for the development of T-helper(Th)2 effector responses. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212841 [Multi-domain] Cd Length: 56 Bit Score: 43.46 E-value: 2.10e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWK-GEVNGQVGLFPSNYV 1202
Cdd:cd11908      3 VIALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRvQDKNGHEGYVPSSYL 53

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 43.51 E-value: 2.11e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11974      5 ALWDHVTMDDQELAFKAGDVIRVLEaSNKDWWWGRNEDREAWFPASFVRL 54

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 43.64 E-value: 2.15e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  740 VYYrALYPFESRSHDEITIQPGDIVMVKREwvdESQTGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd12141      1 VYY-AVYTFKARSPNELSVSANQRVRILEF---SDLTGNKEWWLAEANGQKGYVPSNYIRK 57

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 43.42 E-value: 2.19e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1074 AQVIASYTATGPE-QLTLAPGQLILIRKK-----NPGGWWegelQGKKR--QIGWFPANYV 1126
Cdd:cd11771      2 CRALYDFTPENPEmELSLKKGDIVAVLSKtdplgRDSEWW----KGRTRdgRIGWFPSNYV 58

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 43.68 E-value: 2.21e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  746 YPFESRSHDEITIQPGDIVM-VKRewvdesqTGEPGWLGGELKGKTGWFPANYAEKI 801
Cdd:cd12053      6 YDYDAVHEDELTIRVGEIIRnVKK-------LEEEGWLEGELNGRRGMFPDNFVKEI 55

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 43.48 E-value: 2.21e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  911 LQAQALYPWRAKKDNHLNFNKNDVITVL--EQQDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11946      1 MEAIAKYDFKATADDELSFKRGDILKVLneECDQNWYKAELNGKDGFIPKNYIEM 55

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 43.11 E-value: 2.29e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYV 961
Cdd:cd11796      1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFrGELNGRRGIFPEGFV 51

Src Homology 3 domain of SH3 domain-binding protein 4; SH3 domain-binding protein 4 (SH3BP4) is also called transferrin receptor trafficking protein (TTP). SH3BP4 is an endocytic accessory protein that interacts with endocytic proteins including clathrin and dynamin, and regulates the internalization of the transferrin receptor (TfR). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212691 Cd Length: 52 Bit Score: 43.47 E-value: 2.32e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11757      1 EVVAIKDYCPTNFTTLKFSKGDHLYVLDTSGGEWWYAHNTTEMGYIPSSYVQ 52

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 43.21 E-value: 2.32e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1077 IASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd12017      5 IGEFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKE---GWAPSSYI 51

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212934 Cd Length: 68 Bit Score: 43.88 E-value: 2.32e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQ----DMWWFGEVQGQKGWFPKSYVKLISG 966
Cdd:cd12001      5 AKALYDNVAESPDELSFRKGDIMTVLERDtqglDGWWLCSLHGRQGIVPGNRLKILVG 62

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 43.28 E-value: 2.46e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVmVKREWVDesqtgePGWLGGELKGKTGWFPANYAE 799
Cdd:cd11961      3 KALYDYDAAEDNELSFFENDKI-INIEFVD------DDWWLGECHGSRGLFPSNYVE 52

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 48.65 E-value: 2.55e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  578 RQQLRDQldEVEKETRSKLQEIDIFNNQLKEL-REIHNRQQLQKQK----NLEAERLKQKEQERKTELE----KQKEAQR 648
Cdd:PRK09510    77 AEEQRKK--KEQQQAEELQQKQAAEQERLKQLeKERLAAQEQKKQAeeaaKQAALKQKQAEEAAAKAAAaakaKAEAEAK 154

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  649 RIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKK---ESEDKGKQEIQEK 701
Cdd:PRK09510   155 RAAAAAKKAAAEAKKKAEAEAAKKAAAEAKKKAEAEAAAKaaaEAKKKAEAEAKKK 210

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 43.15 E-value: 2.57e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILV-TKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11806      1 EYVAIADFVATDDSQLSFESGDKLLVlRKPSVDWWWAEHNGCCGYIPASHL 51

Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); MPP6, also called Veli-associated MAGUK 1 (VAM-1) or PALS2, is a scaffolding protein that binds to Veli-1, a homolog of Caenorhabditis Lin-7. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212971 Cd Length: 61 Bit Score: 43.51 E-value: 2.58e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1157 YDYTAQNDD-------ELAFNKGQIINVLNKEDPDWWKG---EVNGQVGLFPSNYV 1202
Cdd:cd12038      6 FDYNPYNDNlipckeaGLKFSKGEILQIVNREDPNWWQAshvKEGGSAGLIPSQFL 61

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 49.35 E-value: 2.59e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  353 KRENFERGNLE---LEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQ 411
Cdd:PTZ00266   441 EKENAHRKALEmkiLEKKRIERLEREERERLERERMERIERERLERERLERERLERDRLERD 502

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 46.19 E-value: 2.59e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  568 KRALEAKelaRQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKteLEKQKEAQ 647
Cdd:pfam05672   13 ARILAEK---RRQAREQREREEQERLEKEEEERLRKEELRRRAEEERARREEEARRLEEERRREEEERQR--KAEEEAEE 87

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2024344592  648 RRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESE 691
Cdd:pfam05672   88 REQREQEEQERLQKQKEEAEAKAREEAERQRQEREKIMQQEEQE 131

C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212693 [Multi-domain] Cd Length: 57 Bit Score: 43.24 E-value: 2.64e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1071 PEIAQVIASY--TATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVKL 1128
Cdd:cd11759      1 PAYARVIQKRvpNAYDKTALALEVGDLVKVTKINVSGQWEGELNGKV---GHFPFTHVEL 57

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 43.11 E-value: 2.64e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWF-GEVQGQKGWFPKSYV 961
Cdd:cd11804      1 EAVAKHDFKATAEDELSFKKGSILKVLnMEDDPNWYkAELDGKEGLIPKNYI 52

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212954 [Multi-domain] Cd Length: 53 Bit Score: 43.02 E-value: 2.75e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd12021      3 RAIADYEKSSKSEMALKTGDVVEVVEKSENGWWFCQLKAKR---GWVPASYLE 52

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 43.44 E-value: 2.75e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQgKKRQIGWFPANYVKLL 1129
Cdd:cd11916      5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSR-RTKQFGTFPGNYVKLL 58

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 43.03 E-value: 2.82e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 964
Cdd:cd11919      2 PARAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYeGEHHGRVGIFPRSYIELL 55

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212858 Cd Length: 57 Bit Score: 43.06 E-value: 2.87e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYV 1202
Cdd:cd11925      4 LALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSlrTGVSGVFPGNYV 54

Centrosomal protein of 63 kDa; CEP63 is a family of eukaryotic proteins involved in centriole activity.

Pssm-ID: 465338 [Multi-domain] Cd Length: 264 Bit Score: 47.51 E-value: 2.98e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  369 QALLEQQRKEQERL-AQLERAEQERKE--RERQEQERKRQLEL-------EKQLEKQRELERQREEERRKEIERREAAKR 438
Cdd:pfam17045   48 RNTLERKHKEIGLLrQQLEELEKGKQElvAKYEQQLQKLQEELsklkrsyEKLQRKQLKEAREEAKSREEDRSELSRLNG 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  439 ELE--RQRQLEWERnrrqellnQRNREQEDIVVLKAKKKTLEFELE---------ALNDKKNQLEGKLQDIRcRLSTQRQ 507
Cdd:pfam17045  128 KLEefRQKSLEWEQ--------QRLQYQQQVASLEAQRKALAEQSSliqsaayqvQLEGRKQCLEASQSEIQ-RLRSKLE 198

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  508 EIESTNKSRELriaEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQ-QNSLHRDSLLTIKRALEAKE 575
Cdd:pfam17045  199 RAQDSLCAQEL---ELERLRMRVSELGDSNRKLLEEQQRLLEELRMSQrQLQVLQNELMELKATLQSQD 264

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 48.97 E-value: 3.09e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  341 LEKKLPVTFEDKKRENFERGNLE-LEKRR-------QALLEQQRKEQERLAQLERAEQERKERERQEQERK 403
Cdd:PTZ00266   455 LEKKRIERLEREERERLERERMErIERERlererleRERLERDRLERDRLDRLERERVDRLERDRLEKARR 525

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 43.06 E-value: 3.13e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd12055      4 VAFSYLPQNEDELELKVGDIIeVVGEVEEGWWEGVLNGKTGMFPSNFIK 52

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 48.79 E-value: 3.19e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  341 LEKKLPVTFEDKKRENFErgNLELEKRRQALLEQQRKEQERLaQLERAEQERKERERQEQErkrQLELEKQLEKQReler 420
Cdd:pfam15709  309 MESEEERSEEDPSKALLE--KREQEKASRDRLRAERAEMRRL-EVERKRREQEEQRRLQQE---QLERAEKMREEL---- 378

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  421 qreeerrkeierreaakrELERQRQLEWERNRRQELLNQRnreqedivvlkakkktlefelealndkknqlegklqdirc 500
Cdd:pfam15709  379 ------------------ELEQQRRFEEIRLRKQRLEEER---------------------------------------- 400

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  501 rlstQRQEIESTNKSRELRIAeithlqqqlqesqqmlgklipekqllndqlkqvqqnslhrdslltikraleaKELARQQ 580
Cdd:pfam15709  401 ----QRQEEEERKQRLQLQAA----------------------------------------------------QERARQQ 424

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  581 lrdqldevEKETRSKLQEIdifnnqlkelreihnrQQLQKQKnlEAERLKQKEQERKtELEKQKEAQRRiqdrdkqRLDR 660
Cdd:pfam15709  425 --------QEEFRRKLQEL----------------QRKKQQE--EAERAEAEKQRQK-ELEMQLAEEQK-------RLME 470

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592  661 VQQEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQ 707
Cdd:pfam15709  471 MAEEERLEYQRQKQEAEEKARLEAEERRQKEEEAARLALEEAMKQAQ 517

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 43.03 E-value: 3.19e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNG--QVGLFPSNYVKL 1204
Cdd:cd11924      2 EAVAQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITGtgRQGIFPASYVQV 56

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 43.00 E-value: 3.21e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD--WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11830      3 KARYDFCARDMRELSLKEGDVVKIYNKKGQqgWWRGEINGRIGWFPSTYV 52

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 48.91 E-value: 3.22e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  435 AAKRELERQRQLEWERNRRQELLNQrnreQEDIvvlKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNK 514
Cdd:PRK03918   163 AYKNLGEVIKEIKRRIERLEKFIKR----TENI---EELIKEKEKELEEVLREINEISSELPELREELEKLEKEVKELEE 235

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  515 SRElRIAEithlqqqlqesqqmlgklipekqlLNDQLKQVQQNslhrdslltiKRALEAKelaRQQLRDQLDEVEKETRs 594
Cdd:PRK03918   236 LKE-EIEE------------------------LEKELESLEGS----------KRKLEEK---IRELEERIEELKKEIE- 276

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  595 KLQEidifnnQLKELREIhnrqqlqKQKNLEAERLKQkeqerktELEKQKEAQRRIqdrdKQRLDRVQQE-EEPQWQKKN 673
Cdd:PRK03918   277 ELEE------KVKELKEL-------KEKAEEYIKLSE-------FYEEYLDELREI----EKRLSRLEEEiNGIEERIKE 332

                          250       260       270
                   ....*....|....*....|....*....|....
gi 2024344592  674 QEDDKQKREEIiKKKESEDKGKQEIQEKPSKLFQ 707
Cdd:PRK03918   333 LEEKEERLEEL-KKKLKELEKRLEELEERHELYE 365

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 47.23 E-value: 3.33e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLEQQRKEQERLAQLERA-EQERKERERQEQERKrqlELEKQLEKqrelerqreeerrkeierreaAKRELE 441
Cdd:COG1579     14 ELDSELDRLEHRLKELPAELAELEDElAALEARLEAAKTELE---DLEKEIKR---------------------LELEIE 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  442 RQRQLEwERNRRQELLNQRNRE----QEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRE 517
Cdd:COG1579     70 EVEARI-KKYEEQLGNVRNNKEyealQKEIESLKRRISDLEDEILELMERIEELEEELAELEAELAELEAELEEKKAELD 148


                   ....*.
gi 2024344592  518 LRIAEI 523
Cdd:COG1579    149 EELAEL 154

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 43.05 E-value: 3.38e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTLGDKTGV-FPSNYV 1050
Cdd:cd11970      8 ALFDYKAQREDELTFTKNAIIQnVEKQEGGWWRGDYGGKKQLwFPSNYV 56

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212789 [Multi-domain] Cd Length: 55 Bit Score: 42.79 E-value: 3.39e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1004 AMYTYESSEQ--GDLTFQQGDMILVTKKDGDWWTGTLGD-KTGVFPSNYVRL 1052
Cdd:cd11855      4 ALYPYDASPDdpNELSFEKGEILEVSDTSGKWWQARKSNgETGICPSNYLQL 55

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 48.97 E-value: 3.60e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  354 RENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKqLEKQRELerqreeerrkeierr 433
Cdd:PTZ00266   432 KDHAERARIEKENAHRKALEMKILEKKRIERLEREERERLERERMERIERERLERER-LERERLE--------------- 495

                           90       100
                   ....*....|....*....|....*....
gi 2024344592  434 eaaKRELERQRQLEWERNRRQELlnQRNR 462
Cdd:PTZ00266   496 ---RDRLERDRLDRLERERVDRL--ERDR 519

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 42.65 E-value: 3.77e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGDWW---TGTLGDKTGVFPSNYV 1050
Cdd:cd11926      2 YVAIYPYTPRKEDELELRKGEMFLVFERCQDGWfkgTSMHTSKIGVFPGNYV 53

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 43.03 E-value: 3.85e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLG--DKTGVFPSNYVRL 1052
Cdd:cd11924      2 EAVAQYTFKGDLEVELSFRKGEHIcLIRKVNENWYEGRITgtGRQGIFPASYVQV 56

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 42.72 E-value: 3.93e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGgWWEGELQGKKrqiGWFPANYVKL 1128
Cdd:cd11990      2 AQALCSWTAKKDNHLNFSKNDIITVLEQQEN-WWFGEVHGGR---GWFPKSYVKL 52

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 42.70 E-value: 4.03e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQ--DMWWFGE-VQGQKGWFPKSYV 961
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITRQDvgDGWLEGRnSRGEVGLFPSSYV 53

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 48.76 E-value: 4.06e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  544 KQLLNDQLKQVQQNSLHRDSLLTIKRALEA------KELARQQLRDQLDEVEKEtrskLQEIDIFNNQLKELREihNRQQ 617
Cdd:COG4913    623 EEELAEAEERLEALEAELDALQERREALQRlaeyswDEIDVASAEREIAELEAE----LERLDASSDDLAALEE--QLEE 696

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  618 LQKQKNlEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQkknQEDDKQKREEIIKKKESE 691
Cdd:COG4913    697 LEAELE-ELEEELDELKGEIGRLEKELEQAEEELDELQDRLEAAEDLARLELR---ALLEERFAAALGDAVERE 766

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 44.70 E-value: 4.13e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHI---TKTMQDTLNPKWNSNCQFFIK--DLEQDVLCITVFERDQFS 1663
Cdd:cd08387     16 GILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNtkqSKIHKKTLNPEFDESFVFEVPpqELPKRTLEVLLYDFDQFS 95

                           90
                   ....*....|....*
gi 2024344592 1664 PDDFLGRTEIRVADI 1678
Cdd:cd08387     96 RDECIGVVELPLAEV 110

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212954 [Multi-domain] Cd Length: 53 Bit Score: 42.64 E-value: 4.23e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVmvkrEWVDESQTGepgWLGGELKGKTGWFPANYAE 799
Cdd:cd12021      2 YRAIADYEKSSKSEMALKTGDVV----EVVEKSENG---WWFCQLKAKRGWVPASYLE 52

chromosome partition protein MukB;

Pssm-ID: 235316 [Multi-domain] Cd Length: 1486 Bit Score: 48.80 E-value: 4.28e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGnLELEKRRQALLEQQRKEQERLAQLERAEQERKERER----------------------QEQERKRQ-- 405
Cdd:PRK04863   278 ANERRVHLEEA-LELRRELYTSRRQLAAEQYRLVEMARELAELNEAESdleqdyqaasdhlnlvqtalrqQEKIERYQad 356

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  406 -LELEKQLEKQrelerqreeerrkEIERREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLkaKKKTLEFE--LE 482
Cdd:PRK04863   357 lEELEERLEEQ-------------NEVVEEADEQQEENEARAEAAEEEVDELKSQLADYQQALDVQ--QTRAIQYQqaVQ 421

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  483 ALnDKKNQLEGK----LQDIRCRLST-QRQEIESTNKSRE----LRIAEITHLqqqlqesqqmlgklIPEK--QLLNDQL 551
Cdd:PRK04863   422 AL-ERAKQLCGLpdltADNAEDWLEEfQAKEQEATEELLSleqkLSVAQAAHS--------------QFEQayQLVRKIA 486

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  552 KQVQQNSLHRDSLLTIKRALEAKELA--RQQLRDQLDEVEKETRSKlqeidifNNQLKELREIHNRQQLQKQKNLEAERL 629
Cdd:PRK04863   487 GEVSRSEAWDVARELLRRLREQRHLAeqLQQLRMRLSELEQRLRQQ-------QRAERLLAEFCKRLGKNLDDEDELEQL 559

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592  630 KQKEQERKTELEKQKE--AQRRIQDRDKQR-LD-RVQQEE--EPQWQK 671
Cdd:PRK04863   560 QEELEARLESLSESVSeaRERRMALRQQLEqLQaRIQRLAarAPAWLA 607

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 42.68 E-value: 4.28e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd12055      3 QVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKT---GMFPSNFIK 52

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 48.43 E-value: 4.28e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  550 QLKQVQQNSLHRDSLLT---IKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEA 626
Cdd:pfam02463  177 KLIEETENLAELIIDLEelkLQELKLKEQAKKALEYYQLKEKLELEEEYLLYLDYLKLNEERIDLLQELLRDEQEEIESS 256

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  627 ERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLF 706
Cdd:pfam02463  257 KQEIEKEEEKLAQVLKENKEEEKEKKLQEEELKLLAKEEEELKSELLKLERRKVDDEEKLKESEKEKKKAEKELKKEKEE 336


                   ....*...
gi 2024344592  707 QPHQEPVK 714
Cdd:pfam02463  337 IEELEKEL 344

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 42.65 E-value: 4.52e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1004 AMYTYESSEQG-DLTFQQGDMILVTKK------DGDWWTGTLGD-KTGVFPSNYV 1050
Cdd:cd11771      4 ALYDFTPENPEmELSLKKGDIVAVLSKtdplgrDSEWWKGRTRDgRIGWFPSNYV 58

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 42.34 E-value: 4.62e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKKDGD--WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11804      1 EAVAKHDFKATAEDELSFKKGSILKVLNMEDDpnWYKAELDGKEGLIPKNYI 52

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212836 [Multi-domain] Cd Length: 59 Bit Score: 42.74 E-value: 4.79e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQD---MWW-FGEVQGQKGWFPKSYVKLIS 965
Cdd:cd11903      4 QTLYPFSSVTEEELNFEKGETMEVIEKPEndpEWWkCKNSRGQVGLVPKNYVVVLS 59

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 42.51 E-value: 4.86e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYVKLL 1129
Cdd:cd12073      9 YQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGH---RGLFPANYVELL 55

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 42.40 E-value: 4.87e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYVKL 1128
Cdd:cd11959      1 TAVALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRG---KYGLFPANYVEL 53

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 47.85 E-value: 4.90e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  362 LELEKRRQALLEQQRKEQE---RLAQLERAEQERKERERQEQE-RKRQLELEKQLekqrelerqreeerrkeierreaaK 437
Cdd:PRK12704    34 KEAEEEAKRILEEAKKEAEaikKEALLEAKEEIHKLRNEFEKElRERRNELQKLE------------------------K 89

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  438 RELERQRQLEwernRRQELLNQRNREqedivvLKAKKKTLEFELEALNDKKNQLEGKLQDircrlstQRQEIES 511
Cdd:PRK12704    90 RLLQKEENLD----RKLELLEKREEE------LEKKEKELEQKQQELEKKEEELEELIEE-------QLQELER 146

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212934 Cd Length: 68 Bit Score: 42.72 E-value: 5.04e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1155 GMYDYTAQNDDELAFNKGQIINVLNKEDP---DWWKGEVNGQVGLFPSNYVKLTTDM 1208
Cdd:cd12001      7 ALYDNVAESPDELSFRKGDIMTVLERDTQgldGWWLCSLHGRQGIVPGNRLKILVGM 63

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 42.31 E-value: 5.08e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1077 IASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYV 1126
Cdd:cd11982      6 VKPYQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGR---VGWFPSDCV 52

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 270064 Cd Length: 100 Bit Score: 43.75 E-value: 5.08e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1454 RKFLHSG--KLYKAKSNK-ELYGFLFNDFLLLTqiiKPLGSSGtDKvfspksnlqYKMYKTPIFLNEVLVKLPTDPSGde 1530
Cdd:cd13244      1 RRLLLEGdlRLKEGKGSKvDVHCFLFTDMLLIC---KPVKRKK-DR---------LKVIRPPYLVDKLVVQELKDPGG-- 65

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2024344592 1531 piFHISHIDR------VYTLRAESINERTAWVQKIK 1560
Cdd:cd13244     66 --FLLVYLNEfhtavaAYTFQTSSQEDTRRWLDAIR 99

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 42.69 E-value: 5.09e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQ---KGWFPKSYVKLI 964
Cdd:cd11965      1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQeWWIGHIEGQperKGVFPVSFVHIL 57

Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that were originally characterized in silico. They are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC2, also called Iporin, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212744 Cd Length: 50 Bit Score: 42.43 E-value: 5.14e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNY 1201
Cdd:cd11810      2 VRALCHHVATDSGQLSFRKGDILRVIARVDDDWLLCTRGSTKGLVPLSY 50

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 42.32 E-value: 5.31e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILI-RKKNPGGWWEGELQGKkrqIGWFPANYVK 1127
Cdd:cd11978      2 IAIARYDFCARDMRELSLLKGDVVKIyTKMSTNGWWRGEVNGR---VGWFPSTYVE 54

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 42.20 E-value: 5.33e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELKGKTGWFPANYAEKI 801
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGK-------DNDGWWEGETGGRVGLVPSTAVEEI 54

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 42.50 E-value: 5.52e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTG---TLGdKTGVFPSNYV 1050
Cdd:cd12005      3 VALYSYEPSHDGDLGFEKGEKLRILEQSGEWWKAqslTTG-QEGFIPFNFV 52

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 42.10 E-value: 5.65e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYV 961
Cdd:cd11833      4 ALYKFKPQENEDLEMRPGDKITLLDDSNEdWWKGKIEDRVGFFPANFV 51

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 48.25 E-value: 5.77e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLEQQRKEQERLAQLERAEQERKErerQEQERKRQLELE-----------KQLEKQRELERQReeerrkeIE 431
Cdd:pfam01576  493 QLEDERNSLQEQLEEEEEAKRNVERQLSTLQA---QLSDMKKKLEEDagtlealeegkKRLQRELEALTQQ-------LE 562

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  432 RREAAKRELERQrqleweRNRRQEllnqrnrEQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIES 511
Cdd:pfam01576  563 EKAAAYDKLEKT------KNRLQQ-------ELDDLLVDLDHQRQLVSNLEKKQKKFDQMLAEEKAISARYAEERDRAEA 629

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  512 TNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQN---SLHrdSLLTIKRALEAkelARQQLRDQLDEV 588
Cdd:pfam01576  630 EAREKETRALSLARALEEALEAKEELERTNKQLRAEMEDLVSSKDDvgkNVH--ELERSKRALEQ---QVEEMKTQLEEL 704

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  589 EKETR----SKLQ-EIDIFNNQLKELREIHNR--------QQLQKQ-KNLEAERLKQKEQ-------ERKTELEkQKEAQ 647
Cdd:pfam01576  705 EDELQatedAKLRlEVNMQALKAQFERDLQARdeqgeekrRQLVKQvRELEAELEDERKQraqavaaKKKLELD-LKELE 783

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  648 RRIQDRDKQRLDRVQQEEEPQWQKKNQ----EDDKQKREEI-IKKKESEDKGK 695
Cdd:pfam01576  784 AQIDAANKGREEAVKQLKKLQAQMKDLqrelEEARASRDEIlAQSKESEKKLK 836

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

Pssm-ID: 175981 [Multi-domain] Cd Length: 132 Bit Score: 44.57 E-value: 6.05e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCR-----SHGKSN-----PYCEVTMgSQCHI--TKTMQDTLNPKWNsncQFFIKDLEQDV-LCIT 1655
Cdd:cd04014      4 GTLKIKICEAVDLKPTDwstrhAVPKKGsqlldPYVSIDV-DDTHIgkTSTKPKTNSPVWN---EEFTTEVHNGRnLELT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1656 VFERDQFSPDDFLGRTEIRVADIKKDQGSKgpvtKCLLLHEVPTGEIVVRLDLQ 1709
Cdd:cd04014     80 VFHDAAIGPDDFVANCTISFEDLIQRGSGS----FDLWVDLEPQGKLHVKIELK 129

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 42.25 E-value: 6.14e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd11984      5 AVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRT---GWFPADCV 52

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 42.37 E-value: 6.14e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQV--GLFPSNYVKL 1204
Cdd:cd11858      5 LYDFAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDESkeGWVPAAYLEE 55

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 42.31 E-value: 6.19e-05

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2024344592  927 LNFNKNDVITVL-EQQDM---WWFGEVQGQKGWFPKSYV 961
Cdd:cd11884     16 LSFHKGDVIKLLpKEGPLdpgWLFGTLDGRSGAFPKEYV 54

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 42.09 E-value: 6.27e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGElqGKKRQIGWFPANYVKL 1128
Cdd:cd11962      2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGT--NSKGESGLFPSNYVEL 54

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 46.83 E-value: 6.63e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  539 KLIPEKQLLNDQLKQVQQNslhRDSLLTikralEAKELA--RQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREihNRQ 616
Cdd:COG1340     12 ELEEKIEELREEIEELKEK---RDELNE-----ELKELAekRDELNAQVKELREEAQELREKRDELNEKVKELKE--ERD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  617 QLQKQKNL---EAERLKQKEQERKTELEKQKEAQRRIqdrdkQRLDRVQQEEE--PQWQKKNQEDDKQKREEiIKKKESE 691
Cdd:COG1340     82 ELNEKLNElreELDELRKELAELNKAGGSIDKLRKEI-----ERLEWRQQTEVlsPEEEKELVEKIKELEKE-LEKAKKA 155

                          170
                   ....*....|
gi 2024344592  692 DKGKQEIQEK 701
Cdd:COG1340    156 LEKNEKLKEL 165

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 44.24 E-value: 6.78e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1591 LMVNIVEGIELKPCRSHGKSNPYCEVTM---GSQCHITKTMQDTLNPKWNSNCQF--F-IKDLEQDVLCITVFERDQFSP 1664
Cdd:cd08386     18 LTLKILKAVELPAKDFSGTSDPFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLFegFpYEKLQQRVLYLQVLDYDRFSR 97

                           90
                   ....*....|....*
gi 2024344592 1665 DDFLGRTEIRVADIK 1679
Cdd:cd08386     98 NDPIGEVSLPLNKVD 112

pneumococcal surface protein PspC, choline-binding form; The pneumococcal surface protein PspC, as described in Streptococcus pneumoniae, is a repetitive and highly variable protein, recognized by a conserved N-terminal domain and also by genomic location. This form, subgroup 1, has variable numbers of a choline-binding repeat in the C-terminal region, and is also known as choline-binding protein A. The other form, subgroup 2, is anchored covalently after cleavage by sortase at a C-terminal LPXTG site.

Pssm-ID: 468201 [Multi-domain] Cd Length: 684 Bit Score: 47.70 E-value: 7.04e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  341 LEKKLpvtfEDKKRENFERGNLELEKRRQALLEQQRKEQErlAQLERAEQERKERERQEQERKRQL-ELEKQLEKQRELE 419
Cdd:NF033838    89 LNKKL----SDIKTEYLYELNVLKEKSEAELTSKTKKELD--AAFEQFKKDTLEPGKKVAEATKKVeEAEKKAKDQKEED 162

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  420 RQREEERRKEIERREAAKRELE-RQRQLEWERNRRQEllnqrNREQEDIVVLKAKKKTLEFELEALNDKKNQLEgklqdi 498
Cdd:NF033838   163 RRNYPTNTYKTLELEIAESDVEvKKAELELVKEEAKE-----PRDEEKIKQAKAKVESKKAEATRLEKIKTDRE------ 231

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  499 RCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLK---QVQQNSLHRDSLLTIKRALEA-- 573
Cdd:NF033838   232 KAEEEAKRRADAKLKEAVEKNVATSEQDKPKRRAKRGVLGEPATPDKKENDAKSsdsSVGEETLPSPSLKPEKKVAEAek 311

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  574 -KELARQQLRDQLDEVEKETRSklqeidifnNQLKELrEIHNRQQLQKQKNLEAERLKQKEQERKTElEKQKEAQRRIQD 652
Cdd:NF033838   312 kVEEAKKKAKDQKEEDRRNYPT---------NTYKTL-ELEIAESDVKVKEAELELVKEEAKEPRNE-EKIKQAKAKVES 380

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  653 RdkqrldrvqqEEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKlfQPHQEPVKPAVQAP---WSNAGKAPL 729
Cdd:NF033838   381 K----------KAEATRLEKIKTDRKKAEEEAKRKAAEEDKVKEKPAEQPQP--APAPQPEKPAPKPEkpaEQPKAEKPA 448


                   ....*..
gi 2024344592  730 TISAQED 736
Cdd:NF033838   449 DQQAEED 455

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 41.94 E-value: 7.08e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2024344592 1159 YTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd12077      9 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 53

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 42.11 E-value: 7.16e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKrewvdeSQTGEPGWLGGELKGKTGWFPANY 797
Cdd:cd11948      4 ALYSFQATESDELPFQKGDILKIL------NMEDDQNWYKAELQGREGYIPKNY 51

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 41.92 E-value: 7.17e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2024344592 1082 ATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRQIGWFPANY 1125
Cdd:cd11821     10 ADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGDPSRRGVFPVSF 53

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212872 [Multi-domain] Cd Length: 55 Bit Score: 41.85 E-value: 7.64e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEV--QGQKGWFPKSYVK 962
Cdd:cd11939      1 QVQCVHPYVSQEPDELSLELADVLNILDKtDDGWIFGERlhDQERGWFPSSVVE 54

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 41.97 E-value: 7.75e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELKGKTGWFPANYAEK 800
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEK-------GEDGWWTVERNGQKGLVPGTYLEK 53

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 47.60 E-value: 7.85e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  564 LLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAE--RLKQKEQERKTELE 641
Cdd:COG4913    283 LWFAQRRLELLEAELEELRAELARLEAELERLEARLDALREELDELEAQIRGNGGDRLEQLEREieRLERELEERERRRA 362

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  642 KQKEAQRRIQ---DRDKQRLDRVQQ------EEEPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQE 700
Cdd:COG4913    363 RLEALLAALGlplPASAEEFAALRAeaaallEALEEELEALEEALAEAEAALRDLRRELRELEAEIAS 430

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 41.99 E-value: 7.92e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRQiGWFPANYVKL 1128
Cdd:cd11858      8 FAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDESKE-GWVPAAYLEE 55

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 41.83 E-value: 8.06e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYVKLL 1129
Cdd:cd11921      9 FQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGR---VGIFPANYVEVL 55

Borrelia P83/100 protein; This family consists of several Borrelia P83/P100 antigen proteins.

Pssm-ID: 114011 [Multi-domain] Cd Length: 489 Bit Score: 47.30 E-value: 8.22e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  572 EAKELAR--QQLRDQLDEVEKETRSKLQEIDIFNNQLKELREiHNRQQLQKQKNL-------EAERLKQKEQERKTELEK 642
Cdd:pfam05262  207 ESQEDAKraQQLKEELDKKQIDADKAQQKADFAQDNADKQRD-EVRQKQQEAKNLpkpadtsSPKEDKQVAENQKREIEK 285

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  643 -QKEAQRRIQDRDK---QRLDRVQQE--EEPQWQKKNQEDDKQKREEIikkKESEDKGKQEIQEKPSKLFQPHQEPVKP 715
Cdd:pfam05262  286 aQIEIKKNDEEALKakdHKAFDLKQEskASEKEAEDKELEAQKKREPV---AEDLQKTKPQVEAQPTSLNEDAIDSSNP 361

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 41.95 E-value: 8.27e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQ----DMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11844      2 ARALYDNVAESPDELAFRRGDILTVLEQNtaglEGWWLCSLRGRQGIAPGNRLKL 56

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 41.92 E-value: 8.46e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKrewvdesQTGEPGWLGGELKGKTGWFPAN 796
Cdd:cd11982      3 FMAVKPYQSQAEGEISLSKGEKIKVL-------SVGEGGFWEGQVKGRVGWFPSD 50

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 42.00 E-value: 8.52e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVKREwvdESQTGEPGWLGGELKGKTGWFPA 795
Cdd:cd11762      1 LVRALYDYEAQSDEELSFPEGAIIRILRK---DDNGVDDGWWEGEFNGRVGVFPS 52

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 41.65 E-value: 8.62e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGD---WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11866      2 YMGLWDCSGNEPDELSFKRGDLIYIISKEYDsfgWWVGELNGKVGLVPKDYL 53

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 42.18 E-value: 8.63e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM----WWFGEVQGQKGWFPKSYVKLI-SGP 967
Cdd:cd12003      3 AKALYDNAAESPEELSFRRGDVLMVLKREHGslpgWWLCSLHGQQGIAPANRLRLLpTAP 62

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

Pssm-ID: 464032 [Multi-domain] Cd Length: 221 Bit Score: 45.85 E-value: 8.65e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  549 DQLKQVQQNSLHRDSL------LTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIfnnqlKELREIHNRQQLQKQK 622
Cdd:pfam13904   39 TYARKLEGLKLERQPLeayenwLAAKQRQRQKELQAQKEEREKEEQEAELRKRLAKEKY-----QEWLQRKARQQTKKRE 113

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  623 NLEAERLKQKEQERKTELEK---QKEAQRRIQD--RDKQRLDRVQQEEEPQWQKKNQEDDKQKREE 683
Cdd:pfam13904  114 ESHKQKAAESASKSLAKPERkvsQEEAKEVLQEweRKKLEQQQRKREEEQREQLKKEEEEQERKQL 179

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212997 Cd Length: 56 Bit Score: 42.02 E-value: 8.74e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVmvkrEWVDESQtgEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd12064      4 KALYACKAEHDSELSFTAGTVF----DNVHPSQ--EPGWLEGTLNGKTGLIPENYVE 54

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1)-like proteins; This subfamily includes MPP1, CASK (Calcium/calmodulin-dependent Serine protein Kinase), Caenorhabditis elegans lin-2, and similar proteins. MPP1 and CASK are scaffolding proteins from the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). In addition, they also have the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. CASK and lin-2 also contain an N-terminal calmodulin-dependent kinase (CaMK)-like domain and two L27 domains. MPP1 is ubiquitously-expressed and plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. CASK is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212968 Cd Length: 62 Bit Score: 42.03 E-value: 8.76e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592 1153 VIGMYDYTAQNDD-------ELAFNKGQIINVLNKEDPDWWKGEV----NGQVGLFPS 1199
Cdd:cd12035      2 VRAQFDYDPSKDDlipcqqaGIAFKTGDILQIISKDDHNWWQARKpgasKEPAGLIPS 59

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212930 [Multi-domain] Cd Length: 56 Bit Score: 41.87 E-value: 8.90e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  740 VYYRALYPFESRSHDEITIQPGDivmvkrEWVDESQTGEPGWLGGEL-KGKTGWFPANYAE 799
Cdd:cd11997      2 VRVRALYDYTGQEADELSFKAGE------ELLKIGEEDEQGWCKGRLlSGRIGLYPANYVE 56

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 41.91 E-value: 8.91e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMIL-VTKKDGDWWTGTL--GDKTGVFPSNYVRL 1052
Cdd:cd11935      3 YRAMYDYSAQDEDEVSFRDGDYIVnVQPIDEGWMYGTVqrTGRTGMLPANYIEF 56

biotin carboxyl carrier protein of acetyl-CoA carboxylase

Pssm-ID: 215533 [Multi-domain] Cd Length: 274 Bit Score: 46.37 E-value: 8.91e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  131 PVPMASIPVVGMSPPLVSSVPAAAVPPLANGAPAVIQ---PLPAFAHPATLPKSS----------SFSRS-GPGS----Q 192
Cdd:PLN02983   142 PQPPPPAPVVMMQPPPPHAMPPASPPAAQPAPSAPASsppPTPASPPPAKAPKSShpplkspmagTFYRSpAPGEppfvK 221


                   ....*....
gi 2024344592  193 LNTKLQKAQ 201
Cdd:PLN02983   222 VGDKVQKGQ 230

First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212845 [Multi-domain] Cd Length: 55 Bit Score: 41.83 E-value: 9.04e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWW----KGevNGQVGLFPSNYVKL 1204
Cdd:cd11912      5 LYDYTASGDDEVSISEGEEVTVLEPDDGSGWtkvrNG--SGEEGLVPTSYIEI 55

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 41.55 E-value: 9.04e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11874      1 RCKVLFSYTPQNEDELELKVGDTIEVLGEvEEGWWEGKLNGKVGVFPSNFVKE 53

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 41.56 E-value: 9.26e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1006 YTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11901      8 FNYTAEREDELSLVKGTKVIVMEKCSDgWWRGSYNGQVGWFPSNYV 53

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 41.75 E-value: 9.41e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVkrewVDESqtgEPGWLGGELKGKTGWFPANY 797
Cdd:cd11949      1 YVQALFDFDPQEDGELGFRRGDFIEV----MDNS---DPNWWKGACHGQTGMFPRNY 50

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 43.73 E-value: 9.69e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTM-GSQCHITKTMQDTLNPKWNsNCQFFIKDLEQDVLCITVFERDQFSPDDF 1667
Cdd:cd04045      1 GVLRLHIRKANDLKNLEGVGKIDPYVRVLVnGIVKGRTVTISNTLNPVWD-EVLYVPVTSPNQKITLEVMDYEKVGKDRS 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2024344592 1668 LGRTEIRVAD-IKKDQ-------GSKGPVTKCLLL 1694
Cdd:cd04045     80 LGSVEINVSDlIKKNEdgkyveyDDEEERLKRLLS 114

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212935 Cd Length: 57 Bit Score: 41.89 E-value: 9.90e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKED---PDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd12002      5 LYDNVPECAEELAFRKGDILTVIEQNTgglEGWWLCSLHGRQGIAPGNRLKL 56

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 41.52 E-value: 1.00e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF---GEVQGQKGWFPKSYVK 962
Cdd:cd11780      3 RALYSYTPQNEDELELREGDIVYVMEKCDDGWFvgtSERTGLFGTFPGNYVA 54

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212698 [Multi-domain] Cd Length: 54 Bit Score: 41.48 E-value: 1.02e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDpDWWKGE-VNGQVGLFPSN 1200
Cdd:cd11764      5 LYDFTARNSKELSVLKGEYLEVLDDSR-QWWKVRnSRGQVGYVPHN 49

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 41.84 E-value: 1.07e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYVKLI 964
Cdd:cd11994      2 AQVTTAYVASGVEQLSLSPGQLILILKKNSSgWWLGELQArgkkrQKGWFPASHVKLL 59

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 41.47 E-value: 1.10e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAE 799
Cdd:cd11927      4 KALYNYEGKEPGDLKFSKGDIIILRRQ-VDEN------WYHGEVNGIHGFFPTNFVQ 53

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 41.52 E-value: 1.11e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTlGDKT---GVFPSNYVRL 1052
Cdd:cd11916      4 YQALYSYAPQNDDELELRDGDIVDVMEKcDDGWFVGT-SRRTkqfGTFPGNYVKL 57

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 41.54 E-value: 1.12e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVkrewVDESQTgepGWLGGELKGKTGWFPANY 797
Cdd:cd11963      5 RALYDFEAVEDNELTFKHGEIIIV----LDDSDA---NWWKGENHRGVGLFPSNF 52

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 41.48 E-value: 1.15e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  999 GEEYVAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGT--LGDKTGVFPSNYV 1050
Cdd:cd11918      1 RTPYKAVYQYRPQNEDELELREGDRVDVMQQcDDGWFVGVsrRTQKFGTFPGNYV 55

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 41.42 E-value: 1.17e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592  917 YPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 962
Cdd:cd12052      6 FDYKAQHEDELTITVGDIITKIKKDDGgWWEGEIKGRRGLFPDNFVR 52

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212830 [Multi-domain] Cd Length: 55 Bit Score: 41.52 E-value: 1.17e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN--GQVGLFPSNYVKL 1204
Cdd:cd11897      5 LYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNsrGDRGLFPASYVEV 55

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 41.43 E-value: 1.18e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVkrewVDESQTgepGWLGGELKGKTGWFPANY 797
Cdd:cd11986      1 YFVALYRFKALEKDDLDFHPGERITV----IDDSNE---EWWRGKIGEKTGYFPMNF 50

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 41.45 E-value: 1.19e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVKL 1128
Cdd:cd11928      4 KALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCH---GFLPASYIQC 54

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 41.56 E-value: 1.19e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592  918 PWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd12077      8 PYTSQGKDEIGFEKGVTVEVIQKNlEGWWYIRYLGKEGWAPASYLK 53

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212856 [Multi-domain] Cd Length: 57 Bit Score: 41.44 E-value: 1.23e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNG--QVGLFPSNYVKL 1204
Cdd:cd11923      2 EAVAKYNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPGtnRQGIFPVSYVEV 56

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 41.53 E-value: 1.24e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1077 IASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYVKLLS 1130
Cdd:cd11972      8 IYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNG---VTGLFPGNYVESIM 58

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 43.33 E-value: 1.26e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592 1608 GKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDlEQDVLCITVFERD---------QFS--PDDFLGRTEIRV 1675
Cdd:cd04027     20 GTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHN-SSDRIKVRVWDEDddiksrlkqKFTreSDDFLGQTIIEV 97

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

Pssm-ID: 464032 [Multi-domain] Cd Length: 221 Bit Score: 45.08 E-value: 1.27e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLEQQRKEQERLAQLERAEQ-ERKERERQEQ--ERKRQLELEKQLEKQRELERQREEERRKEIERREAAkrELE 441
Cdd:pfam13904   63 AKQRQRQKELQAQKEEREKEEQEAELrKRLAKEKYQEwlQRKARQQTKKREESHKQKAAESASKSLAKPERKVSQ--EEA 140

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2024344592  442 RQRQLEWERNRRQELLNQRNREQEDivvlKAKKKTLEFE 480
Cdd:pfam13904  141 KEVLQEWERKKLEQQQRKREEEQRE----QLKKEEEEQE 175

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 41.34 E-value: 1.27e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELqGKKRQiGWFPANYV 1126
Cdd:cd11812      8 YTANRSDELTIHRGDIIRVLYKDNDNWWFGSL-VNGQQ-GYFPANYV 52

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 43.88 E-value: 1.29e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  614 NRQQLQKQKNLEAERLKQKEQERKteLEKQKEAQRRIQDRDKQRLDRVQQEEEpqwQKKNQEDDKQKREEIIKKKESEDK 693
Cdd:pfam05672   19 KRRQAREQREREEQERLEKEEEER--LRKEELRRRAEEERARREEEARRLEEE---RRREEEERQRKAEEEAEEREQREQ 93


                   ....*...
gi 2024344592  694 GKQEIQEK 701
Cdd:pfam05672   94 EEQERLQK 101

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 41.14 E-value: 1.31e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKK---DGDWWTG--TLGdKTGVFPSNYV 1050
Cdd:cd11767      3 VALYPFTGENDEELSFEKGERLEIIEKpedDPDWWKArnALG-TTGLVPRNYV 54

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 41.46 E-value: 1.32e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1159 YTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNG-----QVGLFPSNYVKL 1204
Cdd:cd11994      8 YVASGVEQLSLSPGQLILILKKNSSGWWLGELQArgkkrQKGWFPASHVKL 58

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 46.30 E-value: 1.32e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL-ELEKQLEKqrelerqreeerrkeierreAAKRELE 441
Cdd:COG4942     35 EIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELaALEAELAE--------------------LEKEIAE 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  442 RQRQLEWERNRRQELLN--QRNREQEDIVVLKAKKKTLEFE-----LEALNDKKNQLEGKLQDIRCRLSTQRQEIEStnk 514
Cdd:COG4942     95 LRAELEAQKEELAELLRalYRLGRQPPLALLLSPEDFLDAVrrlqyLKYLAPARREQAEELRADLAELAALRAELEA--- 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  515 srelriaeithlqqqlqesqqmlgklipEKQLLNDQLKQVQQNslhrdslltiKRALEAKELARQQLrdqLDEVEKETRS 594
Cdd:COG4942    172 ----------------------------ERAELEALLAELEEE----------RAALEALKAERQKL---LARLEKELAE 210

                          250       260       270
                   ....*....|....*....|....*....|....
gi 2024344592  595 KLQEIDIFNNQLKELREIHNRqqLQKQKNLEAER 628
Cdd:COG4942    211 LAAELAELQQEAEELEALIAR--LEAEAAAAAER 242

Coiled-coil domain-containing protein 158; CCDC158 is a family of proteins found in eukaryotes. The function is not known.

Pssm-ID: 464943 [Multi-domain] Cd Length: 1112 Bit Score: 47.04 E-value: 1.33e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  341 LEKKLPVTFEDKKREN--FERGNLELE----KRRQALLEQQRKEQERLAQLER----AEQE----RKERERQEQERKrql 406
Cdd:pfam15921  297 IQSQLEIIQEQARNQNsmYMRQLSDLEstvsQLRSELREAKRMYEDKIEELEKqlvlANSElteaRTERDQFSQESG--- 373

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  407 ELEKQLEKqrelerqreeerrkeierREAAKRELERQRQLEWERNRRQellnqRNREQEDIVVLKAKKKtlefELEALND 486
Cdd:pfam15921  374 NLDDQLQK------------------LLADLHKREKELSLEKEQNKRL-----WDRDTGNSITIDHLRR----ELDDRNM 426

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  487 KKNQLEGKLQDIR--CRLSTQRQ--EIESTNKSRElRIAEIThlqQQLQESQQMLGKLIPE----KQLLNDQLKQVQQNS 558
Cdd:pfam15921  427 EVQRLEALLKAMKseCQGQMERQmaAIQGKNESLE-KVSSLT---AQLESTKEMLRKVVEEltakKMTLESSERTVSDLT 502

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  559 LhrdSLLTIKRALEAKELARQQLRDQLDeveketrSKLQEIDIFNNQLKELREIhnrqqlqkQKNLEAERLKQKEQERKT 638
Cdd:pfam15921  503 A---SLQEKERAIEATNAEITKLRSRVD-------LKLQELQHLKNEGDHLRNV--------QTECEALKLQMAEKDKVI 564

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  639 ELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEddkqKREEIIKKKESEDKGKQEIQEKPSKLFQPHQEPVKPAvq 718
Cdd:pfam15921  565 EILRQQIENMTQLVGQHGRTAGAMQVEKAQLEKEIND----RRLELQEFKILKDKKDAKIRELEARVSDLELEKVKLV-- 638

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  719 apwsNAGKAPLtiSAQEDVKIVYYRALYPFESrSHDEITIQPGDIVMVKREWVDESQTGE 778
Cdd:pfam15921  639 ----NAGSERL--RAVKDIKQERDQLLNEVKT-SRNELNSLSEDYEVLKRNFRNKSEEME 691

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212692 [Multi-domain] Cd Length: 55 Bit Score: 41.19 E-value: 1.36e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1001 EYV-AMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTG--TLGdKTGVFPSNYV 1050
Cdd:cd11758      1 EYVrALFDFPGNDDEDLPFKKGEILTVIRKPEEqWWNArnSEG-KTGMIPVPYV 53

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212948 Cd Length: 53 Bit Score: 41.25 E-value: 1.37e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANY 1125
Cdd:cd12015      4 VVADYKKQQPNEISLRAGDVVDVIEKNENGWWFVSLED---EQGWVPATY 50

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 41.53 E-value: 1.39e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELKGKTGWFPANYAEKI 801
Cdd:cd11972      7 AIYDYTKDKEDELSFQEGAIIYVIKK-------NDDGWYEGVMNGVTGLFPGNYVESI 57

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 41.11 E-value: 1.41e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVmvkrewvDESQTGEPGWLGGELKGKTGWFPANYAEKI 801
Cdd:cd12054      4 KVLFEYVPQNEDELELKVGDII-------DINEEVEEGWWSGTLNGKSGLFPSNFVKEL 55

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212781 [Multi-domain] Cd Length: 58 Bit Score: 41.39 E-value: 1.41e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDpDWW----KGEVNGQV--GLFPSNYV 1202
Cdd:cd11847      3 KALWDFKARGDEELSFQAGDQFRIAERSG-DWWtalkLDRAGGVVaqGFVPNNYL 56

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 43.88 E-value: 1.41e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  605 QLKELREIHNRQQLQKQknlEAERLKQKEQERKTELEKQK--------EAQRRIQDRDKQRLDRVQQEEEPQWQKKNQED 676
Cdd:pfam05672   22 QAREQREREEQERLEKE---EEERLRKEELRRRAEEERARreeearrlEEERRREEEERQRKAEEEAEEREQREQEEQER 98

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2024344592  677 DKQKREEiIKKKESEDKGKQEiQEKPSKLFQPHQE 711
Cdd:pfam05672   99 LQKQKEE-AEAKAREEAERQR-QEREKIMQQEEQE 131

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 41.53 E-value: 1.45e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLISGP 967
Cdd:cd11972      7 AIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYeGVMNGVTGLFPGNYVESIMHY 60

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 43.01 E-value: 1.47e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPC-RSHGKSNPYCEV------TMGSQcHITKTMQDTLNPKWNSNCQFFIK--DLEQDVLCITVFER 1659
Cdd:cd08521     14 GSLEVHIKECRNLAYAdEKKKRSNPYVKVyllpdkSKQSK-RKTSVKKNTTNPVFNETLKYHISksQLETRTLQLSVWHH 92

                           90       100
                   ....*....|....*....|..
gi 2024344592 1660 DQFSPDDFLGRTEIRVADIKKD 1681
Cdd:cd08521     93 DRFGRNTFLGEVEIPLDSWDLD 114

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 46.68 E-value: 1.48e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  539 KLIPEKQLLNDQLKQVQQNslhRDSLLTIKRALEAKELARQQLRDQLDEVEK---------ETRSKLQEIDIFNNQLKEL 609
Cdd:COG4717     75 ELEEELKEAEEKEEEYAEL---QEELEELEEELEELEAELEELREELEKLEKllqllplyqELEALEAELAELPERLEEL 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  610 REihnrqQLQKQKNLEaERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEddkqkREEIIKKKE 689
Cdd:COG4717    152 EE-----RLEELRELE-EELEELEAELAELQEELEELLEQLSLATEEELQDLAEELEELQQRLAEL-----EEELEEAQE 220

                          170       180
                   ....*....|....*....|..
gi 2024344592  690 SEDKGKQEIQEKPSKLFQPHQE 711
Cdd:COG4717    221 ELEELEEELEQLENELEAAALE 242

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212703 [Multi-domain] Cd Length: 57 Bit Score: 41.14 E-value: 1.50e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  999 GEEYVAMYTYESSEQGDLTFQQGDMILVTK--KDGDWWTG-TLGDKTGVFPSNYV 1050
Cdd:cd11769      1 GTECIAKYNFNGASEEDLPFKKGDILTIVAvtKDPNWYKAkNKDGREGMIPANYV 55

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212811 [Multi-domain] Cd Length: 54 Bit Score: 41.12 E-value: 1.50e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGE--VNGQVGLFPSNY 1201
Cdd:cd11878      6 YDYRAQTPGELSFSKGDFFHVIGEEDQGeWYEATnpVTGKRGLVPKSY 53

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 41.16 E-value: 1.53e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDM--ILVTKKDGDWWTGTLGDKTGVFPSNYVRLK 1053
Cdd:cd11946      2 EAIAKYDFKATADDELSFKRGDIlkVLNEECDQNWYKAELNGKDGFIPKNYIEMK 56

Mitochondrial inner membrane protein; Mitofilin controls mitochondrial cristae morphology. Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex. The first 78 amino acids contain a typical amino-terminal-cleavable mitochondrial presequence rich in positive-charged and hydroxylated residues and a membrane anchor domain. In addition, it has three centrally located coiled coil domains.

Pssm-ID: 430783 [Multi-domain] Cd Length: 618 Bit Score: 46.29 E-value: 1.58e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  471 KAKKKTLEFELEALNDKKNQLEgKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGK--LIPEKQL-- 546
Cdd:pfam09731  143 SATAVAKEAKDDAIQAVKAHTD-SLKEASDTAEISREKATDSALQKAEALAEKLKEVINLAKQSEEEAAppLLDAAPEtp 221

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  547 --LNDQLKQVQQNSLHRDSL-LTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQ------LKELREIHN-RQ 616
Cdd:pfam09731  222 pkLPEHLDNVEEKVEKAQSLaKLVDQYKELVASERIVFQQELVSIFPDIIPVLKEDNLLSNDdlnsliAHAHREIDQlSK 301

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  617 QLQKQKNLEAERLKQkeqerktELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEddkqKREEIIKKKESEDKGKQ 696
Cdd:pfam09731  302 KLAELKKREEKHIER-------ALEKQKEELDKLAEELSARLEEVRAADEAQLRLEFER----EREEIRESYEEKLRTEL 370

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 2024344592  697 EIQEkpsklfQPHQEPVKPAVQAPwsnagKAPLTISAQEDVK 738
Cdd:pfam09731  371 ERQA------EAHEEHLKDVLVEQ-----EIELQREFLQDIK 401

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212955 [Multi-domain] Cd Length: 53 Bit Score: 40.98 E-value: 1.60e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKK--DGdWWTGTLGDKTGVFPSNYV 1050
Cdd:cd12022      2 YITIKAYTAVEEDELTLLEGEAIEVIHKllDG-WWVVRKGEVTGYFPSMYL 51

Domain of unknown function (DUF4686); This family of proteins is found in eukaryotes. Proteins in this family are typically between 498 and 775 amino acids in length. There is a conserved DLK sequence motif.

Pssm-ID: 464838 [Multi-domain] Cd Length: 384 Bit Score: 46.21 E-value: 1.61e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  366 KRRQALLEQQRKEQERLAQ-LER-------AEQE-RKERER-----------QEQERKRQLELeKQLEKQRELERQREEE 425
Cdd:pfam15742    2 SSGEKLKYQQQEEVQQLRQnLQRlqilctsAEKElRYERGKnldlkqhnsllQEENIKIKAEL-KQAQQKLLDSTKMCSS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  426 RRKEIerreaaKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAK-----KKTLEFE-----------LEALNDKKN 489
Cdd:pfam15742   81 LTAEW------KHCQQKIRELELEVLKQAQSIKSQNSLQEKLAQEKSRvadaeEKILELQqklehahkvclTDTCILEKK 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  490 QLEGKLQDIRCRLSTQRQEIESTNKSRELRiaeithlqqqlqesqqmlgklipeKQLLNDQLKQVQQNslhRDSLLTIKR 569
Cdd:pfam15742  155 QLEERIKEASENEAKLKQQYQEEQQKRKLL------------------------DQNVNELQQQVRSL---QDKEAQLEM 207

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  570 ALEAKELARQQLRDQLDEVEKEtRSKLQEIDIFNNQLKE-----------LREIHnrQQLQKQKNLEAERLKQKEQERKT 638
Cdd:pfam15742  208 TNSQQQLRIQQQEAQLKQLENE-KRKSDEHLKSNQELSEklsslqqekeaLQEEL--QQVLKQLDVHVRKYNEKHHHHKA 284

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  639 ELEKQKE------AQR--RIQDRDKQ-RLDRVQQEEEPQWQKK----NQEDDKQKREEIIKKKESEDKGK 695
Cdd:pfam15742  285 KLRRAKDrlvhevEQRdeRIKQLENEiGILQQQSEKEKAFQKQvtaqNEILLLEKRKLLEQLTEQEELIK 354

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 41.13 E-value: 1.63e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF---GEVQGQKGWFPKSYVKLI 964
Cdd:cd11916      5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFvgtSRRTKQFGTFPGNYVKLL 58

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 40.83 E-value: 1.64e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKT--GVFPSNYV 1050
Cdd:cd11858      2 YKALYDFAGSVANELSLKKDDIVYIVQKEDNgWWLAKKLDESkeGWVPAAYL 53

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 43.09 E-value: 1.67e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1608 GKSNPYCEVTMGSQCHITKTMQDT-LNPKWNSNCQFFIKDLEQDV---LCITVFERDQFSPDDFLGRTEIRVADI 1678
Cdd:cd04049     20 GKIDPYVIIQCRTQERKSKVAKGDgRNPEWNEKFKFTVEYPGWGGdtkLILRIMDKDNFSDDDFIGEATIHLKGL 94

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 46.76 E-value: 1.69e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  370 ALLEQQRKEqeRLAQLERAEQErkERERQEQERKRQLELEKQLEKqrelerqreeerrkeierreaAKRELERQRQ-LEW 448
Cdd:pfam12128  596 AASEEELRE--RLDKAEEALQS--AREKQAAAEEQLVQANGELEK---------------------ASREETFARTaLKN 650

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  449 ERNRRQELLNQRNREQEDIV-VLKAKKKTLEFELEALNDKKNQLEGKLQDIrcrLSTQRQEiestnkSRELRIAEITHLQ 527
Cdd:pfam12128  651 ARLDLRRLFDEKQSEKDKKNkALAERKDSANERLNSLEAQLKQLDKKHQAW---LEEQKEQ------KREARTEKQAYWQ 721

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  528 QQLQESQQMLGKLIPEKQLLNDQLKQvQQNSLHRDSlltiKRALEAKELARQQLRDQLDEVEKETRsKLQEIDIFNNQLK 607
Cdd:pfam12128  722 VVEGALDAQLALLKAAIAARRSGAKA-ELKALETWY----KRDLASLGVDPDVIAKLKREIRTLER-KIERIAVRRQEVL 795

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  608 ELREIHNRQQLQKQKNL---------EAERLKQ----KEQERKT---ELEKQKEAQRRIQDR 653
Cdd:pfam12128  796 RYFDWYQETWLQRRPRLatqlsnierAISELQQqlarLIADTKLrraKLEMERKASEKQQVR 857

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 40.76 E-value: 1.71e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLE-QQDMWWFGE-VQGQKGWFPKSYVKL 963
Cdd:cd11770      4 ALSDFQAEQEGDLSFKKGEVLRIISkRADGWWLAEnSKGNRGLVPKTYLKV 54

Hyaluronan mediated motility receptor N-terminal; HMMR_N is the N-terminal region of eukaryotic hyaluronan-mediated motility receptor proteins. The protein is functionally associated with BRCA1 and thus predicted to be a common, low-penetrance breast cancer candidate.

Pssm-ID: 464932 [Multi-domain] Cd Length: 329 Bit Score: 45.57 E-value: 1.72e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  343 KKLPVTFED-----KKRENFERGNLELEK--------RRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELE 409
Cdd:pfam15905   17 LKGPVSFEKsqrfrKQKAAESQPNLNNSKdastpataRKVKSLELKKKSQKNLKESKDQKELEKEIRALVQERGEQDKRL 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  410 KQLEKQRELERQREEERRKEIERREAAKRELERQRQlewERNRRQELLNQRNREQEDivvlKAKKKTLEFELEALndkKN 489
Cdd:pfam15905   97 QALEEELEKVEAKLNAAVREKTSLSASVASLEKQLL---ELTRVNELLKAKFSEDGT----QKKMSSLSMELMKL---RN 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  490 QLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQqqlqesqqmlGKLIPEKQLLNDQLKQVQQnslhrdsLLTikr 569
Cdd:pfam15905  167 KLEAKMKEVMAKQEGMEGKLQVTQKNLEHSKGKVAQLE----------EKLVSTEKEKIEEKSETEK-------LLE--- 226

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  570 alEAKELarQQLRDQLDEVEKETRsklqeidifnnQLKELreihnrqqlQKQKNLEAERLKQKEQERKTELEKQKEAQRR 649
Cdd:pfam15905  227 --YITEL--SCVSEQVEKYKLDIA-----------QLEEL---------LKEKNDEIESLKQSLEEKEQELSKQIKDLNE 282

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592  650 IQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKrEEIIKKKESEDKGKQE 697
Cdd:pfam15905  283 KCKLLESEKEELLREYEEKEQTLNAELEELK-EKLTLEEQEHQKLQQK 329

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 40.84 E-value: 1.73e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11806      4 AIADFVATDDSQLSFESGDKLLVLRKpSVDWWWAEHNGCCGYIPASHL 51

Centrosomal colon cancer autoantigen protein family; CCCAP is a family of proteins found in eukaryotes. CCCAP is also known as SDCCAG8, serologically defined colon cancer antigen 8. It is associated with the centrosome.

Pssm-ID: 435040 [Multi-domain] Cd Length: 703 Bit Score: 46.44 E-value: 1.77e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQ---LEKQRELERQREEERRKEIERREAAKRELE 441
Cdd:pfam15964  335 EQVKQAVQMTEEANFEKTKALIQCEQLKSELERQKERLEKELASQQEkraQEKEALRKEMKKEREELGATMLALSQNVAQ 414

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  442 RQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKT----LEFELEALNDKKNQLEGKLQDIRCRLSTQ----RQEIE--- 510
Cdd:pfam15964  415 LEAQVEKVTREKNSLVSQLEEAQKQLASQEMDVTKvcgeMRYQLNQTKMKKDEAEKEHREYRTKTGRQleikDQEIEklg 494

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  511 -STNKSRElRIAEITHLQQQLQESQQMLGKLI--PEKQL-LNDQLKQVQQNSLHRDSLltiKRALEAKELAR------QQ 580
Cdd:pfam15964  495 lELSESKQ-RLEQAQQDAARAREECLKLTELLgeSEHQLhLTRLEKESIQQSFSNEAK---AQALQAQQREQeltqkmQQ 570

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  581 LRDQLDEVEKETRSKLQEIDIFNNQLKE--------LREIHNR-----QQLQKQKNLEAERLkQKEQERKTELEKQKEAQ 647
Cdd:pfam15964  571 MEAQHDKTVNEQYSLLTSQNTFIAKLKEecctlakkLEEITQKsrsevEQLSQEKEYLQDRL-EKLQKRNEELEEQCVQH 649

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 2024344592  648 RRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREEIIKKKESED 692
Cdd:pfam15964  650 GRMHERMKQRLRQLDKHCQATAQQLVQLLSKQNQLFKERQNLTEE 694

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212828 Cd Length: 58 Bit Score: 41.10 E-value: 1.79e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-----DGDWWTGTLGDKTGVFPS 1047
Cdd:cd11895      4 ALYSYTGQSPEELSFPEGALIRLLPRaqdgvDDGFWRGEFGGRVGVFPS 52

Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); MPP7 is a scaffolding protein that binds to DLG1 and promotes tight junction formation and epithelial cell polarity. Mutations in the MPP7 gene may be associated with the pathogenesis of diabetes and extreme bone mineral density. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212966 Cd Length: 61 Bit Score: 41.16 E-value: 1.80e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1153 VIGMYDYTAQNDDE-------LAFNKGQIINVLNKEDPDWWK----GEVNGQVGLFPSNY 1201
Cdd:cd12033      2 IKALFDYNPNEDKAipckeagLSFKKGDILQIMSQDDATWWQakheGDANPRAGLIPSKH 61

Src Homology 3 domain of Saccharomyces cerevisiae Nap1-binding protein 2 and similar fungal proteins; This subfamily includes Saccharomyces cerevisiae Nbp2 (Nucleosome assembly protein 1 (Nap1)-binding protein 2), Schizosaccharomyces pombe Skb5, and similar proteins. Nbp2 interacts with Nap1, which is essential for maintaining proper nucleosome structures in transcription and replication. It is also the binding partner of the yeast type II protein phosphatase Ptc1p and serves as a scaffolding protein that brings seven kinases in close contact to Ptc1p. Nbp2 plays a role many cell processes including organelle inheritance, mating hormone response, cell wall stress, mitotic cell growth at elevated temperatures, and high osmolarity. Skb5 interacts with the p21-activated kinase (PAK) homolog Shk1, which is critical for fission yeast cell viability. Skb5 activates Shk1 and plays a role in regulating cell morphology and growth under hypertonic conditions. Nbp2 and Skb5 contain an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212799 Cd Length: 55 Bit Score: 40.96 E-value: 1.81e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWW--KGEVNGQVGLFPSNYVKL 1204
Cdd:cd11865      1 RAVALYDFEPEHDNELGFAEGQILFILYKHGQGWLiaEDESGGKTGLVPEEFVSY 55

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 40.72 E-value: 1.82e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVKLL 1129
Cdd:cd12054      4 KVLFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKS---GLFPSNFVKEL 55

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 41.08 E-value: 1.86e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwvdESQTGEPGWLGGELKG-KTGWFPANY 797
Cdd:cd11864      3 RAEYDFVAESEDELSFRAGDKLRLAPK---ELQPRVRGWLLATVDGqKIGLVPANY 55

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 40.85 E-value: 1.88e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11809      1 EATAQFDYTGRSERELSFKKGDSLTLYRQvSDDWWRGQLNGQDGLVPHKYITL 53

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212969 Cd Length: 63 Bit Score: 41.24 E-value: 1.90e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1157 YDYTAQnDDE--------LAFNKGQIINVLNKEDPDWWK----GEVNGQ--VGLFPS 1199
Cdd:cd12036      6 FDYDPE-DDPyipcrelgLSFQKGDILHVISQEDPNWWQayreGEEDNQslAGLIPS 61

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 40.57 E-value: 1.94e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1006 YTYESSEQGdLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11829      8 FTGEQHQQG-LSFEAGELIRVLQApDGGWWEGEKDGLRGWFPASYV 52

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 41.13 E-value: 1.95e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  999 GEEYVAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTlGDKT---GVFPSNYVR 1051
Cdd:cd11917      4 GEPFQALYNYMPRNEDELELREGDVIDVMEKcDDGWFVGT-SRRTkffGTFPGNYVK 59

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

Pssm-ID: 293879 [Multi-domain] Cd Length: 291 Bit Score: 45.26 E-value: 1.97e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  615 RQQLQKQKNLEAERLK--QKEQERKTELEKQKEAQRRIQDRDKQrldrvQQEEEPQWQKKNQEDDKQKREEI-----IKK 687
Cdd:cd16269    191 QALTEKEKEIEAERAKaeAAEQERKLLEEQQRELEQKLEDQERS-----YEEHLRQLKEKMEEERENLLKEQeraleSKL 265

                           90
                   ....*....|....
gi 2024344592  688 KESEDKGKQEIQEK 701
Cdd:cd16269    266 KEQEALLEEGFKEQ 279

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 40.56 E-value: 2.03e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKD-GDWWT-GTLGDKTGVFPSNY 1049
Cdd:cd11778      4 ALYDYEAQGDDEISIRVGDRIAVIRGDdGSGWTyGEINGVKGLFPTSY 51

Extracytoplasmic sensor domain CHASE3 (specificity unknown) [Signal transduction mechanisms];

Pssm-ID: 444089 [Multi-domain] Cd Length: 530 Bit Score: 46.05 E-value: 2.04e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  355 ENFERGNLELEKRRQAL---LEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEkqrelerqREEERRKEIE 431
Cdd:COG5278     79 EPYEEARAEIDELLAELrslTADNPEQQARLDELEALIDQWLAELEQVIALRRAGGLEAALA--------LVRSGEGKAL 150

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  432 RREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIES 511
Cdd:COG5278    151 MDEIRARLLLLALALAALLLAAAALLLLLLALAALLALAELLLLALARALAALLLLLLLEAELAAAAALLAAAAALAALA 230

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  512 TNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKELARQQLRDQLDEVEKE 591
Cdd:COG5278    231 ALELLAALALALALLLAALLLALLAALALAALLAAALLALAALLLALAAAAALAAAAALELAAAEALALAELELELLLAA 310

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  592 TRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQK 671
Cdd:COG5278    311 AAAAAAAAAAAAAALAALLALALATALAAAAAALALLAALLAEAAAAAAEEAEAAAEAAAAALAGLAEVEAEGAAEAVEL 390

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|
gi 2024344592  672 KNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:COG5278    391 EVLAIAAAAAAAAAEAAAAAAAAAAASAAEALELAEALAE 430

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212890 Cd Length: 52 Bit Score: 40.67 E-value: 2.05e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILV-TKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11957      1 EVKALCHHIATEPGQLSFNKGDILQVlSRADGDWLRCSLGPDSGLVPIAYV 51

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 40.92 E-value: 2.06e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGDWW-------TGtlgdKTGVFPSNYV 1050
Cdd:cd11784      2 CVALHSYSAHRPEELELQKGEGVRVLGKFQEGWlrglslvTG----RVGIFPSNYV 53

DDRGK domain; This is a family of proteins of approximately 300 residues, found in plants and vertebrates. They contain a highly conserved DDRGK motif.

Pssm-ID: 370664 [Multi-domain] Cd Length: 188 Bit Score: 44.26 E-value: 2.08e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLEQQRKEQERLAQleraEQERKERERQEQERKRQLELEKqlekqrelerqreeerrkeierreaAKRELERQR 444
Cdd:pfam09756    5 AKKRAKLELKEAKRQQREAE----EEEREEREKLEEKREEEYKERE-------------------------EREEEAEKE 55

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  445 QLEWERNRRQEllnQRNREQEDIVVLKAkkktlEFELEALNDKKNQLEGKLQDIRC 500
Cdd:pfam09756   56 KEEEERKQEEE---QERKEQEEYEKLKS-----QFVVEEEGTDKLSAEDESQLLED 103

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 40.82 E-value: 2.09e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11824      1 KYSVLYDYTAQEDDELSISKGDVVAVIEKGEDgWWTVERNGQKGLVPGTYL 51

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212935 Cd Length: 57 Bit Score: 40.74 E-value: 2.13e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQ----DMWWFGEVQGQKGWFPKSYVKLI 964
Cdd:cd12002      2 ARALYDNVPECAEELAFRKGDILTVIEQNtgglEGWWLCSLHGRQGIAPGNRLKLL 57

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 40.79 E-value: 2.19e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1077 IASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd12077      6 VQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKE---GWAPASYLK 53

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 46.27 E-value: 2.20e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  342 EKKLPVTFEDKKREnFERGNLELEKRRQAL--LEQQRKEQERlaqlERAEQERKERERQEQERKRQLELEKQLE------ 413
Cdd:pfam17380  434 QREVRRLEEERARE-MERVRLEEQERQQQVerLRQQEEERKR----KKLELEKEKRDRKRAEEQRRKILEKELEerkqam 508

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  414 ----KQRELERQREEERRKEIErreaakrELERQRQLEWERNRRQElLNQRNREQEDIVVLKAKKKtlefELEALNDKKN 489
Cdd:pfam17380  509 ieeeRKRKLLEKEMEERQKAIY-------EEERRREAEEERRKQQE-MEERRRIQEQMRKATEERS----RLEAMERERE 576

                          170       180       190
                   ....*....|....*....|....*....|..
gi 2024344592  490 QLegklqdircrlstqRQEIESTNKSRELRIA 521
Cdd:pfam17380  577 MM--------------RQIVESEKARAEYEAT 594

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 46.08 E-value: 2.27e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  362 LELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEkqrelerqrEEERRKEIERREAAKRELE 441
Cdd:COG1196    651 LEGEGGSAGGSLTGGSRRELLAALLEAEAELEELAERLAEEELELEEALLAE---------EEEERELAEAEEERLEEEL 721

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  442 RQRQLEWERNR-RQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDI------------RCR-----LS 503
Cdd:COG1196    722 EEEALEEQLEAeREELLEELLEEEELLEEEALEELPEPPDLEELERELERLEREIEALgpvnllaieeyeELEerydfLS 801

                          170       180
                   ....*....|....*....|
gi 2024344592  504 TQRQEIESTNKSRELRIAEI 523
Cdd:COG1196    802 EQREDLEEARETLEEAIEEI 821

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 40.76 E-value: 2.35e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11920      5 AVYDFKAQTSKELSFKKGDTVYILRKiDQNWYEGEHHGRVGIFPISYV 52

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 40.39 E-value: 2.56e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKREWVDESqtgepgWLGGELKGKTGWFPANYAE 799
Cdd:cd11946      5 AKYDFKATADDELSFKRGDILKVLNEECDQN------WYKAELNGKDGFIPKNYIE 54

CDK-activating kinase assembly factor MAT1; All proteins in this family for which functions are known are cyclin dependent protein kinases that are components of TFIIH, a complex that is involved in nucleotide excision repair and transcription initiation. Also known as MAT1 (menage a trois 1). This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129661 [Multi-domain] Cd Length: 309 Bit Score: 45.18 E-value: 2.59e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  583 DQLDEVEKETRSKLQEIDIFNNQLK-ELREIHNRQQLQKqkNLEAERLKQKEQERKTELEKQKEAQRRIQdrdkqrldrV 661
Cdd:TIGR00570   97 DYLEEVEDIVYNLTNNIDLENTKKKiETYQKENKDVIQK--NKEKSTREQEELEEALEFEKEEEEQRRLL---------L 165

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  662 QQEEepQWQKKNQEDDKQkreEIIKKKESED----------KGKQEIQEKPSklFQPhqEPVKPAVqapWSNAGKAPLTI 731
Cdd:TIGR00570  166 QKEE--EEQQMNKRKNKQ---ALLDELETSTlpaaeliaqhKKNSVKLEMQV--EKP--KPEKPNT---FSTGIKMGYQI 233

                          170
                   ....*....|....*...
gi 2024344592  732 SAQEDVKIvyYRALYPFE 749
Cdd:TIGR00570  234 SLVPVQKS--EEALYPYQ 249

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 44.90 E-value: 2.59e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  473 KKKTLEFELEALNDKKNQLEGKLQDIRcrlsTQRQEIEStnksrELRiaeithlqqqlqesqqmlgKLIPEKQLLNDQLK 552
Cdd:COG1340      2 KTDELSSSLEELEEKIEELREEIEELK----EKRDELNE-----ELK-------------------ELAEKRDELNAQVK 53

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  553 Q-VQQNSLHRDslltiKRALEAKELarQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIH-NRQQLQKqknlEAERLK 630
Cdd:COG1340     54 ElREEAQELRE-----KRDELNEKV--KELKEERDELNEKLNELREELDELRKELAELNKAGgSIDKLRK----EIERLE 122

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  631 QKEQERKTELEKQKEAQRRIQdRDKQRLDRVQQEEEpqwqkkNQEDDKQKREEIIKKKESEDKGKQEIQE 700
Cdd:COG1340    123 WRQQTEVLSPEEEKELVEKIK-ELEKELEKAKKALE------KNEKLKELRAELKELRKEAEEIHKKIKE 185

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53; IRSp53 is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 can also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRSp53 has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212848 Cd Length: 59 Bit Score: 40.77 E-value: 2.63e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  912 QAQALYPwRAKKDNH--LNFNKNDVITVL--EQQDMWWFGEVQGQK--GWFPKSYVKLI 964
Cdd:cd11915      2 RVQAIFS-HAAGDNStlLSFKEGDYITLLvpEARDGWHYGECEKTKmrGWFPFSYTRVL 59

chromosome partition protein MukB;

Pssm-ID: 235316 [Multi-domain] Cd Length: 1486 Bit Score: 46.10 E-value: 2.64e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  436 AKRElERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTL-------------EFELEALNDKKNQLEGKLQDIRCRL 502
Cdd:PRK04863   782 AARE-KRIEQLRAEREELAERYATLSFDVQKLQRLHQAFSRFigshlavafeadpEAELRQLNRRRVELERALADHESQE 860

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  503 STQRQEIEstnKSRELriaeithlqqqlqesQQMLGKLIPEKQLLND------------QLKQ-------VQQNSLHRDS 563
Cdd:PRK04863   861 QQQRSQLE---QAKEG---------------LSALNRLLPRLNLLADetladrveeireQLDEaeeakrfVQQHGNALAQ 922

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  564 LLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDifnnQLKELREihNRQQL---QKQKNLEAE---------RLKQ 631
Cdd:PRK04863   923 LEPIVSVLQSDPEQFEQLKQDYQQAQQTQRDAKQQAF----ALTEVVQ--RRAHFsyeDAAEMLAKNsdlneklrqRLEQ 996

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  632 KEQERktelEKQKEAQRRIQDRDKQRlDRVQQEEEPQWQKKNQEDDKQKRE 682
Cdd:PRK04863   997 AEQER----TRAREQLRQAQAQLAQY-NQVLASLKSSYDAKRQMLQELKQE 1042

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 40.35 E-value: 2.65e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQ--QDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11882      1 RARALYACKAEDESELSFEPGQIITNVQPsdEPGWLEGTLNGRTGLIPENYVEF 54

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 40.42 E-value: 2.66e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREWVDesqtgePGWLGGELKGKTGWFPANY 797
Cdd:cd11804      3 VAKHDFKATAEDELSFKKGSILKVLNMEDD------PNWYKAELDGKEGLIPKNY 51

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 40.40 E-value: 2.71e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11781      4 ALYPFKAQSAKELSLKKGDIIYIRRQiDKNWYEGEHNGRVGIFPASYV 51

Second Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212865 Cd Length: 57 Bit Score: 40.59 E-value: 2.76e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1150 VCQVIGMYDY----TAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11932      1 LCRALYNFDLkeknREESKDCLKFQKDDIITVISRVDENWAEGKLGDQVGIFPILFV 57

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 40.16 E-value: 2.76e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11947      1 EARGKFDFTASGEDELSFKKGDVLKILSSDDIWFKAELNGEEGYVPKNFV 50

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.

Pssm-ID: 402959 [Multi-domain] Cd Length: 164 Bit Score: 43.52 E-value: 2.78e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  589 EKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDR--DKQRLDRVQQEEE 666
Cdd:pfam11600   12 EKEKQRLEKDKERLRRQLKLEAEKEEKERLKEEAKAEKERAKEEARRKKEEEKELKEKERREKKEkdEKEKAEKLRLKEE 91

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  667 PQWQKKN----QEDDKQKREEIIKKKESEDKGKQEIQEKpSKLFQPHQEPVKPAVQAPW 721
Cdd:pfam11600   92 KRKEKQEaleaKLEEKRKKEEEKRLKEEEKRIKAEKAEI-TRFLQKPKTQQAPKTLAGS 149

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 40.53 E-value: 2.80e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1159 YTAQNDDELAFNKGQIINVLNKEDPDWWKG--EVNGQVGLFPSNYVK 1203
Cdd:cd11785      8 YPPQSEAELELKEGDIVFVHKKREDGWFKGtlQRTGKTGLFPGSFVE 54

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 40.16 E-value: 2.85e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGeLQGKKRQIGWFPANYVKL 1128
Cdd:cd11940      3 QCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEG-VRLSDGERGWFPQSHVEE 55

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 40.18 E-value: 2.87e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592 1000 EEYVAMYTYESSEQGDLTFQQG-DMILVTKKDGDWWTGTlgDK---TGVFPSNYVRLK 1053
Cdd:cd11905      1 EIVVAMYDFQPTEPHDLRLETGeEYVILEKNDVHWWKAR--DKygkEGYIPSNYVTGK 56

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 40.20 E-value: 2.92e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVK 962
Cdd:cd11870      1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLeGHSDGRVGIFPKCFVV 52

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 45.53 E-value: 2.94e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  408 LEKQLEKQRElerqreeerrkeierreaakrELERQRQLEWERNrrqelLNQRNREQEDIVVLKAKKKtlefELEALNDK 487
Cdd:COG4717     47 LLERLEKEAD---------------------ELFKPQGRKPELN-----LKELKELEEELKEAEEKEE----EYAELQEE 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  488 KNQLEGKLQDIRCRLSTQRQEIESTNKSRELRiaeithlqqqlqesqqmlgKLIPEKQLLNDQLKQVQQNslhrdsllti 567
Cdd:COG4717     97 LEELEEELEELEAELEELREELEKLEKLLQLL-------------------PLYQELEALEAELAELPER---------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  568 KRALEAKELARQQLRDQLDEVEKETRSKLQEIDifnnQLKELREIHNRQQLQKQKNlEAERLKQKEQERKTELEkqkEAQ 647
Cdd:COG4717    148 LEELEERLEELRELEEELEELEAELAELQEELE----ELLEQLSLATEEELQDLAE-ELEELQQRLAELEEELE---EAQ 219

                          250       260
                   ....*....|....*....|....*...
gi 2024344592  648 RRIQDRDKQRLDRVQQEEEPQWQKKNQE 675
Cdd:COG4717    220 EELEELEEELEQLENELEAAALEERLKE 247

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212972 Cd Length: 62 Bit Score: 40.33 E-value: 3.01e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1156 MYDYTAQNDDE-------LAFNKGQIINVLNKEDPDWWK----GEVNGQVGLFPS 1199
Cdd:cd12039      5 LFDYNPYEDRAipcqeagLPFKRRDILEVVSQDDPTWWQakrvGDTNLRAGLIPS 59

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176070 [Multi-domain] Cd Length: 110 Bit Score: 41.91 E-value: 3.01e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1605 RSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSncQFFI-----KDLEQDVLCITVFERDQFSPDDFLGRTEI 1673
Cdd:cd08688     16 RSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNS--EWFRfevddEELQDEPLQIRVMDHDTYSANDAIGKVYI 87

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 40.05 E-value: 3.04e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYVKL 1128
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNG---QKGLVPGTYLEK 53

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

Pssm-ID: 405931 [Multi-domain] Cd Length: 151 Bit Score: 42.73 E-value: 3.04e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  362 LELEKRRQALLEQQRKEQERLAQLE--RAEQERKERERQEQERKRQLELEKQLE----KQRELERQREEERRkeierrea 435
Cdd:pfam15346   35 IEAEVERRVEEARKIMEKQVLEELEreREAELEEERRKEEEERKKREELERILEennrKIEEAQRKEAEERL-------- 106

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592  436 akRELERQRQLEWERNRRQELLNQR-NREQEDIVVLKAKKKTLEFEL 481
Cdd:pfam15346  107 --AMLEEQRRMKEERQRREKEEEEReKREQQKILNKKNSRPKLSFSL 151

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 45.83 E-value: 3.06e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  349 FEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELE-KQLEKQrelerqreeerr 427
Cdd:TIGR02169  830 YLEKEIQELQEQRIDLKEQIKSIEKEIENLNGKKEELEEELEELEAALRDLESRLGDLKKErDELEAQ------------ 897

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  428 keierreaaKRELE-RQRQLEWERNRRQELLNQrnreqedivvLKAKKKTLEFELEALNDKKNQLE---------GKLQD 497
Cdd:TIGR02169  898 ---------LRELErKIEELEAQIEKKRKRLSE----------LKAKLEALEEELSEIEDPKGEDEeipeeelslEDVQA 958

                          170
                   ....*....|....*.
gi 2024344592  498 IRCRLSTQRQEIESTN 513
Cdd:TIGR02169  959 ELQRVEEEIRALEPVN 974

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 40.49 E-value: 3.06e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGD-------KTGVFPSNY 1049
Cdd:cd11773      2 YKALYDYEPQTEDELTIQEDDILyLLEKSDDDWWKVKLKVnssdddePVGLVPATY 57

Second Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212865 Cd Length: 57 Bit Score: 40.21 E-value: 3.10e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1004 AMYTYE-----SSEQGD-LTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11932      4 ALYNFDlkeknREESKDcLKFQKDDIITVISRvDENWAEGKLGDQVGIFPILFV 57

Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full length form of the previously-identified tumor supressor, p53-binding protein 2 (p53BP2). ASPP2 activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). It plays a central role in regulating apoptosis and cell growth; ASPP2-deficient mice show postnatal death. Downregulated expression of ASPP2 is frequently found in breast tumors, lung cancer, and diffuse large B-cell lymphoma where it is correlated with a poor clinical outcome. ASPP2 contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP2 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212886 [Multi-domain] Cd Length: 57 Bit Score: 40.32 E-value: 3.14e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGD-MILVTKKDGD---WWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11953      5 ALWDYEGESDDELSFKEGDcMTILRREDEDeteWWWARLNDKEGYVPRNLLGL 57

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 40.08 E-value: 3.15e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGelQGKKRQIGWFPANYVKL 1128
Cdd:cd11960      2 ARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRG--TGPDGTYGLFPANYVEL 54

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212830 [Multi-domain] Cd Length: 55 Bit Score: 40.36 E-value: 3.17e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM--WWFG-EVQGQKGWFPKSYVKL 963
Cdd:cd11897      1 RARALYDFRSENPGEISLREHEVLSLCSEQDIegWLEGvNSRGDRGLFPASYVEV 55

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 40.34 E-value: 3.25e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd12054      2 QCKVLFEYVPQNEDELELKVGDIIDINEEvEEGWWSGTLNGKSGLFPSNFVK 53

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212736 [Multi-domain] Cd Length: 52 Bit Score: 39.96 E-value: 3.27e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINV--LNKEDPDWWKGEVNGQVGLFPSNY 1201
Cdd:cd11802      5 LYDYDAEDSTELSLLADEVITVyeLPGMDEDYMMGERGSQRGKVPVAY 52

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 40.26 E-value: 3.28e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  746 YPFESRSHDEITIQPGDIVM-VKREwvdesqtgEPGWLGGELKGKTGWFPANY 797
Cdd:cd12052      6 FDYKAQHEDELTITVGDIITkIKKD--------DGGWWEGEIKGRRGLFPDNF 50

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 40.38 E-value: 3.30e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1005 MYTYESSEQGDLTFQQGDMILVT-KKDGDWWTGTLG---DKTGVFPSNYVRL 1052
Cdd:cd11965      5 IYDCQADNDDELTFVEGEVIIVTgEEDQEWWIGHIEgqpERKGVFPVSFVHI 56

putative mechanosensitive channel protein; Provisional

Pssm-ID: 236798 [Multi-domain] Cd Length: 1109 Bit Score: 45.82 E-value: 3.33e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  364 LEKRRQALLEQQRKEQ--ERLAQLERaeqerkererQEQERKRQL-ELEKQLEKQRELERQREEERRKEIERREAAKR-- 438
Cdd:PRK10929   119 LEKSRQAQQEQDRAREisDSLSQLPQ----------QQTEARRQLnEIERRLQTLGTPNTPLAQAQLTALQAESAALKal 188

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  439 --ELERQrQLEweRNRRQELLNQRnreqedivvlkakkktlefeLEALNDKKNQLEGKLQDIRCRLSTQRQ-EIESTNKS 515
Cdd:PRK10929   189 vdELELA-QLS--ANNRQELARLR--------------------SELAKKRSQQLDAYLQALRNQLNSQRQrEAERALES 245

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  516 RELrIAEithlqqqlqesqqMLGKLIPE--KQL-LNDQLKQVQQNSLHRDSLLTIKRALEAKELarQQLRDQLDEVeket 592
Cdd:PRK10929   246 TEL-LAE-------------QSGDLPKSivAQFkINRELSQALNQQAQRMDLIASQQRQAASQT--LQVRQALNTL---- 305

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  593 RSKLQEIDIFN-------NQLKELREIHNRQQL-QKQKNLEAERLKQKEQerkteLEKQKEAQRRIQDrDKQRLDRVQQE 664
Cdd:PRK10929   306 REQSQWLGVSNalgealrAQVARLPEMPKPQQLdTEMAQLRVQRLRYEDL-----LNKQPQLRQIRQA-DGQPLTAEQNR 379

                          330
                   ....*....|.
gi 2024344592  665 -EEPQWQKKNQ 674
Cdd:PRK10929   380 iLDAQLRTQRE 390

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 45.53 E-value: 3.40e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  566 TIKRALEAkeLARQQLRDQLDEVEKETRSK----LQEIDIFNNQLKELREIHNR-QQLQKQKNLEAERLKQKEQERKT-- 638
Cdd:COG4717     38 TLLAFIRA--MLLERLEKEADELFKPQGRKpelnLKELKELEEELKEAEEKEEEyAELQEELEELEEELEELEAELEElr 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  639 ----ELEKQKEAQRRIQDRdkQRLDRVQQEEEPQWQ--KKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQPHQEP 712
Cdd:COG4717    116 eeleKLEKLLQLLPLYQEL--EALEAELAELPERLEelEERLEELRELEEELEELEAELAELQEELEELLEQLSLATEEE 193


                   ....*..
gi 2024344592  713 VKPAVQA 719
Cdd:COG4717    194 LQDLAEE 200

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 40.06 E-value: 3.43e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREwvdesqtgEPG--WLGGELKG-KTGWFPANYAE 799
Cdd:cd11858      2 YKALYDFAGSVANELSLKKDDIVYIVQK--------EDNgwWLAKKLDEsKEGWVPAAYLE 54

Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212855 [Multi-domain] Cd Length: 58 Bit Score: 40.36 E-value: 3.46e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNG--QVGLFPSNYVKL 1204
Cdd:cd11922      2 EAIAKFNFNGDTQVEMSFRKGERITLLRQVDENWYEGRIPGtsRQGIFPITYVDV 56

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 40.21 E-value: 3.47e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKK--DGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd12053      1 EYIVEYDYDAVHEDELTIRVGEIIRNVKKleEEGWLEGELNGRRGMFPDNFVK 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 39.93 E-value: 3.55e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKDGD--WWTGTL-GDKTGVFPSNYV 1050
Cdd:cd11998      5 ALYDYDGQEQDELSFKAGDELTKLEDEDEqgWCKGRLdSGQVGLYPANYV 54

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 39.99 E-value: 3.56e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKRewvdesQTGEpgWLGGELKGKTGWFPANY 797
Cdd:cd11992      2 YIALYPYSSSEPGDLTFNEGEEILVTQ------KDGE--WWTGSIEDRTGIFPSNY 49

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 44.91 E-value: 3.56e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLEQQRKEQERLAQLER-AEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQ 443
Cdd:pfam13868  247 LKERRLAEEAEREEEEFERMLRKqAEDEEIEQEEAEKRRMKRLEHRRELEKQIEEREEQRAAEREEELEEGERLREEEAE 326

                           90
                   ....*....|...
gi 2024344592  444 RQLEWERNRRQEL 456
Cdd:pfam13868  327 RRERIEEERQKKL 339

Src Homology 3 domain of Cdc42-Interacting Protein 4, Bzz1 and similar domains; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4) and similar proteins such as Formin Binding Protein 17 (FBP17) and FormiN Binding Protein 1-Like (FNBP1L), as well as yeast Bzz1 (or Bzz1p). CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. Bzz1 is also a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Members of this subfamily contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain as well as at least one C-terminal SH3 domain. Bzz1 contains a second SH3 domain at the C-terminus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212711 [Multi-domain] Cd Length: 55 Bit Score: 39.90 E-value: 3.65e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKKD-GDWWTGTLGDK--TGVFPSNYVRL 1052
Cdd:cd11777      1 ECKALYAFVGSSEGTISMTEGEKLSLVEEDkGDGWTRVRRDTgeEGYVPTSYIRI 55

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 40.00 E-value: 3.65e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1079 SYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQGKkrqIGWFPANYVK 1127
Cdd:cd11977      8 NFAARDMRELSLREGDVVRIYSRIGGdqGWWKGETNGR---IGWFPSTYVE 55

Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442298 [Multi-domain] Cd Length: 485 Bit Score: 45.03 E-value: 3.72e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  348 TFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQrelerqreeERR 427
Cdd:COG3064      4 ALEEKAAEAAAQERLEQAEAEKRAAAEAEQKAKEEAEEERLAELEAKRQAEEEAREAKAEAEQRAAEL---------AAE 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  428 KEIERREAAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTlEFELEALNDKKNQLEgKLQDIRCRLSTQRQ 507
Cdd:COG3064     75 AAKKLAEAEKAAAEAEKKAAAEKAKAAKEAEAAAAAEKAAAAAEKEKAE-EAKRKAEEEAKRKAE-EERKAAEAEAAAKA 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  508 EIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKELARQQLRDQLDE 587
Cdd:COG3064    153 EAEAARAAAAAAAAAAAAAARAAAGAAAALVAAAAAAVEAADTAAAAAAALAAAAAAAAADAALLALAVAARAAAASREA 232

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  588 VEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRL--DRVQQEE 665
Cdd:COG3064    233 ALAAVEATEEAALGGAEEAADLAAVGVLGAALAAAAAGAAALSSGLVVVAAALAGLAAAAAGLVLDDSAALaaELLGAVA 312

                          330       340       350
                   ....*....|....*....|....*....|....*....
gi 2024344592  666 EPQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSK 704
Cdd:COG3064    313 AEEAVLAAAAAAGALVVRGGGAASLEAALSLLAAGAAAA 351

Src Homology 3 domain of Melanoma Inhibitory Activity protein and similar proteins; MIA is a single domain protein that adopts a SH3 domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands. MIA is a member of the recently identified family that also includes MIA-like (MIAL), MIA2, and MIA3 (also called TANGO); the biological functions of this family are not yet fully understood.

Pssm-ID: 212694 Cd Length: 76 Bit Score: 40.54 E-value: 3.73e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNK---EDPDWWKGEVNGQ---VGLFPSNYVK 1203
Cdd:cd11760     17 LEDYHGPDCRFLNFKKGDTIYVYSKlagERQDLWAGSVGGDaglFGYFPKNLVQ 70

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212858 Cd Length: 57 Bit Score: 39.98 E-value: 3.78e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGDWW---TGTLGDKTGVFPSNYV 1050
Cdd:cd11925      3 YLALYAYKPQKNDELELRKGEMYRVIEKCQDGWfkgTSLRTGVSGVFPGNYV 54

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 40.01 E-value: 3.87e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD--WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11978      4 IARYDFCARDMRELSLLKGDVVKIYTKMSTngWWRGEVNGRVGWFPSTYV 53

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 39.75 E-value: 3.95e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd12016      5 TTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKE---GWAPATYLK 53

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 40.00 E-value: 3.98e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQD----MWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11954      3 VYALWDYEAQNADELSFQEGDAITILRRKDdsetEWWWARLNDKEGYVPKNLLGL 57

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 42.18 E-value: 4.00e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITKT-----MQDTLNPKWNSNCQFFI--KDLEQDVLCITVFERDQ 1661
Cdd:cd08410     14 GRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKLIKTkktscMRGTIDPFYNESFSFKVpqEELENVSLVFTVYGHNV 93

                           90
                   ....*....|..
gi 2024344592 1662 FSPDDFLGRTEI 1673
Cdd:cd08410     94 KSSNDFIGRIVI 105

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 39.71 E-value: 4.03e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIV-MVKREwvdESQTGepgWLGGELKGKTGWFPANYAE 799
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIItILKKS---DSQND---WWTGRIGGREGIFPANYVE 54

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 39.81 E-value: 4.09e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd12056      5 KALFHYEGTNEDELDFKEGEIILIISKdtgEPGWWKGELNGKEGVFPDNFVSQ 57

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 39.61 E-value: 4.12e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGD-MILVTKKDGDWW--TGTLGDkTGVFPSNYVR 1051
Cdd:cd11849      2 YRALYDFKSAEPNTLSFSEGEtFLLLERSNAHWWlvTNHSGE-TGYVPANYVK 53

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 39.68 E-value: 4.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKrewvdeSQTG-EPGWLGGELKGKTGWFPANY 797
Cdd:cd11841      4 ALYSFEGQQPCDLSFQAGDRITVL------TRTDsQFDWWEGRLRGRVGIFPANY 52

RIB43A; This family consists of several RIB43A-like eukaryotic proteins. Ciliary and flagellar microtubules contain a specialized set of protofilaments, termed ribbons, that are composed of tubulin and several associated proteins. RIB43A was first characterized in the unicellular biflagellate, Chlamydomonas reinhardtii although highly related sequences are present in several higher eukaryotes including humans. The function of this protein is unknown although the structure of RIB43A and its association with the specialized protofilament ribbons and with basal bodies is relevant to the proposed role of ribbons in forming and stabilising doublet and triplet microtubules and in organizing their three-dimensional structure. Human RIB43A homologs could represent a structural requirement in centriole replication in dividing cells.

Pssm-ID: 461780 [Multi-domain] Cd Length: 372 Bit Score: 44.50 E-value: 4.44e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  374 QQRKEQERLAQLERAEQERKER----------------ERQEQERKRQLELEKQLEKQRELERQREEERRKEIErreaaK 437
Cdd:pfam05914    1 VDLKEAAAIERRRQREEERKSRifnarnrtigvdvealDKQVEEKKRQEAAEKAREEAFAEEMVQNDKIALMLE-----K 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  438 RELERQRQLEwernrrQELLNQRNREQedivvlkAKKKTLEFELEALNDKKNQLEGKL--QDIRCRLST-QRQEIESTNk 514
Cdd:pfam05914   76 REEEDRRRLN------KELNEFRQQHQ-------RPETRREFDLNDPDALKKDLPARVsdDDPRCGPSSmQKFEGEDLN- 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  515 sRELRIAEithlqqqlqesqqmlgkliPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEAKELARQQLRDQLDEVEKETRS 594
Cdd:pfam05914  142 -REERKKL-------------------QQEQMREWLEQQIEEKKQAEEEEKHAELLYDQKRLERDRRALELAKLEEECRR 201

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  595 KL-QEIDIFN-NQLKELREihnRQQLQKQKNLEA----------------------------------------ERLK-- 630
Cdd:pfam05914  202 AVnAATKNFNqALAAEQAE---RRRLEKRQEQEDnlaeiynhltsdlltenpevaqsslgphrvipdrwkgmspEQLKei 278

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  631 QKEQER-KTELEKQKEAQRRIQ-DRDKQRL--DRVQQEEEPQWQKKNQEDDKQKREE 683
Cdd:pfam05914  279 RKEQEQqREEKERRREEEKQRDaEWDRQRLelARAALLLEREQQRLRRELRRQLDEE 335

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212872 [Multi-domain] Cd Length: 55 Bit Score: 39.93 E-value: 4.49e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVK 1203
Cdd:cd11939      1 QVQCVHPYVSQEPDELSLELADVLNILDKTDDGWIFGERlhDQERGWFPSSVVE 54

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212955 [Multi-domain] Cd Length: 53 Bit Score: 39.82 E-value: 4.54e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1158 DYTAQNDDELAFNKGQIINVLNKEDPDWW---KGEvngQVGLFPSNYVK 1203
Cdd:cd12022      7 AYTAVEEDELTLLEGEAIEVIHKLLDGWWvvrKGE---VTGYFPSMYLQ 52

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 39.82 E-value: 4.59e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1075 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYVK 1127
Cdd:cd11870      1 QVVAlhRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDGR---VGIFPKCFVV 52

Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces cerevisiae proteins BOI1 and BOI2, and similar proteins. They contain an N-terminal SH3 domain, a Sterile alpha motif (SAM), and a Pleckstrin homology (PH) domain at the C-terminus. BOI1 and BOI2 interact with the SH3 domain of Bem1p, a protein involved in bud formation. They promote polarized cell growth and participates in the NoCut signaling pathway, which is involved in the control of cytokinesis. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212819 Cd Length: 55 Bit Score: 39.62 E-value: 4.60e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMV---KREWVDesqtgepGW-LGGELK-GKTGWFPANY 797
Cdd:cd11886      1 LLIVIHDFNARSEDELTLKPGDKIELiedDEEFGD-------GWyLGRNLRtGETGLFPVVF 55

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 39.79 E-value: 4.60e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQ--GQKGWFPKSYV 961
Cdd:cd11889      2 VKAVYSWAGETEGDLGFLEGDLIEVLSIGDgSWWSGKLRrnGAEGIFPSNFV 53

Nop53 (60S ribosomal biogenesis); This nucleolar family of proteins are involved in 60S ribosomal biogenesis. They are specifically involved in the processing beyond the 27S stage of 25S rRNA maturation. This family contains sequences that bear similarity to the glioma tumour suppressor candidate region gene 2 protein (p60). This protein has been found to interact with herpes simplex type 1 regulatory proteins.

Pssm-ID: 462259 [Multi-domain] Cd Length: 353 Bit Score: 44.59 E-value: 4.69e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  362 LELEKRRQALLEQQRKEQERLAQLERAEQERK------------ERERQEQERKRQLELEKQLEKqrelerqreeerrke 429
Cdd:pfam07767  209 KKRLKEEEKLERVLEKIAESAATAEAREEKRKtkaqrnkekrrkEEEREAKEEKALKKKLAQLER--------------- 273

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592  430 ierreaAKRELERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKK 475
Cdd:pfam07767  274 ------LKEIAKEIAEKEKEREEKAEARKREKRKKKKEEKKLRPRK 313

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 43.76 E-value: 4.69e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  561 RDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTEL 640
Cdd:COG1579     37 EDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEARIKKYEEQLGNVRNNKEYEALQKEIESLKRRISDLEDEILELM 116

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  641 EKQKEAQRRIQDRdKQRLDRVQQEEepqwqkknqEDDKQKREEIIKKKESE 691
Cdd:COG1579    117 ERIEELEEELAEL-EAELAELEAEL---------EEKKAELDEELAELEAE 157

PH domain; PH stands for pleckstrin homology.

Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 41.39 E-value: 4.72e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1458 HSGKLYK-----AKSNKELYGFLFNDFLLLtqiikplgssgtdkvFSPKSNLQYKMYKTPIFLNEV-LVKLPTDPSGDEP 1531
Cdd:pfam00169    3 KEGWLLKkgggkKKSWKKRYFVLFDGSLLY---------------YKDDKSGKSKEPKGSISLSGCeVVEVVASDSPKRK 67

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2024344592 1532 -IFHISHID----RVYTLRAESINERTAWVQKIKAASE 1564
Cdd:pfam00169   68 fCFELRTGErtgkRTYLLQAESEEERKDWIKAIQSAIR 105

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 39.76 E-value: 4.75e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGeLQGKKRQIGWFPANYV 1126
Cdd:cd11784      4 ALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRG-LSLVTGRVGIFPSNYV 53

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 39.56 E-value: 4.76e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGD-MILVTKKDGDWWT--GTLGDKtGVFPSNYVR 1051
Cdd:cd11768      3 VALYDFQPIEPGDLPLEKGEeYVVLDDSNEHWWRarDKNGNE-GYIPSNYVT 53

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212725 [Multi-domain] Cd Length: 59 Bit Score: 39.98 E-value: 4.77e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592 1150 VCQVIgmYDYTAQNDDELAFNKGQIINV----LNKEDPDWWKG--EVNGQVGLFPSNYV 1202
Cdd:cd11791      1 VLRVL--YPYTPQEEDELELVPGDYIYVspeeLDSSSDGWVEGtsWLTGCSGLLPENYT 57

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 44.91 E-value: 4.87e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  341 LEKklPVTFE--DKKRENFErgnlELEKRRQALLeqqrKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQrel 418
Cdd:COG4913    218 LEE--PDTFEaaDALVEHFD----DLERAHEALE----DAREQIELLEPIRELAERYAAARERLAELEYLRAALRLW--- 284

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  419 erqreeerrkeierreaakrelERQRQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKlqdi 498
Cdd:COG4913    285 ----------------------FAQRRLELLEAELEELRAELARLEAELERLEARLDALREELDELEAQIRGNGGD---- 338

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  499 rcRLSTQRQEIESTNKSRELRiaeithlqqqlqesqqmlgklipeKQLLNDQLKQVQQnslhrdslLTIKRALEAKELA- 577
Cdd:COG4913    339 --RLEQLEREIERLERELEER------------------------ERRRARLEALLAA--------LGLPLPASAEEFAa 384

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  578 -RQQLRDQLDEVEKEtrsklqeidifnnqlkelreihnRQQLQKQKNlEAERLKQKEQERKTELEKQKEAQRR 649
Cdd:COG4913    385 lRAEAAALLEALEEE-----------------------LEALEEALA-EAEAALRDLRRELRELEAEIASLER 433

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 39.67 E-value: 4.97e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVL----EQQDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11807      2 VVYALFDYEAENGDELSFREGDELTVLrkgdDDETEWWWARLNDKEGYVPRNLLGL 57

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 39.82 E-value: 5.02e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  911 LQAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11956      2 VEAVACFDYTGRTAQELSFKRGDVLLLHSKASSdWWRGEHNGMRGLIPHKYISV 55

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 39.53 E-value: 5.03e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLE---QQDMWWFGEVQGQKGWFPKSYVKL 963
Cdd:cd11952      5 ALWDYSAEFPDELSFKEGDMVTVLRkdgEGTDWWWASLCGREGYVPRNYFGL 56

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 39.55 E-value: 5.03e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVT-KKDGDWWTGTL-GDKT--GVFPSNYV 1050
Cdd:cd11966      4 ALYNCVADNPDELTFSEGEIIIVDgEEDKEWWIGHIdGEPTrrGAFPVSFV 54

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 44.37 E-value: 5.06e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  367 RRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQlELEKQLEKQRelerqreeerrkeierreaakrelERQRQL 446
Cdd:COG4942    136 RRLQYLKYLAPARREQAEELRADLAELAALRAELEAERA-ELEALLAELE------------------------EERAAL 190

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  447 EWERNRRQELLNQrnreqedivvLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSR 516
Cdd:COG4942    191 EALKAERQKLLAR----------LEKELAELAAELAELQQEAEELEALIARLEAEAAAAAERTPAAGFAA 250

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 39.64 E-value: 5.10e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAE 799
Cdd:cd11782      3 RAKYNFNADTGVELSFRKGDVITLTRR-VDEN------WYEGRIGGRQGIFPVSYVQ 52

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 42.02 E-value: 5.23e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEV-TMGSQCHITK----TMQDTLNPKWNSNCQFFI--KDLEQDVLCITVFERDQ 1661
Cdd:cd08405     15 NRITVNIIKARNLKAMDINGTSDPYVKVwLMYKDKRVEKkktvIKKRTLNPVFNESFIFNIplERLRETTLIITVMDKDR 94


                   ....*....
gi 2024344592 1662 FSPDDFLGR 1670
Cdd:cd08405     95 LSRNDLIGK 103

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 39.49 E-value: 5.47e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVkrewVDESQtgEPGWLGGELK-GKTGWFPANY 797
Cdd:cd11845      2 YVALYDYEARTDDDLSFKKGDRLQI----LDDSD--GDWWLARHLStGKEGYIPSNY 52

chromosome segregation protein; Provisional

Pssm-ID: 100796 [Multi-domain] Cd Length: 895 Bit Score: 44.89 E-value: 5.50e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  452 RRQELLNQR---NREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRcRLSTQRQEIESTnksreLRIaeithlqq 528
Cdd:PRK01156   150 QRKKILDEIleiNSLERNYDKLKDVIDMLRAEISNIDYLEEKLKSSNLELE-NIKKQIADDEKS-----HSI-------- 215

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  529 qlqesqqmlgkLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALEakelarqQLRDQLDEVEKETRSKLQEIDIFNNQLKE 608
Cdd:PRK01156   216 -----------TLKEIERLSIEYNNAMDDYNNLKSALNELSSLE-------DMKNRYESEIKTAESDLSMELEKNNYYKE 277

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  609 LREIHNRQ----------------QLQKQ--------KNLEAERLKQKEQERK-TELEKQK----EAQRRIQDRDKQRLD 659
Cdd:PRK01156   278 LEERHMKIindpvyknrnyindyfKYKNDienkkqilSNIDAEINKYHAIIKKlSVLQKDYndyiKKKSRYDDLNNQILE 357

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 2024344592  660 RVQQEEEPQWQKKNQEDDKQKREEIIKKKE------SEDKGKQEI 698
Cdd:PRK01156   358 LEGYEMDYNSYLKSIESLKKKIEEYSKNIErmsafiSEILKIQEI 402

Src homology 3 domain of Endophilin-B2; Endophilin-B2, also called SH3GLB2 (SH3-domain GRB2-like endophilin B2), is a cytoplasmic protein that interacts with the apoptosis inducer Bax. It is overexpressed in prostate cancer metastasis and has been identified as a cancer antigen with potential utility in immunotherapy. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain. The related protein endophilin-B1 interacts with amphiphysin 1 and dynamin 1 through its SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212877 Cd Length: 55 Bit Score: 39.59 E-value: 5.77e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINV--LNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11944      5 LYDYEAADSSELALLADELITVysLPGMDPDWLIGERGNQKGKVPVTYLEL 55

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 44.63 E-value: 5.79e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  351 DKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERK------ERERQEQERK-RQLELE-KQLEKQRELERQR 422
Cdd:TIGR04523  411 DEQIKKLQQEKELLEKEIERLKETIIKNNSEIKDLTNQDSVKEliiknlDNTRESLETQlKVLSRSiNKIKQNLEQKQKE 490

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  423 EEERRKEIERREAAKRELERQ-----RQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELealndKKNQLEGKLQD 497
Cdd:TIGR04523  491 LKSKEKELKKLNEEKKELEEKvkdltKKISSLKEKIEKLESEKKEKESKISDLEDELNKDDFEL-----KKENLEKEIDE 565

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  498 IRCRLSTQRQEIES---TNKSRELRIAEITHLQQQLQESQQMLGKLIPEkqlLNDQLKQVQQNslHRDSLLTIKRALEAK 574
Cdd:TIGR04523  566 KNKEIEELKQTQKSlkkKQEEKQELIDQKEKEKKDLIKEIEEKEKKISS---LEKELEKAKKE--NEKLSSIIKNIKSKK 640

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  575 ELARQQLRdQLDEVEKETRSKLQEIDIFNNQLKELreIHNRQQLQKQKNLEAERLKQK---EQERKTELEKQKEAQRRIQ 651
Cdd:TIGR04523  641 NKLKQEVK-QIKETIKEIRNKWPEIIKKIKESKTK--IDDIIELMKDWLKELSLHYKKyitRMIRIKDLPKLEEKYKEIE 717


                   .
gi 2024344592  652 D 652
Cdd:TIGR04523  718 K 718

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 39.62 E-value: 6.21e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1077 IASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYVK 1127
Cdd:cd11971      5 IYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNG---VTGLFPGNYVE 52

Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212946 Cd Length: 61 Bit Score: 39.67 E-value: 6.26e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1002 YVAMYTYESSE-------QGDLTFQQGDMILV---TKKDGdWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd12013      2 MVALFDYDPREsspnvdaEVELSFRAGDIITVfgeMDEDG-FYYGELNGQRGLVPSNFLE 60

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 39.30 E-value: 6.27e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGE--VQGQKGWFPKSYVKL 963
Cdd:cd11783      4 ALYPYKPQKPDELELRKGEMYTVTEKcQDGWFKGTslRTGQSGVFPGNYVQP 55

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 39.40 E-value: 6.30e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKrewvdeSQTGEPGWLGgELKGKTGWFPANYAE 799
Cdd:cd11813      3 KALLDFERHDDDELGFRKNDIITII------SQKDEHCWVG-ELNGLRGWFPAKFVE 52

Coiled-coil domain-containing protein 66; This protein family, named Coiled-coil domain-containing protein 66 (CCDC) refers to a protein domain found in eukaryotes, and is approximately 160 amino acids in length. CCDC66 protein is detected mainly in the inner segments of photoreceptors in many vertebrates including mice and humans. It has been found in dogs, that a mutation in the CCDC66 gene causes generalized progressive retinal atrophy (gPRA). This shows that the protein encoded for by this gene is vital for healthy vision and guards against photoreceptor cell degeneration. The structure of CCDC66 proteins includes a heptad repeat pattern which contains at least one coiled-coil domain. There are at least two or more alpha-helices which form a cable-like structure.

Pssm-ID: 434558 [Multi-domain] Cd Length: 154 Bit Score: 42.09 E-value: 6.37e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLE------QQRKEQERLAQLERaEQERKERERQEQERKRQLELE---------KQLEKQRELERQREEERR 427
Cdd:pfam15236   46 ERERKRQKALEhqnaikKQLEEKERQKKLEE-ERRRQEEQEEEERLRREREEEqkqfeeerrKQKEKEEAMTRKTQALLQ 124

                           90       100
                   ....*....|....*....|....*
gi 2024344592  428 KEIERREAAKRELERQRQLEWERNR 452
Cdd:pfam15236  125 AMQKAQELAQRLKQEQRIRELAEKG 149

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 39.40 E-value: 6.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKREWVDEsqtgepgWLGGELKGKTGWFPANYAE 799
Cdd:cd12046      4 ALFSYEASQPEDLEFQKGDVILVLSKVNED-------WLEGQCKGKIGIFPSAFVE 52

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 39.29 E-value: 6.51e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYVKL 1128
Cdd:cd11828      8 HVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRD---EEGWFPASFVRL 53

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 39.10 E-value: 6.62e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTG-TLGDKT--GVFPSNYVRLK 1053
Cdd:cd11872      3 VAIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGfSLRNKSlkGIFPKSYVHIK 56

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212742 [Multi-domain] Cd Length: 53 Bit Score: 39.01 E-value: 6.88e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 962
Cdd:cd11808      4 ALYDYQEKSPREVSMKKGDILTLLNSSNKdWWKVEVNDRQGFVPAAYVK 52

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 39.28 E-value: 7.12e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILV-----TKKDGDWWTGTLGDKTGVFPSNYVR 1051
Cdd:cd11800      2 YYALYTFEARSPGELSVTEGQVVTVlekhdLKGNPEWWLVEDRGKQGYVPSNYLA 56

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212731 Cd Length: 50 Bit Score: 38.94 E-value: 7.20e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILV--TKKDGdWWTGTLGDKTGVFPSNY 1049
Cdd:cd11797      3 VALYRFQALEPNELDFEVGDRIRIiaTLEDG-WLEGELKGRRGIFPHRF 50

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 39.22 E-value: 7.32e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTLGDKTGVFPSNYV 1050
Cdd:cd11902      4 FVKFAYVAEREDELSLVKGSRVTVMEKCSDgWWRGSYNGQIGWFPSNYV 52

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 38.88 E-value: 7.37e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYV 1126
Cdd:cd11796      2 ARVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRR---GIFPEGFV 51

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212844 [Multi-domain] Cd Length: 55 Bit Score: 39.17 E-value: 7.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWW----KGevNGQVGLFPSNYVKL 1204
Cdd:cd11911      1 TCTALYDFDGTSEGTLSMEEGEILLVLEEDGGDGWtrvrKN--NGDEGYVPTSYIEV 55

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 39.23 E-value: 7.40e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPG-GWWEGelQGKKRQIGWFPANYV 1126
Cdd:cd11763      2 VRALYDFDSQPSGELSLRAGEVLTITRQDVGdGWLEG--RNSRGEVGLFPSSYV 53

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein A; UBASH3A is also called Cbl-Interacting Protein 4 (CLIP4), T cell Ubiquitin LigAnd (TULA), or T cell receptor Signaling (STS)-2. It is only found in lymphoid cells and exhibits weak phosphatase activity. UBASH3A facilitates T cell-induced apoptosis through interaction with the apoptosis-inducing factor AIF. It is involved in regulating the level of phosphorylation of the zeta-associated protein (ZAP)-70 tyrosine kinase. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212870 [Multi-domain] Cd Length: 60 Bit Score: 39.23 E-value: 7.48e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVmvkreWVDESQTGE--PGWLGG--ELKGKTGWFPANYAEK 800
Cdd:cd11937      4 RALFQYKPQNIDELMLSPGDYI-----FVDPTQQSEasEGWVIGisHRTGCRGFLPENYTER 60

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 39.12 E-value: 7.51e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11986      4 ALYRFKALEKDDLDFHPGERITVIdDSNEEWWRGKIGEKTGYFPMNFI 51

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 39.16 E-value: 7.61e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1154 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11984      4 IAVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRTGWFPADCV 52

Src Homology 3 domain of the p85beta regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85beta binds CD28 and may be involved in the activation and differentiation of antigen-stimulated T cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212842 Cd Length: 74 Bit Score: 39.81 E-value: 7.77e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWV--------DESQTGEPGWLGG--ELKGKTGWFPANYAEKI 801
Cdd:cd11909      3 YRALYPYRKEREEDIDLLPGDVLTVSRAALqalgvkegGEQCPQSIGWILGlnERTKQRGDFPGTYVEFL 72

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 39.15 E-value: 7.90e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd11805      2 VQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRV---GIFPANYVQ 52

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 39.24 E-value: 8.12e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGGELKGKTGWFPANYAEK 800
Cdd:cd12077      3 YVTVQPYTSQGKDEIGFEKGVTVEVIQKNLE-------GWWYIRYLGKEGWAPASYLKK 54

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 39.23 E-value: 8.34e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGElqgKKRQIGWFPANYV 1126
Cdd:cd11963     10 FEAVEDNELTFKHGEIIIVLDDSDANWWKGE---NHRGVGLFPSNFV 53

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 38.83 E-value: 8.47e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGE-VQGQKGWFPKSYVKL 963
Cdd:cd11767      2 VVALYPFTGENDEELSFEKGERLEIIEKpedDPDWWKARnALGTTGLVPRNYVEV 56

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 44.36 E-value: 8.48e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  384 QLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNRE 463
Cdd:PTZ00121  1068 QDEGLKPSYKDFDFDAKEDNRADEATEEAFGKAEEAKKTETGKAEEARKAEEAKKKAEDARKAEEARKAEDARKAEEARK 1147

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  464 QEDivvlkakKKTLEFELEALNDKKNQLEGKLQDIRcRLSTQRQEIEsTNKSRELRIAEITHLQqqlqesqqmlgklipE 543
Cdd:PTZ00121  1148 AED-------AKRVEIARKAEDARKAEEARKAEDAK-KAEAARKAEE-VRKAEELRKAEDARKA---------------E 1203

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  544 KQLLNDQLKQVQQnslhrdslltIKRALEAKELarQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNRQQLQKQKN 623
Cdd:PTZ00121  1204 AARKAEEERKAEE----------ARKAEDAKKA--EAVKKAEEAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAA 1271

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  624 LEAERLKQKEQERKTElekqkeaqrriqdrDKQRLDRVQQEEEpqwqKKNQEDDKQKREEiiKKKESEDKGKQEIQEKPS 703
Cdd:PTZ00121  1272 IKAEEARKADELKKAE--------------EKKKADEAKKAEE----KKKADEAKKKAEE--AKKADEAKKKAEEAKKKA 1331

                          330       340       350
                   ....*....|....*....|....*....|....*
gi 2024344592  704 KLFQPHQEPVKPAVQAPWSNAGKAPLTISAQEDVK 738
Cdd:PTZ00121  1332 DAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKA 1366

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 38.84 E-value: 8.54e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYVKLL 1129
Cdd:cd11920      3 ARAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGR---VGIFPISYVEKL 55

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 38.99 E-value: 8.59e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGTL--GDKTGVFPSNYV 1050
Cdd:cd11785      2 YRVIVPYPPQSEAELELKEGDIVFVHKKREDgWFKGTLqrTGKTGLFPGSFV 53

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 38.82 E-value: 8.60e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwVDEsqtgepGWLGGELKGKTGWFPANY 797
Cdd:cd12055      3 QVAFSYLPQNEDELELKVGDIIEVVGE-VEE------GWWEGVLNGKTGMFPSNF 50

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 44.36 E-value: 8.70e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEKRRQAllEQQRKEQERLAQLERAEQERKERERQEQERKRQLE-------LEKQLEKQRELERQR 422
Cdd:PTZ00121  1644 EEKKKAEELKKAEEENKIKAA--EEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKEAEeakkaeeLKKKEAEEKKKAEEL 1721

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  423 EEERRKEIERREAAKRELERQ-------RQLEWERNRRQELLNQRNREQEDIvvLKAKKKTLEFELEALNDKKN-QLEGK 494
Cdd:PTZ00121  1722 KKAEEENKIKAEEAKKEAEEDkkkaeeaKKDEEEKKKIAHLKKEEEKKAEEI--RKEKEAVIEEELDEEDEKRRmEVDKK 1799

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  495 LQDIRCRLST-QRQEIEST---NKSRELRIAEIThlqqqlqesqqmlgKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRA 570
Cdd:PTZ00121  1800 IKDIFDNFANiIEGGKEGNlviNDSKEMEDSAIK--------------EVADSKNMQLEEADAFEKHKFNKNNENGEDGN 1865

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  571 LEAKELARQQLRDQLDEVEKETRsklqEIDIFNNQLKElREIHNRQQLQKQKNLEAERLkQKEQERKTELEKQKEAQRRI 650
Cdd:PTZ00121  1866 KEADFNKEKDLKEDDEEEIEEAD----EIEKIDKDDIE-REIPNNNMAGKNNDIIDDKL-DKDEYIKRDAEETREEIIKI 1939


                   ....
gi 2024344592  651 QDRD 654
Cdd:PTZ00121  1940 SKKD 1943

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 38.78 E-value: 8.74e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2024344592  760 PGDIVMVKREWVDESQTGEPGWLGGELKGKTGWFPAN 796
Cdd:cd11984     14 EGEIQLNRGERVKVLSIGEGGFWEGTVKGRTGWFPAD 50

Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); MPP2 is a scaffolding protein that interacts with the non-receptor tyrosine kinase c-Src in epithelial cells to negatively regulate its activity and morphological function. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212970 Cd Length: 59 Bit Score: 39.16 E-value: 8.93e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1157 YDYTAQNDD-------ELAFNKGQIINVLNKEDPDWWKG--EVNGQVGLFPS 1199
Cdd:cd12037      6 FDYDPSSDSlipckeaGLKFRAGDLLQIVNQEDPNWWQAchVEGGSAGLIPS 57

Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. It has been shown to interact with CSF1R, c-Cbl, LAT, CD247, and Zap70. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212944 Cd Length: 55 Bit Score: 38.96 E-value: 8.95e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGDWWT--GTLGDKTGVFPSNYV 1050
Cdd:cd12011      3 VALCNFPSGGPTELSIRMGEQLTILSEDGDWWKvsSAVTGRECYIPSNYV 52

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 39.23 E-value: 9.03e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKK---DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11977      4 VARYNFAARDMRELSLREGDVVRIYSRiggDQGWWKGETNGRIGWFPSTYV 54

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 39.03 E-value: 9.82e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQ------DMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11876      4 ALFDYDARGEDELTLRRGQPVEVLSKDaavsgdEGWWTGKIGDKVGIFPSNYV 56

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176047 [Multi-domain] Cd Length: 136 Bit Score: 41.23 E-value: 9.95e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTM---GSQCHITKTM--QDTLNPKWNSNCQFFI--KDLEQDVLCITVFERDQ 1661
Cdd:cd08402     15 GKLTVVILEAKNLKKMDVGGLSDPYVKIHLmqnGKRLKKKKTTikKRTLNPYYNESFSFEVpfEQIQKVHLIVTVLDYDR 94


                   ....*....
gi 2024344592 1662 FSPDDFLGR 1670
Cdd:cd08402     95 IGKNDPIGK 103

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 38.84 E-value: 9.96e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd11977      3 AVARYNFAARDMRELSLREGDVVRIYSRiggDQGWWKGETNGRIGWFPSTYVE 55

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 38.98 E-value: 9.99e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQ------DMWWFGEVQGQKGWFPKSYV 961
Cdd:cd12059      4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsgdEGWWTGKINDRVGIFPSNYV 56

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176011 [Multi-domain] Cd Length: 126 Bit Score: 40.72 E-value: 1.03e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1593 VNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLcITVFERDQFSpDDFLGRTE 1672
Cdd:cd04046      7 VHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIK-IQVWNSNLLC-DEFLGQAT 84


                   .
gi 2024344592 1673 I 1673
Cdd:cd04046     85 L 85

Mitochondrial inner membrane protein; Mitofilin controls mitochondrial cristae morphology. Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex. The first 78 amino acids contain a typical amino-terminal-cleavable mitochondrial presequence rich in positive-charged and hydroxylated residues and a membrane anchor domain. In addition, it has three centrally located coiled coil domains.

Pssm-ID: 430783 [Multi-domain] Cd Length: 618 Bit Score: 43.98 E-value: 1.04e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  543 EKQLLNDQLKQVQQNsLHRDSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIdiFNNQLKELREIHN-------R 615
Cdd:pfam09731  310 EEKHIERALEKQKEE-LDKLAEELSARLEEVRAADEAQLRLEFEREREEIRESYEEK--LRTELERQAEAHEehlkdvlV 386

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  616 QQLQKQKNLEAERLKQK-EQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEE 666
Cdd:pfam09731  387 EQEIELQREFLQDIKEKvEEERAGRLLKLNELLANLKGLEKATSSHSEVEDE 438

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 38.67 E-value: 1.04e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1080 YTATGPEQLTLAPGQLIL-IRKKNPGGWWEGELQGKKrqiGWFPANYVK 1127
Cdd:cd12053      8 YDAVHEDELTIRVGEIIRnVKKLEEEGWLEGELNGRR---GMFPDNFVK 53

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 43.99 E-value: 1.05e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  351 DKKRENFERGNLELEKRRQALLEQQRKEQERLA-QLERAEQERKERERQEQERKRQLE-LEKQLEKqrelerqreeerrk 428
Cdd:COG4717    166 EELEAELAELQEELEELLEQLSLATEEELQDLAeELEELQQRLAELEEELEEAQEELEeLEEELEQ-------------- 231

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  429 eierREAAKRELERQRQLEWERN-------------RRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKL 495
Cdd:COG4717    232 ----LENELEAAALEERLKEARLllliaaallallgLGGSLLSLILTIAGVLFLVLGLLALLFLLLAREKASLGKEAEEL 307

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  496 QDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLkQVQQNSLHRDSLLTIKRALEAKE 575
Cdd:COG4717    308 QALPALEELEEEELEELLAALGLPPDLSPEELLELLDRIEELQELLREAEELEEEL-QLEELEQEIAALLAEAGVEDEEE 386

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  576 LARQQLRDQLDEVEKETRSKLQE-IDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQD-R 653
Cdd:COG4717    387 LRAALEQAEEYQELKEELEELEEqLEELLGELEELLEALDEEELEEELEELEEELEELEEELEELREELAELEAELEQlE 466

                          330
                   ....*....|...
gi 2024344592  654 DKQRLDRVQQEEE 666
Cdd:COG4717    467 EDGELAELLQELE 479

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 38.45 E-value: 1.09e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWK-GEVNGQVGLFPSNYVK 1203
Cdd:cd11849      5 LYDFKSAEPNTLSFSEGETFLLLERSNAHWWLvTNHSGETGYVPANYVK 53

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 38.77 E-value: 1.11e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILV----TKKDGDWWTGTLGDKTGVFPS 1047
Cdd:cd11894      4 ALYDYEGQTDDELSFPEGAIIRIlnkeNQDDDGFWEGEFNGRIGVFPS 51

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 40.25 E-value: 1.11e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1593 VNIVEGIELKpcrsHGKSNPYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDV----LCITVFERDQFSPDDFL 1668
Cdd:cd04011      8 VRVIEARQLV----GGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESPDELfdkiIKISVYDSRSLRSDTLI 83

                           90
                   ....*....|
gi 2024344592 1669 GRTEIRVADI 1678
Cdd:cd04011     84 GSFKLDVGTV 93

Spc7 kinetochore protein; This domain is found in cell division proteins which are required for kinetochore-spindle association.

Pssm-ID: 197874 [Multi-domain] Cd Length: 312 Bit Score: 43.08 E-value: 1.16e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592   543 EKQLLNDQLKQVQQNSlhrdslltikrALEAKELA---RQQ----LRDQLDEVEKETRSKLQEIDIFNNQLKELREihnr 615
Cdd:smart00787  111 VKLLMDKQFQLVKTFA-----------RLEAKKMWyewRMKllegLKEGLDENLEGLKEDYKLLMKELELLNSIKP---- 175

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592   616 qqlqkqknleaeRLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQ-----QEEEPQWQKKNQEDDKQKREEIIKKKES 690
Cdd:smart00787  176 ------------KLRDRKDALEEELRQLKQLEDELEDCDPTELDRAKeklkkLLQEIMIKVKKLEELEEELQELESKIED 243

                           170
                    ....*....|
gi 2024344592   691 EDKGKQEIQE 700
Cdd:smart00787  244 LTNKKSELNT 253

Src homology 3 domain of DBL's Big Sister (DBS), a guanine nucleotide exchange factor; DBS, also called MCF2L (MCF2-transforming sequence-like protein) or OST, is a Rho GTPase guanine nucleotide exchange factor (RhoGEF), facilitating the exchange of GDP and GTP. It was originally isolated from a cDNA screen for sequences that cause malignant growth. It plays roles in regulating clathrin-mediated endocytosis and cell migration through its activation of Rac1 and Cdc42. Depending on cell type, DBS can also activate RhoA and RhoG. DBS contains a Sec14-like domain, spectrin-like repeats, a RhoGEF [or Dbl homology (DH)] domain, a Pleckstrin homology (PH) domain, and an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212791 Cd Length: 55 Bit Score: 38.42 E-value: 1.23e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPG-WLGGEL-KGKTGWFPAN 796
Cdd:cd11857      2 YTVVADYEKGGPDDLTVKSGDLVQLIHE-------GDEGqWLVKNLsTRKEGWVPAA 51

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 43.63 E-value: 1.25e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLEQQRKEQERLAQLEraeQERKERERQEQERKRQLELEK------QLEKQRELERQREEERRKEIERREAA 436
Cdd:pfam01576   72 ELEEILHELESRLEEEEERSQQLQ---NEKKKMQQHIQDLEEQLDEEEaarqklQLEKVTTEAKIKKLEEDILLLEDQNS 148

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  437 KRELERQ----------RQLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIR---CRLS 503
Cdd:pfam01576  149 KLSKERKlleeriseftSNLAEEEEKAKSLSKLKNKHEAMISDLEERLKKEEKGRQELEKAKRKLEGESTDLQeqiAELQ 228

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  504 TQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQ-VQQNSLHRDSLLTIKRAL-EAKELARQQL 581
Cdd:pfam01576  229 AQIAELRAQLAKKEEELQAALARLEEETAQKNNALKKIRELEAQISELQEdLESERAARNKAEKQRRDLgEELEALKTEL 308

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  582 RDQLDE--VEKETRSKLQ------------EIDIFNNQLKELREIHNRQQLQKQKNLE-AERLKQKEQERKTELEKQ-KE 645
Cdd:pfam01576  309 EDTLDTtaAQQELRSKREqevtelkkaleeETRSHEAQLQEMRQKHTQALEELTEQLEqAKRNKANLEKAKQALESEnAE 388

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  646 AQrriqdRDKQRLDRVQQEEEpqwqKKNQEDDKQKREEIIKKKESEdKGKQEIQEKPSKL 705
Cdd:pfam01576  389 LQ-----AELRTLQQAKQDSE----HKRKKLEGQLQELQARLSESE-RQRAELAEKLSKL 438

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 43.60 E-value: 1.31e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  481 LEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQmlgklipEKQLLNDQLKQVQQNSLH 560
Cdd:COG4717     48 LERLEKEADELFKPQGRKPELNLKELKELEEELKEAEEKEEEYAELQEELEELEE-------ELEELEAELEELREELEK 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  561 RDSLLTIKRALEAKELARQQLR------DQLDEVEKETRSKLQEIDIFNNQLKELREIhnRQQLQKQKNLEAERLKQKEQ 634
Cdd:COG4717    121 LEKLLQLLPLYQELEALEAELAelperlEELEERLEELRELEEELEELEAELAELQEE--LEELLEQLSLATEEELQDLA 198

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  635 ERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKKNQEDDKQKREE 683
Cdd:COG4717    199 EELEELQQRLAELEEELEEAQEELEELEEELEQLENELEAAALEERLKE 247

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 38.85 E-value: 1.33e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVT------KKDGDWWTGTLGDKT--GVFPSNYVR 1051
Cdd:cd11790      7 ATHDYTAEDTDELTFEKGDVILVIpfddpeEQDEGWLMGVKESTGcrGVFPENFTE 62

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212874 Cd Length: 57 Bit Score: 38.35 E-value: 1.33e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-----WWFGEVQGQKGWFPKSYV 961
Cdd:cd11941      1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDKkgspeWSLVEVNGQRGYVPSSYL 55

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 38.33 E-value: 1.37e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGE--VQGQKGWFPKSY 960
Cdd:cd11845      4 ALYDYEARTDDDLSFKKGDRLQILDDsDGDWWLARhlSTGKEGYIPSNY 52

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212856 [Multi-domain] Cd Length: 57 Bit Score: 38.36 E-value: 1.42e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1075 QVIASY--TATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRQiGWFPANYVKLL 1129
Cdd:cd11923      2 EAVAKYnfNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPGTNRQ-GIFPVSYVEVI 57

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 38.40 E-value: 1.47e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQ---KGWFPKSYV 961
Cdd:cd11966      1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKeWWIGHIDGEptrRGAFPVSFV 54

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 38.85 E-value: 1.52e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYVRLK 1053
Cdd:cd11973     22 ALWDHVTMDDQELGFKAGDVIeVMDATNKEWWWGRVLDSEGWFPASFVRLR 72

hypothetical protein; Provisional

Pssm-ID: 237178 [Multi-domain] Cd Length: 508 Bit Score: 43.16 E-value: 1.53e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  379 QERLAQLERAEQERKERERQEQERKRQLELEKQLEKqrelerqreeerrkeierreaakrELERQRQLEWERNRRQELLN 458
Cdd:PRK12705    26 KKRQRLAKEAERILQEAQKEAEEKLEAALLEAKELL------------------------LRERNQQRQEARREREELQR 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  459 QRNReqedivvLKAKKKTLEFELEALNDKKNQLEGKLQdircRLSTQRQEIESTNKSREL---RIAEITHLQQQLQESQQ 535
Cdd:PRK12705    82 EEER-------LVQKEEQLDARAEKLDNLENQLEEREK----ALSARELELEELEKQLDNelyRVAGLTPEQARKLLLKL 150

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 2024344592  536 MLGKLIPEKQLLNDQLKQVQQNSLHRDSLLTIKRALE 572
Cdd:PRK12705   151 LDAELEEEKAQRVKKIEEEADLEAERKAQNILAQAMQ 187

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 38.42 E-value: 1.55e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVkrewVDESqtgEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11996      5 AMYDYTANNEDELSFSKGQLINV----LNKD---DPDWWQGEINGVTGLFPSNYVK 53

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 38.54 E-value: 1.58e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMI-LVTKKDGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11975      9 AVWDHVTMANRELAFKAGDVIkVLDASNKDWWWGQIDDEEGWFPASFVRL 58

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 43.59 E-value: 1.60e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSNPYCEVTM-GSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDDF 1667
Cdd:COG5038   1040 GYLTIMLRSGENLPSSDENGYSDPFVKLFLnEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDL 1119

                           90       100
                   ....*....|....*....|....
gi 2024344592 1668 LGRTEIRVADIK--KDQGSKGPVT 1689
Cdd:COG5038   1120 LGTAEIDLSKLEpgGTTNSNIPLD 1143

YscO-like protein; This family of proteins is similar to the type III secretion protein YscO. The family includes Chlamydia trachomatis CT670 which is found in a type III secretion gene cluster. CT670 interacts with CT671, a putative YscP homolog and CT670 and CT671 may form a chaperone-effector pair.

Pssm-ID: 435583 [Multi-domain] Cd Length: 160 Bit Score: 40.97 E-value: 1.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  568 KRALEAKELARQQLRDQLDEVEKETRSKLQEidiFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQ 647
Cdd:pfam16789   27 KRALEKEKEKLAELEAERDKVRKHKKAKMQQ---LRDEMDRGTTSDKILQMKRYIKVVKERLKQEEKKVQDQKEQVRTAA 103

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  648 RRIQDRdKQRLDRVQQEEEpQWQKKNQEDDKQkreeiiKKKESEDKGKQEIQEKPSKLFQPHQ 710
Cdd:pfam16789  104 RNLEIA-REELKKKRQEVE-KLEKHKKEWVKE------MKKEEEDQEEREQDEIGSALHLANQ 158

C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212693 [Multi-domain] Cd Length: 57 Bit Score: 38.24 E-value: 1.61e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1157 YDYTAqnddeLAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd11759     15 YDKTA-----LALEVGDLVKVTKINVSGQWEGELNGKVGHFPFTHVEL 57

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 43.37 E-value: 1.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  350 EDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERkrqleLEKQLEKQRELERQREEERRKE 429
Cdd:COG4913    297 LEELRAELARLEAELERLEARLDALREELDELEAQIRGNGGDRLEQLEREIER-----LERELEERERRRARLEALLAAL 371

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  430 IERREAAKRELERQRQ-----LEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLST 504
Cdd:COG4913    372 GLPLPASAEEFAALRAeaaalLEALEEELEALEEALAEAEAALRDLRRELRELEAEIASLERRKSNIPARLLALRDALAE 451


                   .
gi 2024344592  505 Q 505
Cdd:COG4913    452 A 452

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 38.19 E-value: 1.63e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPS 1047
Cdd:cd11832      2 FIAVKSYSPQEEGEISLHKGDRVKVLSiGEGGFWEGSVRGRTGWFPS 48

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 38.14 E-value: 1.65e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGGE--LKGKTGWFPANY 797
Cdd:cd11783      2 YVALYPYKPQKPDELELRKGEMYTVTEKCQD-------GWFKGTslRTGQSGVFPGNY 52

CDK-activating kinase assembly factor MAT1; MAT1 is an assembly/targeting factor for cyclin-dependent kinase-activating kinase (CAK), which interacts with the transcription factor TFIIH. The domain found to the N-terminal side of this domain is a C3HC4 RING finger.

Pssm-ID: 461894 [Multi-domain] Cd Length: 202 Bit Score: 41.46 E-value: 1.65e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  583 DQLDEVEKETRSKLQEIDIFNNQLK-ELREIHNRQQLQKQKnleaERLKQKEQERKT--ELEKQKEAQRRIQDRdkqrld 659
Cdd:pfam06391   45 DYLEEVEDIVFNLTNGIDVEETEKKiEQYEKENKDLILKNK----MKLSQEEEELEEllELEKREKEERRKEEK------ 114

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  660 rvQQEEEpqwQKKNQEDDKQK-----------REEIIKKKESEDKgKQEIQEKPSKLFQPHQEPVKPAVQAPWSNAGKAP 728
Cdd:pfam06391  115 --QEEEE---EKEKKEKAKQElidelmtsnkdAEEIIAQHKKTAK-KRKSERRRKLEELNRVLEQKPTQFSTGIKFGQLP 188

                          170       180
                   ....*....|....*....|.
gi 2024344592  729 LTISAQEDvkivyyraLYPFE 749
Cdd:pfam06391  189 VPKIEEGP--------LYPFT 201

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 37.93 E-value: 1.65e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVK 962
Cdd:cd11815      1 HAVVLHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYrGKCKNTTGIFPANHVK 52

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 38.31 E-value: 1.65e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKK---DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11988      4 YRALYPFEARNHDEMSFNAGDIIQVDEKtvgEPGWLYGSFQGNFGWFPCNYV 55

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212890 Cd Length: 52 Bit Score: 37.97 E-value: 1.67e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1152 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11957      1 EVKALCHHIATEPGQLSFNKGDILQVLSRADGDWLRCSLGPDSGLVPIAYV 51

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212731 Cd Length: 50 Bit Score: 37.79 E-value: 1.71e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVkrewvdeSQTGEPGWLGGELKGKTGWFP 794
Cdd:cd11797      1 YGVALYRFQALEPNELDFEVGDRIRI-------IATLEDGWLEGELKGRRGIFP 47

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 43.37 E-value: 1.71e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  566 TIKRALEAKELARQQlRDQLDEVEkETRSKLQEIDIFNNQLKELREIHNRQQLQKQKNL----------EAERLKQKEQE 635
Cdd:COG4913    236 DLERAHEALEDAREQ-IELLEPIR-ELAERYAAARERLAELEYLRAALRLWFAQRRLELleaeleelraELARLEAELER 313

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  636 RKTELEKQKE----AQRRIQDRDKQRLDRVQQEEEpqwQKKNQEDDKQKREE 683
Cdd:COG4913    314 LEARLDALREeldeLEAQIRGNGGDRLEQLEREIE---RLERELEERERRRA 362

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 37.99 E-value: 1.77e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKD------GdWWTGTLGD-KTGVFPSNYVRL 1052
Cdd:cd11864      3 RAEYDFVAESEDELSFRAGDKLRLAPKElqprvrG-WLLATVDGqKIGLVPANYVKI 58

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 37.89 E-value: 1.83e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVKL 1128
Cdd:cd11961      2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSR---GLFPSNYVEL 53

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212977 Cd Length: 53 Bit Score: 37.92 E-value: 1.83e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1002 YVAMYTYESSEQGDLTFQQGDMILVTKKDGD---WWTGTLGDKTGVFPSNYV 1050
Cdd:cd12044      2 YQGLWDCFGDNPDELSFQRGDLIYILSKEYNmygWWVGELNGIVGIVPKDYL 53

Crescentin protein; This entry represents a bacterial equivalent to Intermediate Filament proteins, named crescentin, whose cytoskeletal function is required for the vibrioid and helical shapes of Caulobacter crescentus. Without crescentin, the cells adopt a straight-rod morphology. Crescentin has characteriztic features of IF proteins including the ability to assemble into filaments in vitro without energy or cofactor requirements. In vivo, crescentin forms a helical structure that colocalizes with the inner cell curvatures beneath the cytoplasmic membrane.

Pssm-ID: 437057 [Multi-domain] Cd Length: 401 Bit Score: 42.75 E-value: 1.90e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLEQQRKEQERLAQLERAEQERkERERQEQeRKRQLELEKQLEkqrelerqreeerrkeierreaakrELER 442
Cdd:pfam19220   73 GLTRRLSAAEGELEELVARLAKLEAALREA-EAAKEEL-RIELRDKTAQAE-------------------------ALER 125

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  443 QRQLEWERNRRQELLNQRNREQedivvLKAKKKTL---EFELEALNDKKNQLEGKLQDIRCRLSTQRQEIES-TNKSREL 518
Cdd:pfam19220  126 QLAAETEQNRALEEENKALREE-----AQAAEKALqraEGELATARERLALLEQENRRLQALSEEQAAELAElTRRLAEL 200

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  519 RIAEITHLQQQLQEsqqmlgklipEKQLLNDQlkqvqqnSLHRDSLLTIKRALEAKELARQQLRDQLDEVEketrSKLQE 598
Cdd:pfam19220  201 ETQLDATRARLRAL----------EGQLAAEQ-------AERERAEAQLEEAVEAHRAERASLRMKLEALT----ARAAA 259

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  599 IDIFNNQLKE-LREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQR-RIQDRDKQRLD 659
Cdd:pfam19220  260 TEQLLAEARNqLRDRDEAIRAAERRLKEASIERDTLERRLAGLEADLERRTqQFQEMQRARAE 322

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 213001 Cd Length: 55 Bit Score: 37.93 E-value: 1.92e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVKL 1204
Cdd:cd12068      2 VVALRSYITDDKSLLSFHRGDLIKLLPMAglEPGWQFGSTGGRSGLFPADIVQP 55

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176004 [Multi-domain] Cd Length: 108 Bit Score: 39.54 E-value: 1.93e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1589 GRLMVNIVEGIELKPCRSHGKSN----PYCEVTMGSQCHITKTMQDTLNPKWNSNCQFFIKDLEQDV-LCITVFERDQFS 1663
Cdd:cd04039      1 GVVFMEIKSITDLPPLKNMTRTGfdmdPFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVYPHEKNFdIQFKVLDKDKFS 80

                           90       100
                   ....*....|....*....|....*..
gi 2024344592 1664 PDDFLGRTEIRVADIKKDQGSKGPVTK 1690
Cdd:cd04039     81 FNDYVATGSLSVQELLNAAPQPDPETG 107

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 38.33 E-value: 1.95e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMV-KREwvdesQTGEPGWLGGELKGKTGWFPANYAEKIPES 804
Cdd:cd12003      4 KALYDNAAESPEELSFRRGDVLMVlKRE-----HGSLPGWWLCSLHGQQGIAPANRLRLLPTA 61

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 38.39 E-value: 1.95e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  223 KYRQLFNSHDKTMSGHLT----GPQARTILMQSSLPQAQLATIWNLSDIDQDGKLTAEEFILAM 282
Cdd:pfam13499    3 KLKEAFKLLDSDGDGYLDveelKKLLRKLEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66

rRNA biogenesis protein RRP36; RRP36 is involved in the early processing steps of the pre-rRNA.

Pssm-ID: 461829 [Multi-domain] Cd Length: 158 Bit Score: 40.62 E-value: 1.96e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  585 LDEVEKETRSKLQEidifnnQLKELREIHNRQQLQKQKNLEAERLKQKEQERKtelEKQKEAQRRiqdrdKQRLDRVQQE 664
Cdd:pfam06102   54 LDEYRKKEIEELKK------QLKKTKDPEEKEELKRTLQSMESRLKAKKRKDR---EREVLKEHK-----KEEKEKVKQG 119

                           90       100       110
                   ....*....|....*....|....*....|..
gi 2024344592  665 EEPQWQKKNqeddKQKREEIIKKKESEDKGKQ 696
Cdd:pfam06102  120 KKPFYLKKS----EKKKLLLKEKFEELKKSGK 147

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 38.01 E-value: 1.98e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGG--ELKGKTGWFPANY 797
Cdd:cd11918      4 YKAVYQYRPQNEDELELREGDRVDVMQQCDD-------GWFVGvsRRTQKFGTFPGNY 54

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 38.00 E-value: 2.02e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVmvkREWVDESQTGEPGWlGGELKGKTGWFPANYAE 799
Cdd:cd11894      1 FVKALYDYEGQTDDELSFPEGAII---RILNKENQDDDGFW-EGEFNGRIGVFPSVLVE 55

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 37.72 E-value: 2.07e-03

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2024344592 1015 DLTFQQGDMILVTK-KDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11796     15 ELDLREGDVVTITGiLDKGWFRGELNGRRGIFPEGFV 51

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 40.16 E-value: 2.09e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  211 VAEWAVPQSSRLKYRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLATIWNLSDIDQDGKLTAEEFILAMH 283
Cdd:COG5126     58 GMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEFVAAVR 130

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 38.05 E-value: 2.10e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  743 RALYPFESRSHDEITiqpgdivMVKREWVDESQTGEPGWLGGELKGKTG-WFPANYAEKI 801
Cdd:cd11970      7 KALFDYKAQREDELT-------FTKNAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEEI 59

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 37.82 E-value: 2.11e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGGELKGKTGWFPANYAEK 800
Cdd:cd12016      3 YITTQAYKAENEDEIGFETGVVVEVIQKNLD-------GWWKIRYQGKEGWAPATYLKK 54

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 37.73 E-value: 2.12e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKrewvdESQtgEPGWLGGELKGKTGWFPANY 797
Cdd:cd11837      2 ATALYPWRAKKENHLSFAKGDIITVL-----EQQ--EMWWFGELEGGEEGWFPKSY 50

Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. Vertebrates contain two SLAPs, named SLAP (or SLA1) and SLAP2 (or SLA2). SLAP has been shown to interact with the EphA receptor, EpoR, Lck, PDGFR, Syk, CD79a, among others, while SLAP2 interacts with CSF1R. Both SLAPs interact with c-Cbl, LAT, CD247, and Zap70. SLAP modulates TCR surface expression levels as well as surface and total BCR levels. As an adaptor to c-Cbl, SLAP increases the ubiquitination, intracellular retention, and targeted degradation of the BCR complex components. SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212782 Cd Length: 55 Bit Score: 37.94 E-value: 2.18e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTgTLGDKTG---VFPSNYV 1050
Cdd:cd11848      3 VALGDYPSGGPAELSLRLGEPLTIVSDEGDWWK-VLSEVTGresYIPSVHV 52

Laminin Domain I; coiled-coil structure. It has been suggested that the domains I and II from laminin A, B1 and B2 may come together to form a triple helical coiled-coil structure.

Pssm-ID: 310534 [Multi-domain] Cd Length: 258 Bit Score: 42.01 E-value: 2.18e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  445 QLEWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRcrlstqrQEIESTNKSRELRIAEIT 524
Cdd:pfam06008   20 NLENLTKQLQEYLSPENAHKIQIEILEKELSSLAQETEELQKKATQTLAKAQQVN-------AESERTLGHAKELAEAIK 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  525 HLQQQLQESQQMLGKL------IPEKQLLNDQ------LKQVQQNSLHRDSLLTIKRALEAKEL-AR-----QQLRDQLD 586
Cdd:pfam06008   93 NLIDNIKEINEKVATLgendfaLPSSDLSRMLaeaqrmLGEIRSRDFGTQLQNAEAELKAAQDLlSRiqtwfQSPQEENK 172

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  587 EVEKETRSKLQEidiFNNQLKELREIHNRQQLQKQknlEAERLKQKEQERKTELEKQKEAQRRIQ 651
Cdd:pfam06008  173 ALANALRDSLAE---YEAKLSDLRELLREAAAKTR---DANRLNLANQANLREFQRKKEEVSEQK 231

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212871 Cd Length: 55 Bit Score: 37.90 E-value: 2.21e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGE-LQGKKRqiGWFPANYVK 1127
Cdd:cd11938      3 EIIKAYTAKQPDELSLQQADVVLVLQTESDGWYYGErLRDGER--GWFPSSCAK 54

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 38.08 E-value: 2.22e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVL------EQQDMWWFG--EVQGQKGWFPKSYVKLI 964
Cdd:cd11790      5 VRATHDYTAEDTDELTFEKGDVILVIpfddpeEQDEGWLMGvkESTGCRGVFPENFTERI 64

Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called Dock180, and Dock5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock1 binds to DHR-2 in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212984 [Multi-domain] Cd Length: 56 Bit Score: 37.88 E-value: 2.26e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGDWWTG-TLGDKT--GVFPSNYVRLK 1053
Cdd:cd12051      3 VAIYNYDARGPDELSLQIGDTVHILETYEGWYRGyTLRKKSkkGIFPASYIHLK 56

putative monovalent cation/H+ antiporter subunit G; Reviewed

Pssm-ID: 183610 Cd Length: 197 Bit Score: 41.21 E-value: 2.28e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  580 QLRDQLDEVEKETRSKLQEIDIFNNQLKELREihNRQQLQKQknLEAERLKQKEQERKTELEKQKEaqrriqdRDKQRLD 659
Cdd:PRK12585   102 RIRDQLRSVKKDDIKKKKSLIIRQEQIEKARQ--EREELEER--MEWERREEKIDEREDQEEQERE-------REEQTIE 170

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2024344592  660 RvqqeeepqwqkknQEDDKQkrEEIIKKKESEDKGKQEIQEK 701
Cdd:PRK12585   171 E-------------QSDDSE--HEIIEQDESETESDDDKTEK 197

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 38.06 E-value: 2.29e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  910 GLQAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQ--GQKGWFPKSYVKLI 964
Cdd:cd11933      1 GKSFRAMYDYRAADDDEVSFKDGDTIVNVQTIDEgWMYGTVQrtGKTGMLPANYVEAI 58

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 40.05 E-value: 2.29e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1591 LMVNIVEGIELKPCRShGKSNPYCEVTMGSQCHI----TKTMQDTLNPKWNSNCQF---------------FIKDLEQDV 1651
Cdd:cd08675      1 LSVRVLECRDLALKSN-GTCDPFARVTLNYSSKTdtkrTKVKKKTNNPRFDEAFYFeltigfsyekksfkvEEEDLEKSE 79

                           90       100
                   ....*....|....*....|....
gi 2024344592 1652 LCITVFERDQFSPDDFLGrtEIRV 1675
Cdd:cd08675     80 LRVELWHASMVSGDDFLG--EVRI 101

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 37.68 E-value: 2.34e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRQIGWFPANYVKLL 1129
Cdd:cd11965      3 KTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHIL 57

N-terminal (or first) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. The N-terminal SH3 domain increases the affinity of p67phox for the oxidase complex. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212804 Cd Length: 54 Bit Score: 37.57 E-value: 2.36e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592 1156 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1203
Cdd:cd11871      5 LYEFVPETKEELQVLPGNIVFVLKKGTDNWATVVFNGKKGLVPCNFLE 52

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 37.72 E-value: 2.38e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELKGKTGWFPANY 797
Cdd:cd11796      3 RVLQDLSAQLDEELDLREGDVVTITGI-------LDKGWFRGELNGRRGIFPEGF 50

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 37.91 E-value: 2.40e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  223 KYRQLFNSHDKTMSGHLTGPQARTIL--MQSSLPQAQLATIWNLSDIDQDGKLTAEEFILAMH 283
Cdd:cd00051      1 ELREAFRLFDKDGDGTISADELKAALksLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

Second Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212864 Cd Length: 55 Bit Score: 37.59 E-value: 2.43e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1155 GMYDYTAQNDDE----LAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd11931      4 ALYDFEIKDKDQdkdcLTFTKDEILTVIRRVDENWAEGMLGDKIGIFPILYV 55

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 37.63 E-value: 2.46e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2024344592 1081 TATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRQIGWFPANYV 1126
Cdd:cd11966      9 VADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPTRRGAFPVSFV 54

hypothetical protein; Provisional

Pssm-ID: 237178 [Multi-domain] Cd Length: 508 Bit Score: 42.39 E-value: 2.48e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  354 RENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKER---ERQEQERKRQLELEKQLEKQRELERQREEERRKEI 430
Cdd:PRK12705    43 QKEAEEKLEAALLEAKELLLRERNQQRQEARREREELQREEErlvQKEEQLDARAEKLDNLENQLEEREKALSARELELE 122

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  431 ERREAAKRELERQRQLEWERnRRQELLNQRNREQEDIVVLKAKKKTLEFELEAlnDKKNQ 490
Cdd:PRK12705   123 ELEKQLDNELYRVAGLTPEQ-ARKLLLKLLDAELEEEKAQRVKKIEEEADLEA--ERKAQ 179

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 42.82 E-value: 2.54e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1586 TGIGRLMVNIVEGIELKPCRSH--GKSNPYCEVTMGSQCH-ITKTMQDTLNPKWNSNCQFFIKDLEqDVLCITVFERDQF 1662
Cdd:COG5038    433 TAIGVVEVKIKSAEGLKKSDSTinGTVDPYITVTFSDRVIgKTRVKKNTLNPVWNETFYILLNSFT-DPLNLSLYDFNSF 511

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1663 SPDDFLGRTEIRVADIKKDQGSKGPVTKcLLLHEVPTGEIVvrLDLQLF 1711
Cdd:COG5038    512 KSDKVVGSTQLDLALLHQNPVKKNELYE-FLRNTKNVGRLT--YDLRFF 557

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 37.43 E-value: 2.61e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2024344592 1158 DYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1202
Cdd:cd12017      7 EFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEGWAPSSYI 51

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).

Pssm-ID: 129694 [Multi-domain] Cd Length: 1311 Bit Score: 42.73 E-value: 2.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLEQQR--KEQERLAQLeRAEQERKERERQEQERKRQLELEKQLE-KQRELERQREEErrkeierreaAKRE 439
Cdd:TIGR00606  170 ALKQKFDEIFSATRyiKALETLRQV-RQTQGQKVQEHQMELKYLKQYKEKACEiRDQITSKEAQLE----------SSRE 238

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  440 LERQRQLEWE--RNRRQELLNQRNREQEDIVVLKAKKKTlefELEALNDKKnQLEGKLQDIRCRLSTQRQEIE----STN 513
Cdd:TIGR00606  239 IVKSYENELDplKNRLKEIEHNLSKIMKLDNEIKALKSR---KKQMEKDNS-ELELKMEKVFQGTDEQLNDLYhnhqRTV 314

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  514 KSRELRIAEIthlqqqlqesQQMLGKLIPEKQLLNdQLKQVQQNSLHRDSLLT--IKRALEAKELARQ--QLRDQLDEVE 589
Cdd:TIGR00606  315 REKERELVDC----------QRELEKLNKERRLLN-QEKTELLVEQGRLQLQAdrHQEHIRARDSLIQslATRLELDGFE 383

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  590 KETRSKLQeIDIFNNQLKELREIHNRQQLQKQKNL-EAERLKQKEqerKTELEKQKEAQRRIQDRDKQRLDRVQQE-EEP 667
Cdd:TIGR00606  384 RGPFSERQ-IKNFHTLVIERQEDEAKTAAQLCADLqSKERLKQEQ---ADEIRDEKKGLGRTIELKKEILEKKQEElKFV 459

                          330       340
                   ....*....|....*....|....*..
gi 2024344592  668 QWQKKNQE---DDKQKREEIIKKKESE 691
Cdd:TIGR00606  460 IKELQQLEgssDRILELDQELRKAERE 486

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 37.61 E-value: 2.70e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1073 IAQVIASYTATGPEQLTLAPGQLILI--RKKNPG--GWWEGELQGKKrqIGWFPANYVKL 1128
Cdd:cd11864      1 VARAEYDFVAESEDELSFRAGDKLRLapKELQPRvrGWLLATVDGQK--IGLVPANYVKI 58

Src Homology 3 domain of Melanoma Inhibitory Activity protein and similar proteins; MIA is a single domain protein that adopts a SH3 domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands. MIA is a member of the recently identified family that also includes MIA-like (MIAL), MIA2, and MIA3 (also called TANGO); the biological functions of this family are not yet fully understood.

Pssm-ID: 212694 Cd Length: 76 Bit Score: 38.23 E-value: 2.73e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGW---WEGELQGKKRQIGWFPANYVKLL 1129
Cdd:cd11760     14 ARALEDYHGPDCRFLNFKKGDTIYVYSKLAGERqdlWAGSVGGDAGLFGYFPKNLVQEL 72

Mitotic checkpoint protein; This family consists of several eukaryotic mitotic checkpoint (Mitotic arrest deficient or MAD) proteins. The mitotic spindle checkpoint monitors proper attachment of the bipolar spindle to the kinetochores of aligned sister chromatids and causes a cell cycle arrest in prometaphase when failures occur. Multiple components of the mitotic spindle checkpoint have been identified in yeast and higher eukaryotes. In S.cerevisiae, the existence of a Mad1-dependent complex containing Mad2, Mad3, Bub3 and Cdc20 has been demonstrated.

Pssm-ID: 461677 [Multi-domain] Cd Length: 660 Bit Score: 42.42 E-value: 2.76e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  402 RKRQLELEKQLEKqrelerqreeerrkeierreaAKRELERQrQLEWERNRrqellnqrnreqediVVLKAKKKTLEFEL 481
Cdd:pfam05557    1 RAELIESKARLSQ---------------------LQNEKKQM-ELEHKRAR---------------IELEKKASALKRQL 43

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  482 EALNDKKNQLEGKLQDIRcrlstqRQEIESTNKSRElriaeithlqqqlqesqqmlgklipekqllndqlkQVQQNSLHR 561
Cdd:pfam05557   44 DRESDRNQELQKRIRLLE------KREAEAEEALRE-----------------------------------QAELNRLKK 82

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  562 DSLLTIKRALEAKELARQQLRDQLDEVEKETRSKLQEIDIFNNQLK----ELREIHNRQQLQKQKNLEAERLKQ----KE 633
Cdd:pfam05557   83 KYLEALNKKLNEKESQLADAREVISCLKNELSELRRQIQRAELELQstnsELEELQERLDLLKAKASEAEQLRQnlekQQ 162

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  634 QERKTELEKQKEAQRRI--QDRDKQRLDRVQQEEE--PQWQKknqeDDKQKREEIIKKKE-SEDKG--KQEIQEKPSKLF 706
Cdd:pfam05557  163 SSLAEAEQRIKELEFEIqsQEQDSEIVKNSKSELAriPELEK----ELERLREHNKHLNEnIENKLllKEEVEDLKRKLE 238


                   .
gi 2024344592  707 Q 707
Cdd:pfam05557  239 R 239

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 37.73 E-value: 2.79e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKrEWVDESqtgepGWLGG-ELKGKTGWFPANYAEK 800
Cdd:cd11761      6 VLYSYEAQRPDELTITEGEELEVI-EDGDGD-----GWVKArNKSGEVGYVPENYLQF 57

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 37.51 E-value: 2.81e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVI-TVLEQQDMWWFGEVQGQ-KGWFPKSYVK 962
Cdd:cd11969      3 KALYDYRAKRSDELSFCKGALIhNVSKETGGWWKGDYGGKvQHYFPSNYVE 53

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 37.54 E-value: 2.84e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQGkkrQIGWFPANYVK 1127
Cdd:cd11988     10 FEARNHDEMSFNAGDIIQVDEKTVGepGWLYGSFQG---NFGWFPCNYVE 56

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212769 [Multi-domain] Cd Length: 54 Bit Score: 37.43 E-value: 2.90e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1008 YESSEQGDLTFQQGDMILV----TKKDGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11835      8 YTAQAPDELSLEVGDIVSVidmpPPEESTWWRGKKGFQVGFFPSECV 54

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 37.62 E-value: 2.91e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVKL 1128
Cdd:cd11927      3 AKALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNGIH---GFFPTNFVQI 54

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

Pssm-ID: 405931 [Multi-domain] Cd Length: 151 Bit Score: 40.03 E-value: 2.92e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  586 DEVEKETRSKLQEidifnnqLKELREIHNRQQLQKQKNLEAERLKQKEQE---RKTELE--------KQKEAQRRIQDRD 654
Cdd:pfam15346   33 DEIEAEVERRVEE-------ARKIMEKQVLEELEREREAELEEERRKEEEerkKREELErileennrKIEEAQRKEAEER 105

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 2024344592  655 KQRLDRVQQEEEPQWQKKNQEDDKQKREE--IIKKKESEDK 693
Cdd:pfam15346  106 LAMLEEQRRMKEERQRREKEEEEREKREQqkILNKKNSRPK 146

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 37.26 E-value: 3.00e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMV--KrewvDESqtgepGWLGGEL-----KGKTGWFPANY 797
Cdd:cd11883      3 VALYDFTPKSKNQLSFKAGDIIYVlnK----DPS-----GWWDGVIisssgKVKRGWFPSNY 55

Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; This subfamily is composed of Rho GTPase-activating proteins including mammalian ARHGAP9, and vertebrate ARHGAPs 12 and 27. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP9 functions as a GAP for Rac and Cdc42, but not for RhoA. It negatively regulates cell migration and adhesion. It also acts as a docking protein for the MAP kinases Erk2 and p38alpha, and may facilitate cross-talk between the Rho GTPase and MAPK pathways to control actin remodeling. ARHGAP27, also called CAMGAP1, shows GAP activity towards Rac1 and Cdc42. It binds the adaptor protein CIN85 and may play a role in clathrin-mediated endocytosis. ARHGAP12 has been shown to display GAP activity towards Rac1. It plays a role in regulating HFG-driven cell growth and invasiveness. ARHGAPs in this subfamily contain SH3, WW, Pleckstin homology (PH), and RhoGAP domains. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212821 [Multi-domain] Cd Length: 54 Bit Score: 37.35 E-value: 3.01e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2024344592 1157 YDYTAQNDDELAFNKGQIINVLNKEDPDWW--KGEVNGQVGLFPSNY 1201
Cdd:cd11888      8 FEYTGKDGRKVSIKEGERFLLLKKSNDDWWqvRRPGDSKPFYVPAQY 54

C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1)) is a newly identified HECT-type E3 ubiquitin protein ligase highly expressed in favorable neuroblastomas. In vertebrates it is found primarily in neuronal tissues, including the spinal cord. NEDL1 is thought to normally function in the quality control of cellular proteins by eliminating misfolded proteins. This is thought to be accomplished via a mechanism analogous to that of ER-associated degradation by forming tight complexes and aggregating misfolded proteins that have escaped ubiquitin-mediated degradation. NEDL1, is composed of a C2 domain, two WW domains, and a ubiquitin ligase Hect domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176073 [Multi-domain] Cd Length: 137 Bit Score: 39.69 E-value: 3.04e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1619 GSQCHiTKTMQDTLNPKWNSNcQFFIKDLEQDVLCITVfeRDQFSPD-----DFLGRTEIRVADI 1678
Cdd:cd08691     44 GQECR-TSIVENTINPVWHRE-QFVFVGLPTDVLEIEV--KDKFAKSrpiirRFLGKLSIPVQRL 104

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 37.61 E-value: 3.05e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKGKTGWFPANYAE 799
Cdd:cd11929      4 KALCNYRGHNPGDLKFNKGDVILLRRQ-LDEN------WYLGEINGVSGIFPASSVE 53

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 37.19 E-value: 3.15e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQ-DM--WWFGEVQGQKGWFPKSYV 961
Cdd:cd12045      3 QGLWDCTGDQPDELSFKRGDTIYILSKEyNRfgWWVGEMKGTIGLVPKAYI 53

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 37.56 E-value: 3.25e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKKDGD----WWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd12003      5 ALYDNAAESPEELSFRRGDVLMVLKREHGslpgWWLCSLHGQQGIAPANRLRL 57

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 37.30 E-value: 3.29e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVkreWVDESQTGepgWLGGEL--KGKTGWFPANYAEK 800
Cdd:cd11779      4 KALYPHAAGGETQLSFEEGDVITL---LGPEPRDG---WHYGENerSGRRGWFPIAYTEP 57

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176046 [Multi-domain] Cd Length: 121 Bit Score: 39.34 E-value: 3.30e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1591 LMVNIVEGIELKPcRSHGKS--NPYCEVTMgSQCHI--TKTMQDTLNPKWNSNCQFFI-KDLEQdvLCITVFERDQFSPD 1665
Cdd:cd08401      2 LKIKIGEAKNLPP-RSGPNKmrDCYCTVNL-DQEEVfrTKTVEKSLCPFFGEDFYFEIpRTFRH--LSFYIYDRDVLRRD 77

                           90
                   ....*....|....*....
gi 2024344592 1666 DFLGRTEIRVADIKKDQGS 1684
Cdd:cd08401     78 SVIGKVAIKKEDLHKYYGK 96

Transcriptional activator LAG-3; The C.elegans Notch pathway, involved in the control of growth, differentiation and patterning in animal development, relies on either of the receptors GLP-1 or LIN-12. Both these receptors promote signalling by the recruitment of LAG-3 to target promoters, where it then acts as a transcriptional activator. LAG-3 works as a ternary complex together with the DNA binding protein, LAG-1. Its N-terminal region adopts an elongated kinked helix that is required for complex assembly.

Pssm-ID: 151935 [Multi-domain] Cd Length: 476 Bit Score: 41.87 E-value: 3.31e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  605 QLKELREIHNRQQLQKQKNLEAERLkqkEQERKTELEKQKEAQRRIQDRDKQRLDRvQQEEEPQWQKKNQEDD-----KQ 679
Cdd:pfam11498  321 HIAQLAQQQNKMRLLQQQEMEMQRI---EQQRQQQIMHQHQQQQQQEHQQQQMLLQ-QQQQMHQLQQHHQMNGggqfaTQ 396

                           90       100       110
                   ....*....|....*....|....*....|..
gi 2024344592  680 KREEIIKKKESEDKGKQEIQEKPSKLFQPHQE 711
Cdd:pfam11498  397 AHQHAAYLQQMQHMRLQEQIQHQQQQAQHHQQ 428

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 37.45 E-value: 3.41e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1075 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQgKKRQIGWFPANYVK 1127
Cdd:cd11785      3 RVIVPYPPQSEAELELKEGDIVFVHKKREDGWFKGTLQ-RTGKTGLFPGSFVE 54

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 37.29 E-value: 3.46e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWF-GEVQGQKGWFPKSYVK 962
Cdd:cd11849      3 RALYDFKSAEPNTLSFSEGETFLLLERSNAhWWLvTNHSGETGYVPANYVK 53

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 37.09 E-value: 3.60e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 964
Cdd:cd11869      1 RAEALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLeGTVRGATGIFPLSFVKII 54

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 41.93 E-value: 3.62e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  451 NRRQELLNQRNREQEDIVVLKAKKKTLEFEL-------EALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKS-----REL 518
Cdd:TIGR04523   33 TEEKQLEKKLKTIKNELKNKEKELKNLDKNLnkdeekiNNSNNKIKILEQQIKDLNDKLKKNKDKINKLNSDlskinSEI 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  519 RI---------AEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVqqNSLHRDsllTIKRaleakelaRQQLRDQLDEVE 589
Cdd:TIGR04523  113 KNdkeqknkleVELNKLEKQKKENKKNIDKFLTEIKKKEKELEKL--NNKYND---LKKQ--------KEELENELNLLE 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  590 KETRSKLQEIDIFNNQL--KELREIHNRQQLQKQKNLEAERLKQKEQerKTELEKQKEA-QRRIQDRdKQRLDRVQQE-- 664
Cdd:TIGR04523  180 KEKLNIQKNIDKIKNKLlkLELLLSNLKKKIQKNKSLESQISELKKQ--NNQLKDNIEKkQQEINEK-TTEISNTQTQln 256

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 2024344592  665 --EEPQWQKKNQEDDKQKREEIIKKKESE-DKGKQEIQEKPSKL 705
Cdd:TIGR04523  257 qlKDEQNKIKKQLSEKQKELEQNNKKIKElEKQLNQLKSEISDL 300

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 37.32 E-value: 3.66e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1003 VAMYTYESSEQGDLTFQQGDMILVTKKDGD-WWTGT-LGD-KTGVFPSNYVR 1051
Cdd:cd11793      3 QCVHAYTAQQPDELTLEEGDVVNVLRKMPDgWYEGErLRDgERGWFPSSYTE 54

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 37.06 E-value: 3.68e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVKREWVDesqtgepGWLGGE--LKGKTGWFPANY 797
Cdd:cd11784      2 CVALHSYSAHRPEELELQKGEGVRVLGKFQE-------GWLRGLslVTGRVGIFPSNY 52

alpha-xenorhabdolysin family binary toxin subunit B;

Pssm-ID: 411488 [Multi-domain] Cd Length: 223 Bit Score: 40.69 E-value: 3.87e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  470 LKAKKKTLEFELEALNDKKNQLEGKLQDIrcrlsTQRQE-IESTN-----KSRELRIAEIthlqqqlqesqqmlgKLI-- 541
Cdd:NF033927    39 LQEQIAELEAQIAALESKLNELAEDRKVI-----IEAIDlIEKYNiadlfKDLLPTAEEI---------------DSLgl 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  542 --PEKQLLN---DQLKQVqqnslhrdsLLTIKRALEAKEL--ARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHn 614
Cdd:NF033927    99 ppPEKDLVKaaiERLKKL---------LGKISEGLTYIDLveARDKLRDRINALLAESRTLDKDIKALAGKLEELTAIA- 168

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 2024344592  615 rqQLQKQKNL---EAERLKQKEQERKTELEKQKEAQRRIQDRDKQ 656
Cdd:NF033927   169 --AIDEERATwvaEARKVEQAWESFLDQLTELTSDSANLAQLITQ 211

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 36.91 E-value: 3.89e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELKGK---TGWFPANY 797
Cdd:cd11821      3 RALYDCQADNDDELTFSEGEIIVVTGE-------EDDEWWEGHIEGDpsrRGVFPVSF 53

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212708 [Multi-domain] Cd Length: 52 Bit Score: 37.06 E-value: 4.05e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILV-TKKDGDW-WTGTLGDKTGVFPSNYV 1050
Cdd:cd11774      4 ALYDYDKQTEEELSFNEGDTLDVyDDSDSDWiLVGFNGTQFGFVPANYI 52

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 37.24 E-value: 4.06e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMV-KREwvdesqtgEPGWLGGELKGKTGWFPANYAE 799
Cdd:cd11995      5 GMYDYTAQNDDELAFSKGQIINVlNKE--------DPDWWKGELNGQVGLFPSNYVK 53

Periplasmic chaperone for outer membrane proteins, Skp family [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 442073 [Multi-domain] Cd Length: 171 Bit Score: 39.82 E-value: 4.07e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  627 ERLKQKEQERKTELE-KQKEAQRRIQDRDKQRldrvqqeeepqwqKKNQEDDKQKREEIIKKKESE-----DKGKQEIQE 700
Cdd:COG2825     46 KKLEKEFKKRQAELQkLEKELQALQEKLQKEA-------------ATLSEEERQKKERELQKKQQElqrkqQEAQQDLQK 112

                           90
                   ....*....|....*....
gi 2024344592  701 KPSKLFQPHQEPVKPAVQA 719
Cdd:COG2825    113 RQQELLQPILEKIQKAIKE 131

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

Pssm-ID: 461098 [Multi-domain] Cd Length: 140 Bit Score: 39.48 E-value: 4.08e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  627 ERLKQKEQERKTELE-KQKEAQRRIQDRDKQrldrvqqeeepqwqKKNQEDDKQKREEIIKKKESE-----DKGKQEIQE 700
Cdd:pfam03938   22 AQLEKKFKKRQAELEaKQKELQKLYEELQKD--------------GALLEEEREEKEQELQKKEQElqqlqQKAQQELQK 87

                           90
                   ....*....|....*....
gi 2024344592  701 KPSKLFQPHQEPVKPAVQA 719
Cdd:pfam03938   88 KQQELLQPIQDKINKAIKE 106

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 37.06 E-value: 4.09e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2024344592 1087 QLTLAPGQLILIRKKNPGGWWEGELQgkkRQIGWFPANYVK 1127
Cdd:cd11820     16 ELTFKAGEIITVLDDSDPNWWKGSNH---RGEGLFPANFVT 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 37.03 E-value: 4.12e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  741 YYRALYPFESRSHDEITIQPGDIVMVkrewvdeSQTGEPGWLGGELKGKTGWFPA 795
Cdd:cd11832      1 YFIAVKSYSPQEEGEISLHKGDRVKV-------LSIGEGGFWEGSVRGRTGWFPS 48

putative inner membrane protein translocase component YidC; Validated

Pssm-ID: 178945 [Multi-domain] Cd Length: 429 Bit Score: 41.76 E-value: 4.13e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  582 RDQLDEVEKETRSKLQEIDifNNQLKELREIHNRQQLQKQ----KNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQR 657
Cdd:PRK00247   291 RAQYREKQKEKKAFLWTLR--RNRLRMIITPWRAPELHAEnaeiKKTRTAEKNEAKARKKEIAQKRRAAEREINREARQE 368

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  658 LDRVQQEEEPQWQKKnqeddKQKREEIIKKKESEDKGKQEIQekpSKLFQPHQEPVKPA 716
Cdd:PRK00247   369 RAAAMARARARRAAV-----KAKKKGLIDASPNEDTPSENEE---SKGSPPQVEATTTA 419

Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are similar to the coiled-coil transcriptional coactivator protein coexpressed by Mus musculus (CoCoA/CALCOCO1). This protein binds to a highly conserved N-terminal domain of p160 coactivators, such as GRIP1, and thus enhances transcriptional activation by a number of nuclear receptors. CALCOCO1 has a central coiled-coil region with three leucine zipper motifs, which is required for its interaction with GRIP1 and may regulate the autonomous transcriptional activation activity of the C-terminal region.

Pssm-ID: 462303 [Multi-domain] Cd Length: 488 Bit Score: 41.80 E-value: 4.14e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  351 DKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKqlekqRELERQREEERRK-- 428
Cdd:pfam07888   58 EKEKERYKRDREQWERQRRELESRVAELKEELRQSREKHEELEEKYKELSASSEELSEEK-----DALLAQRAAHEARir 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  429 --EIERREAAKRELERQRQLEWERNRRQELLNQRNREQEDivvlkakKKTLEFELEALNDKKNQLEGKLQDIRcrlSTQR 506
Cdd:pfam07888  133 elEEDIKTLTQRVLERETELERMKERAKKAGAQRKEEEAE-------RKQLQAKLQQTEEELRSLSKEFQELR---NSLA 202

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  507 QEIESTNKSRElRIAEITHLQQQLQESQQMLGKLIPEKQLLNDQLKQVQQNS--LHRD--SLLTIK--------RA-LEA 573
Cdd:pfam07888  203 QRDTQVLQLQD-TITTLTQKLTTAHRKEAENEALLEELRSLQERLNASERKVegLGEElsSMAAQRdrtqaelhQArLQA 281

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  574 KEL------ARQQLRDQLDEVEKETRSKLQEIDIFNNQLKELreihNRQQLQKQKNLEAERLKQkeQERKTELEKQKEA- 646
Cdd:pfam07888  282 AQLtlqladASLALREGRARWAQERETLQQSAEADKDRIEKL----SAELQRLEERLQEERMER--EKLEVELGREKDCn 355

                          330       340       350
                   ....*....|....*....|....*....|....
gi 2024344592  647 --QRRIQDRDKQRLD---RVQQEEEPQWQKKNQE 675
Cdd:pfam07888  356 rvQLSESRRELQELKaslRVAQKEKEQLQAEKQE 389

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2; Shank2, also called ProSAP1 (Proline-rich synapse-associated protein 1) or CortBP1 (Cortactin-binding protein 1), is found in neurons, glia, endocrine cells, liver, and kidney. It plays a role in regulating dendritic spine volume and branching and postsynaptic clustering. Mutations in the Shank2 gene are associated with autism spectrum disorder and mental retardation. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212916 Cd Length: 52 Bit Score: 36.83 E-value: 4.17e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGkkrQIGWFPANYV 1126
Cdd:cd11983      5 VVKSYQPQVEGEIPLHKGDRVKVLSIGEGGFWEGSARG---HVGWFPAECV 52

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213014 Cd Length: 62 Bit Score: 37.19 E-value: 4.20e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592 1153 VIGMYDYTAQNDD-------ELAFNKGQIINVLNKEDPDWWKGE----VNGQVGLFPS 1199
Cdd:cd12081      2 VRAQFEYDPLKDDlipckqaGIRFRVGDILQIISKDDHNWWQAKlensKNGTAGLIPS 59

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 36.90 E-value: 4.29e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWFGEVQGQKGWFPKSYVK 962
Cdd:cd12055      1 RCQVAFSYLPQNEDELELKVGDIIEVVgEVEEGWWEGVLNGKTGMFPSNFIK 52

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212926 Cd Length: 65 Bit Score: 37.40 E-value: 4.40e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344592  913 AQALYPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQG-----QKGWFPKSYVKLIS 965
Cdd:cd11993      6 AQVIASYTATGPEQLTLAPGQLILIRKKNpGGWWEGELQArgkkrQIGWFPANYVKLLS 64

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

Pssm-ID: 274303 [Multi-domain] Cd Length: 346 Bit Score: 41.37 E-value: 4.40e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  365 EKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQR 444
Cdd:TIGR02794   87 EQARQKELEQRAAAEKAAKQAEQAAKQAEEKQKQAEEAKAKQAAEAKAKAEAEAERKAKEEAAKQAEEEAKAKAAAEAKK 166

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2024344592  445 qlewernRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKK 488
Cdd:TIGR02794  167 -------KAEEAKKKAEAEAKAKAEAEAKAKAEEAKAKAEAAKA 203

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 37.08 E-value: 4.53e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592  912 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQ---GQKGWFPKSYVKL 963
Cdd:cd11940      1 QVQCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGVRlsdGERGWFPQSHVEE 55

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 36.74 E-value: 4.74e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592 1080 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKrqiGWFPANYVKL 1128
Cdd:cd11956     10 YTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMR---GLIPHKYISV 55

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 37.02 E-value: 4.82e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  742 YRALYPFESRSHDEITIQPGDIVMVkrewvdeSQTGEPGWLGGELK-------GKTGWFPANY 797
Cdd:cd11773      2 YKALYDYEPQTEDELTIQEDDILYL-------LEKSDDDWWKVKLKvnssdddEPVGLVPATY 57

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 37.28 E-value: 4.83e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQK--GWFPKSYVK 962
Cdd:cd11917      8 QALYNYMPRNEDELELREGDVIDVMEKCDDGWFvGTSRRTKffGTFPGNYVK 59

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 41.69 E-value: 4.87e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  351 DKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKER-ER-----QEQERKRQLE-LEKQLEKQ 415
Cdd:PRK12704    99 DRKLELLEKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQElERisgltAEEAKEILLEkVEEEARHE 170

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212856 [Multi-domain] Cd Length: 57 Bit Score: 36.82 E-value: 4.92e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1001 EYVAMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTL--GDKTGVFPSNYVRL 1052
Cdd:cd11923      2 EAVAKYNFNADTNVELSLRKGDRVVLLKQvDQNWYEGKIpgTNRQGIFPVSYVEV 56

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.

Pssm-ID: 431111 [Multi-domain] Cd Length: 766 Bit Score: 41.73 E-value: 5.06e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  370 ALLEQQRKEQERLAQLERAEQERKERERQE---QERKRQLELEKQLEKQrelerqreeerrkeierreaakrelerQRQL 446
Cdd:pfam10174  439 TTLEEALSEKERIIERLKEQREREDRERLEeleSLKKENKDLKEKVSAL---------------------------QPEL 491

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  447 EWERNRRQELLNQRNREQEDIVVLKAKKKTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIaEITHl 526
Cdd:pfam10174  492 TEKESSLIDLKEHASSLASSGLKKDSKLKSLEIAVEQKKEECSKLENQLKKAHNAEEAVRTNPEINDRIRLLEQ-EVAR- 569

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  527 qqqlqeSQQMLGKLIPEKQLLNDQLKQVQQNSLHRDslltiKRALEAKELARQQLRDQLDEVEKetrsklqeidIFNNQL 606
Cdd:pfam10174  570 ------YKEESGKAQAEVERLLGILREVENEKNDKD-----KKIAELESLTLRQMKEQNKKVAN----------IKHGQQ 628

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  607 KELREihNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQ---EEEPQWQKKNQEDDKQkREE 683
Cdd:pfam10174  629 EMKKK--GAQLLEEARRREDNLADNSQQLQLEELMGALEKTRQELDATKARLSSTQQslaEKDGHLTNLRAERRKQ-LEE 705


                   ....*.
gi 2024344592  684 IIKKKE 689
Cdd:pfam10174  706 ILEMKQ 711

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 36.64 E-value: 5.07e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  914 QALYPWRAKKDNHLNFNKNDVITVLEQQ---DMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11866      3 MGLWDCSGNEPDELSFKRGDLIYIISKEydsFGWWVGELNGKVGLVPKDYL 53

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175988 [Multi-domain] Cd Length: 125 Bit Score: 38.80 E-value: 5.11e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1596 VEGIELKPCRSHGKSNPYCEVTMGSQcHITKT--MQDTLNPKWNSncQFFIKDLEQDVLCITVFERDQFSPDDFLGRTEI 1673
Cdd:cd04021      8 VESAKLKSNSKSFKPDPYVEVTVDGQ-PPKKTevSKKTSNPKWNE--HFTVLVTPQSTLEFKVWSHHTLKADVLLGEASL 84

                           90
                   ....*....|.
gi 2024344592 1674 RVADI-KKDQG 1683
Cdd:cd04021     85 DLSDIlKNHNG 95

Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; LARG (also called RhoGEF12) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. LARG contains a N-terminal extension, followed by Dbl homology (DH)-PH domains which bind and catalyze the exchange of GDP for GTP on RhoA in addition to a RGS domain. The active site of RhoA adopts two distinct GDP-excluding conformations among the four unique complexes in the asymmetric unit. The LARG PH domain also contains a potential protein-docking site. LARG forms a homotetramer via its DH domains. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 275425 Cd Length: 138 Bit Score: 39.20 E-value: 5.28e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1451 LGPRKFLHSGKL-YKAKSNK--ELYGFLFNDFLLLTQ----------IIKPLGSSGTDK-VFSPKsnlqykmyktpIFLN 1516
Cdd:cd13390     21 LTKRKMIHEGPLtWKVNRDKtiDLYTLLLEDILVLLQkqddrlvlrcHSKILASTADSKhTFSPV-----------IKLN 89

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2024344592 1517 EVLVK-LPTDpsgDEPIFHISHID---RVYTLRAESINERTAW 1555
Cdd:cd13390     90 TVLVRqVATD---NKAFFVISMSEngaQIYELVAQTVSEKTVW 129

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 36.54 E-value: 5.41e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVM-VKREwvdesqtgEPGWLGGELKGKT-GWFPANYAEK 800
Cdd:cd11825      3 KALYDYRAQRPDELSFCKHAIITnVEKE--------DGGWWRGDYGGKKqKWFPANYVEE 54

RNase Y N-terminal region;

Pssm-ID: 463456 [Multi-domain] Cd Length: 201 Bit Score: 39.87 E-value: 5.42e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  351 DKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKER-ER-----QEQERKRQL-ELEKQLEK 414
Cdd:pfam12072   95 DRKDESLEKKEESLEKKEKELEAQQQQLEEKEEELEELIEEQRQElERisgltSEEAKEILLdEVEEELRH 165

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

Pssm-ID: 464032 [Multi-domain] Cd Length: 221 Bit Score: 40.07 E-value: 5.54e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  614 NRQQLQKQKNLEAERlkqkEQERKTELEKQKEAQRRIQD--RDKQRLDRVQQEEE------------------------- 666
Cdd:pfam13904   65 QRQRQKELQAQKEER----EKEEQEAELRKRLAKEKYQEwlQRKARQQTKKREEShkqkaaesaskslakperkvsqeea 140

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2024344592  667 ----PQWQKKNQEDDKQKREEIIKKKESEDKGKQEIQEKPSKLFQ 707
Cdd:pfam13904  141 kevlQEWERKKLEQQQRKREEEQREQLKKEEEEQERKQLAEKAWQ 185

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 36.69 E-value: 5.85e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  748 FESRSHDEITIQPGDIVMVKrewvdesQTGEPGWLGGEL--KGKTGWFPANYAE 799
Cdd:cd11940      8 YKAQENDELTLEKADIIMVR-------QQSSDGWLEGVRlsDGERGWFPQSHVE 54

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212926 Cd Length: 65 Bit Score: 37.02 E-value: 5.85e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGEL-----KGKTGWFPANYAE 799
Cdd:cd11993      7 QVIASYTATGPEQLTLAPGQLILIRKK-------NPGGWWEGELqargkKRQIGWFPANYVK 61

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 36.94 E-value: 5.90e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  743 RALYPFESRSHDEITIQPGDIVMVKREwVDESqtgepgWLGGELKG-----KTGWFPANYAEK 800
Cdd:cd11887      5 KALYPYESDHEDDLNFDVGQLITVTEE-EDAD------WYFGEYVDsngntKEGIFPKNFVEV 60

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212871 Cd Length: 55 Bit Score: 36.75 E-value: 5.93e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  748 FESRSHDEITIQPGDIVMVkrewvdeSQTGEPGWLGGEL--KGKTGWFPANYAE 799
Cdd:cd11938      8 YTAKQPDELSLQQADVVLV-------LQTESDGWYYGERlrDGERGWFPSSCAK 54

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 36.73 E-value: 6.05e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592 1074 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKkrqIGWFPANYVK 1127
Cdd:cd11950      2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGK---LGLFPANYVA 52

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 36.44 E-value: 6.07e-03

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2024344592 1015 DLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11921     16 ELTLQKGDIVYIHKEvDKNWLEGEHHGRVGIFPANYVEV 54

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 36.62 E-value: 6.15e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 961
Cdd:cd11816      4 ARFDFEGEQEDELSFSEGDVITLKEYvGEEWAKGELNGKIGIFPLNFV 51

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 36.51 E-value: 6.36e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGE--VQGQKGWFPKSYV 961
Cdd:cd12004      4 ALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARslTTKKEGFIPSNYV 52

Mechanosensitive ion channel porin domain; The small mechanosensitive channel, MscS, is a part of the turgor-driven solute efflux system that protects bacteria from lysis in the event of osmotic shock. The MscS protein alone is sufficient to form a functional mechanosensitive channel gated directly by tension in the lipid bilayer. The MscS proteins are heptamers of three transmembrane subunits with seven converging M3 domains, and this MscS_porin is towards the N-terminal of the molecules. The high concentration of negative charges at the extracellular entrance of the pore helps select the cations for efflux.

Pssm-ID: 432790 [Multi-domain] Cd Length: 238 Bit Score: 40.36 E-value: 6.62e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  363 ELEKRRQALLEQQRKEQERLAQLE---RAEQERKERERQEQE--RKRQLELEKQLEkqrelerqreEERRKEIERREAAK 437
Cdd:pfam12795   82 ELEQRLLQTSAQLQELQNQLAQLNsqlIELQTRPERAQQQLSeaRQRLQQIRNRLN----------GPAPPGEPLSEAQR 151

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  438 RELERQRQLEWERN--RRQELLNQRNREQedivvlkakkkTLEFELEALNDKKNQLEGKLQDIRCRLSTQRQE 508
Cdd:pfam12795  152 WALQAELAALKAQIdmLEQELLSNNNRQD-----------LLKARRDLLTLRIQRLEQQLQALQELLNEKRLQ 213

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 36.52 E-value: 6.75e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592 1076 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQGKKRqiGWFPANYVKL 1128
Cdd:cd11770      4 ALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAENSKGNR--GLVPKTYLKV 54

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 36.28 E-value: 6.92e-03

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 2024344592  927 LNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYV 961
Cdd:cd12017     16 ISFQKGQKVEVIDKNpSGWWYVKIDGKEGWAPSSYI 51

hypothetical protein; Provisional

Pssm-ID: 237178 [Multi-domain] Cd Length: 508 Bit Score: 40.85 E-value: 6.93e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  568 KRALEAKELARQQLRDQLDEVEKETRSKLqeIDIFNNQLKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQ 647
Cdd:PRK12705    33 KEAERILQEAQKEAEEKLEAALLEAKELL--LRERNQQRQEARREREELQREEERLVQKEEQLDARAEKLDNLENQLEER 110

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024344592  648 -RRIQDRDKQRLDRVQQEEEPQWQKKNQEDDkQKREEIIK--KKESEDKGKQEI 698
Cdd:PRK12705   111 eKALSARELELEELEKQLDNELYRVAGLTPE-QARKLLLKllDAELEEEKAQRV 163

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 36.33 E-value: 6.99e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024344592 1072 EIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGelQGKKRQIGWFPANYV 1126
Cdd:cd11905      1 EIVVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWWKA--RDKYGKEGYIPSNYV 53

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 38.80 E-value: 7.03e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1591 LMVNIVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTMQD-TLNPKWNSNCQFFIKDLEQDVLCITVFERDQFSPDDFLG 1669
Cdd:cd04019      2 LRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPSQTrNGNPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDEPLG 81

                           90
                   ....*....|.
gi 2024344592 1670 RTEIRVADIKK 1680
Cdd:cd04019     82 RAVIPLNDIER 92

First Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The first SH3 domain of Nck2 binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212832 [Multi-domain] Cd Length: 58 Bit Score: 36.65 E-value: 7.12e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1153 VIGMYDYTAQNDDELAFNKGQIINVLNkEDPDWWK-GEVNGQVGLFPSNYVK 1203
Cdd:cd11899      6 VIAKWDYTAQQDQELDIKKNERLWLLD-DSKTWWRvRNAANRTGYVPSNYVE 56

Apg6 coiled-coil region; In yeast, 15 Apg proteins coordinate the formation of autophagosomes. Autophagy is a bulk degradation process induced by starvation in eukaryotic cells. Apg6/Vps30p has two distinct functions in the autophagic process, either associated with the membrane or in a retrieval step of the carboxypeptidase Y sorting pathway.

Pssm-ID: 465452 [Multi-domain] Cd Length: 127 Bit Score: 38.35 E-value: 7.20e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  575 ELARQQLRDQLDEVEKEtrsklqeIDIFNNQLKELREIH--NRQQLQKQ-KNLEAER------LKQKEQERKtELEKQKE 645
Cdd:pfam17675    8 DLLLEELDKQLEDAEKE-------RDAYISFLKKLEKETpeELEELEKElEKLEKEEeellqeLEELEKERE-ELDAELE 79

                           90       100
                   ....*....|....*....|....*....
gi 2024344592  646 AQrriqdrdKQRLDRVQQEEEPQWQKKNQ 674
Cdd:pfam17675   80 AL-------EEELEALDEEEEEFWREYNA 101

Src Homology 3 domain of Amphiphysin I; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213016 Cd Length: 72 Bit Score: 36.80 E-value: 7.24e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344592  745 LYPFESRSHDEITIQPGDIVMVKREWVDESQtgEPGWLGG----------ELKGKTGWFPANYAEKI 801
Cdd:cd12140      8 LHDFEAANSDELELKRGDIVLVVPSETAADQ--DAGWLTGvkesdwlqyrDASAYKGLFPENFTRRL 72

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.

Pssm-ID: 402959 [Multi-domain] Cd Length: 164 Bit Score: 39.29 E-value: 7.55e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  606 LKELREIHNRQQLQKQKNLEAERLKQKEQERKTELEKQKEAQRRIQDRDKQRLDRVQQEEEPQWQKK---NQEDDKQKRE 682
Cdd:pfam11600    4 QKSVQSQEEKEKQRLEKDKERLRRQLKLEAEKEEKERLKEEAKAEKERAKEEARRKKEEEKELKEKErreKKEKDEKEKA 83

                           90       100
                   ....*....|....*....|....*..
gi 2024344592  683 EIIKKKESEDKGKQE-----IQEKPSK 704
Cdd:pfam11600   84 EKLRLKEEKRKEKQEaleakLEEKRKK 110

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 36.48 E-value: 7.63e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2024344592 1004 AMYTYESSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYVRL 1052
Cdd:cd11919      5 AKFDFKAQTLKELPLQKGDIVYIYKQiDQNWYEGEHHGRVGIFPRSYIEL 54

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 36.34 E-value: 8.03e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGE--VQGQKGWFPKSYV 961
Cdd:cd12005      4 ALYSYEPSHDGDLGFEKGEKLRILEQSGEWWKAQslTTGQEGFIPFNFV 52

Second Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212863 Cd Length: 55 Bit Score: 36.12 E-value: 8.50e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024344592 1004 AMYTYE----SSEQGDLTFQQGDMILVTKK-DGDWWTGTLGDKTGVFPSNYV 1050
Cdd:cd11930      4 ALYDFEvkdkEADKDCLPFAKDDILTVIRRvDENWAEGMLGDKIGIFPISYV 55

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 36.15 E-value: 8.62e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  915 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 964
Cdd:cd11971      4 AIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYeGVCNGVTGLFPGNYVESI 54

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 40.98 E-value: 8.62e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  347 VTFEDKKRENFERGNLELEKRRQALlEQQRKEQERLAQLERA---------EQERKERERQEQERKRQLELEKQLEKQRE 417
Cdd:pfam12128  456 ATATPELLLQLENFDERIERAREEQ-EAANAEVERLQSELRQarkrrdqasEALRQASRRLEERQSALDELELQLFPQAG 534

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  418 LERQREEERRKEIERREA--AKRELERQRQLE---WERNRRQELlnqrnreqeDIVVLKAKKKTLE-----FELEALNDK 487
Cdd:pfam12128  535 TLLHFLRKEAPDWEQSIGkvISPELLHRTDLDpevWDGSVGGEL---------NLYGVKLDLKRIDvpewaASEEELRER 605

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  488 KNQLEGKLQDIRCRLSTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGKLIPEKQllNDQLKQVQQNSLHRDSLLTI 567
Cdd:pfam12128  606 LDKAEEALQSAREKQAAAEEQLVQANGELEKASREETFARTALKNARLDLRRLFDEKQ--SEKDKKNKALAERKDSANER 683

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  568 KRALEAK--------ELARQQLRDQLDEVEKETRSKLQE-IDIFNNQLKELREihnrQQLQKQKNLEAErLKQKEQERKT 638
Cdd:pfam12128  684 LNSLEAQlkqldkkhQAWLEEQKEQKREARTEKQAYWQVvEGALDAQLALLKA----AIAARRSGAKAE-LKALETWYKR 758

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  639 ELEKQ--------------KEAQRRIQD--RDKQRLDRVQQEEEPQWQKKNQEDDKQKREeiIKKKESEDKGKQEIQEKP 702
Cdd:pfam12128  759 DLASLgvdpdviaklkreiRTLERKIERiaVRRQEVLRYFDWYQETWLQRRPRLATQLSN--IERAISELQQQLARLIAD 836


                   ....
gi 2024344592  703 SKLF 706
Cdd:pfam12128  837 TKLR 840

The Bin/Amphiphysin/Rvs (BAR) domain of yeast Sorting Nexin Vps17p; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. Vsp17p forms a dimer with Vps5p, the yeast counterpart of human SNX1, and is part of the retromer complex that mediates the transport of the carboxypeptidase Y receptor Vps10p from endosomes to Golgi. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

Pssm-ID: 153309 Cd Length: 230 Bit Score: 39.67 E-value: 8.74e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  609 LREIHNRQQLQKQKNLEAERLKQKEQERKTELE---KQKEAQRRIQDRDKQRLDRVQQE---EEPQWQKKNQEDDKQK-R 681
Cdd:cd07625    128 MRELIQAQQNTKSKQEAARRLKAKRDINPLKVDeaiRQLEEATKHEHDLSLKLKRITGNmliERKEWTDWTEEDLQSAiR 207

                           90
                   ....*....|..
gi 2024344592  682 EEIIKKKESEDK 693
Cdd:cd07625    208 EYTLRKIEYERK 219

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 36.15 E-value: 8.79e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024344592  744 ALYPFESRSHDEITIQPGDIVMVKREwvdesqtGEPGWLGGELKGKTGWFPANYAEKI 801
Cdd:cd11971      4 AIYDYSKDKDDELSFMEGAIIYVIKK-------NDDGWYEGVCNGVTGLFPGNYVESI 54

Flagellar biosynthesis chaperone FliJ [Cell motility];

Pssm-ID: 442129 [Multi-domain] Cd Length: 142 Bit Score: 38.35 E-value: 8.81e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  564 LLTIKRALEAKELARQQLRDQLDEVEKETRSKLQE-IDI--------FNNQLKELREIHNRQQLQKQKNLEAER--LKQK 632
Cdd:COG2882     25 LGQAQQALEQAEEQLEQLEQYREEYEQRLQQKLQQgLSAaqlrnyqqFIARLDEAIEQQQQQVAQAEQQVEQARqaWLEA 104

                           90       100
                   ....*....|....*....|....*....
gi 2024344592  633 EQERK---TELEKQKEAQRRIQDRDKQRL 658
Cdd:COG2882    105 RQERKaleKLKERRREEERQEENRREQKE 133

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

Pssm-ID: 293879 [Multi-domain] Cd Length: 291 Bit Score: 39.87 E-value: 9.41e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  369 QALLEQQRKEQErlaqlERAEQERKERERQEQERKRQlELEKQLEKQRelerqreeerrkeierreaaKRELERQRQLE- 447
Cdd:cd16269    191 QALTEKEKEIEA-----ERAKAEAAEQERKLLEEQQR-ELEQKLEDQE--------------------RSYEEHLRQLKe 244

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2024344592  448 -WERNRRQELlnqrnREQEDIVVLKAKKKTLEFElEALNDKKNQLEGKLQDIR 499
Cdd:cd16269    245 kMEEERENLL-----KEQERALESKLKEQEALLE-EGFKEQAELLQEEIRSLK 291

Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442439 [Multi-domain] Cd Length: 687 Bit Score: 40.77 E-value: 9.53e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  354 RENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKER-------ERQEQERKRQLELEKQLEK---QRELERQRE 423
Cdd:COG3206    163 EQNLELRREEARKALEFLEEQLPELRKELEEAEAALEEFRQKnglvdlsEEAKLLLQQLSELESQLAEaraELAEAEARL 242

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  424 EERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNREQE-------DIVVLKAKKKTLEfelealndkkNQLEGKLQ 496
Cdd:COG3206    243 AALRAQLGSGPDALPELLQSPVIQQLRAQLAELEAELAELSArytpnhpDVIALRAQIAALR----------AQLQQEAQ 312

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  497 DIRCRLSTQRQEIESTNKSRELRIAEIthlqqqlqesqqmlgklipEKQLLNDQLKQVQQNSLHRDslLTIKRALEAKEL 576
Cdd:COG3206    313 RILASLEAELEALQAREASLQAQLAQL-------------------EARLAELPELEAELRRLERE--VEVARELYESLL 371

                          250       260
                   ....*....|....*....|....
gi 2024344592  577 ARQQlrdQLDEVEKETRSKLQEID 600
Cdd:COG3206    372 QRLE---EARLAEALTVGNVRVID 392

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

Pssm-ID: 293879 [Multi-domain] Cd Length: 291 Bit Score: 39.87 E-value: 9.58e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  362 LELEKRRQALLEQQRKEQERlaQLERAEQERKERERQEQERKRQLEleKQLEKqrelerqreeerrkeierreaakrelE 441
Cdd:cd16269    200 IEAERAKAEAAEQERKLLEE--QQRELEQKLEDQERSYEEHLRQLK--EKMEE--------------------------E 249

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2024344592  442 RQRQL-EWERNRRQELLNQRNREQEDivvLKAKKKTLEFELEAL 484
Cdd:cd16269    250 RENLLkEQERALESKLKEQEALLEEG---FKEQAELLQEEIRSL 290

RNase Y N-terminal region;

Pssm-ID: 463456 [Multi-domain] Cd Length: 201 Bit Score: 39.10 E-value: 9.92e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344592  566 TIKR--ALEAKELARQQLRdqldEVEKETRSKLQEIDIFNNQLKELREIHNRQQ----------LQKQKNLEAE--RLKQ 631
Cdd:pfam12072   49 TKKKeaLLEAKEEIHKLRA----EAERELKERRNELQRQERRLLQKEETLDRKDeslekkeeslEKKEKELEAQqqQLEE 124

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344592  632 KEQERKTELEKQKEAQRRI----QDRDKQRL-DRVQQEeepqwqkknqeddkQKREEIIKKKESEDKGKQE 697
Cdd:pfam12072  125 KEEELEELIEEQRQELERIsgltSEEAKEILlDEVEEE--------------LRHEAAVMIKEIEEEAKEE 181