NCBI Conserved Domain Search

The Bin/Amphiphysin/Rvs (BAR) domain of Dynamin Binding Protein; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. DyNamin Binding Protein (DNMBP), also called Tuba, is a Cdc42-specific Guanine nucleotide Exchange Factor (GEF) that binds dynamin and various actin regulatory proteins. It serves as a link between dynamin function, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. DNMBP contains BAR and SH3 domains as well as a Dbl Homology domain (DH domain), which harbors GEF activity. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of DNMBP may be involved in binding to membranes. The gene encoding DNMBP is a candidate gene for late onset Alzheimer's disease.

Pssm-ID: 153273 Cd Length: 195 Bit Score: 231.05 E-value: 2.68e-69

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1017 QIKDEVFEETEKNFRMQERLIKSFIRDLSLYLQHIRESACVKVVAAVSMWDVCMERGHRD---LEQFERVHRYISDQLFT 1093
Cdd:cd07589    1 QTKDKEFDELEKKFGSLEKQVQLVVRNVELYLQHVQESVLVKVLALEVVLDLYPSNHPRLeskWERFRRVVRGISSKALP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1094 NFKERTERLVISPLNQLLSMFTGPHKLVQKRFDKLLDFYNCTERAEklKDKKTLEELQSARNNYEALNAQLLDELPKFHQ 1173
Cdd:cd07589   81 EFKSRVRKLVIEPLSSLLKLFSGPQKLIQKRYDKLLDYERYKEKKE--RGGKVDEELEEAANQYEALNAQLKEELPKFNQ 158

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 39930351 1174 YAQGLFTNCVHGYAEAHCDFVHQALEQ--LKPLLSLL 1208
Cdd:cd07589  159 LTAQLLETCLKSFVELQRDLYDTLLKRaeLLPLLDSS 195

BAR domain; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different protein families. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysin, endophilin, BRAP and Nadrin. BAR domains are also frequently found alongside domains that determine lipid specificity, like pfam00169 and pfam00787 domains in beta centaurins and sorting nexins respectively.

Pssm-ID: 460810 [Multi-domain] Cd Length: 235 Bit Score: 185.62 E-value: 7.91e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351    997 IIKKSNRVSSHLKHLTGFAPQIK-DEVFEETEKNFRMQERLIKSFIRDLSLYLQHIRESACVKVVA-------AVSMWDV 1068
Cdd:pfam03114    1 LKKQFNRASQLLGEKVGGAEKTKlDEDFEELERRFDTTEKEIKKLQKDTKGYLQPNPGARAKQTVLeqpeellAESMIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351   1069 CMERGHRD-----LEQFERVHRYIsDQLFTNFKERTERLVISPLNQLLSMFTGPHKLVQKRFDKLLDFYNCTERAEKLKD 1143
Cdd:pfam03114   81 GKDLGEDSsfgkaLEDYGEALKRL-AQLLEQLDDRVETNFLDPLRNLLKEFKEIQKHRKKLERKRLDYDAAKTRVKKAKK 159

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351   1144 KKT---------LEELQSARNNYEALNAQLLDELPKFHQYAQGLFTNCVHGYAEAHCDFVHQA---LEQLKPLLSL 1207
Cdd:pfam03114  160 KKSskakdesqaEEELRKAQAKFEESNEQLKALLPNLLSLEVEFVVNQLVAFVEAQLDFHRQCyqlLEQLQQQLGK 235

BAR domain;

Pssm-ID: 214787 [Multi-domain] Cd Length: 239 Bit Score: 162.94 E-value: 6.96e-45

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351     996 SIIKKSNRVSSHLKHLTGFAPQIK-DEVFEETEKNFRMQERLIKSFIRDLSLYLQHireSACVKVVAAVSM--WDVCMER 1072
Cdd:smart00721    1 GFKKQFNRAKQKVGEKVGKAEKTKlDEDFEELERRFDTTEAEIEKLQKDTKLYLQP---NPAVRAKLASQKklSKSLGEV 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351    1073 --GHRDLEQFERVHRY--ISDQLFTNFKERTE----------RLVISPLNQLLSMFTGPHKLVQKRFDKLLDFYNCTER- 1137
Cdd:smart00721   78 yeGGDDGEGLGADSSYgkALDKLGEALKKLLQveeslsqvkrTFILPLLNFLLGEFKEIKKARKKLERKLLDYDSARHKl 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351    1138 --AEKLKDKKTL-------EELQSARNNYEALNAQLLDELPKFHQYAQGLFTNCVHGYAEAHCDFVHQALEQLKPLLSLL 1208
Cdd:smart00721  158 kkAKKSKEKKKDeklakaeEELRKAKQEFEESNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQQQL 237


                    .
gi 39930351    1209 K 1209
Cdd:smart00721  238 D 238

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: 141.28 E-value: 3.67e-38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351  785 RAKVIEELLQTERDYIRDLEMCIERIMVPMQQAQVPNI--DFEGLFGNMQMVIKVSKQLLAALE--------ISDAVGPV 854
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSpeEVELLFGNIEEIYEFHRIFLKSLEerveewdkSGPRIGDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351  855 FLGHRDELEgTYKIYCQNHDEAialLEIYEKDEKIQKHLQDSLADLKSLynewgcTNYINLGSFLIKPVQRVMRYPLLLM 934
Cdd:cd00160   81 FLKLAPFFK-IYSEYCSNHPDA---LELLKKLKKFNKFFQEFLEKAESE------CGRLKLESLLLKPVQRLTKYPLLLK 150

                        170       180       190
                 ....*....|....*....|....*....|.
gi 39930351  935 ELLNSTPESHPDKVPLTNAVLAVKEINVNIN 965
Cdd:cd00160  151 ELLKHTPDGHEDREDLKKALEAIKEVASQVN 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: 139.74 E-value: 1.09e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351    788 VIEELLQTERDYIRDLEMCIERIMVPMQQA-QVPNIDFEGLFGNMQMVIKVSKQLL-----AALEISDAVGPVFLGHRDE 861
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPlSESEEEIKTIFSNIEEIYELHRQLLleellKEWISIQRIGDIFLKFAPG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351    862 LEgTYKIYCQNHDEAIALL-EIYEKDEKIQKHLQDSLADLKSlynewgctNYINLGSFLIKPVQRVMRYPLLLMELLNST 940
Cdd:pfam00621   81 FK-VYSTYCSNYPKALKLLkKLLKKNPKFRAFLEELEANPEC--------RGLDLNSFLIKPVQRIPRYPLLLKELLKHT 151

                          170       180
                   ....*....|....*....|....*
gi 39930351    941 PESHPDKVPLTNAVLAVKEINVNIN 965
Cdd:pfam00621  152 PPDHPDYEDLKKALEAIKEVAKQIN 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: 139.74 E-value: 1.30e-37

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351     788 VIEELLQTERDYIRDLEMCIERIMVPMQQAQV--PNIDFEGLFGNMQMVIKVSKQLLAALE--------ISDAVGPVFLG 857
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKllSPNELETLFGNIEEIYEFHRDFLDELEerieewddSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351     858 HRDELEgTYKIYCQNHDEAIALLEIYEKDEKIQKHLQDSLADLKslynewgcTNYINLGSFLIKPVQRVMRYPLLLMELL 937
Cdd:smart00325   81 LEEFFK-IYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQ--------CRRLTLESLLLKPVQRLTKYPLLLKELL 151

                           170       180
                    ....*....|....*....|....*....
gi 39930351     938 NSTPESHPDKVPLTNAVLAVKEINVNINE 966
Cdd:smart00325  152 KHTPEDHEDREDLKKALKAIKELANQVNE 180

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: 125.30 E-value: 3.35e-34

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEFKDVTGNTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12141    1 VYYAVYTFKARSPNELSVSANQRVRILEFSDLTGNKEWWLAEANGQKGYVPSNYIRK 57

First C-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, 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: 212732 Cd Length: 57 Bit Score: 124.72 E-value: 6.30e-34

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1289 LFQAERNFNAAQDLDVSLLEGDLVGVIKKKDPMGSQNRWLIDNGVTKGFVYSSFLKP 1345
Cdd:cd11798    1 LFQADRNFNAAQDLDVSLQEGDLVGVIKQQDPMGSQNRWLIDNGVTKGFVYSSFLKP 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: 110.54 E-value: 4.55e-29

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEFKDVTGNTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11800    1 YYYALYTFEARSPGELSVTEGQVVTVLEKHDLKGNPEWWLVEDRGKQGYVPSNYLAK 57

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: 109.37 E-value: 1.22e-28

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11796    1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRRGIFPEGFV 51

Second 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: 212729 Cd Length: 54 Bit Score: 108.30 E-value: 2.76e-28

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351   70 LFVCICEFTSQELDNLPLHRGDLVILDGIPTAGWLQGRSCWGARGFFPSSCVRE 123
Cdd:cd11795    1 LVVCIEAFTSQEPGHLNLQRGDLVELTGTTDSGWLQGRSCWGSSGFFPSSCVQE 54

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: 102.50 E-value: 2.95e-26

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRF 296
Cdd:cd11797    1 YGVALYRFQALEPNELDFEVGDRIRIIATLEDGWLEGELKGRRGIFPHRF 50

First 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: 212728 Cd Length: 51 Bit Score: 102.21 E-value: 3.62e-26

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11794    1 VVRAIFDFCPSVSEELPLFAGDVIEVLKVVDEFWLLGTKEGVTGQFPSSFV 51

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.

Pssm-ID: 153271 [Multi-domain] Cd Length: 194 Bit Score: 95.20 E-value: 6.34e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1029 NFRMQERLIKSFIRDLSLYLQHIREsacvKVVAAVSMWDVCMERGH-----------RDLEQFERVHRYIsDQLFTNFKE 1097
Cdd:cd07307    1 KLDELEKLLKKLIKDTKKLLDSLKE----LPAAAEKLSEALQELGKelpdlsntdlgEALEKFGKIQKEL-EEFRDQLEQ 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1098 RTERLVISPLNQLLSM-FTGPHKLVQKRFDKLLDFYNCTERAEKLKDKK--------TLEELQSARNNYEALNAQLLDEL 1168
Cdd:cd07307   76 KLENKVIEPLKEYLKKdLKEIKKRRKKLDKARLDYDAAREKLKKLRKKKkdssklaeAEEELQEAKEKYEELREELIEDL 155

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 39930351 1169 PKFHQYAQGLFTNCVHGYAEAHCDFVHQALEQLKPLLS 1206
Cdd:cd07307  156 NKLEEKRKELFLSLLLSFIEAQSEFFKEVLKILEQLLP 193

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: 72.38 E-value: 1.34e-15

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIG--VPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11875    1 KARVLFDYEAENEDELTLREGDIVTILSkdCEDKGWWKGELNGKRGVFPDNFVEP 55

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: 67.24 E-value: 7.85e-14

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11941    4 AAYPFTARSKHEVSLQAGQPVTVLEPHDKKGSPEWSLVEVNGQRGYVPSSYL 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: 66.79 E-value: 1.35e-13

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351     244 PGTYGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLK-GRTGIFPYRFVK 298
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56

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: 64.21 E-value: 7.59e-13

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  248 GVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11873    2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMFPDNFVK 52

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: 63.25 E-value: 1.63e-12

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSL-KGRTGIFP 293
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELnGGREGLFP 48

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: 62.87 E-value: 2.16e-12

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELE-GRRGIFPEGF 198
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNgGREGLFPANY 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: 63.33 E-value: 2.25e-12

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 39930351     148 GQARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELE-GRRGIFPEGFVE 200
Cdd:smart00326    3 PQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56

The Bin/Amphiphysin/Rvs (BAR) domain of Amphiphysins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Amphiphysins function primarily in endocytosis and other membrane remodeling events. They 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. This subfamily is composed of different isoforms of amphiphysin and Bridging integrator 2 (Bin2). 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. 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. Bin2 is mainly expressed in hematopoietic cells and is upregulated during granulocyte differentiation. The N-BAR domains of amphiphysins form a curved dimer with a positively-charged concave face that can drive membrane bending and curvature.

Pssm-ID: 153272 Cd Length: 211 Bit Score: 67.76 E-value: 2.95e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1013 GFAPQIKDEVFEETEKNFRMQERLIKSFIRDLSLYLqhiresACVKV-VAAVSMWDVCMER-------GHRDL-EQFERv 1083
Cdd:cd07588    4 GKADETRDEVFDEHVNNFNKQQASANRLQKDLKNYL------NSVRAmKQASKTLSETLKElyepdwpGREHLaSIFEQ- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1084 hryiSDQLFTNFKERTERLVISPLNQLLSMFTGPHKLVQKRFDKLLDF------YNCTERAEKLKDKK---TLEELQSAR 1154
Cdd:cd07588   77 ----LDLLWNDLEEKLSDQVLGPLTAYQSQFPEVKKRIAKRGRKLVDYdsarhnLEALKAKKKVDDQKltkAEEELQQAK 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1155 NNYEALNAQLLDELPKFHQYAQGLFTNCVHGYAEAHCDFVHQALEQLKPLLSLLK 1209
Cdd:cd07588  153 KVYEELNTELHEELPALYDSRIAFYVDTLQSIFAAESVFHKEIGKVNTKLNDVMD 207

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: 61.84 E-value: 6.57e-12

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIG--VPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd12057    1 YCKVLFPYEAQNEDELTIKEGDIVTLISkdCIDAGWWEGELNGRRGVFPDNFVKLL 56

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: 61.58 E-value: 7.94e-12

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11874    3 KVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 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: 61.64 E-value: 8.21e-12

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATL--EDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11841    4 ALYSFEGQQPCDLSFQAGDRITVLTRTdsQFDWWEGRLRGRVGIFPANYVS 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: 61.29 E-value: 1.07e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLE--DGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11842    1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDsqNDWWTGRIGGREGIFPANYVEL 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: 61.01 E-value: 1.33e-11

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 39930351       7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKED-VTGQFPSSFVE 57
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRgKEGLFPSNYVE 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: 60.77 E-value: 1.48e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIgVP--EPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11882    1 RARALYACKAEDESELSFEPGQIITNV-QPsdEPGWLEGTLNGRTGLIPENYVEF 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: 60.74 E-value: 1.69e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd11803    2 CCRALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGFFPVNYVEVL 55

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: 60.33 E-value: 2.08e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11805    1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYVQ 52

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: 60.24 E-value: 2.61e-11

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 39930351    1520 AVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAEVN-GKKGYVPSNYIR 1572
Cdd:smart00326    7 ALYDYTAQDPDELSFKKGDIITVLE----KSDDGWWKGRLGrGKEGLFPSNYVE 56

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: 59.59 E-value: 3.43e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11873    2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMFPDNFVK 52

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: 59.40 E-value: 3.64e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKED-VTGQFPSSF 55
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGgREGLFPANY 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: 59.33 E-value: 5.14e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITII-----GVPEpGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11762    2 VRALYDYEAQSDEELSFPEGAIIRILrkddnGVDD-GWWEGEFNGRVGVFPSLVVE 56

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: 59.07 E-value: 6.27e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11961    2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGLFPSNYVEL 53

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 58.78 E-value: 7.59e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 39930351    152 ALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

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: 58.36 E-value: 9.42e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAE--VNGKKGYVPSNY 1570
Cdd:cd11845    1 IYVALYDYEARTDDDLSFKKGDRLQILD----DSDGDWWLARhlSTGKEGYIPSNY 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: 57.98 E-value: 1.29e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 39930351    249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLK-GRTGIFP 293
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKgGKEGLIP 46

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: 58.15 E-value: 1.38e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11824    2 YSVLYDYTAQEDDELSISKGDVVAVIE-KGEDG---WWTVERNGQKGLVPGTYLEK 53

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: 57.81 E-value: 1.44e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11840    1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVEP 53

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: 57.89 E-value: 1.64e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd12046    3 VALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGKIGIFPSAFVE 52

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: 57.86 E-value: 1.64e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAEVN-GKKGYVPSNY 1570
Cdd:cd00174    4 ALYDYEAQDDDELSFKKGDIITVLE----KDDDGWWEGELNgGREGLFPANY 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: 57.71 E-value: 1.75e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11877    1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVKE 53

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: 1.76e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIG--VPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd12142    3 RVLFDYNPVAPDELALKKGDVIEVISkeTEDEGWWEGELNGRRGFFPDNFVMP 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: 57.27 E-value: 2.42e-10

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11803    5 ALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGFFPVNYV 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: 57.21 E-value: 2.50e-10

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 39930351  158 AQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd12052   10 AQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRGLFPDNFV 51

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: 57.34 E-value: 2.60e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11874    4 VLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 53

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 56.86 E-value: 2.93e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 39930351    250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

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: 56.57 E-value: 4.77e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11874    1 RCKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 53

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: 56.48 E-value: 4.79e-10

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11805    4 ALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYVQ 52

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: 56.48 E-value: 5.72e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKIL--EFK-DVTGnteWWLAEVNGKK-GYVPSNYIR 1572
Cdd:cd11864    4 AEYDFVAESEDELSFRAGDKLRLApkELQpRVRG---WLLATVDGQKiGLVPANYVK 57

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: 56.37 E-value: 6.31e-10

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIG--VPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd12056    5 KALFHYEGTNEDELDFKEGEIILIISkdTGEPGWWKGELNGKEGVFPDNFV 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: 55.77 E-value: 7.74e-10

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11772    1 VFRALYDYEAQHPDELSFEEGDLLYISDKSD----PNWWKATCGGKTGLIPSNYV 51

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: 55.82 E-value: 7.93e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11782    1 EARAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQ 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: 55.78 E-value: 8.36e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEG---RRGIFPEGF 198
Cdd:cd11821    2 VRALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGdpsRRGVFPVSF 53

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: 55.79 E-value: 8.61e-10

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11826    3 VALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYV 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: 55.42 E-value: 1.06e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11781    2 ARALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGIFPASYVEI 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: 55.61 E-value: 1.13e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11870    3 VALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDGRVGIFPKCFVV 52

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: 55.12 E-value: 1.17e-09

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 39930351  152 ALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGF 198
Cdd:cd11797    4 ALYRFQALEPNELDFEVGDRIRIIATLEDGWLEGELKGRRGIFPHRF 50

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: 55.34 E-value: 1.37e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11856    2 YVAIADYEAQGDDEISLQEGEVVEVLE-KNDSG---WWYVRKGDKEGWVPASYLEP 53

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: 55.11 E-value: 1.38e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11827    1 QCKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 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: 55.04 E-value: 1.74e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11823    1 RCKALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVE 52

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: 1.79e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11826    3 VALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYVE 52

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: 54.67 E-value: 1.95e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11804    4 AKHDFKATAEDELSFKKGSILKVLNMED---DPNWYKAELDGKEGLIPKNYI 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: 54.61 E-value: 2.56e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  249 VALYRFQALEPNELDFEVGDKI-RILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11882    3 RALYACKAEDESELSFEPGQIItNVQPSDEPGWLEGTLNGRTGLIPENYVEF 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: 54.27 E-value: 3.20e-09

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11823    3 KALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYV 51

First 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: 212733 Cd Length: 54 Bit Score: 54.07 E-value: 3.21e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351 1289 LFQAERNFNAAQDLDVSLLEGDLVGVIKKKDPMGSQNRWLIDNGVTKGFV 1338
Cdd:cd11799    1 IYQVMSNVSGTRDLDLTLTRGEIVAVLQEADTKGNTGRWLVDAGGKRGYV 50

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: 54.14 E-value: 3.65e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11986    1 YFVALYRFKALEKDDLDFHPGERITVIDDSNEEWWRGKIGEKTGYFPMNFI 51

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: 54.05 E-value: 4.04e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfkdvtGNTEWWLAE--VNGKKGYVPSNYI 1571
Cdd:cd12009    1 CVIAQYDFVPSNERDLQLKKGEKLQVLK-----SDGEWWLAKslTTGKEGYIPSNYV 52

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: 53.63 E-value: 5.08e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEG-SLK-GRTGIFPYRFV 297
Cdd:cd11784    3 VALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGlSLVtGRVGIFPSNYV 53

The Bin/Amphiphysin/Rvs (BAR) domain of Saccharomyces cerevisiae Reduced viability upon starvation protein 161 and similar proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of fungal proteins with similarity to Saccharomyces cerevisiae Reduced viability upon starvation protein 161 (Rvs161p) and Schizosaccharomyces pombe Hob3 (homolog of Bin3). S. cerevisiae Rvs161p plays a role in regulating cell polarity, actin cytoskeleton polarization, vesicle trafficking, endocytosis, bud formation, and the mating response. It forms a heterodimer with another BAR domain protein Rvs167p. Rvs161p and Rvs167p share common functions but are not interchangeable. Their BAR domains cannot be replaced with each other and the overexpression of one cannot suppress the mutant phenotypes of the other. S. pombe Hob3 is important in regulating filamentous actin localization and may be required in activating Cdc42 and recruiting it to cell division sites. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

Pssm-ID: 153275 Cd Length: 224 Bit Score: 58.12 E-value: 6.02e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1012 TGFAPQIKDEVFEETEKNFRMQERLIKSFIRDLSLYLQHIR--ESACVKVVAAVSMW--DVCMERGHRDLEQFERVHRYI 1087
Cdd:cd07591    2 TGQVERTVDREFEFEERRYRTMEKASTKLQKEAKGYLDSLRalTSSQARIAETISSFygDAGDKDGAMLSQEYKQAVEEL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1088 SDQLFTNFKERTERLVISPLNQLLSMFTGPHKLVQKRFDKLLDFYNCTERAEKLKDK---------KTLEELQSARNNYE 1158
Cdd:cd07591   82 DAETVKELDGPYRQTVLDPIGRFNSYFPEINEAIKKRNHKLLDYDAARAKVRKLIDKpsedptklpRAEKELDEAKEVYE 161

                        170
                 ....*....|...
gi 39930351 1159 ALNAQLLDELPKF 1171
Cdd:cd07591  162 TLNDQLKTELPQL 174

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: 53.28 E-value: 6.41e-09

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd12047    3 VAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDGRIGIFPKCFA 51

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: 53.52 E-value: 6.42e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIG--VPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11836    3 RALYAFEARNPDEISFQPGDIIQVDEsqVAEPGWLAGELKGKTGWFPANYVE 54

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: 53.46 E-value: 6.56e-09

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 39930351  260 NELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd12055   14 DELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIK 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: 53.11 E-value: 6.74e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11781    4 ALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGIFPASYVEI 53

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: 53.43 E-value: 6.80e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd11919    2 PARAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIELL 55

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: 53.28 E-value: 6.92e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgNTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11948    4 ALYSFQATESDELPFQKGDILKILNMED---DQNWYKAELQGREGYIPKNYIK 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: 53.09 E-value: 6.98e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSL-KGRTGIFPYRFVKL 299
Cdd:cd11819    3 KALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNaKGQKGLFPANYVEL 54

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: 53.15 E-value: 7.13e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1516 QVYfAVYTFKARNPNELSVSANQKLKILEFKDvTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11807    2 VVY-ALFDYEAENGDELSFREGDELTVLRKGD-DDETEWWWARLNDKEGYVPRNLL 55

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: 53.09 E-value: 8.34e-09

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11877    4 AKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVKE 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: 52.79 E-value: 8.53e-09

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11816    3 VARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51

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: 52.50 E-value: 1.19e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd12046    1 QVVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGKIGIFPSAFVE 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: 52.49 E-value: 1.26e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGF 198
Cdd:cd11818    1 KARALYDFTGENEDELSFKAGDIITELESIDEEWMSGELRGKSGIFPKNF 50

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: 52.42 E-value: 1.29e-08

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  249 VALYRFQALEPNELDFEVGDKIriLATLEDG-WLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11838    3 IALYPYESNEPGDLTFNAGDVI--LVTKKDGeWWTGTIGDRTGIFPSNYVRP 52

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: 52.32 E-value: 1.37e-08

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELE-GRRGIFPEGFVEL 201
Cdd:cd11819    1 RAKALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAkGQKGLFPANYVEL 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: 52.32 E-value: 1.37e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd11920    3 ARAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYVEKL 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: 51.97 E-value: 1.66e-08

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  248 GVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11782    2 ARAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQ 52

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: 51.91 E-value: 2.07e-08

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVP-EPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd12065    1 KAKAVYPCEAEHSSELSFEVGAIFEDVTLSrEPGWLEGTLNGKRGLIPENYVEI 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: 51.92 E-value: 2.07e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11772    4 ALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYV 51

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: 51.93 E-value: 2.33e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11920    5 AVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYVE 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: 51.94 E-value: 2.41e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEFKDVTgNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11954    2 MVYALWDYEAQNADELSFQEGDAITILRRKDDS-ETEWWWARLNDKEGYVPKNLL 55

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: 51.75 E-value: 2.61e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11950    4 ALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 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: 51.76 E-value: 2.62e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11870    1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDGRVGIFPKCFVV 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: 51.36 E-value: 2.94e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11950    1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 52

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: 51.53 E-value: 3.07e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11772    3 RALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYVE 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: 51.35 E-value: 3.15e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11833    3 VALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIEDRVGFFPANFV 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: 51.33 E-value: 3.21e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRF 296
Cdd:cd11817    3 VALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50

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: 51.36 E-value: 3.32e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd12047    1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDGRIGIFPKCFA 51

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: 51.15 E-value: 3.64e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 39930351  159 QLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd12055   11 QNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIK 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: 51.31 E-value: 3.73e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11820    1 RKVRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFV 52

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: 50.95 E-value: 3.80e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11808    4 ALYDYQEKSPREVSMKKGDILTLLN----SSNKDWWKVEVNDRQGFVPAAYVKK 53

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: 51.08 E-value: 4.32e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd11921    3 ARLKFDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGRVGIFPANYVEVL 55

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: 50.86 E-value: 4.71e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILAT----LEDGWLEGSLKGRTGIFP 293
Cdd:cd11762    4 ALYDYEAQSDEELSFPEGAIIRILRKddngVDDGWWEGEFNGRVGVFP 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: 50.81 E-value: 4.76e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILA-TLED-GWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11875    4 VLFDYEAENEDELTLREGDIVTILSkDCEDkGWWKGELNGKRGVFPDNFVEP 55

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: 50.93 E-value: 4.77e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11820    5 ALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFVT 53

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: 50.78 E-value: 4.91e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIriLATLEDG-WLEGSLKGRTGIFPYRFVK 298
Cdd:cd11992    3 IALYPYSSSEPGDLTFNEGEEI--LVTQKDGeWWTGSIEDRTGIFPSNYVR 51

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: 50.93 E-value: 4.94e-08

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                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  251 LYRFQALEPNELDFEVGDKIRILA--TLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd12142    5 LFDYNPVAPDELALKKGDVIEVISkeTEDEGWWEGELNGRRGFFPDNFV 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: 50.72 E-value: 5.02e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11964    2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFV 52

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: 50.58 E-value: 5.47e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11813    1 RAKALLDFERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRGWFPAKFVEL 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: 50.61 E-value: 5.60e-08

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351      67 GERLFVCICEFTSQELDNLPLHRGDLVILDGIPTAGWLQGRSCWGARGFFPSSCVR 122
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56

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: 50.60 E-value: 5.64e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11961    4 ALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGLFPSNYVEL 53

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: 6.01e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 39930351    151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGEL-EGRRGIFP 195
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNkGGKEGLIP 46

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: 50.61 E-value: 6.11e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  252 YRFQALEPNELDFEVGDKIRILATL-EDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd12053    6 YDYDAVHEDELTIRVGEIIRNVKKLeEEGWLEGELNGRRGMFPDNFVK 53

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: 50.39 E-value: 6.61e-08

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgNTEWWLAE--VNGKKGYVPSNYI 1571
Cdd:cd11775    5 VLYDFDAQSDDELTVKEGDVVYILDDKK---SKDWWMVEnvSTGKEGVVPASYI 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: 50.49 E-value: 6.70e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11959    3 VALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYGLFPANYVEL 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: 50.57 E-value: 6.74e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11951    2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGFFPRNYV 51

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: 50.57 E-value: 7.05e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11869    4 ALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRGATGIFPLSFVKI 53

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: 50.22 E-value: 7.37e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd12073    3 AVALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVELL 55

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: 9.19e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 39930351   1520 AVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:pfam07653    4 VIFDYVGTDKNGLTLKKGDVVKVLG----KDNDGWWEGETGGRVGLVPSTAVEE 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: 49.80 E-value: 9.73e-08

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  152 ALMGLSAQLDEELDFREGDVITII-GVPEPGWFEGELEGRRGIFPEGF 198
Cdd:cd11778    4 ALYDYEAQGDDEISIRVGDRIAVIrGDDGSGWTYGEINGVKGLFPTSY 51

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: 50.11 E-value: 1.02e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  149 QARALMGLSAQLDEELDFREGDVI-TIIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd12064    2 KAKALYACKAEHDSELSFTAGTVFdNVHPSQEPGWLEGTLNGKTGLIPENYVEFL 56

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: 49.97 E-value: 1.05e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  251 LYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd12054    6 LFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVK 53

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: 49.72 E-value: 1.15e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11827    4 ALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYV 51

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: 49.38 E-value: 1.22e-07

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351   71 FVCICEFTSQELDNLPLHRGDLVILDGIPTAGWLQGRSCWGARGFFPSSC 120
Cdd:cd00174    2 ARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGGREGLFPANY 51

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: 49.89 E-value: 1.22e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEdGWLEGSL---KGRTGIFPYRFVKLC 300
Cdd:cd11872    1 YGVAIYNFQGDGEHQLSLQVGDTVQILEECE-GWYRGFSlrnKSLKGIFPKSYVHIK 56

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: 49.51 E-value: 1.23e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 39930351   1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVN-GKKGYVPS 1568
Cdd:pfam00018    2 ALYDYTAQEPDELSFKKGDIIIVLEKSE----DGWWKGRNKgGKEGLIPS 47

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: 49.57 E-value: 1.26e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11995    2 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGLFPSNYVKL 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: 49.83 E-value: 1.29e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd12073    4 VALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVEL 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: 49.65 E-value: 1.30e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11781    1 KARALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGIFPASYVEI 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: 49.57 E-value: 1.31e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEIV 59
Cdd:cd11803    4 RALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGFFPVNYVEVL 55

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: 49.70 E-value: 1.32e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11806    1 EYVAIADFVATDDSQLSFESGDKLLVLR----KPSVDWWWAEHNGCCGYIPASHL 51

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: 49.61 E-value: 1.42e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd12055    3 QVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIK 52

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: 49.62 E-value: 1.43e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLA-EVNGKKGYVPSNYIR 1572
Cdd:cd11849    1 MYRALYDFKSAEPNTLSFSEGETFLLLE----RSNAHWWLVtNHSGETGYVPANYVK 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: 49.43 E-value: 1.49e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILaTLED--GWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11948    3 VALYSFQATESDELPFQKGDILKIL-NMEDdqNWYKAELQGREGYIPKNYIKV 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: 49.43 E-value: 1.52e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 39930351  159 QLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11829   12 QHQQGLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 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: 49.34 E-value: 1.56e-07

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gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11840    3 IALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVEP 53

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: 49.59 E-value: 1.58e-07

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gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfKDvtgNTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11996    5 AMYDYTANNEDELSFSKGQLINVLN-KD---DPDWWQGEINGVTGLFPSNYVK 53

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: 49.12 E-value: 1.71e-07

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gi 39930351      8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGK-KEDVTGQFPS 53
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRnKGGKEGLIPS 47

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: 49.07 E-value: 2.01e-07

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11949    2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 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: 49.30 E-value: 2.03e-07

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gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd12061    4 AKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVR 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: 48.85 E-value: 2.03e-07

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gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11877    1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVKE 53

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: 49.05 E-value: 2.07e-07

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gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEdGWLEG-SL--KGRTGIFPYRFVKL 299
Cdd:cd12051    1 YGVAIYNYDARGPDELSLQIGDTVHILETYE-GWYRGyTLrkKSKKGIFPASYIHL 55

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: 48.89 E-value: 2.10e-07

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gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATL--EDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11836    4 ALYAFEARNPDEISFQPGDIIQVDESQvaEPGWLAGELKGKTGWFPANYV 53

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: 49.06 E-value: 2.10e-07

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gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11961    4 ALYDYDAAEDNELSFFENDKIINIEFVD----DDWWLGECHGSRGLFPSNYV 51

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: 49.17 E-value: 2.22e-07

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gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKdvtGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11976    4 ARYDFCARDRSELSLKEGDIIKILNKK---GQQGWWRGEIYGRVGWFPANYV 52

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: 49.03 E-value: 2.26e-07

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gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEIV 59
Cdd:cd11869    4 ALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRGATGIFPLSFVKII 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: 48.88 E-value: 2.38e-07

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gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11823    4 ALYSYTANREDELSLQPGDIIEVHE-KQDDG---WWLGELNGKKGIFPATYV 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: 48.48 E-value: 3.11e-07

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gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILefkDVTGNTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11946    5 AKYDFKATADDELSFKRGDILKVL---NEECDQNWYKAELNGKDGFIPKNYIE 54

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: 48.49 E-value: 3.47e-07

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gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd12024    2 YYATRAYEAQKEDELSVPAGVVVEVLQ----KSDNGWWLIRYNGRAGYVPSMYLQ 52

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: 48.46 E-value: 3.70e-07

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gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfkDVTGNTEWWLAE-VNGKKGYVPSNYI 1571
Cdd:cd11767    4 ALYPFTGENDEELSFEKGERLEIIE--KPEDDPDWWKARnALGTTGLVPRNYV 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: 48.17 E-value: 3.76e-07

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gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFeGELEGRRGIFPEGFVEL 201
Cdd:cd11989    1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKL 52

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: 48.40 E-value: 3.83e-07

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gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIG---VPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11894    3 KALYDYEGQTDDELSFPEGAIIRILNkenQDDDGFWEGEFNGRIGVFPSVLVE 55

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: 48.36 E-value: 3.88e-07

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gi 39930351    247 YGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKLC 300
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVEEI 54

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: 48.41 E-value: 4.01e-07

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gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11964    5 AIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFV 52

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: 48.04 E-value: 4.26e-07

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLA-EVNGKKGYVPSNYIRK 1573
Cdd:cd11768    4 ALYDFQPIEPGDLPLEKGEEYVVLD----DSNEHWWRArDKNGNEGYIPSNYVTE 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: 48.26 E-value: 4.38e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd12046    2 VVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGKIGIFPSAFVE 52

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: 48.19 E-value: 4.45e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1520 AVYTFKA--RNPNELSVSANQklkILEFKDVTGNteWWLAEV-NGKKGYVPSNYIR 1572
Cdd:cd11855    4 ALYPYDAspDDPNELSFEKGE---ILEVSDTSGK--WWQARKsNGETGICPSNYLQ 54

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: 48.01 E-value: 5.02e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11805    2 VQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYVQ 52

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: 47.80 E-value: 5.45e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPG--WFEGELEGRRGIFPEGFVEL 201
Cdd:cd11842    1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSQndWWTGRIGGREGIFPANYVEL 55

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: 47.77 E-value: 5.65e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEP--GWFEGELEGRRGIFPEGFV 199
Cdd:cd11841    1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRLRGRVGIFPANYV 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: 47.91 E-value: 5.90e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11949    4 ALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 52

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 47.61 E-value: 6.13e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 39930351      9 AIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

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: 47.63 E-value: 6.53e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11985    3 VALYKFLPQENNDLPLQPGDRVMVVDDSNEDWWKGKSGDRVGFFPANFVQ 52

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: 47.49 E-value: 6.82e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11951    2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGFFPRNYV 51

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: 47.34 E-value: 7.03e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11782    3 RAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQV 53

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: 47.48 E-value: 7.16e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  248 GVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRF 296
Cdd:cd11818    2 ARALYDFTGENEDELSFKAGDIITELESIDEEWMSGELRGKSGIFPKNF 50

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: 47.53 E-value: 7.23e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 39930351  161 DEELDFREGDVI-TIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd12053   13 EDELTIRVGEIIrNVKKLEEEGWLEGELNGRRGMFPDNFVK 53

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: 47.41 E-value: 8.09e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfKDvtgNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11840    4 ALFPYTAQNEDELSFQKGDIINVLS-KD---DPDWWRGELNGQTGLFPSNYV 51

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: 47.64 E-value: 8.28e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEFKDvTGNTEWWLAEVNGKKGYVPSN 1569
Cdd:cd11953    2 VVYALWDYEGESDDELSFKEGDCMTILRRED-EDETEWWWARLNDKEGYVPRN 53

Src Homology 3 domain of Class A Dedicator of Cytokinesis protein 2; Dock2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. 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 Dock2 binds to DHR-2 in an autoinhibitory manner; binding of the scaffold protein Elmo to the SH3 domain of Dock2 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: 212983 Cd Length: 56 Bit Score: 47.53 E-value: 8.44e-07

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEDgWLEGSL---KGRTGIFPYRFVKL 299
Cdd:cd12050    1 YGVAIYNFKGSGVPQLSLQIGDVVHIQETCED-WYKGYLvrhKDLQGIFPKSFIHI 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: 47.37 E-value: 9.38e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd12061    3 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYV 51

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: 46.94 E-value: 1.04e-06

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGV-PEPGWFEGE-LEGRRGIFPEGFVE 200
Cdd:cd11763    1 KVRALYDFDSQPSGELSLRAGEVLTITRQdVGDGWLEGRnSRGEVGLFPSSYVE 54

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: 47.37 E-value: 1.06e-06

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 39930351  161 DEELDFREGDVITIIG-VPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd12013   20 EVELSFRAGDIITVFGeMDEDGFYYGELNGQRGLVPSNFLE 60

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: 46.92 E-value: 1.12e-06

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAE-VNGKKGYVPSNYIRK 1573
Cdd:cd11770    2 YEALSDFQAEQEGDLSFKKGEVLRIISKRA----DGWWLAEnSKGNRGLVPKTYLKV 54

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: 46.62 E-value: 1.37e-06

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEG-ELEGRRGIFPEGFVEL 201
Cdd:cd11960    2 ARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRGtGPDGTYGLFPANYVEL 54

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: 46.57 E-value: 1.52e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFeGELEGRRGIFPEGFVEL 201
Cdd:cd11990    1 KAQALCSWTAKKDNHLNFSKNDIITVLEQQENWWF-GEVHGGRGWFPKSYVKL 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: 46.62 E-value: 1.54e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLK-GRTGIFPYRFVKL 299
Cdd:cd11960    4 ALYDYQAADDTEISFDPGDIITDIEQIDEGWWRGTGPdGTYGLFPANYVEL 54

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: 46.64 E-value: 1.60e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIG-VPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11843    3 RALYDYEGQESDELSFKAGDILTKLEeEDEQGWCKGRLDGRVGLYPANYVE 53

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: 46.59 E-value: 1.63e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  149 QARALMGLSAQLDEELDFREGDVIT-IIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd12066    1 QAKAMYSCKAEHSHELSFPQGAIFSnVYPSVEPGWLKATYEGKTGLVPENYVVFL 55

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 46.46 E-value: 1.68e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351   1520 AVYTFKARNPNELSVSANQKLKilefkdVTGNTE--WWLAEVNGKKGYVPSNYIR 1572
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVIT------VIEESEdgWWEGINTGRTGLVPANYVE 49

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: 46.45 E-value: 1.70e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11928    2 CGKALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCHGFLPASYIQC 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: 46.48 E-value: 1.71e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVP-EPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11976    2 AKARYDFCARDRSELSLKEGDIIKILNKKgQQGWWRGEIYGRVGWFPANYVE 53

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: 46.50 E-value: 1.79e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd12054    2 QCKVLFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVKEL 55

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: 46.22 E-value: 1.80e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11828    4 ALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVRL 53

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: 46.55 E-value: 1.85e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEFKDVtgntEWWLAE-VNGKKGYVPSNYI 1571
Cdd:cd11908    2 LVIALYDYQTNDPQELALRYNEEYHLLDSSEI----HWWRVQdKNGHEGYVPSSYL 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: 46.44 E-value: 1.98e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 39930351    162 EELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:pfam07653   14 NGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVEEI 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: 46.10 E-value: 2.07e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351 1521 VYTFKARNPNELSVSANQKLKILEfkdvtGNTEWWLAE-VNGKKGYVPSN 1569
Cdd:cd11764    5 LYDFTARNSKELSVLKGEYLEVLD-----DSRQWWKVRnSRGQVGYVPHN 49

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: 46.11 E-value: 2.08e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd12054    4 KVLFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVK 53

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: 46.36 E-value: 2.16e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWL--EGSLKGRTGIFPYRFVKL 299
Cdd:cd11865    3 VALYDFEPEHDNELGFAEGQILFILYKHGQGWLiaEDESGGKTGLVPEEFVSY 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: 46.18 E-value: 2.23e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11823    3 KALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVE 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: 46.15 E-value: 2.32e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd12060    5 KARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVR 54

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: 46.16 E-value: 2.41e-06

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 39930351  164 LDFREGDVITII---GVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11884   16 LSFHKGDVIKLLpkeGPLDPGWLFGTLDGRSGAFPKEYVQ 55

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: 2.42e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11950    2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 52

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: 46.08 E-value: 2.51e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11830    4 ARYDFCARDMRELSLKEGDVVKIYNKKGQQG---WWRGEINGRIGWFPSTYVEE 54

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: 45.96 E-value: 2.60e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPE-PGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11948    1 EAVALYSFQATESDELPFQKGDILKILNMEDdQNWYKAELQGREGYIPKNYIKV 54

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: 45.74 E-value: 2.74e-06

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11996    1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 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: 46.11 E-value: 2.77e-06

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEIV 59
Cdd:cd11919    4 RAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIELL 55

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: 45.72 E-value: 2.97e-06

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                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11766    3 VVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYV 51

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: 45.78 E-value: 3.12e-06

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRIL-ATLEDGWLEG-SLKGRTGIFPYRFV 297
Cdd:cd11763    4 ALYDFDSQPSGELSLRAGEVLTITrQDVGDGWLEGrNSRGEVGLFPSSYV 53

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: 45.75 E-value: 3.28e-06

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                 ....*....|....*....|....*....|....*....|.
gi 39930351  161 DEELDFREGDVITIIGVPEP-GWFEGELEGRRGIFPEGFVE 200
Cdd:cd12012   21 EEELPFKEGQLIKVYGDKDAdGFYLGEINGRRGLVPCNMVS 61

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: 45.53 E-value: 3.62e-06

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELE--GRRGIFPEGFVE 200
Cdd:cd11785    3 RVIVPYPPQSEAELELKEGDIVFVHKKREDGWFKGTLQrtGKTGLFPGSFVE 54

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: 45.59 E-value: 3.78e-06

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLA-EVNGKKGYVPSNYI 1571
Cdd:cd11906    5 ALYDYTPMNAQDLQLRKGEEYVILE----ESNLPWWRArDKNGREGYIPSNYV 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: 45.45 E-value: 3.91e-06

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11828    2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVRL 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: 45.32 E-value: 3.98e-06

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11964    3 VRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFV 52

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: 45.48 E-value: 4.08e-06

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gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVtgnteWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11989    4 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-----WWFGEVQGQKGWFPKSYVK 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: 45.17 E-value: 4.10e-06

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEpGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11947    1 EARGKFDFTASGEDELSFKKGDVLKILSSDD-IWFKAELNGEEGYVPKNFVDI 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: 45.53 E-value: 4.17e-06

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gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVL---AVV--DEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd12059    4 AVFDYEASAEDELTLRRGDRVEVLskdSAVsgDEGWWTGKINDRVGIFPSNYV 56

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: 4.32e-06

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  250 ALYRFQALEPNELDFEVGDkirILATLED----GWLEGSLKGRTGIFPYRFV 297
Cdd:cd11843    4 ALYDYEGQESDELSFKAGD---ILTKLEEedeqGWCKGRLDGRVGLYPANYV 52

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: 45.30 E-value: 4.35e-06

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gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfKDVTGnTEWWLAEVNGKKGYVPSNY 1570
Cdd:cd11952    2 VVYALWDYSAEFPDELSFKEGDMVTVLR-KDGEG-TDWWWASLCGREGYVPRNY 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: 45.10 E-value: 4.50e-06

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11959    2 AVALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYGLFPANYVEL 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: 45.05 E-value: 4.77e-06

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11786    2 AKALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQGFFPASYVQ 52

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: 45.16 E-value: 4.77e-06

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                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGF 198
Cdd:cd11817    2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50

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: 45.05 E-value: 5.11e-06

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gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11786    1 CAKALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQGFFPASYVQ 52

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: 45.34 E-value: 5.14e-06

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1520 AVYTFKARNP-NELSVSANQKLKILEFKDVTGN-TEWWLAEV-NGKKGYVPSNYI 1571
Cdd:cd11771    4 ALYDFTPENPeMELSLKKGDIVAVLSKTDPLGRdSEWWKGRTrDGRIGWFPSNYV 58

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: 45.15 E-value: 5.23e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11820    3 VRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFV 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: 45.10 E-value: 5.43e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11827    4 ALYAYDAQDTDELSFNEGDIIEILK-EDPSG---WWTGRLRGKEGLFPGNYVEK 53

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: 45.05 E-value: 5.62e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11837    3 TALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELEGGEEGWFPKSYVKE 53

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: 45.19 E-value: 5.73e-06

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1516 QVYFAVYTFKARNPNELSVSANQKLKILEFKDVtgntEWWLA-EVNGKKGYVPSNYI 1571
Cdd:cd11905    1 EIVVAMYDFQPTEPHDLRLETGEEYVILEKNDV----HWWKArDKYGKEGYIPSNYV 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: 44.91 E-value: 5.75e-06

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEG--RRGIFPEGFVELL 202
Cdd:cd11923    1 GEAVAKYNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPGtnRQGIFPVSYVEVI 57

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: 45.03 E-value: 5.77e-06

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                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfkdvtgNTE--WWLAE--VNGKKGYVPSNYI 1571
Cdd:cd12007    2 IFVALYDYEARTTEDLSFKKGERFQIIN------NTEgdWWEARsiATGKNGYIPSNYV 54

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: 45.01 E-value: 6.02e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTGnteWWLAE-VNGKKGYVPSNYI 1571
Cdd:cd11763    4 ALYDFDSQPSGELSLRAGEVLTITRQDVGDG---WLEGRnSRGEVGLFPSSYV 53

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: 45.01 E-value: 6.12e-06

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITIIGvPEP--GWFEGELE--GRRGIFPEGFVE 200
Cdd:cd11779    1 PRVKALYPHAAGGETQLSFEEGDVITLLG-PEPrdGWHYGENErsGRRGWFPIAYTE 56

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: 44.96 E-value: 6.13e-06

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                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 39930351    7 VRAIFDFCPSVSE-ELPLFVGDIIEVLAVVD------EFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11771    2 CRALYDFTPENPEmELSLKKGDIVAVLSKTDplgrdsEWWKGRTRDGRIGWFPSNYVEV 60

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: 6.19e-06

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                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd12060    6 ARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVR 54

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: 44.86 E-value: 6.35e-06

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  151 RALMGLSAQLDEELDFREGDVITI--IGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11988    5 RALYPFEARNHDEMSFNAGDIIQVdeKTVGEPGWLYGSFQGNFGWFPCNYVE 56

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: 45.03 E-value: 6.65e-06

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKED-----VTGQFPSSFVE 57
Cdd:cd11887    4 VKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEYVDsngntKEGIFPKNFVE 59

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: 44.63 E-value: 6.80e-06

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351   72 VCICEFTSQELDNLPLHRGDLV-ILDGIPTaGWLQG-RSCWGARGFFPSSCVRE 123
Cdd:cd11793    3 QCVHAYTAQQPDELTLEEGDVVnVLRKMPD-GWYEGeRLRDGERGWFPSSYTEE 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: 44.89 E-value: 6.80e-06

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                 ....*....|....*....|....*....|....*....|....*..
gi 39930351  252 YRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd12052    6 FDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRGLFPDNFVR 52

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: 44.79 E-value: 7.09e-06

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd11869    1 RAEALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRGATGIFPLSFVKII 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: 44.56 E-value: 7.17e-06

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11995    5 GMYDYTAQNDDELAFSKGQIINVLNKED----PDWWKGELNGQVGLFPSNYVK 53

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: 45.00 E-value: 7.18e-06

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEG---RRGIFPEGFVELL 202
Cdd:cd11965    1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFVHIL 57

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: 44.40 E-value: 7.18e-06

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                 ....*....|....*....|....*....|....*....|....*...
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSF 55
Cdd:cd11818    3 RALYDFTGENEDELSFKAGDIITELESIDEEWMSGELRGKSGIFPKNF 50

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: 44.89 E-value: 7.47e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILAT--LEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd12057    1 YCKVLFPYEAQNEDELTIKEGDIVTLISKdcIDAGWWEGELNGRRGVFPDNFVKL 55

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: 44.62 E-value: 7.48e-06

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11963    6 ALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGLFPSNFV 53

The Bin/Amphiphysin/Rvs (BAR) domain of Bridging integrator 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Bridging integrator 2 (Bin2) is a BAR domain containing protein that is mainly expressed in hematopoietic cells. It is upregulated during granulocyte differentiation and is thought to function primarily in this lineage. The BAR domain of Bin2 is closely related to the BAR domains of amphiphysins, which function primarily in endocytosis and other membrane remodeling events. 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. Unlike amphiphysins, Bin2 does not appear to contain a C-terminal SH3 domain. Amphiphysin I proteins, enriched in the brain and nervous system, function in synaptic vesicle endocytosis. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), function in intracellular vessicle trafficking. Bin2 can form a stable complex with Bin1 in cells but cannot replace the function of Bin1, and thus, appears to harbor a nonredundant function. The N-BAR domain of amphiphysin forms a curved dimer with a positively-charged concave face that can drive membrane bending and curvature.

Pssm-ID: 153296 Cd Length: 211 Bit Score: 48.70 E-value: 7.56e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1013 GFAPQIKDEVFEETEKNFRMQERLIKSFIRDLSLYLQHI---RESAcvKVVAAvSMWDVCMER--GHRDLEQFERVhryi 1087
Cdd:cd07612    4 GKTVETKDEQFEQCAMNLNMQQSDGNRLYKDLKAYLNAVkvmHESS--KRLSQ-TLQDIYEPDwdGHEDLGAIVEG---- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1088 SDQLFTNFKERTERLVISPLNQLLSMFTGPHKLVQKRFDKLLDFYNCTERAEKL---------KDKKTLEELQSARNNYE 1158
Cdd:cd07612   77 EDLLWNDYEAKLHDQALRTMESYMAQFPDVKERVAKRGRKLVDYDSARHHLEALqnakkkddaKIAKAEEEFNRAQVVFE 156

                        170
                 ....*....|....*
gi 39930351 1159 ALNAQLLDELPKFHQ 1173
Cdd:cd07612  157 DINRELREELPILYD 171

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: 44.32 E-value: 8.48e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11816    2 CVARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51

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: 44.72 E-value: 8.48e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfkdvtgNTE--WWLAE--VNGKKGYVPSNYI 1571
Cdd:cd12008    2 FVALYDYESRTETDLSFKKGERLQIVN------NTEgdWWLAHslTTGQTGYIPSNYV 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: 44.56 E-value: 8.57e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11873    2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMFPDNFVKV 53

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: 44.61 E-value: 8.73e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELE--GRRGIFPEGFVELL 202
Cdd:cd11935    4 RAMYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGTVQrtGRTGMLPANYIEFV 57

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: 44.44 E-value: 8.77e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11949    2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 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: 44.60 E-value: 9.48e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIG--VPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11987    3 RALYPFEARSHDEITIQPGDIVMVDEsqTGEPGWLGGELKGKTGWFPANYAE 54

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: 44.42 E-value: 9.97e-06

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11833    4 ALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIEDRVGFFPANFV 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: 44.29 E-value: 1.02e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11828    4 ALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVRL 53

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: 44.63 E-value: 1.06e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEP-----GWFEGELE--GRRGIFPEGFVELL 202
Cdd:cd11790    5 VRATHDYTAEDTDELTFEKGDVILVIPFDDPeeqdeGWLMGVKEstGCRGVFPENFTERI 64

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: 44.21 E-value: 1.08e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  250 ALYRFQALEPNELDFEVGDKIR-ILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd12065    4 AVYPCEAEHSSELSFEVGAIFEdVTLSREPGWLEGTLNGKRGLIPENYVEI 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: 44.04 E-value: 1.10e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQAlEPNE--LDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11829    4 TLYAFTG-EQHQqgLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 52

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: 44.13 E-value: 1.10e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11986    2 FVALYRFKALEKDDLDFHPGERITVID----DSNEEWWRGKIGEKTGYFPMNFI 51

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: 44.50 E-value: 1.12e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITII---GVPEPGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd12003    3 AKALYDNAAESPEELSFRRGDVLMVLkreHGSLPGWWLCSLHGQQGIAPANRLRLL 58

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: 44.25 E-value: 1.13e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGS--LKGRTGIFPYRFV 297
Cdd:cd11793    3 QCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGErlRDGERGWFPSSYT 53

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: 44.21 E-value: 1.14e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfkdvtGNTEWWLAE--VNGKKGYVPSNYIRK 1573
Cdd:cd12004    1 IVVALYPYDGIHEDDLSFKKGEKLKVIE-----EHGEWWKARslTTKKEGFIPSNYVAK 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: 44.20 E-value: 1.15e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  249 VALYRFQALEPNELDFEVGDKIriLATLEDG-WLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11991    3 VAMYTYESNEQGDLTFQQGDVI--LVTKKDGdWWTGTVGDKTGVFPSNYVRP 52

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: 44.15 E-value: 1.17e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITIIGVP--EPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11952    1 GVVYALWDYSAEFPDELSFKEGDMVTVLRKDgeGTDWWWASLCGREGYVPRNYFGL 56

The Bin/Amphiphysin/Rvs (BAR) domain of Saccharomyces cerevisiae Reduced viability upon starvation protein 167 and similar proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of fungal proteins with similarity to Saccharomyces cerevisiae Reduced viability upon starvation protein 167 (Rvs167p) and Schizosaccharomyces pombe Hob1 (homolog of Bin1). S. cerevisiae Rvs167p plays a role in regulation of the actin cytoskeleton, endocytosis, and sporulation. It forms a heterodimer with another BAR domain protein Rvs161p. Rvs161p and Rvs167p share common functions but are not interchangeable. Their BAR domains cannot be replaced with each other and the overexpression of one cannot suppress the mutant phenotypes of the other. Rvs167p also interacts with the GTPase activating protein (GAP) Gyp5p, which is involved in ER to Golgi vesicle trafficking. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

Pssm-ID: 153283 [Multi-domain] Cd Length: 216 Bit Score: 48.02 E-value: 1.21e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1020 DEVFEETEKNFRMQERLIKSFIRDLSLYlqhirESACVKVVAAVSMWDVCMER-----GHRDLEQFERVHRYISDQLFTN 1094
Cdd:cd07599    1 DEQFEELEKDFKSLEKSLKKLIEQSKAF-----RDSWRSILTHQIAFAKEFAElydpiVGPKESVGSHPAPESTLARLSR 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1095 FKERTERL--------------VISPLNQLLSMFTGPHKLVQKRFDKLLDFYNCTERAEK-LKDKKTLE----------- 1148
Cdd:cd07599   76 YVKALEELkkelleeleffeerVILPAKELKKYIKKIRKTIKKRDHKKLDYDKLQNKLNKlLQKKKELSlkdekqlakle 155

                        170       180       190
                 ....*....|....*....|....*....|....
gi 39930351 1149 -ELQSARNNYEALNAQLLDELPKFHQYAQGLFTN 1181
Cdd:cd07599  156 rKLEEAKEEYEALNELLKSELPKLLALADEFLPP 189

The Bin/Amphiphysin/Rvs (BAR) domain of Amphiphysin I and II; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Amphiphysins function primarily in endocytosis and other membrane remodeling events. They 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. 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. 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. The N-BAR domain of amphiphysin forms a curved dimer with a positively-charged concave face that can drive membrane bending and curvature. Human autoantibodies to amphiphysin-1 hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Mutations in amphiphysin-2 (BIN1) are associated with autosomal recessive centronuclear myopathy.

Pssm-ID: 153295 Cd Length: 211 Bit Score: 48.01 E-value: 1.25e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1013 GFAPQIKDEVFEETEKNFRMQERLIKSFIRDLSLYLQHIR--ESACVKVVAAVSM-----W---DVCMERGHRDLEQFER 1082
Cdd:cd07611    4 GKADETKDEQFEEYVQNFKRQETEGTRLQRELRAYLAAIKgmQEASKKLTESLHEvyepdWygrDDVKTIGEKCDLLWED 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1083 VHRYISDQlftnfkerterlVISPLNQLLSMFTGPHKLVQKRFDKLLDFYNCTERAE-----KLKDKKTL----EELQSA 1153
Cdd:cd07611   84 FHQKLVDG------------ALLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEalqtsKRKDEGRIakaeEEFQKA 151

                        170       180
                 ....*....|....*....|....*...
gi 39930351 1154 RNNYEALNAQLLDELPKFHQYAQGLFTN 1181
Cdd:cd07611  152 QKVFEEFNVDLQEELPSLWSRRVGFYVN 179

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: 43.86 E-value: 1.27e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  247 YGVALYRFQALEPNELD---FEVGDKIRILATLEDGWLEGSLKGRTGIFPYRF 296
Cdd:cd11787    1 QCKALYDFEMKDEDEKDcltFKKGDVITVIRRVDENWAEGRLGDKIGIFPISF 53

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: 43.84 E-value: 1.28e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELE--GRRGIFPEGFVEL 201
Cdd:cd11789    3 RAMYDYAAADDDEVSFQEGDVIINVEIIDDGWMEGTVQrtGQSGMLPANYVEL 55

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: 44.02 E-value: 1.33e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgntEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11947    4 GKFDFTASGEDELSFKKGDVLKILSSDD-----IWFKAELNGEEGYVPKNFV 50

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: 43.98 E-value: 1.33e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12017    2 YFTIGEFQATIQDGISFQKGQKVEVID-KNPSG---WWYVKIDGKEGWAPSSYIEK 53

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: 44.10 E-value: 1.37e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRIL--ATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd12068    1 YVVALRSYITDDKSLLSFHRGDLIKLLpmAGLEPGWQFGSTGGRSGLFPADIVQP 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: 43.85 E-value: 1.43e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKIleFKDVTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11977    5 ARYNFAARDMRELSLREGDVVRI--YSRIGGDQGWWKGETNGRIGWFPSTYV 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: 44.02 E-value: 1.47e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGE-LEGRRGIFPEGFVEL 201
Cdd:cd11962    2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTnSKGESGLFPSNYVEL 54

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: 43.83 E-value: 1.49e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRI--LATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11987    1 YYRALYPFEARSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAE 54

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: 43.85 E-value: 1.55e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFP 293
Cdd:cd11982    4 MAVKPYQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFP 48

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: 43.85 E-value: 1.56e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAV-VDEFWLLGKK-EDVTGQFPSSFVEI 58
Cdd:cd11763    2 VRALYDFDSQPSGELSLRAGEVLTITRQdVGDGWLEGRNsRGEVGLFPSSYVEI 55

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: 1.57e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVtgNTEWWLAEVNGKKGYVPSNY 1570
Cdd:cd11802    4 VLYDYDAEDSTELSLLADEVITVYELPGM--DEDYMMGERGSQRGKVPVAY 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: 43.85 E-value: 1.60e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11972    6 VAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVE 55

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: 43.50 E-value: 1.67e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQklKILEFKDVTGNTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11836    2 YRALYAFEARNPDEISFQPGD--IIQVDESQVAEPGWLAGELKGKTGWFPANYVEK 55

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: 43.41 E-value: 1.72e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11766    1 PAVVKFNYEAQREDELSLRKGDRVLVLE-KSSDG---WWRGECNGQVGWFPSNYVTE 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: 43.57 E-value: 1.83e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILefKDVTGNTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11842    4 ALYDFAGEQPGDLAFQKGDIITIL--KKSDSQNDWWTGRIGGREGIFPANYVE 54

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: 43.58 E-value: 1.83e-05

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                 ....*....|....*....|....*....|....*....|....*
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFP 293
Cdd:cd11832    3 IAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFP 47

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: 43.53 E-value: 1.88e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNG--KKGYVPSNYI 1571
Cdd:cd11858    2 YKALYDFAGSVANELSLKKDDIVYIVQ-KEDNG---WWLAKKLDesKEGWVPAAYL 53

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: 43.50 E-value: 1.94e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPE-PGWFEGELEGRRGIFPEGFV 199
Cdd:cd11804    1 EAVAKHDFKATAEDELSFKKGSILKVLNMEDdPNWYKAELDGKEGLIPKNYI 52

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: 43.39 E-value: 2.07e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIG-VPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11830    2 AKARYDFCARDMRELSLKEGDVVKIYNkKGQQGWWRGEINGRIGWFPSTYVE 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: 43.47 E-value: 2.27e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11963    3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGLFPSNFV 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: 43.11 E-value: 2.32e-05

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLA--VVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11875    1 KARVLFDYEAENEDELTLREGDIVTILSkdCEDKGWWKGELNGKRGVFPDNFVEP 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: 43.47 E-value: 2.35e-05

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRIL---ATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11884    1 YVVAVRAYITRDQTLLSFHKGDVIKLLpkeGPLDPGWLFGTLDGRSGAFPKEYV 54

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: 43.37 E-value: 2.37e-05

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                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  252 YRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11921    7 FDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGRVGIFPANYVEV 54

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: 43.46 E-value: 2.41e-05

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                 ....*....|....*....|....*....|....*....|....*
gi 39930351  161 DEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE-LLGP 204
Cdd:cd11972   16 EDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVEsIMHY 60

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: 43.50 E-value: 2.44e-05

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAE--VNGKKGYVPSNYI 1571
Cdd:cd12006    2 LFVALYDYEARTEDDLSFHKGEKFQILN----SSEGDWWEARslTTGETGYIPSNYV 54

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: 43.26 E-value: 2.56e-05

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                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  152 ALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11833    4 ALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIEDRVGFFPANFV 51

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: 43.47 E-value: 2.63e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  152 ALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11971    4 AIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVE 52

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: 43.09 E-value: 2.66e-05

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEFKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11978    2 IAIARYDFCARDMRELSLLKGDVVKIYTKMSTNG---WWRGEVNGRVGWFPSTYVEE 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: 43.27 E-value: 2.73e-05

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILA--TLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd12056    3 YCKALFHYEGTNEDELDFKEGEIILIISkdTGEPGWWKGELNGKEGVFPDNFVSQ 57

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: 43.47 E-value: 2.81e-05

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILAT-----LEDGWLEGSLK--GRTGIFPYRFVK 298
Cdd:cd11790    7 ATHDYTAEDTDELTFEKGDVILVIPFddpeeQDEGWLMGVKEstGCRGVFPENFTE 62

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: 42.94 E-value: 2.93e-05

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11815    1 HAVVLHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYRGKCKNTTGIFPANHVK 52

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: 43.00 E-value: 2.97e-05

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351  248 GVALYRFQALEPNELDFEVGDKIRI----LATLEDGWLEGSLKG-RTGIFPYRFVKL 299
Cdd:cd11864    2 ARAEYDFVAESEDELSFRAGDKLRLapkeLQPRVRGWLLATVDGqKIGLVPANYVKI 58

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: 43.02 E-value: 2.99e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11927    5 ALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNGIHGFFPTNFVQI 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: 43.07 E-value: 3.11e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKED-VTGQFPSSFVEI 58
Cdd:cd11819    3 KALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAKgQKGLFPANYVEL 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: 43.10 E-value: 3.14e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  254 FQALEPNELDFEVGDKIRILATLEDGWLEGSLKGR-----TGIFPYRFVKL 299
Cdd:cd11839    8 FTATAENQLSLAVGQLVLVRKKSPSGWWEGELQARgkkrqIGWFPANYVKL 58

Second 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: 212812 [Multi-domain] Cd Length: 56 Bit Score: 42.70 E-value: 3.37e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTG---IFPYRFVKL 299
Cdd:cd11879    1 FGIVLYDFKAERPDELDAKAGDAIIICAHSNYEWFVAKPIGRLGgpgLIPVSFVEI 56

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: 3.42e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11919    5 AKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIEL 54

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: 43.07 E-value: 3.44e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLK--GRTGIFPYRFVK 298
Cdd:cd11933    6 AMYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGTVQrtGKTGMLPANYVE 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: 42.65 E-value: 3.67e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLG-----KKEDVTGQFPSSF 55
Cdd:cd11883    1 VVVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGviissSGKVKRGWFPSNY 55

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: 42.80 E-value: 3.71e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEF--WLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11842    2 AVALYDFAGEQPGDLAFQKGDIITILKKSDSQndWWTGRIGGREGIFPANYVEL 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: 42.64 E-value: 3.72e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEG--RRGIFPEGFVEL 201
Cdd:cd11924    1 GEAVAQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITGtgRQGIFPASYVQV 56

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: 42.67 E-value: 4.24e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEG--RRGIFPEGFVELL 202
Cdd:cd11922    1 GEAIAKFNFNGDTQVEMSFRKGERITLLRQVDENWYEGRIPGtsRQGIFPITYVDVI 57

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: 42.50 E-value: 4.26e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILeFKDvtgNTEWWLAE-VNGKKGYVPSNYI 1571
Cdd:cd11812    4 ALYDYTANRSDELTIHRGDIIRVL-YKD---NDNWWFGSlVNGQQGYFPANYV 52

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: 42.63 E-value: 4.37e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTGNTEwwLAEVNGKKGYVPSNYIR 1572
Cdd:cd11911    4 ALYDFDGTSEGTLSMEEGEILLVLEEDGGDGWTR--VRKNNGDEGYVPTSYIE 54

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: 42.48 E-value: 4.60e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11951    4 AQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGFFPRNYV 51

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: 42.35 E-value: 4.72e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1519 FAVYTFKARNPNELSVSANQKLKILEFKDVTGntewWLAEVN--GKKGYVPSNYI 1571
Cdd:cd11761    5 KVLYSYEAQRPDELTITEGEELEVIEDGDGDG----WVKARNksGEVGYVPENYL 55

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: 42.30 E-value: 5.10e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGS-LKGRTGIFPYRFVK 298
Cdd:cd11849    4 ALYDFKSAEPNTLSFSEGETFLLLERSNAHWWLVTnHSGETGYVPANYVK 53

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: 42.25 E-value: 5.22e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEG---RRGIFPEGFV 199
Cdd:cd11966    1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGeptRRGAFPVSFV 54

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: 42.17 E-value: 5.62e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATL--EDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11988    6 ALYPFEARNHDEMSFNAGDIIQVDEKTvgEPGWLYGSFQGNFGWFPCNYVE 56

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: 42.30 E-value: 5.69e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1520 AVYTFKARNPNELSVsanQKLKILEfkdVTGNTE--WWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11877    4 AKFNFEGTNEDELSF---DKGDIIT---VTQVVEggWWEGTLNGKTGWFPSNYVK 52

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: 42.26 E-value: 5.79e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITII-----GVPEpGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd11895    2 ARALYSYTGQSPEELSFPEGALIRLLpraqdGVDD-GFWRGEFGGRVGVFPSLLVEEL 58

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: 42.28 E-value: 5.93e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11996    4 IAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 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: 42.29 E-value: 5.98e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDvTGQ---FPSSFVE 57
Cdd:cd11780    3 RALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGTSER-TGLfgtFPGNYVA 54

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: 42.02 E-value: 6.12e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfkdvtGNTEWWLAE-VNGKKGYVPSNYI 1571
Cdd:cd11765    4 AKYDYTAQGDQELSIKKNEKLTLLD-----DSKHWWKVQnSSNQTGYVPSNYV 51

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: 41.91 E-value: 6.32e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDG-WLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11770    3 EALSDFQAEQEGDLSFKKGEVLRIISKRADGwWLAENSKGNRGLVPKTYLKV 54

Src homology 3 domain of JNK-interacting proteins 1 and 2, and similar domains; JNK-interacting proteins (JIPs) function as scaffolding proteins for c-Jun N-terminal kinase (JNK) signaling pathways. They bind to components of Mitogen-activated protein kinase (MAPK) pathways such as JNK, MKK, and several MAP3Ks such as MLK and DLK. There are four JIPs (JIP1-4); all contain a JNK binding domain. JIP1 and JIP2 also contain SH3 and Phosphotyrosine-binding (PTB) domains. Both are highly expressed in the brain and pancreatic beta-cells. JIP1 functions as an adaptor linking motor to cargo during axonal transport and also is involved in regulating insulin secretion. JIP2 form complexes with fibroblast growth factor homologous factors (FHFs), which facilitates activation of the p38delta MAPK. The SH3 domain of JIP1 homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212735 Cd Length: 55 Bit Score: 41.91 E-value: 6.37e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEG-SLK-GRTGIFPYRFV 297
Cdd:cd11801    3 RALHKFIPRHEDEIELDIGDPVYVEQEADDLWCEGtNLRtGQRGIFPAAYV 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: 42.29 E-value: 6.50e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGelEGRR----GIFPEGFVELL 202
Cdd:cd11916    5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVG--TSRRtkqfGTFPGNYVKLL 58

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: 42.30 E-value: 6.67e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12060    6 ARFNFKQTNEDELSVCKGDIIYVTRVEE----GGWWEGTLNGKTGWFPSNYVRE 55

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: 42.04 E-value: 6.70e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILefkdvTGNTEWWL--AEVNGKKGYVPSNYIRK 1573
Cdd:cd12011    1 VAVALCNFPSGGPTELSIRMGEQLTIL-----SEDGDWWKvsSAVTGRECYIPSNYVAK 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: 42.11 E-value: 6.80e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfKD--VTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11876    1 LWTALFDYDARGEDELTLRRGQPVEVLS-KDaaVSGDEGWWTGKIGDKVGIFPSNYV 56

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: 41.85 E-value: 6.89e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILA---TLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11894    4 ALYDYEGQTDDELSFPEGAIIRILNkenQDDDGFWEGEFNGRIGVFPSVLVE 55

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: 41.91 E-value: 7.32e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGE-LEGRRGIFPEGFVEL 201
Cdd:cd11770    3 EALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAEnSKGNRGLVPKTYLKV 54

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: 7.61e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfKDVTGNTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11844    4 ALYDNVAESPDELAFRRGDILTVLE-QNTAGLEGWWLCSLRGRQGIAPGNRLK 55

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: 41.54 E-value: 7.71e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11826    2 VVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYVE 52

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: 41.86 E-value: 7.80e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11985    4 ALYKFLPQENNDLPLQPGDRVMVVDDSNEDWWKGKSGDRVGFFPANFVQ 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: 41.94 E-value: 7.90e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRR-----GIFPEGFVEL 201
Cdd:cd11839    2 AQVIAPFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQARGkkrqiGWFPANYVKL 58

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: 41.71 E-value: 8.50e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTGnteWWLAEVNGKKGYVPSNY 1570
Cdd:cd11778    4 ALYDYEAQGDDEISIRVGDRIAVIRGDDGSG---WTYGEINGVKGLFPTSY 51

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: 41.90 E-value: 8.61e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTGntewWLAEVN--GKKGYVPSNYIR 1572
Cdd:cd11897    4 ALYDFRSENPGEISLREHEVLSLCSEQDIEG----WLEGVNsrGDRGLFPASYVE 54

Src homology 3 domain of yeast cell fusion protein Fus1p; Fus1p is required at the cell surface for cell fusion during the mating response in yeast. It requires Bch1p and Bud7p, which are Chs5p-Arf1p binding proteins, for localization to the plasma membrane. It acts as a scaffold protein to assemble a cell surface complex which is involved in septum degradation and inhibition of the NOG pathway to promote cell fusion. The SH3 domain of Fus1p interacts with Bin1p, a formin that controls the assembly of actin cables in response to Cdc42 signaling. It has been shown to bind the motif, R(S/T)(S/T)SL, instead of PxxP motifs. 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: 212788 [Multi-domain] Cd Length: 56 Bit Score: 41.54 E-value: 8.72e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLE----GSLKGRTGIFP 293
Cdd:cd11854    3 TVISTFEPSLDDELLIKVGETVRVLAEYDDGWCLveraDGLNGDRGMVP 51

The Bin/Amphiphysin/Rvs (BAR) domain of Bridging integrator 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Bridging integrator 3 (Bin3) is widely expressed in many tissues except in the brain. It plays roles in regulating filamentous actin localization and in cell division. In humans, the Bin3 gene is located in chromosome 8p21.3, a region that is implicated in cancer suppression. Homozygous inactivation of the Bin3 gene in mice led to the development of cataracts and an increased likelihood of lymphomas during aging, suggesting a role for Bin3 in lens development and cancer suppression. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

Pssm-ID: 153274 Cd Length: 225 Bit Score: 45.82 E-value: 8.95e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351 1103 VISPLNQLLSMFTGPHKLVQKRFDKLLDFYNCTERAEKLKDKKT-----------LEELQSARNNYEALNAQLLDELPKF 1171
Cdd:cd07590   96 FIEPLKRLRSVFPSVNAAIKRREQSLQEYERLQAKVEKLAEKEKtgpnlakleqaEKALAAARADFEKQNIKLLEELPKF 175

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 39930351 1172 HQYAQGLFTNCVHGYAEAHCDF---VHQALEQLKPLLSL 1207
Cdd:cd07590  176 YNGRTDYFQPCFEALIKSQVLYysqSTKIFTQLAPNLDN 214

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: 41.57 E-value: 8.98e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLED-GWLEGSLKGRTGIFPYRFV 297
Cdd:cd11804    3 VAKHDFKATAEDELSFKKGSILKVLNMEDDpNWYKAELDGKEGLIPKNYI 52

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: 41.80 E-value: 9.46e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLE---DGWLEGSLKGRTGIFPYRFVKLCPDT 303
Cdd:cd12003    5 ALYDNAAESPEELSFRRGDVLMVLKREHgslPGWWLCSLHGQQGIAPANRLRLLPTA 61

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: 41.36 E-value: 9.50e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11961    2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGLFPSNYVE 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: 41.68 E-value: 9.73e-05

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLA--VVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd12142    3 RVLFDYNPVAPDELALKKGDVIEVISkeTEDEGWWEGELNGRRGFFPDNFVMP 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: 41.57 E-value: 9.77e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11796    3 RVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRRGIFPEGFV 51

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: 41.53 E-value: 1.00e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 39930351  161 DEELDFREGDVITIIG-VPEPGWFEGELEG-RRGIFPEGFVE 200
Cdd:cd11851   20 EEELSFHAGDVVRVYGpMDEDGFYYGELEGgRKGLVPSNFVQ 61

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: 41.54 E-value: 1.00e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITI---IGvPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11977    1 GTAVARYNFAARDMRELSLREGDVVRIysrIG-GDQGWWKGETNGRIGWFPSTYVE 55

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: 41.52 E-value: 1.01e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  245 GTYGVALYRFQALEPNELDFEVGDKIRILATLEDG--WLEGSLKGRTGIFPYRFVK 298
Cdd:cd11769    1 GTECIAKYNFNGASEEDLPFKKGDILTIVAVTKDPnwYKAKNKDGREGMIPANYVQ 56

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: 41.61 E-value: 1.02e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGS--LKGRTGIFPYRFVKL 299
Cdd:cd11783    3 VALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTslRTGQSGVFPGNYVQP 55

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: 41.36 E-value: 1.02e-04

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11870    2 VVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDGRVGIFPKCFVV 52

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: 41.36 E-value: 1.04e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11956    3 EAVACFDYTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMRGLIPHKYISV 55

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: 41.40 E-value: 1.09e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfkDVTGNTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11988    4 YRALYPFEARNHDEMSFNAGDIIQVDE--KTVGEPGWLYGSFQGNFGWFPCNYVEK 57

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: 41.53 E-value: 1.09e-04

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLK--GRTGIFPYRFVKL 299
Cdd:cd11935    5 AMYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGTVQrtGRTGMLPANYIEF 56

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: 41.51 E-value: 1.12e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITII-----GVpePGWFEGELEGRRGIFPEGFVELL 202
Cdd:cd12002    2 ARALYDNVPECAEELAFRKGDILTVIeqntgGL--EGWWLCSLHGRQGIAPGNRLKLL 57

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: 41.21 E-value: 1.14e-04

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEIV 59
Cdd:cd12061    1 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVREI 54

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: 41.46 E-value: 1.18e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11929    5 ALCNYRGHNPGDLKFNKGDVILLRRQLDENWYLGEINGVSGIFPASSVEV 54

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: 41.19 E-value: 1.20e-04

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11786    3 KALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQGFFPASYVQV 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: 41.33 E-value: 1.20e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEFKdvtgNTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11833    2 YVALYKFKPQENEDLEMRPGDKITLLDDS----NEDWWKGKIEDRVGFFPANFVQR 53

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: 41.08 E-value: 1.23e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLED-GWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11830    3 KARYDFCARDMRELSLKEGDVVKIYNKKGQqGWWRGEINGRIGWFPSTYVE 53

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: 41.06 E-value: 1.26e-04

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTGnteWWLAEVN-GKKGYVPSNYI 1571
Cdd:cd11912    4 VLYDYTASGDDEVSISEGEEVTVLEPDDGSG---WTKVRNGsGEEGLVPTSYI 53

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: 41.49 E-value: 1.26e-04

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLE----DGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11895    4 ALYSYTGQSPEELSFPEGALIRLLPRAQdgvdDGFWRGEFGGRVGVFPSLLVE 56

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: 41.06 E-value: 1.38e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEIV 59
Cdd:cd11921    4 RLKFDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGRVGIFPANYVEVL 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: 41.09 E-value: 1.44e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11995    4 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGLFPSNYVKL 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: 41.08 E-value: 1.45e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATL-EDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11976    4 ARYDFCARDRSELSLKEGDIIKILNKKgQQGWWRGEIYGRVGWFPANYVE 53

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: 40.89 E-value: 1.46e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSF 55
Cdd:cd11810    1 VVRALCHHVATDSGQLSFRKGDILRVIARVDDDWLLCTRGSTKGLVPLSY 50

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: 40.86 E-value: 1.47e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDvtgnTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11838    2 YIALYPYESNEPGDLTFNAGDVILVTK-KD----GEWWTGTIGDRTGIFPSNYVRP 52

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: 40.96 E-value: 1.48e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  152 ALMGLSAQLDEELDFREGDVITII----GVP-EPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11876    4 ALFDYDARGEDELTLRRGQPVEVLskdaAVSgDEGWWTGKIGDKVGIFPSNYV 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: 41.13 E-value: 1.55e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEG--ELEGRRGIFPEGFVE 200
Cdd:cd11780    3 RALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGtsERTGLFGTFPGNYVA 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: 40.79 E-value: 1.56e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12076    3 YTVIYPYTARDQDEINLEKGAVVEVIQ-KNLEG---WWKIRYQGKEGWAPASYLKK 54

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: 40.76 E-value: 1.57e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKG---RTGIFPYRF 296
Cdd:cd11821    4 ALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGdpsRRGVFPVSF 53

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: 40.76 E-value: 1.57e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLK--GRTGIFPYRFVKL 299
Cdd:cd11789    3 RAMYDYAAADDDEVSFQEGDVIINVEIIDDGWMEGTVQrtGQSGMLPANYVEL 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: 41.10 E-value: 1.66e-04

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKG--RTGIFPYRFVKL 299
Cdd:cd11924    4 VAQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITGtgRQGIFPASYVQV 56

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: 40.66 E-value: 1.66e-04

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 39930351      6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEIV 59
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVEEI 54

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: 41.16 E-value: 1.67e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11971    3 VAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVE 52

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: 41.08 E-value: 1.72e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfKD--VTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd12058    1 LWTALYDYEASGEDELSLRRGDVVEVLS-QDaaVSGDDGWWAGKIRHRLGIFPANYV 56

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: 40.91 E-value: 1.81e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEfKD--VTGNTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd12059    1 VWTAVFDYEASAEDELTLRRGDRVEVLS-KDsaVSGDEGWWTGKINDRVGIFPSNYVT 57

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: 40.75 E-value: 1.84e-04

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLK--GRTGIFPYRFVK 298
Cdd:cd11934    7 AVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGTVErtGDTGMLPANYVE 57

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: 40.70 E-value: 1.84e-04

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11856    3 VAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLE 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: 40.76 E-value: 1.87e-04

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKE---DVTGQFPSSF 55
Cdd:cd11821    2 VRALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEgdpSRRGVFPVSF 53

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: 41.00 E-value: 1.88e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEFKDvtgntEWWLAEVNGK------KGYVPSNYI 1571
Cdd:cd11847    1 IYKALWDFKARGDEELSFQAGDQFRIAERSG-----DWWTALKLDRaggvvaQGFVPNNYL 56

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: 40.78 E-value: 1.89e-04

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVP-EPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11946    2 EAIAKYDFKATADDELSFKRGDILKVLNEEcDQNWYKAELNGKDGFIPKNYIEM 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: 40.42 E-value: 1.91e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 39930351   80 QELDnlpLHRGDLVILDGIPTAGWLQGrSCWGARGFFPSSCV 121
Cdd:cd11796   14 EELD---LREGDVVTITGILDKGWFRG-ELNGRRGIFPEGFV 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: 41.18 E-value: 2.02e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfKDVTGNTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd12001    7 ALYDNVAESPDELSFRKGDIMTVLE-RDTQGLDGWWLCSLHGRQGIVPGNRLK 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: 40.79 E-value: 2.22e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKG-----RTGIFPYRFV 297
Cdd:cd11887    5 KALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEYVDsngntKEGIFPKNFV 58

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: 40.38 E-value: 2.29e-04

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11920    4 RAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYVE 53

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: 40.64 E-value: 2.41e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKIlefkdVTGNTEWW--LAEVNGKKGYVPSNYIRK 1573
Cdd:cd11848    4 ALGDYPSGGPAELSLRLGEPLTI-----VSDEGDWWkvLSEVTGRESYIPSVHVAK 54

First 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: 212947 Cd Length: 62 Bit Score: 40.80 E-value: 2.41e-04

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gi 39930351  161 DEELDFREGDVITIIGVP-EPGWFEGEL-EGRRGIFPEGFVE 200
Cdd:cd12014   20 EAELPLNAGDYVYVYGDMdEDGFYEGELlDGRRGLVPSNFVE 61

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: 40.46 E-value: 2.43e-04

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11809    3 TAQFDYTGRSERELSFKKGDSLTLYRQVSDDWWRGQLNGQDGLVPHKYITL 53

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: 40.44 E-value: 2.44e-04

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12061    4 AKFNFQQTNEDELSFSKGDVIHVTRVEE----GGWWEGTHNGRTGWFPSNYVRE 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: 40.19 E-value: 2.45e-04

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSL-KGRTGIFPYRFV 297
Cdd:cd11812    3 VALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLvNGQQGYFPANYV 52

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: 40.32 E-value: 2.45e-04

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gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIG-VPEPGWFEGELE-GRRGIFPEGFVE 200
Cdd:cd11998    2 RVRALYDYDGQEQDELSFKAGDELTKLEdEDEQGWCKGRLDsGQVGLYPANYVE 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: 40.25 E-value: 2.70e-04

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gi 39930351  150 ARALMGLSAQLDEELDFREGDVITII--GVPEP-GWFEGELEGRRGIFP 195
Cdd:cd12000    3 ARALYDNKADCSDELAFRRGDILTVLeqNVPGSeGWWKCLLHGRQGLAP 51

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: 40.11 E-value: 2.71e-04

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gi 39930351  157 SAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFP 195
Cdd:cd11832    9 SPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFP 47

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: 40.31 E-value: 2.84e-04

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILA-----TLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd12058    4 ALYDYEASGEDELSLRRGDVVEVLSqdaavSGDDGWWAGKIRHRLGIFPANYV 56

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: 40.10 E-value: 2.87e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVN-------GKKGYVPSNY 1570
Cdd:cd11773    1 VYKALYDYEPQTEDELTIQEDDILYLLEKSD----DDWWKVKLKvnssdddEPVGLVPATY 57

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: 40.04 E-value: 2.89e-04

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFeGELE-GRRGIFPEGFVEL 201
Cdd:cd11837    1 TATALYPWRAKKENHLSFAKGDIITVLEQQEMWWF-GELEgGEEGWFPKSYVKE 53

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: 40.27 E-value: 2.92e-04

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1521 VYTFKARNPNELSVSANQKLKILEfKDVTgNTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd12057    5 LFPYEAQNEDELTIKEGDIVTLIS-KDCI-DAGWWEGELNGRRGVFPDNFVK 54

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: 40.33 E-value: 2.94e-04

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVP-EPGWFEGELE-GRRGIFPEGFVE 200
Cdd:cd11997    3 RVRALYDYTGQEADELSFKAGEELLKIGEEdEQGWCKGRLLsGRIGLYPANYVE 56

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: 2.94e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  250 ALYRFQALEPNE------LDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11932    4 ALYNFDLKEKNReeskdcLKFQKDDIITVISRVDENWAEGKLGDQVGIFPILFV 57

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: 40.31 E-value: 3.00e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11929    2 RAKALCNYRGHNPGDLKFNKGDVILLRRQLDENWYLGEINGVSGIFPASSVEV 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: 39.94 E-value: 3.04e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 39930351  158 AQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11766   10 AQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYVT 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: 40.28 E-value: 3.08e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKG--RTGIFPYRFVKL 299
Cdd:cd11923    4 VAKYNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPGtnRQGIFPVSYVEV 56

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: 3.14e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFP 293
Cdd:cd11824    3 SVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVP 47

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: 40.09 E-value: 3.22e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  152 ALMGLSAQLDEELDFREGDVITIIGvPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11838    4 ALYPYESNEPGDLTFNAGDVILVTK-KDGEWWTGTIGDRTGIFPSNYVRP 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: 39.77 E-value: 3.22e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNY 1570
Cdd:cd11818    4 ALYDFTGENEDELSFKAGDIITELESID----EEWMSGELRGKSGIFPKNF 50

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: 40.01 E-value: 3.34e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLE---DGWLEGS--LKGRTGIFPYRF 296
Cdd:cd11886    3 IVIHDFNARSEDELTLKPGDKIELIEDDEefgDGWYLGRnlRTGETGLFPVVF 55

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: 40.00 E-value: 3.35e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11963    4 VRALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGLFPSNFV 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: 40.03 E-value: 3.46e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILefKDVTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11875    4 VLFDYEAENEDELTLREGDIVTIL--SKDCEDKGWWKGELNGKRGVFPDNFV 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: 39.98 E-value: 3.53e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLG--KKEDVTGQFPSSFVEIV 59
Cdd:cd11916    5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGtsRRTKQFGTFPGNYVKLL 58

Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (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: 212784 Cd Length: 56 Bit Score: 40.09 E-value: 3.54e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFkdvTGNTEWWLAEV--NGKKGYVPSNYI 1571
Cdd:cd11850    4 ALYDFVASGENQLSIKKGEQLRVLGY---NKNGEWCEAESksTGGQGWVPSNYI 54

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: 40.14 E-value: 3.56e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  253 RFQALEP------NELDFEVGDKIRILATLEDGWLEGSLK--GRTGIFPYRFVK 298
Cdd:cd11785    1 RYRVIVPyppqseAELELKEGDIVFVHKKREDGWFKGTLQrtGKTGLFPGSFVE 54

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: 39.80 E-value: 3.61e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSL-KGRTGIFPYRFV 297
Cdd:cd12009    3 IAQYDFVPSNERDLQLKKGEKLQVLKSDGEWWLAKSLtTGKEGYIPSNYV 52

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: 39.93 E-value: 3.80e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFP 293
Cdd:cd11984    4 IAVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRTGWFP 48

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: 39.89 E-value: 4.02e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351     71 FVCICEFTSQELDNLPLHRGDLV-ILDGIPTaGWLQGRSCwGARGFFPSSCVREL 124
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVkVLGKDND-GWWEGETG-GRVGLVPSTAVEEI 54

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: 39.99 E-value: 4.06e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 39930351    4 GSVVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLG--KKEDVTGQFPSSFVEIV 59
Cdd:cd11933    1 GKSFRAMYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGtvQRTGKTGMLPANYVEAI 58

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: 39.66 E-value: 4.16e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11974    3 AEALWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFVRL 54

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: 39.63 E-value: 4.22e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKK--EDVTGQFPSSFVE 57
Cdd:cd11793    2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGERlrDGERGWFPSSYTE 54

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: 39.64 E-value: 4.27e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgntEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11990    4 ALCSWTAKKDNHLNFSKNDIITVLEQQE-----NWWFGEVHGGRGWFPKSYVK 51

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: 39.99 E-value: 4.47e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEIVTIPS 63
Cdd:cd11972    5 VVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVESIMHYS 61

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: 40.00 E-value: 4.62e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAV-----VDEFWLLGKKEDVT--GQFPSSFVE 57
Cdd:cd11790    5 VRATHDYTAEDTDELTFEKGDVILVIPFddpeeQDEGWLMGVKESTGcrGVFPENFTE 62

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: 39.66 E-value: 5.02e-04

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11974    2 YAEALWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFVRL 54

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: 39.29 E-value: 5.26e-04

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQ--FPSSFVE 57
Cdd:cd11858    3 KALYDFAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDESKEgwVPAAYLE 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: 39.37 E-value: 5.30e-04

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTgnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11820    5 ALYDFEAAEDNELTFKAGEIITVLDDSDPN----WWKGSNHRGEGLFPANFVTA 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: 39.42 E-value: 5.57e-04

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVL---AVV--DEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11876    4 ALFDYDARGEDELTLRRGQPVEVLskdAAVsgDEGWWTGKIGDKVGIFPSNYV 56

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: 39.22 E-value: 5.68e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDvtgnTEWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11992    2 YIALYPYSSSEPGDLTFNEGEEILVTQ-KD----GEWWTGSIEDRTGIFPSNYVR 51

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: 39.33 E-value: 5.80e-04

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  250 ALYRFQALEPNELDFEVGDKI-RILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd12064    5 ALYACKAEHDSELSFTAGTVFdNVHPSQEPGWLEGTLNGKTGLIPENYVEF 55

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: 39.28 E-value: 5.82e-04

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11974    5 ALWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFVRL 54

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: 39.61 E-value: 5.94e-04

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  248 GVALYRFQALEPNELDFEVGDKIRILATL--EDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11977    3 AVARYNFAARDMRELSLREGDVVRIYSRIggDQGWWKGETNGRIGWFPSTYVE 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: 39.60 E-value: 6.03e-04

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEG-SLK-GRTGIFPYRFV 297
Cdd:cd11925    4 LALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGtSLRtGVSGVFPGNYV 54

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: 39.44 E-value: 6.08e-04

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfkdvTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11956    6 ACFDYTGRTAQELSFKRGDVLLLHS----KASSDWWRGEHNGMRGLIPHKYI 53

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: 39.27 E-value: 6.32e-04

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gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGE-LEGRRGIFPEGFVE 200
Cdd:cd11758    4 RALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNARnSEGKTGMIPVPYVE 54

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: 39.22 E-value: 6.34e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLG--KKEDVTGQFPSSFVEIV 59
Cdd:cd11935    2 TYRAMYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGtvQRTGRTGMLPANYIEFV 57

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: 39.16 E-value: 6.42e-04

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11927    3 AKALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNGIHGFFPTNFVQI 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: 39.19 E-value: 6.75e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEG-----SLKGRTGIFP 293
Cdd:cd11883    3 VALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGviissSGKVKRGWFP 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: 38.93 E-value: 6.78e-04

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11827    2 CKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 52

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: 39.14 E-value: 6.81e-04

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11928    4 KALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCHGFLPASYIQC 54

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: 39.36 E-value: 6.91e-04

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gi 39930351  152 ALMGLSAQLDEELDFREGDVITIIGVP-----EPGWFEGELEGRRGIFPEGFV 199
Cdd:cd12059    4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsgDEGWWTGKINDRVGIFPSNYV 56

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: 39.23 E-value: 7.09e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEIV 59
Cdd:cd11971    2 VVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVESI 54

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: 39.16 E-value: 7.21e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11964    5 AIYDFEAAEDNELTFKAGDIITILDDSD----PNWWKGETPQGTGLFPSNFV 52

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: 38.96 E-value: 7.25e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351   70 LFVCICEFTSQELDNLPLHRGDLVILDGIPTAGWLQGRSCwGARGFFPSSC 120
Cdd:cd11832    1 YFIAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVR-GRTGWFPSDC 50

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: 39.09 E-value: 7.44e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 39930351  164 LDFREGDVITIIGVP--EPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd12068   16 LSFHRGDLIKLLPMAglEPGWQFGSTGGRSGLFPADIVQP 55

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: 39.62 E-value: 7.59e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 39930351    4 GSVV--RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11973   15 GSVVcaEALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFVRL 71

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: 38.99 E-value: 7.91e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1516 QVYFAvytFKARNPNELSVSANQKLKILefKDVTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd12142    3 RVLFD---YNPVAPDELALKKGDVIEVI--SKETEDEGWWEGELNGRRGFFPDNFV 53

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: 39.02 E-value: 8.10e-04

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGEL--EGRRGIFPEGFV 199
Cdd:cd11889    2 VKAVYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLrrNGAEGIFPSNFV 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: 39.05 E-value: 8.15e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTgnteWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11949    4 ALFDFDPQEDGELGFRRGDFIEVMDNSDPN----WWKGACHGQTGMFPRNYVT 52

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: 38.99 E-value: 8.28e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  152 ALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGE--LEGRRGIFPEGFV 199
Cdd:cd11784    4 ALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLslVTGRVGIFPSNYV 53

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: 38.85 E-value: 8.31e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    8 RAIFDFCPSVSEE---LPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSF 55
Cdd:cd11787    3 KALYDFEMKDEDEkdcLTFKKGDVITVIRRVDENWAEGRLGDKIGIFPISF 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: 38.94 E-value: 8.39e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12015    2 YVVVADYKKQQPNEISLRAGDVVDVIE-KNENG---WWFVSLEDEQGWVPATYLEP 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: 38.84 E-value: 8.58e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELE--GRRGIFPEGFVE 200
Cdd:cd11933    5 RAMYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGTVQrtGKTGMLPANYVE 56

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: 38.93 E-value: 8.65e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATlEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11989    4 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 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: 38.81 E-value: 8.85e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351 1520 AVYTFKARNPNELSVSANQKlkileFKDVTGNTE--WWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11882    4 ALYACKAEDESELSFEPGQI-----ITNVQPSDEpgWLEGTLNGRTGLIPENYVE 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: 38.92 E-value: 8.86e-04

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11975    9 AVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDEEGWFPASFVRL 58

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: 38.85 E-value: 8.90e-04

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  149 QARALMGL-SAQLDEE--LDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGF 198
Cdd:cd11787    1 QCKALYDFeMKDEDEKdcLTFKKGDVITVIRRVDENWAEGRLGDKIGIFPISF 53

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: 38.82 E-value: 8.95e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 39930351    3 AGSVVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDV--TGQFPSSFVEIV 59
Cdd:cd11934    1 GGKRYRAVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGTVERTgdTGMLPANYVEAI 59

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: 39.04 E-value: 9.31e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfKDvTGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd12056    6 ALFHYEGTNEDELDFKEGEIILIIS-KD-TGEPGWWKGELNGKEGVFPDNFV 55

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: 38.61 E-value: 9.36e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSF 55
Cdd:cd11817    4 ALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50

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: 9.44e-04

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1520 AVYTFKARNPNELsvsanqKLKILEFKDVTGNTE--WWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12055    4 VAFSYLPQNEDEL------ELKVGDIIEVVGEVEegWWEGVLNGKTGMFPSNFIKE 53

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: 38.65 E-value: 1.01e-03

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    8 RAIFDFCPSVSEE-LPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11829    3 RTLYAFTGEQHQQgLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 52

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: 38.62 E-value: 1.05e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 39930351  256 ALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11759   14 AYDKTALALEVGDLVKVTKINVSGQWEGELNGKVGHFPFTHVEL 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: 38.51 E-value: 1.05e-03

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1292 AERNFNAAQDLDVSLLEGDLVGVIKKKDPMGSQNRWLIDNGVTKGFVYSSFLKP 1345
Cdd:cd11800    4 ALYTFEARSPGELSVTEGQVVTVLEKHDLKGNPEWWLVEDRGKQGYVPSNYLAK 57

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: 38.59 E-value: 1.11e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATL-----EDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd12059    1 VWTAVFDYEASAEDELTLRRGDRVEVLSKDsavsgDEGWWTGKINDRVGIFPSNYV 56

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: 38.51 E-value: 1.14e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11824    3 SVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLEK 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: 38.45 E-value: 1.14e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPE--PGWFEGE-LEGRRGIFPEGFVEL 201
Cdd:cd11767    2 VVALYPFTGENDEELSFEKGERLEIIEKPEddPDWWKARnALGTTGLVPRNYVEV 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: 38.50 E-value: 1.15e-03

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGK-KEDVTGQFPSSFVE 57
Cdd:cd11758    3 VRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNARnSEGKTGMIPVPYVE 54

Src homology 3 domain of JNK-interacting protein 1; JNK-interacting protein 1 (JIP1) is also called Islet-brain 1 (IB1) or Mitogen-activated protein kinase 8-interacting protein 1 (MAPK8IP1). It is highly expressed in neurons, where it functions as an adaptor linking motor to cargo during axonal transport. It also affects microtubule dynamics in neurons. JIP1 is also found in pancreatic beta-cells, where it is involved in regulating insulin secretion. In addition to a JNK binding domain, JIP1 also contains SH3 and Phosphotyrosine-binding (PTB) domains. Its SH3 domain homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212876 Cd Length: 55 Bit Score: 38.43 E-value: 1.18e-03

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                 ....*....|....*....|....*....|....*....|....*.
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEG--SLKGRTGIFP 293
Cdd:cd11943    4 AVFRFVPRHPDELELEVDDPLLVEVQAEDYWYEAynMRTGARGIFP 49

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: 38.39 E-value: 1.18e-03

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  250 ALYRFQALEPNELDFEVGDKiriLATLED----GWLEGSL-KGRTGIFPYRFVK 298
Cdd:cd11998    5 ALYDYDGQEQDELSFKAGDE---LTKLEDedeqGWCKGRLdSGQVGLYPANYVE 55

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: 38.67 E-value: 1.20e-03

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gi 39930351   77 FTSQELDNLPLHRGDLVILDGIPTAGWLQG-RSCWGARGFFPSSCVRE 123
Cdd:cd11938    8 YTAKQPDELSLQQADVVLVLQTESDGWYYGeRLRDGERGWFPSSCAKE 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: 38.25 E-value: 1.21e-03

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                 ....*....|....*....|....*....|....*....|....*..
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILAtlED---GWLEGSLKGRTGIFP 293
Cdd:cd11778    4 ALYDYEAQGDDEISIRVGDRIAVIR--GDdgsGWTYGEINGVKGLFP 48

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: 38.50 E-value: 1.23e-03

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                 ....*....|....*....|....*....|....*....|....*...
gi 39930351   74 ICEFTSQELDNLPLHRGDLVILDGIPTAGWLQGRsCWGARGFFPSSCV 121
Cdd:cd11786    5 LYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGE-CNGKQGFFPASYV 51

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: 38.48 E-value: 1.24e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEP---GWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11844    2 ARALYDNVAESPDELAFRRGDILTVLEQNTAgleGWWLCSLRGRQGIAPGNRLKL 56

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: 38.17 E-value: 1.25e-03

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11840    2 VIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVE 52

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: 38.43 E-value: 1.27e-03

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gi 39930351 1528 NPN----ELSVSANQKLKILEFKDVTGnteWWLAEVNGKKGYVPSNYI 1571
Cdd:cd12012   16 NPDaaeeELPFKEGQLIKVYGDKDADG---FYLGEINGRRGLVPCNMV 60

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: 38.27 E-value: 1.29e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgntEWWLAE--VNGKKGYVPSNYIRK 1573
Cdd:cd12005    4 ALYSYEPSHDGDLGFEKGEKLRILEQSG-----EWWKAQslTTGQEGFIPFNFVAK 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: 38.23 E-value: 1.30e-03

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351   73 CICEFTSQELDNLPLHRGDLVILDGIPTAGWLQG-RSCWGARGFFPSSCVRE 123
Cdd:cd11940    4 CIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGvRLSDGERGWFPQSHVEE 55

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: 38.43 E-value: 1.32e-03

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  248 GVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKG--RTGIFPYRFVKL 299
Cdd:cd11922    3 AIAKFNFNGDTQVEMSFRKGERITLLRQVDENWYEGRIPGtsRQGIFPITYVDV 56

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: 38.16 E-value: 1.34e-03

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                 ....*....|....*....|....*....|....*....|....*....
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11816    3 VARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51

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: 38.32 E-value: 1.38e-03

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfKDVTGNTEWWLAEVNGKKGYVPSN 1569
Cdd:cd12000    5 ALYDNKADCSDELAFRRGDILTVLE-QNVPGSEGWWKCLLHGRQGLAPAN 53

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: 38.40 E-value: 1.41e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLG--KKEDVTGQFPSSFVEIV 59
Cdd:cd11918    5 KAVYQYRPQNEDELELREGDRVDVMQQCDDGWFVGvsRRTQKFGTFPGNYVAPV 58

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: 37.99 E-value: 1.49e-03

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351   69 RLFVCICEFTSQELDNLPLHRGDLVILDGIPTAGWLQGrSCWGARGFFPSSCV 121
Cdd:cd11983    1 RHFVVVKSYQPQVEGEIPLHKGDRVKVLSIGEGGFWEG-SARGHVGWFPAECV 52

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: 38.08 E-value: 1.59e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATL-EDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd11978    4 IARYDFCARDMRELSLLKGDVVKIYTKMsTNGWWRGEVNGRVGWFPSTYVE 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: 38.27 E-value: 1.62e-03

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                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLK-GRTGIFPYRFV 297
Cdd:cd12005    3 VALYSYEPSHDGDLGFEKGEKLRILEQSGEWWKAQSLTtGQEGFIPFNFV 52

Third 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 third 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: 213011 Cd Length: 53 Bit Score: 38.13 E-value: 1.68e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12078    2 YYTIADFQTTIPDGISFQAGLKVEVIE-KNLSG---WWYIQIEDKEGWAPATFIDK 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: 38.08 E-value: 1.70e-03

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITI-IGVPEPGWFEGELEGRRGIFPEGFVE 200
Cdd:cd11978    1 GIAIARYDFCARDMRELSLLKGDVVKIyTKMSTNGWWRGEVNGRVGWFPSTYVE 54

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: 37.83 E-value: 1.71e-03

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKK-GYVPSNYI 1571
Cdd:cd11774    4 ALYDYDKQTEEELSFNEGDTLDVYDDSD----SDWILVGFNGTQfGFVPANYI 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: 37.88 E-value: 1.74e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTgnteWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd11950    4 ALYDFEALEDDELGFNSGDVIEVLDSSNPS----WWKGRLHGKLGLFPANYVA 52

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: 38.01 E-value: 1.79e-03

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVN-GKKGYVPSNYI 1571
Cdd:cd11907    5 ALYDFLPREPSNLALKRAEEYLILEQYD----PHWWKARDRyGNEGLIPSNYV 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: 37.84 E-value: 1.83e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNY 1570
Cdd:cd11817    4 ALYDFTGETEEDLSFQRGDRILVTEHLD----AEWSRGRLNGREGIFPRAF 50

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: 37.88 E-value: 1.96e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPGWF--EGELEGRRGIFPEGFVEL 201
Cdd:cd11865    1 RAVALYDFEPEHDNELGFAEGQILFILYKHGQGWLiaEDESGGKTGLVPEEFVSY 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: 37.69 E-value: 1.99e-03

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                 ....*....|....*....|....*....|....*....|....*..
gi 39930351   76 EFTSQELDNLPLHRGD-LVILDGIPTAGWLQGRSCWGARGFFPSSCV 121
Cdd:cd11763    7 DFDSQPSGELSLRAGEvLTITRQDVGDGWLEGRNSRGEVGLFPSSYV 53

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: 2.07e-03

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVtgnteWWLAEV-NGKKGYVPSNYI 1571
Cdd:cd11837    4 ALYPWRAKKENHLSFAKGDIITVLEQQEM-----WWFGELeGGEEGWFPKSYV 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: 37.90 E-value: 2.08e-03

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 39930351  164 LDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFV 199
Cdd:cd11932   22 LKFQKDDIITVISRVDENWAEGKLGDQVGIFPILFV 57

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: 37.70 E-value: 2.13e-03

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILefKDVTGNteWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11781    4 ALYPFKAQSAKELSLKKGDIIYIR--RQIDKN--WYEGEHNGRVGIFPASYV 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: 37.74 E-value: 2.22e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 39930351  249 VALYRF--QALEPN-----ELDFEVGDKIRILATL-EDGWLEGSLKGRTGIFPYRFVK 298
Cdd:cd12013    3 VALFDYdpRESSPNvdaevELSFRAGDIITVFGEMdEDGFYYGELNGQRGLVPSNFLE 60

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: 37.77 E-value: 2.27e-03

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                 ....*....|....*....|....*....|....*....|....
gi 39930351  158 AQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11809   10 GRSERELSFKKGDSLTLYRQVSDDWWRGQLNGQDGLVPHKYITL 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: 37.67 E-value: 2.33e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 39930351  161 DEELDFREGDVITIIGV-PEPGWFEGE-LEGRRGIFPEGFVE 200
Cdd:cd11769   15 EEDLPFKKGDILTIVAVtKDPNWYKAKnKDGREGMIPANYVQ 56

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: 37.76 E-value: 2.42e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtGNTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11841    4 ALYSFEGQQPCDLSFQAGDRITVLTRTD--SQFDWWEGRLRGRVGIFPANYV 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: 37.95 E-value: 2.50e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDVTGNTeWWLAEVNGKKGYVPSNYIR 1572
Cdd:cd12003    5 ALYDNAAESPEELSFRRGDVLMVLKREHGSLPG-WWLCSLHGQQGIAPANRLR 56

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: 37.71 E-value: 2.57e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 39930351  252 YRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11901    8 FNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYV 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: 37.70 E-value: 2.57e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEV--NGKK---GYVPSNYIRK 1573
Cdd:cd11839    4 VIAPFTATAENQLSLAVGQLVLVRK-KSPSG---WWEGELqaRGKKrqiGWFPANYVKL 58

First 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: 212728 Cd Length: 51 Bit Score: 37.49 E-value: 2.68e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFV 297
Cdd:cd11794    4 AIFDFCPSVSEELPLFAGDVIEVLKVVDEFWLLGTKEGVTGQFPSSFV 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: 37.51 E-value: 2.69e-03

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 39930351   18 SEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd11932   19 KDCLKFQKDDIITVISRVDENWAEGKLGDQVGIFPILFV 57

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: 37.77 E-value: 2.70e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  146 SMGQARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11975    3 SIVSAEAVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDEEGWFPASFVRL 58

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: 37.47 E-value: 2.70e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGS-LKGRTGIFPYRFVKL 299
Cdd:cd11962    3 VVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTnSKGESGLFPSNYVEL 54

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: 37.67 E-value: 2.79e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRT-GIFPYRFV 297
Cdd:cd12004    3 VALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARSLTTKKeGFIPSNYV 52

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: 37.47 E-value: 2.81e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 39930351   76 EFTSQELDNLPLHRGDLV-ILDGiPTAGWLQGRSCwGARGFFPSSCV 121
Cdd:cd11951    7 DFSAEDPSQLSFRRGDIIeVLDC-PDPNWWRGRIS-GRVGFFPRNYV 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: 37.29 E-value: 3.10e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd12060    3 VVKARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVR 54

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: 37.33 E-value: 3.24e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLeGSLKGRTGIFPYRFVKL 299
Cdd:cd11990    4 ALCSWTAKKDNHLNFSKNDIITVLEQQENWWF-GEVHGGRGWFPKSYVKL 52

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: 37.29 E-value: 3.30e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVN-GKKGYVPSNYI 1571
Cdd:cd11819    4 ALYDYQAAEDNEISFVEGDIITQIEQID----EGWWLGVNAkGQKGLFPANYV 52

Src Homology 3 domain of SH3 domain and tetratricopeptide repeat-containing (SH3TC) proteins and similar domains; This subfamily is composed of vertebrate SH3TC proteins and hypothetical fungal proteins containing BAR and SH3 domains. Mammals contain two SH3TC proteins, SH3TC1 and SH3TC2. The function of SH3TC1 is unknown. SH3TC2 is localized in Schwann cells in the peripheral nervous system, where it interacts with Rab11 and plays a role in peripheral nerve myelination. Mutations in SH3TC2 are associated with Charcot-Marie-Tooth disease type 4C, a severe hereditary peripheral neuropathy with symptoms that include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. 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: 212818 Cd Length: 55 Bit Score: 37.30 E-value: 3.31e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  149 QARALMGLSAQLDEELDFREGDVITIIGVPEPG--WFEG--ELEGRRGIFP 195
Cdd:cd11885    1 SCTAKMDFEGVEPGELSFRQGDSIEIIGDLIPGlqWFVGrsKSSGRVGFVP 51

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: 37.34 E-value: 3.34e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRIlatLEDGWLEGSLKGRT-----GIFPYRFVKL 299
Cdd:cd11761    5 KVLYSYEAQRPDELTITEGEELEV---IEDGDGDGWVKARNksgevGYVPENYLQF 57

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: 37.05 E-value: 3.53e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12016    3 YITTQAYKAENEDEIGFETGVVVEVIQ-KNLDG---WWKIRYQGKEGWAPATYLKK 54

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: 37.00 E-value: 3.61e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11809    4 AQFDYTGRSERELSFKKGDSLTLYRQVS----DDWWRGQLNGQDGLVPHKYI 51

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: 3.68e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351    4 GSVVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLG--KKEDVTGQFPSSFVE 57
Cdd:cd11917    4 GEPFQALYNYMPRNEDELELREGDVIDVMEKCDDGWFVGtsRRTKFFGTFPGNYVK 59

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: 37.31 E-value: 3.74e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEV-LAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11978    5 ARYDFCARDMRELSLLKGDVVKIyTKMSTNGWWRGEVNGRVGWFPSTYVE 54

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: 36.88 E-value: 3.85e-03

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEfkDVTGNtEWWLAE--VNGKKGYVPSNY 1570
Cdd:cd11878    4 ALYDYRAQTPGELSFSKGDFFHVIG--EEDQG-EWYEATnpVTGKRGLVPKSY 53

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: 36.99 E-value: 4.05e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVL-----AVVDEFW---LLGKKedvtGQFPSSFVEI 58
Cdd:cd11762    2 VRALYDYEAQSDEELSFPEGAIIRILrkddnGVDDGWWegeFNGRV----GVFPSLVVEE 57

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: 36.91 E-value: 4.07e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11920    5 AVYDFKAQTSKELSFKKGDTVYILRKID----QNWYEGEHHGRVGIFPISYVEK 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: 36.95 E-value: 4.08e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLA--VVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11836    3 RALYAFEARNPDEISFQPGDIIQVDEsqVAEPGWLAGELKGKTGWFPANYVE 54

Src homology 3 domain of Srms Protein Tyrosine Kinase; Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (Srms) is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. 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, Srms 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. 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: 212780 Cd Length: 55 Bit Score: 37.06 E-value: 4.17e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1518 YFAVYTFKARNPNELSVSANQKLKILE-------FKDVTGNTEwwlaevngkKGYVPSNYIRK 1573
Cdd:cd11846    2 FTALYDFTARSTHELSVEQGDKLCVIEeegdyifARKLTGNPE---------SGLVPASYVAQ 55

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: 36.94 E-value: 4.34e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRIL---ATLEDGWLEGSLKGRTGIFPYRFVKL 299
Cdd:cd11844    4 ALYDNVAESPDELAFRRGDILTVLeqnTAGLEGWWLCSLRGRQGIAPGNRLKL 56

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: 36.88 E-value: 4.51e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEI 58
Cdd:cd11996    3 VIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 54

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: 36.93 E-value: 4.58e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEF---WLLGK--KEDVTGQFPSSF 55
Cdd:cd11886    1 LLIVIHDFNARSEDELTLKPGDKIELIEDDEEFgdgWYLGRnlRTGETGLFPVVF 55

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: 36.91 E-value: 4.71e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 39930351 1289 LFQAERNFNAAQDLDVSLLEGDLVGVIKKKDpmgsQNRWLIDNGV-TKGFVYSSFLKP 1345
Cdd:cd11770    1 LYEALSDFQAEQEGDLSFKKGEVLRIISKRA----DGWWLAENSKgNRGLVPKTYLKV 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: 36.89 E-value: 4.79e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGI-FPEGFVE 200
Cdd:cd11970    7 KALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 57

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: 36.58 E-value: 4.81e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11824    2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLEK 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: 36.80 E-value: 5.25e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1522 YTFKARNPNELSVSANQKLKILEfKDVTGnteWWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd12052    6 FDYKAQHEDELTITVGDIITKIK-KDDGG---WWEGEIKGRRGLFPDNFVRE 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: 36.72 E-value: 5.27e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFV 56
Cdd:cd12047    2 MVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDGRIGIFPKCFA 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: 36.45 E-value: 5.34e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 39930351    9 AIFDFCPSVSEELPLFVGDIIEVLAVV-DEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11830    4 ARYDFCARDMRELSLKEGDVVKIYNKKgQQGWWRGEINGRIGWFPSTYVE 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: 36.48 E-value: 5.39e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1522 YTFKARNPNELSVsanQKLKILefKDVTGNTE-WWLAEVNGKKGYVPSNYIRK 1573
Cdd:cd11873    6 FDYDAEEPDELTL---KVGDII--TNVKKMEEgWWEGTLNGKRGMFPDNFVKV 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: 36.87 E-value: 5.47e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 39930351  250 ALYRFQALEP-NELDFEVGDKIRILATL-----EDGWLEGSLK-GRTGIFPYRFV 297
Cdd:cd11771    4 ALYDFTPENPeMELSLKKGDIVAVLSKTdplgrDSEWWKGRTRdGRIGWFPSNYV 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: 36.68 E-value: 5.50e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    8 RAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLG--KKEDVTGQFPSSFVE 57
Cdd:cd11785    3 RVIVPYPPQSEAELELKEGDIVFVHKKREDGWFKGtlQRTGKTGLFPGSFVE 54

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: 36.33 E-value: 5.67e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGkkEDVTGQ---FPSSFV 56
Cdd:cd11812    2 VVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFG--SLVNGQqgyFPANYV 52

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: 36.33 E-value: 6.02e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 39930351  152 ALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGEL-EGRRGIFPEGFV 199
Cdd:cd11812    4 ALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLvNGQQGYFPANYV 52

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: 36.41 E-value: 6.08e-03

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                 ....*....|....*....|....*....|....*....|....*..
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILA-TLEDGWLEGSLK-GRTGIFP 293
Cdd:cd11845    3 VALYDYEARTDDDLSFKKGDRLQILDdSDGDWWLARHLStGKEGYIP 49

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: 36.37 E-value: 6.18e-03

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351  247 YGVALYRFQALEPNELDFEVGDKIRILATLED--GWLEGSLKGRTGIFPYRFV 297
Cdd:cd12044    1 YYQGLWDCFGDNPDELSFQRGDLIYILSKEYNmyGWWVGELNGIVGIVPKDYL 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: 36.59 E-value: 6.21e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 39930351  148 GQARALMGLSAQLDEELDFREGDVITII---GVPEPGWFEGELEGRRGIFPEgfvELLG 203
Cdd:cd11807    1 GVVYALFDYEAENGDELSFREGDELTVLrkgDDDETEWWWARLNDKEGYVPR---NLLG 56

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: 36.27 E-value: 6.30e-03

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gi 39930351  151 RALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGF 198
Cdd:cd11810    3 RALCHHVATDSGQLSFRKGDILRVIARVDDDWLLCTRGSTKGLVPLSY 50

Src homology 3 domain of yeast cell fusion protein Fus1p; Fus1p is required at the cell surface for cell fusion during the mating response in yeast. It requires Bch1p and Bud7p, which are Chs5p-Arf1p binding proteins, for localization to the plasma membrane. It acts as a scaffold protein to assemble a cell surface complex which is involved in septum degradation and inhibition of the NOG pathway to promote cell fusion. The SH3 domain of Fus1p interacts with Bin1p, a formin that controls the assembly of actin cables in response to Cdc42 signaling. It has been shown to bind the motif, R(S/T)(S/T)SL, instead of PxxP motifs. 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: 212788 [Multi-domain] Cd Length: 56 Bit Score: 36.53 E-value: 6.50e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351 1517 VYFAVYTFKARNPNELSVSANQKLKIL-EFKDvtgntEWWLAE----VNGKKGYVP 1567
Cdd:cd11854    1 LMTVISTFEPSLDDELLIKVGETVRVLaEYDD-----GWCLVEradgLNGDRGMVP 51

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: 36.16 E-value: 6.51e-03

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 39930351 1520 AVYTFKARNPNELsvsanqKLKILEFKDVTGNTE--WWLAEVNGKKGYVPSNYI 1571
Cdd:cd11874    4 VLFSYTPQNEDEL------ELKVGDTIEVLGEVEegWWEGKLNGKVGVFPSNFV 51

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: 36.12 E-value: 6.54e-03

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    6 VVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11772    1 VFRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYVE 52

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: 36.48 E-value: 6.62e-03

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                 ....*....|....*....|....*....|.
gi 39930351   91 DLVILDGIPTAGWLQGRSCWGARGFFPSSCV 121
Cdd:cd11896   23 ELVIFSENSLDGWLQGQNSRGETGLFPASYV 53

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: 36.32 E-value: 7.01e-03

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gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGK--KEDVTGQFPSSFV 56
Cdd:cd11889    2 VKAVYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKlrRNGAEGIFPSNFV 53

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 36.06 E-value: 7.19e-03

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gi 39930351     74 ICEFTSQELDNLPLHRGDLVILDGIPTAGWLQGRSCwGARGFFPSSCVR 122
Cdd:pfam14604    2 LYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINT-GRTGLVPANYVE 49

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: 36.92 E-value: 7.20e-03

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEPGWFEGELEGRRGIFPEGFVEL 201
Cdd:cd11973   20 AEALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFVRL 71

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: 36.03 E-value: 7.32e-03

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                   ....*....|....*....|....*....|....*....|..
gi 39930351     77 FTSQELDNLPLHRGDLVILDGIPTAGWLQGRSCWGARGFFPS 118
Cdd:pfam00018    6 YTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGKEGLIPS 47

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: 36.13 E-value: 7.66e-03

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 39930351  250 ALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLK--GRTGIFPYRFVK 298
Cdd:cd11780    4 ALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGTSErtGLFGTFPGNYVA 54

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: 36.56 E-value: 8.15e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 39930351  150 ARALMGLSAQLDEELDFREGDVITIIGVPEP---GWFEGELEGRRGIFPEGFVELL 202
Cdd:cd12001    5 AKALYDNVAESPDELSFRKGDIMTVLERDTQgldGWWLCSLHGRQGIVPGNRLKIL 60

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: 36.16 E-value: 8.31e-03

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILEFKDvtgnTEWWLAEVNGKK-GYVPSNYI 1571
Cdd:cd11825    4 ALYDYRAQRPDELSFCKHAIITNVEKED----GGWWRGDYGGKKqKWFPANYV 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: 35.86 E-value: 8.84e-03

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351    7 VRAIFDFCPSVSEELPLFVGDIIEVLAVVDE-FWLLGKKEDVTGQFPSSFVE 57
Cdd:cd11843    2 VRALYDYEGQESDELSFKAGDILTKLEEEDEqGWCKGRLDGRVGLYPANYVE 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: 35.79 E-value: 9.19e-03

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 39930351 1520 AVYTFKARNPNELSVSANQKLKILefKDVTGNteWWLAEVNGKKGYVPSNYI 1571
Cdd:cd11782    4 AKYNFNADTGVELSFRKGDVITLT--RRVDEN--WYEGRIGGRQGIFPVSYV 51

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: 35.77 E-value: 9.59e-03

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                 ....*....|....*....|....*....|....*....|....*..
gi 39930351  157 SAQLDEELDFREGDVITIIGVPE---PGWFEGE--LEGRRGIFPEGF 198
Cdd:cd11886    9 NARSEDELTLKPGDKIELIEDDEefgDGWYLGRnlRTGETGLFPVVF 55

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: 35.83 E-value: 9.85e-03

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                 ....*....|....*....|....*....|....*....|....*
gi 39930351  249 VALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFP 293
Cdd:cd11806    3 VAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIP 47