SLA1 homology domain 1, SHD1; NPFXD peptides specifically interact with the SHD1 domain. NPFXD is a clathrin-facilitated endocytic targeting signal. NPFXD was originally discovered in the cytoplasmic domain of the furin-like protease Kex2p. Sla1 is thought to function as an endocytic adaptor.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19115125    641 SVSKPDSSKLRTWTDRTGAFKVEAEFLGYSDDKIHLHKTNGVKISVPSAKMSYKDLDYVELMTGKK 706
Cdd:pfam03983    1 SKSKPDPAKVRTWTDRTGTFKVEAQFLGFKDGKIRLHKTNGVKIAVPVEKMSKEDLEYVERVTGKS 66

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 19115125  511 KMGTVLYDFIAEAADELTVKANMRVVIVNDTASSDWWKCSVD--GKEGVVPSNFIKP 565
Cdd:cd11775    1 KRGKVLYDFDAQSDDELTVKEGDVVYILDDKKSKDWWMVENVstGKEGVVPASYIEI 57

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 19115125    9 IYKVLYSYEPQEinpgeeipenEREISIVEDEIVCLLEKGEDDWYLVKRNVNSNDDDEEIGIVPSNY 75
Cdd:cd11773    1 VYKALYDYEPQT----------EDELTIQEDDILYLLEKSDDDWWKVKLKVNSSDDDEPVGLVPATY 57

Domain of unknown function (DUF1720); This domain is found in different combinations with cortical patch components EF hand, SH3 and ENTH and is therefore likely to be involved in cytoskeletal processes. This family contains many hypothetical proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1140 MQPQATGIISQptgiraQATGIMTQPTGLHTQATGMMQPtgmQPQATGIMPQATGMMQPTGMQPQVTG-IMPQSMPMQPQ 1218
Cdd:pfam08226    1 MQPQQTGYMPP------QQQQPQQTQQPLQPQPTGFMPQ---QQTGQGLQPQPTGMGQFQPLQPQQTGfQPQAQQGLQPQ 71

                   ...
gi 19115125   1219 MTG 1221
Cdd:pfam08226   72 ATG 74

DNA translocase FtsK; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   918 PSPPATRPKSTTPQKFDDDAWANKPVTEPPVRASSVTVEPARVTESMNKMNISEEAKKPEAPSRPRTAPIPE--PEEQKK 995
Cdd:PRK10263  342 QTPPVASVDVPPAQPTVAWQPVPGPQTGEPVIAPAPEGYPQQSQYAQPAVQYNEPLQQPVQPQQPYYAPAAEqpAQQPYY 421

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 19115125   996 APVEKKDAEKSVQAPIPAQPTGNITIQNA---YFTAPQPMA--ADPFQSPLyVQPTGFQPPPsalPIQPTGYMQPIPV 1068
Cdd:PRK10263  422 APAPEQPAQQPYYAPAPEQPVAGNAWQAEeqqSTFAPQSTYqtEQTYQQPA-AQEPLYQQPQ---PVEQQPVVEPEPV 495

SLA1 homology domain 1, SHD1; NPFXD peptides specifically interact with the SHD1 domain. NPFXD is a clathrin-facilitated endocytic targeting signal. NPFXD was originally discovered in the cytoplasmic domain of the furin-like protease Kex2p. Sla1 is thought to function as an endocytic adaptor.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19115125    641 SVSKPDSSKLRTWTDRTGAFKVEAEFLGYSDDKIHLHKTNGVKISVPSAKMSYKDLDYVELMTGKK 706
Cdd:pfam03983    1 SKSKPDPAKVRTWTDRTGTFKVEAQFLGFKDGKIRLHKTNGVKIAVPVEKMSKEDLEYVERVTGKS 66

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 19115125  511 KMGTVLYDFIAEAADELTVKANMRVVIVNDTASSDWWKCSVD--GKEGVVPSNFIKP 565
Cdd:cd11775    1 KRGKVLYDFDAQSDDELTVKEGDVVYILDDKKSKDWWMVENVstGKEGVVPASYIEI 57

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 19115125    9 IYKVLYSYEPQEinpgeeipenEREISIVEDEIVCLLEKGEDDWYLVKRNVNSNDDDEEIGIVPSNY 75
Cdd:cd11773    1 VYKALYDYEPQT----------EDELTIQEDDILYLLEKSDDDWWKVKLKVNSSDDDEPVGLVPATY 57

Domain of unknown function (DUF1720); This domain is found in different combinations with cortical patch components EF hand, SH3 and ENTH and is therefore likely to be involved in cytoskeletal processes. This family contains many hypothetical proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1140 MQPQATGIISQptgiraQATGIMTQPTGLHTQATGMMQPtgmQPQATGIMPQATGMMQPTGMQPQVTG-IMPQSMPMQPQ 1218
Cdd:pfam08226    1 MQPQQTGYMPP------QQQQPQQTQQPLQPQPTGFMPQ---QQTGQGLQPQPTGMGQFQPLQPQQTGfQPQAQQGLQPQ 71

                   ...
gi 19115125   1219 MTG 1221
Cdd:pfam08226   72 ATG 74

ARC105 or Med15 subunit of Mediator complex non-fungal; The approx. 70 residue Med15 domain of the ARC-Mediator co-activator is a three-helix bundle with marked similarity to the KIX domain. The sterol regulatory element binding protein (SREBP) family of transcription activators use the ARC105 subunit to activate target genes in the regulation of cholesterol and fatty acid homeostasis. In addition, Med15 is a critical transducer of gene activation signals that control early metazoan development.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1004 EKSVQAPIPAQPTGNItiQNAYFTAPQPMAADPFQSpLYVQPTGFQPPPSALPIQPTGymQPIPVQATGyqPLMVQPTGL 1083
Cdd:pfam09606   52 DMSKKAAQQQQPQGGQ--GNGGMGGGQQGMPDPINA-LQNLAGQGTRPQMMGPMGPGP--GGPMGQQMG--GPGTASNLL 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1084 QPHMTGVMPQVTGVMPQMTGVV------PQMTGVMPQMTGVQVQktgAMPQQPVNYGYQVAGMQPQATGiiSQPTGIRAQ 1157
Cdd:pfam09606  125 ASLGRPQMPMGGAGFPSQMSRVgrmqpgGQAGGMMQPSSGQPGS---GTPNQMGPNGGPGQGQAGGMNG--GQQGPMGGQ 199

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1158 ATGIMTQPTGL-HTQATGMMQP-----TGMQPQATGIMPQATGMMQ-PTGMQPQ--VTGIMPQSMPMQPQMTGvQVQKTG 1228
Cdd:pfam09606  200 MPPQMGVPGMPgPADAGAQMGQqaqanGGMNPQQMGGAPNQVAMQQqQPQQQGQqsQLGMGINQMQQMPQGVG-GGAGQG 278

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1229 MVAQPMlsQYTGYQQNYTPTAMPAADG------YGMQPSMNDTQAYYNMNAQTPVNYGFAGGQDTSFGYeqqqMYSPMQQ 1302
Cdd:pfam09606  279 GPGQPM--GPPGQQPGAMPNVMSIGDQnnyqqqQTRQQQQQQGGNHPAAHQQQMNQSVGQGGQVVALGG----LNHLETW 352

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1303 QQQQYYGTEMQPDMGYQQPMMS--NYYDPMQMQQQTPygyNQtGMEGYSEYGYAQPAGNMANPMSYDP----VSNASLYM 1376
Cdd:pfam09606  353 NPGNFGGLGANPMQRGQPGMMSspSPVPGQQVRQVTP---NQ-FMRQSPQPSVPSPQGPGSQPPQSHPggmiPSPALIPS 428

                          410       420       430
                   ....*....|....*....|....*....|.
gi 19115125   1377 PSDYNQQTQPANYYDSSFGGAQGANEAGKKA 1407
Cdd:pfam09606  429 PSPQMSQQPAQQRTIGQDSPGGSLNTPGQSA 459

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.

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 19115125       7 IGIYKVLYSYEPQeinpgeeipeNEREISIVEDEIVCLLEKGEDDWYLVKRNvnsnddDEEIGIVPSNYIT 77
Cdd:smart00326    2 GPQVRALYDYTAQ----------DPDELSFKKGDIITVLEKSDDGWWKGRLG------RGKEGLFPSNYVE 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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 19115125    514 TVLYDFIAEAADELTVKANMRVVIVNDTAsSDWWKC-SVDGKEGVVPS 560
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSE-DGWWKGrNKGGKEGLIPS 47

EBNA-3A; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   911 KEVVEKA-------PSPPATRPKSTTPQKfDDDAWANKPVTEP-PVRASSVTVEPARVTESMNKMNISEEAKKPEAP--- 979
Cdd:PHA03379  402 REALEKAseptygtPRPPVEKPRPEVPQS-LETATSHGSAQVPePPPVHDLEPGPLHDQHSMAPCPVAQLPPGPLQDlep 480

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   980 ----------SRPRTAPIPEPEEQKKAPVEKKDAEKSVQAPIPAQPtgnitiqnayftapQPMAADPFQSPLYVQPTGFQ 1049
Cdd:PHA03379  481 gdqlpgvvqdGRPACAPVPAPAGPIVRPWEASLSQVPGVAFAPVMP--------------QPMPVEPVPVPTVALERPVC 546

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125  1050 PPPSAL----PIQPTGYMQ-----------PIPVQATGYQPLMVQPTGLQPHMTGVMPQVTGVMPQMTGVVPQMTGVMPQ 1114
Cdd:PHA03379  547 PAPPLIamqgPGETSGIVRvrerwrpapwtPNPPRSPSQMSVRDRLARLRAEAQPYQASVEVQPPQLTQVSPQQPMEYPL 626

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125  1115 MTGVQVQKTGAMPQ-QPVNYGYQVAGMQPQATGI-ISQPTGIRAQATgiMTQPTGLHTQATGMMQPTGMQPQATGIMPQA 1192
Cdd:PHA03379  627 EPEQQMFPGSPFSQvADVMRAGGVPAMQPQYFDLpLQQPISQGAPLA--PLRASMGPVPPVPATQPQYFDIPLTEPINQG 704

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 19115125  1193 TGMMQPTGMQPQVTGIMPQSMpMQPQMTGVQVQKTGmVAQpmlSQYTG 1240
Cdd:PHA03379  705 ASAAHFLPQQPMEGPLVPERW-MFQGATLSQSVRPG-VAQ---SQYFD 747

N-terminal domain of transcription factor Specificity Protein (SP) 1-4 from arthropods; Specificity Proteins (SPs) are transcription factors that are involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. There are many SPs in vertebrates (9 SPs in humans and mice, 7 SPs in the chicken, and 11 SPs in teleost fish), but arthropods only have 3 SPs. One SP is clade SP1-4, which is expressed ubiquitously throughout development. SP1-4 belongs to a family of proteins, called the SP/Kruppel or Krueppel-like Factor (KLF) family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. SP factors preferentially bind GC boxes, while KLFs bind CACCC boxes. Another characteristic hallmark of SP factors is the presence of the Buttonhead (BTD) box CXCPXC, just N-terminal to the zinc fingers. The function of the BTD box is unknown, but it is thought to play an important physiological role. Another feature of most SP factors is the presence of a conserved amino acid stretch, the so-called SP box, located close to the N-terminus. This model represents the N-terminal domain of SP1-4 from arthropods.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125 1008 QAPIPAQPTGNITIQNAYFTAPQPMA-------ADPFQSPLYVQPTGFQPppsALPIQPTGYMQPIPVQATGYQPLMVQP 1080
Cdd:cd22553   50 QQIITAQSSGSAAGGVAYSVSPAVQTvtvdgheAIFIPANSGLLQTNNQQ---AIQLAPGGTQAILANQQTLIRPNTVQG 126

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125 1081 TGLQPHMTGVMPQVTGVMPQMTGVVPQMTGVMP------QMTGVQVQKTGAMPQQPVNYGYQVAGMQPQATGIISQptgi 1154
Cdd:cd22553  127 QANASNVLQNIAQIASGGNAVQLPLNNMTQTIPvqvpvsTANGQTVYQTIQVPIQAIQSGNAGGGNQALQAQVIPQ---- 202

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125 1155 raqatgimtqptglhtqatgMMQPTGMQPQAtgimpqatgMMQPTGmQPQVTGIMPQSMPMQPQMtgVQVQKTGMVAQPM 1234
Cdd:cd22553  203 --------------------LAQAAQLQPQQ---------LAQVSS-QGYIQQIPANASQQQPQM--VQQGPNQSGQIIG 250

                        250       260       270
                 ....*....|....*....|....*....|..
gi 19115125 1235 LSQYTGYQQNYTPTAMPAADGYGMQPSMNDTQ 1266
Cdd:cd22553  251 QVASASSIQAAAIPLTVYTGALAGQNGSNQQQ 282

Ribosomal protein L12p. This subfamily includes archaeal L12p, the protein that is functionally equivalent to L7/L12 in bacteria and the P1 and P2 proteins in eukaryotes. L12p is homologous to P1 and P2 but is not homologous to bacterial L7/L12. It is located in the L12 stalk, with proteins L10, L11, and 23S rRNA. L12p is the only protein in the ribosome to occur as multimers, always appearing as sets of dimers. Recent data indicate that most archaeal species contain six copies of L12p (three homodimers), while eukaryotes have four copies (two heterodimers), and bacteria may have four or six copies (two or three homodimers), depending on the species. The organization of proteins within the stalk has been characterized primarily in bacteria, where L7/L12 forms either two or three homodimers and each homodimer binds to the extended C-terminal helix of L10. L7/L12 is attached to the ribosome through L10 and is the only ribosomal protein that does not directly interact with rRNA. Archaeal L12p is believed to function in a similar fashion. However, hybrid ribosomes containing the large subunit from E. coli with an archaeal stalk are able to bind archaeal and eukaryotic elongation factors but not bacterial elongation factors. In several mesophilic and thermophilic archaeal species, the binding of 23S rRNA to protein L11 and to the L10/L12p pentameric complex was found to be temperature-dependent and cooperative.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 19115125  939 ANKPVTEPPV----RASSVTVEPARV---TESMNKMNIsEEAKKPEAPSRPRTAPIPEPEEQKKAPVEKKDAEK 1005
Cdd:cd05832   13 AGKEINEENLkkvlEAAGIEVDEARVkalVAALEEVNI-DEAIKKAAVAAAAAAPAAAAAAAAEEKAEEKEEEK 85

SLA1 homology domain 1, SHD1; NPFXD peptides specifically interact with the SHD1 domain. NPFXD is a clathrin-facilitated endocytic targeting signal. NPFXD was originally discovered in the cytoplasmic domain of the furin-like protease Kex2p. Sla1 is thought to function as an endocytic adaptor.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19115125    641 SVSKPDSSKLRTWTDRTGAFKVEAEFLGYSDDKIHLHKTNGVKISVPSAKMSYKDLDYVELMTGKK 706
Cdd:pfam03983    1 SKSKPDPAKVRTWTDRTGTFKVEAQFLGFKDGKIRLHKTNGVKIAVPVEKMSKEDLEYVERVTGKS 66

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 19115125  511 KMGTVLYDFIAEAADELTVKANMRVVIVNDTASSDWWKCSVD--GKEGVVPSNFIKP 565
Cdd:cd11775    1 KRGKVLYDFDAQSDDELTVKEGDVVYILDDKKSKDWWMVENVstGKEGVVPASYIEI 57

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 19115125    9 IYKVLYSYEPQEinpgeeipenEREISIVEDEIVCLLEKGEDDWYLVKRNVNSNDDDEEIGIVPSNY 75
Cdd:cd11773    1 VYKALYDYEPQT----------EDELTIQEDDILYLLEKSDDDWWKVKLKVNSSDDDEPVGLVPATY 57

Domain of unknown function (DUF1720); This domain is found in different combinations with cortical patch components EF hand, SH3 and ENTH and is therefore likely to be involved in cytoskeletal processes. This family contains many hypothetical proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1140 MQPQATGIISQptgiraQATGIMTQPTGLHTQATGMMQPtgmQPQATGIMPQATGMMQPTGMQPQVTG-IMPQSMPMQPQ 1218
Cdd:pfam08226    1 MQPQQTGYMPP------QQQQPQQTQQPLQPQPTGFMPQ---QQTGQGLQPQPTGMGQFQPLQPQQTGfQPQAQQGLQPQ 71

                   ...
gi 19115125   1219 MTG 1221
Cdd:pfam08226   72 ATG 74

Domain of unknown function (DUF1720); This domain is found in different combinations with cortical patch components EF hand, SH3 and ENTH and is therefore likely to be involved in cytoskeletal processes. This family contains many hypothetical proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1118 VQVQKTGAMPQQPVNYGYQVAGMQPQATGIISQPTgiraqatgimtQPTGLHTQATGMMQPTGMQPQATGIMPQATGmmq 1197
Cdd:pfam08226    1 MQPQQTGYMPPQQQQPQQTQQPLQPQPTGFMPQQQ-----------TGQGLQPQPTGMGQFQPLQPQQTGFQPQAQQ--- 66

                           90
                   ....*....|
gi 19115125   1198 ptGMQPQVTG 1207
Cdd:pfam08226   67 --GLQPQATG 74

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.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 19115125     509 GQKMGTVLYDFIAEAADELTVKANMRVVIVNDTaSSDWWKCSV-DGKEGVVPSNFIK 564
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKS-DDGWWKGRLgRGKEGLFPSNYVE 56

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.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 19115125      81 PSTKMKALYDYTQQSVDEISFQADQTLDCYGDTDSDWiLVGFNNN--FGLAPRNYVE 135
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGW-WKGRLGRgkEGLFPSNYVE 56

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.

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 19115125       7 IGIYKVLYSYEPQeinpgeeipeNEREISIVEDEIVCLLEKGEDDWYLVKRNvnsnddDEEIGIVPSNYIT 77
Cdd:smart00326    2 GPQVRALYDYTAQ----------DPDELSFKKGDIITVLEKSDDGWWKGRLG------RGKEGLFPSNYVE 56

Domain of unknown function (DUF1720); This domain is found in different combinations with cortical patch components EF hand, SH3 and ENTH and is therefore likely to be involved in cytoskeletal processes. This family contains many hypothetical proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19115125   1058 QPTGYMQPIPVQ-ATGYQPLMVQPTGLQPhmtgVMPQVTGVMPQMTGvVPQMTGVMPQMTGVQVQKTGampqqpvnygyq 1136
Cdd:pfam08226    4 QQTGYMPPQQQQpQQTQQPLQPQPTGFMP----QQQTGQGLQPQPTG-MGQFQPLQPQQTGFQPQAQQ------------ 66

                           90
                   ....*....|
gi 19115125   1137 vaGMQPQATG 1146
Cdd:pfam08226   67 --GLQPQATG 74

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 19115125  515 VLYDFIAEAADELTVKANMRVVIVN-DTASSDWWKCSVDGKEGVVPSNFIKP 565
Cdd:cd11875    4 VLFDYEAENEDELTLREGDIVTILSkDCEDKGWWKGELNGKRGVFPDNFVEP 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 19115125  516 LYDFIAEAADELTVKANmRVVIVNDTASSDWWKCSVDGKEGVVPSNFIKP 565
Cdd:cd11772    5 LYDYEAQHPDELSFEEG-DLLYISDKSDPNWWKATCGGKTGLIPSNYVEE 53

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 19115125  516 LYDFIAEAADELTVKANMRVVIV---NDTASSDWWKCSVDGKEGVVPSNFIK 564
Cdd:cd12141    5 VYTFKARSPNELSVSANQRVRILefsDLTGNKEWWLAEANGQKGYVPSNYIR 56

Variant SH3 domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 19115125     87 ALYDYTQQSVDEISFQADQTLDCYGDTDSDWILVGFNNNFGLAPRNYVE 135
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 19115125  517 YDFIAEAADELTVKANMRVVIVNDTASSDWWKCSVDGKEGVVPSNFIK 564
Cdd:cd11946    7 YDFKATADDELSFKRGDILKVLNEECDQNWYKAELNGKDGFIPKNYIE 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 19115125  512 MGTVLYDFIAEAADELTV-KANMRVVIVNDTASSD-WWKCSVDGKEGVVPSNFIK 564
Cdd:cd12001    4 LAKALYDNVAESPDELSFrKGDIMTVLERDTQGLDgWWLCSLHGRQGIVPGNRLK 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 19115125  516 LYDFIAEAADELTVKANmRVVIVNDTASSDWWKCSVDGKEGVVPSNFIK 564
Cdd:cd11820    6 LYDFEAAEDNELTFKAG-EIITVLDDSDPNWWKGSNHRGEGLFPANFVT 53

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19115125   10 YKVLYSYEPQEINpgeeipenerEISIVEDEIVCLLEKGEDDWYLVKRNvnsndDDEEIGIVPSNYITE 78
Cdd:cd11858    2 YKALYDFAGSVAN----------ELSLKKDDIVYIVQKEDNGWWLAKKL-----DESKEGWVPAAYLEE 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 19115125  516 LYDFIAEAADELTV-KANMRVVIVNDTASSD-WWKCSVDGKEGVVPSNFIK 564
Cdd:cd11844    5 LYDNVAESPDELAFrRGDILTVLEQNTAGLEgWWLCSLRGRQGIAPGNRLK 55

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 19115125   87 ALYDYTQQSVDEISFQADQTLDCYGDTDSDWILVGFNNNFGLAPRNYVE 135
Cdd:cd11856    4 AIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLE 52

Variant SH3 domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 19115125    515 VLYDFIAEAADELTVKANMRVVIVNDTaSSDWWKCSVDGKEGVVPSNFIK 564
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEES-EDGWWEGINTGRTGLVPANYVE 49

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 19115125  516 LYDFIAEAADELTVK-ANMRVVIVNDTASSDWWKCSVDGKEGVVPSNF 562
Cdd:cd11952    6 LWDYSAEFPDELSFKeGDMVTVLRKDGEGTDWWWASLCGREGYVPRNY 53