Helically-extended SH3 domain; This domain is the 70 C-terminal residues of ADAP - Adhesion and de-granulation promoting adapter protein. It shows homology to SH3 domains; however, conserved residues of the fold are absent. It thus represents an altered SH3 domain fold. An N-terminal, amphipathic, helix makes extensive contacts to residues of the regular SH3 domain fold thereby creating a composite surface with unusual surface properties. The domain can no longer bind conventional proline-rich peptides. There are key phosphorylation sites within the two hSH3 domains and it would appear that binding at these sites does not materially affect the folding of these regions although the equilibrium towards the unfolded state may be slightly altered. The binding partners of the hSH3 domains are still unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462601907 518 GPIQVIH---LAKACCDVKGGKNELSFKQGEQIEIIRITDnpEGKWLGRTARGSYGYIKTTAVeidydslklkkdslgap 594
Cdd:pfam14603   9 GEIKVLYsmtVDPNLTIKKWGGKDLPVKPGEVLDVIQKTD--DTKVLCRNEEGKYGYVLRSNL----------------- 69

                          90       100
                  ....*....|....*....|
gi 2462601907 595 srpIEDDQEVYDDVAEqDDI 614
Cdd:pfam14603  70 ---LQNDGEIYDDIGD-DCI 85

Helically-extended SH3 domain; This domain is the 70 C-terminal residues of ADAP - Adhesion and de-granulation promoting adapter protein. It shows homology to SH3 domains; however, conserved residues of the fold are absent. It thus represents an altered SH3 domain fold. An N-terminal, amphipathic, helix makes extensive contacts to residues of the regular SH3 domain fold thereby creating a composite surface with unusual surface properties. The domain can no longer bind conventional proline-rich peptides. There are key phosphorylation sites within the two hSH3 domains and it would appear that binding at these sites does not materially affect the folding of these regions although the equilibrium towards the unfolded state may be slightly altered. The binding partners of the hSH3 domains are still unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462601907 518 GPIQVIH---LAKACCDVKGGKNELSFKQGEQIEIIRITDnpEGKWLGRTARGSYGYIKTTAVeidydslklkkdslgap 594
Cdd:pfam14603   9 GEIKVLYsmtVDPNLTIKKWGGKDLPVKPGEVLDVIQKTD--DTKVLCRNEEGKYGYVLRSNL----------------- 69

                          90       100
                  ....*....|....*....|
gi 2462601907 595 srpIEDDQEVYDDVAEqDDI 614
Cdd:pfam14603  70 ---LQNDGEIYDDIGD-DCI 85

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2462601907 537 NELSFKQGEQIEIIRITDnpEGKWLGRTARGSYGYIKTTAVEI 579
Cdd:cd11819    14 NEISFVEGDIITQIEQID--EGWWLGVNAKGQKGLFPANYVEL 54

Helically-extended SH3 domain; This domain is the 70 C-terminal residues of ADAP - Adhesion and de-granulation promoting adapter protein. It shows homology to SH3 domains; however, conserved residues of the fold are absent. It thus represents an altered SH3 domain fold. An N-terminal, amphipathic, helix makes extensive contacts to residues of the regular SH3 domain fold thereby creating a composite surface with unusual surface properties. The domain can no longer bind conventional proline-rich peptides. There are key phosphorylation sites within the two hSH3 domains and it would appear that binding at these sites does not materially affect the folding of these regions although the equilibrium towards the unfolded state may be slightly altered. The binding partners of the hSH3 domains are still unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462601907 518 GPIQVIH---LAKACCDVKGGKNELSFKQGEQIEIIRITDnpEGKWLGRTARGSYGYIKTTAVeidydslklkkdslgap 594
Cdd:pfam14603   9 GEIKVLYsmtVDPNLTIKKWGGKDLPVKPGEVLDVIQKTD--DTKVLCRNEEGKYGYVLRSNL----------------- 69

                          90       100
                  ....*....|....*....|
gi 2462601907 595 srpIEDDQEVYDDVAEqDDI 614
Cdd:pfam14603  70 ---LQNDGEIYDDIGD-DCI 85

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462601907 526 AKACCDVKG-GKNELSFKQGEQIEIIRiTDNPEGkWLGRTaRGSYGYIKTTAVEID 580
Cdd:pfam07653   2 GRVIFDYVGtDKNGLTLKKGDVVKVLG-KDNDGW-WEGET-GGRVGLVPSTAVEEI 54

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2462601907 526 AKACCDVKGGK-NELSFKQGEQIEIIRITDnpEGKWLGRTARGSYGYI 572
Cdd:cd00174     2 ARALYDYEAQDdDELSFKKGDIITVLEKDD--DGWWEGELNGGREGLF 47

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462601907   50 NNQGNASPPAGPSNVPkfgsPKPPVAVKPsseekPDKEPKPPFLKPTGAGQRFGTPA-SLTTRDPEAKVGflKPVGPKPI 128
Cdd:PHA03247  2546 DDAGDPPPPLPPAAPP----AAPDRSVPP-----PRPAPRPSEPAVTSRARRPDAPPqSARPRAPVDDRG--DPRGPAPP 2614

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462601907  129 NLPKEDSKPTFPWPPGNKPSLHSVNQDHDL---KPLGPKSGPTPPtseneqKQAFPKLTGVKGKFMSASQDLE-PKPLFP 204
Cdd:PHA03247  2615 SPLPPDTHAPDPPPPSPSPAANEPDPHPPPtvpPPERPRDDPAPG------RVSRPRRARRLGRAAQASSPPQrPRRRAA 2688

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462601907  205 KPAFGQKPPLSTENSHEDESPMKNVSSSKGSPAPLGVRSKSGPLKPAREDSENKDHAGEISSLPFPGVVLKPAASRGGPG 284
Cdd:PHA03247  2689 RPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPA 2768

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462601907  285 LSKNGEEKKEDRKIDAAKNTFQSKINQEELASGTPPARFPKAPSKLTVGGPWGQSQEKEKGDKNSATPKQKPLPPLFTLG 364
Cdd:PHA03247  2769 PAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPP 2848

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462601907  365 PPPPKPNRPPNVDLTKFHKTSSGNSTSKGQTSYSTTSLPPPPPSHPASQPPLPASHPSQPPVPSLPPRNIKPP 437
Cdd:PHA03247  2849 SLPLGGSVAPGGDVRRRPPSRSPAAKPAAPARPPVRRLARPAVSRSTESFALPPDQPERPPQPQAPPPPQPQP 2921

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2462601907 536 KNELSFKQGEQIEIIRITDNpEGKWLGRTARGSYGYIKTTAVEI 579
Cdd:cd11763    13 SGELSLRAGEVLTITRQDVG-DGWLEGRNSRGEVGLFPSSYVEI 55

Helically extended Src Homology 3 domain of Adhesion and Degranulation-promoting Adaptor Protein; ADAP, also called Fyn T-binding protein (FYB) or SLP-76-associated protein (SLAP), is expressed mainly in hematopoietic cells but not in B cells. It is required for the proliferation of mature T-cells and plays an important role in T-cell activation, TCR-induced integrin clustering, and T-cell adhesion. ADAP has been shown to bind many partners including SLP-76, Fyn, Src, SKAP1, SKAP2, dynein, Ena/VASP, Carma1, among others. It is connected to cytoskeleton via its binding to Ena and VASP, which impacts actin cytoskeletal remodeling upon TCR ligation. The SH3 domain of ADAP adopts an altered fold referred to as a helically extended SH3 (hSH3) domain characterized by clusters of positive charges. The hSH3 domain can no longer bind conventional proline-rich peptides, instead, it functions as a novel lipid interaction domain and can bind acidic lipids such as phosphatidylserine, phosphatidylinositol, phosphatidic acid, and polyphosphoinositides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462601907 517 TGPIQVIHLAKACCDV---KGGKNELSFKQGEQIEIIRITDnpEGKWLGRTARGSYGYIKTTAVE 578
Cdd:cd11867    14 NGEIKVLYSTTVLQTLtikKFGSKDLQVKPGESLEVIQHTD--DTKVLCRNEEGKYGYVLRSNLE 76

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2462601907 536 KNELSFKQGEQIEIIRITD---NPEGKWLGRTARGSYGYIKTTAVEI 579
Cdd:cd11771    14 EMELSLKKGDIVAVLSKTDplgRDSEWWKGRTRDGRIGWFPSNYVEV 60