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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155  26 QNLGKVDRTADEIFDDHLNNFNRQQASANRLQKEFNNYIRCVRAAQAASKTLMDSVCEIYEPQWSGYDALQAQTGASESL 105
Cdd:cd07588   1 QKLGKADETRDEVFDEHVNNFNKQQASANRLQKDLKNYLNSVRAMKQASKTLSETLKELYEPDWPGREHLASIFEQLDLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155 106 WADFAHKLGDQVLIPLNTYTGQFPEMKKKVEKRNRKLIDYDGQRHSFQNLQanANKRKDDVKLTKGREQLEEARRTYEIL 185
Cdd:cd07588  81 WNDLEEKLSDQVLGPLTAYQSQFPEVKKRIAKRGRKLVDYDSARHNLEALK--AKKKVDDQKLTKAEEELQQAKKVYEEL 158

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 17647155 186 NTELHDELPALYDSRILFLVTNLQTLFATEQVFHNETAKIYSELEAIVDKLAT 238
Cdd:cd07588 159 NTELHEELPALYDSRIAFYVDTLQSIFAAESVFHKEIGKVNTKLNDVMDGLAD 211

104 kDa microneme/rhoptry antigen; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155  275 SNYQNQITTNGGSSLANSPTSTSSSLQEPRFDSVSSTPEpRPESPAAALVSATPSSPvengVTTKSLERPELSGLNASAK 354
Cdd:PTZ00449 551 ETKEGEVGKKPGPAKEHKPSKIPTLSKKPEFPKDPKHPK-DPEEPKKPKRPRSAQRP----TRPKSPKLPELLDIPKSPK 625

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 17647155  355 ATTTTQTSPTEDKAvvSEAVKPSETEGAAVAAsvTPAPPATP 396
Cdd:PTZ00449 626 RPESPKSPKRPPPP--QRPSSPERPEGPKIIK--SPKPPKSP 663

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155  26 QNLGKVDRTADEIFDDHLNNFNRQQASANRLQKEFNNYIRCVRAAQAASKTLMDSVCEIYEPQWSGYDALQAQTGASESL 105
Cdd:cd07588   1 QKLGKADETRDEVFDEHVNNFNKQQASANRLQKDLKNYLNSVRAMKQASKTLSETLKELYEPDWPGREHLASIFEQLDLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155 106 WADFAHKLGDQVLIPLNTYTGQFPEMKKKVEKRNRKLIDYDGQRHSFQNLQanANKRKDDVKLTKGREQLEEARRTYEIL 185
Cdd:cd07588  81 WNDLEEKLSDQVLGPLTAYQSQFPEVKKRIAKRGRKLVDYDSARHNLEALK--AKKKVDDQKLTKAEEELQQAKKVYEEL 158

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 17647155 186 NTELHDELPALYDSRILFLVTNLQTLFATEQVFHNETAKIYSELEAIVDKLAT 238
Cdd:cd07588 159 NTELHEELPALYDSRIAFYVDTLQSIFAAESVFHKEIGKVNTKLNDVMDGLAD 211

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17647155 539 VLYRVKATYGYAKEDVDELSFEIGDLIRVIEYDDPEDQEEGWLMGQKEGTNEKGLFPANFTRPI 602
Cdd:cd11790   1 VLYKVRATHDYTAEDTDELTFEKGDVILVIPFDDPEEQDEGWLMGVKESTGCRGVFPENFTERI 64

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155    541 YRVKATYGYAKEDVDELSFEIGDLIRVIeyddpEDQEEGWLMGQKeGTNEKGLFPANFTR 600
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITVL-----EKSDDGWWKGRL-GRGKEGLFPSNYVE 56

104 kDa microneme/rhoptry antigen; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155  275 SNYQNQITTNGGSSLANSPTSTSSSLQEPRFDSVSSTPEpRPESPAAALVSATPSSPvengVTTKSLERPELSGLNASAK 354
Cdd:PTZ00449 551 ETKEGEVGKKPGPAKEHKPSKIPTLSKKPEFPKDPKHPK-DPEEPKKPKRPRSAQRP----TRPKSPKLPELLDIPKSPK 625

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 17647155  355 ATTTTQTSPTEDKAvvSEAVKPSETEGAAVAAsvTPAPPATP 396
Cdd:PTZ00449 626 RPESPKSPKRPPPP--QRPSSPERPEGPKIIK--SPKPPKSP 663

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155  26 QNLGKVDRTADEIFDDHLNNFNRQQASANRLQKEFNNYIRCVRAAQAASKTLMDSVCEIYEPQWSGYDALQAQTGASESL 105
Cdd:cd07588   1 QKLGKADETRDEVFDEHVNNFNKQQASANRLQKDLKNYLNSVRAMKQASKTLSETLKELYEPDWPGREHLASIFEQLDLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155 106 WADFAHKLGDQVLIPLNTYTGQFPEMKKKVEKRNRKLIDYDGQRHSFQNLQanANKRKDDVKLTKGREQLEEARRTYEIL 185
Cdd:cd07588  81 WNDLEEKLSDQVLGPLTAYQSQFPEVKKRIAKRGRKLVDYDSARHNLEALK--AKKKVDDQKLTKAEEELQQAKKVYEEL 158

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 17647155 186 NTELHDELPALYDSRILFLVTNLQTLFATEQVFHNETAKIYSELEAIVDKLAT 238
Cdd:cd07588 159 NTELHEELPALYDSRIAFYVDTLQSIFAAESVFHKEIGKVNTKLNDVMDGLAD 211

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155     12 SVQKHAGRAKEKILQNLGKVDRT-ADEIFDDHLNNFNRQQASANRLQKEFNNYIR---CVRAAQAASKTLMDSVCEIYEP 87
Cdd:smart00721   1 GFKKQFNRAKQKVGEKVGKAEKTkLDEDFEELERRFDTTEAEIEKLQKDTKLYLQpnpAVRAKLASQKKLSKSLGEVYEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155     88 --QWSGYDALQAQTGASESLWADFAHKLG----------DQVLIPLNTYTGQFPEMKKKVEKRNRKLIDYDGQRHSFQNL 155
Cdd:smart00721  81 gdDGEGLGADSSYGKALDKLGEALKKLLQveeslsqvkrTFILPLLNFLLGEFKEIKKARKKLERKLLDYDSARHKLKKA 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155    156 QANANKRKDDvKLTKGREQLEEARRTYEILNTELHDELPALYDSRILFLVTNLQTLFATEQVFHNETAKIYSELEAIVDK 235
Cdd:smart00721 161 KKSKEKKKDE-KLAKAEEELRKAKQEFEESNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQQQLDK 239

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17647155 539 VLYRVKATYGYAKEDVDELSFEIGDLIRVIEYDDPEDQEEGWLMGQKEGTNEKGLFPANFTRPI 602
Cdd:cd11790   1 VLYKVRATHDYTAEDTDELTFEKGDVILVIPFDDPEEQDEGWLMGVKESTGCRGVFPENFTERI 64

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155  29 GKVDRTADEIFDDHLNNFNRQQASANRLQKEFNNYIRCVRAAQAASKTLMDSVCEIY--EPQWSGYDALQAQTGASESLW 106
Cdd:cd07591   3 GQVERTVDREFEFEERRYRTMEKASTKLQKEAKGYLDSLRALTSSQARIAETISSFYgdAGDKDGAMLSQEYKQAVEELD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155 107 ADFAHKLgDQ-----VLIPLNTYTGQFPEMKKKVEKRNRKLIDYDGQRHSFQNLQANANKrkDDVKLTKGREQLEEARRT 181
Cdd:cd07591  83 AETVKEL-DGpyrqtVLDPIGRFNSYFPEINEAIKKRNHKLLDYDAARAKVRKLIDKPSE--DPTKLPRAEKELDEAKEV 159

                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 17647155 182 YEILNTELHDELPALYDSRILFL------VTNLQTLFATE 215
Cdd:cd07591 160 YETLNDQLKTELPQLVDLRIPYLdpsfeaFVKIQLRFFTE 199

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155  30 KVDRTADEIFDDHLNNFNRQQASANRLQKEFNNYIRCV----RAAQAASKTLMD-SVCEIYEPQWSGYDALQAQTGASES 104
Cdd:cd07590   4 ILSKTVDRELEREVQKLQQLESTTKKLYKDMKKYIEAVlalsKAEQRLSQDLASgPLCEDNDELRNLVEALDSVTTQLDK 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155 105 LWADFAHKLGDQVLIPLNTYTGQFPEMKKKVEKRNRKLIDYDGQRHSFQNLQANANKRKDDVKLTKGREQLEEARRTYEI 184
Cdd:cd07590  84 TVQELVNLIQKTFIEPLKRLRSVFPSVNAAIKRREQSLQEYERLQAKVEKLAEKEKTGPNLAKLEQAEKALAAARADFEK 163

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 17647155 185 LNTELHDELPALYDSRILFLVTNLQTLFATEQVFHNETAKIYSELEAIVD 234
Cdd:cd07590 164 QNIKLLEELPKFYNGRTDYFQPCFEALIKSQVLYYSQSTKIFTQLAPNLD 213

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        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVIeyddpEDQEEGWLMGQKEGtNEKGLFPANF 598
Cdd:cd00174   1 YARALYDYEAQDDDELSFKKGDIITVL-----EKDDDGWWEGELNG-GREGLFPANY 51

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155  58 KEFNNYIRCVRAAQAASKTLMDSVCEIYEPQWSGYDALQAQT-----GASESLWADFAHKLGDQVLIPLNTYTGQFPEMK 132
Cdd:cd07589  26 RNVELYLQHVQESVLVKVLALEVVLDLYPSNHPRLESKWERFrrvvrGISSKALPEFKSRVRKLVIEPLSSLLKLFSGPQ 105

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17647155 133 KKVEKRNRKLIDYDGQRhsfqnlqananKRKDDVKLTKgrEQLEEARRTYEILNTELHDELPALY 197
Cdd:cd07589 106 KLIQKRYDKLLDYERYK-----------EKKERGGKVD--EELEEAANQYEALNAQLKEELPKFN 157

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVIEYDDpedqEEGWLMGQKEGTNEkGLFPANF 598
Cdd:cd11999   3 RVRAVYDYTGQEPDELSFKAGEELLKVEDED----EQGWCKGVTDGGAV-GLYPANY 54

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVIeyddpEDQEEGWLMGQKEGtnEKGLFPANF 598
Cdd:cd11874   1 RCKVLFSYTPQNEDELELKVGDTIEVL-----GEVEEGWWEGKLNG--KVGVFPSNF 50

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVIeYDDPEDqeeGWLMGQKEGTNEKGLFPANFTRP 601
Cdd:cd11779   2 RVKALYPHAAGGETQLSFEEGDVITLL-GPEPRD---GWHYGENERSGRRGWFPIAYTEP 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVIEYDDpedqeEGWLMGQKEGTNEKGLFPANFTRPI 602
Cdd:cd11934   4 RYRAVYDYNAADEDEVSFQDGDTIVNVQQID-----DGWMYGTVERTGDTGMLPANYVEAI 59

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.

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gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVIEYDDpedqEEGWLMGQKEGtnEKGLFPANFTRP 601
Cdd:cd11882   1 RARALYACKAEDESELSFEPGQIITNVQPSD----EPGWLEGTLNG--RTGLIPENYVEF 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.

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                ....*....|....*....|....*....|....*....|....*....|....*...
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVIEYDDpedqeEGWLMGQ-KEGTNekGLFPANF 598
Cdd:cd11960   1 RARALYDYQAADDTEISFDPGDIITDIEQID-----EGWWRGTgPDGTY--GLFPANY 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.

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                ....*....|....*....|....*....|....*....|....*....|
gi 17647155 549 YAKEDVDELSFEIGDLIRVIEYDdpEDQEEGWLMGQKEGTNEKGLFPANF 598
Cdd:cd11886   8 FNARSEDELTLKPGDKIELIEDD--EEFGDGWYLGRNLRTGETGLFPVVF 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.

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17647155 543 VKATYGYAKEDVDELSFEIGDLIRVIEYDDpedqEEGWLMGQKEGtnEKGLFPANF 598
Cdd:cd11778   2 VEALYDYEAQGDDEISIRVGDRIAVIRGDD----GSGWTYGEING--VKGLFPTSY 51

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.

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gi 17647155 540 LYRVKATYGYAKEDVDELSFEIGDLIRVIEYDDpedqeEGWLMGQKEGTNEKGLFPANFTRPI 602
Cdd:cd11916   1 AYSYQALYSYAPQNDDELELRDGDIVDVMEKCD-----DGWFVGTSRRTKQFGTFPGNYVKLL 58

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

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gi 17647155 543 VKATYGYAKEDVDELSFEIGDLIRvieydDPEDQEEGWLMGQKEGtnEKGLFPANFTR 600
Cdd:cd11873   2 VIVEFDYDAEEPDELTLKVGDIIT-----NVKKMEEGWWEGTLNG--KRGMFPDNFVK 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.

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17647155 543 VKATYGYAKEDVDELSFEIGDLIRVIEYDDPedqeeGWLMGQKEGtnEKGLFPANF 598
Cdd:cd11772   2 FRALYDYEAQHPDELSFEEGDLLYISDKSDP-----NWWKATCGG--KTGLIPSNY 50

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.

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                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVIEYDDpedqeEGWLMGQKEGtNEKGLFPANF 598
Cdd:cd11819   1 RAKALYDYQAAEDNEISFVEGDIITQIEQID-----EGWWLGVNAK-GQKGLFPANY 51

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17647155 543 VKATYGYAKEDVDELSFEIGDLIRVIEYDDPEdqeegWLMGQKEGtnEKGLFPANFTRP 601
Cdd:cd11950   2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPS-----WWKGRLHG--KLGLFPANYVAP 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.

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                ....*....|....*....|....*....|....*....|....*....|....*
gi 17647155 544 KATYGYAKEDVDELSFEIGDLIRVIEyddPEDqeEGWLMGQKEGTNEKGLFPANF 598
Cdd:cd11935   4 RAMYDYSAQDEDEVSFRDGDYIVNVQ---PID--EGWMYGTVQRTGRTGMLPANY 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.

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                ....*....|....*....|....*....|....*....|....*....|....*...
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVI-EYDDpedqeeGWLMGQKEGTneKGLFPANF 598
Cdd:cd11826   1 KVVALYDYTADKDDELSFQEGDIIYVTkKNDD------GWYEGVLNGV--TGLFPGNY 50

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.

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                ....*....|....*....|....*....|....*....|....*....|....*...
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVieyDDPEDQEegWLMGQKEGT-NEKGLFPANF 598
Cdd:cd11966   1 RVKALYNCVADNPDELTFSEGEIIIV---DGEEDKE--WWIGHIDGEpTRRGAFPVSF 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.

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17647155 545 ATYGYAKEDVDELSFEIGDLIRVIEYDDpedqeEGWLMGQKEGtnEKGLFPANFTR 600
Cdd:cd12073   5 ALYDYQGEGDDEISFDPQETITDIEMVD-----EGWWKGTCHG--HRGLFPANYVE 53

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17647155 543 VKATYGYAKEDVDELSFEIGDLIrvieYDDPEDQE---EGWLMGQKEGTNEKGLFPANFTR 600
Cdd:cd11791   2 LRVLYPYTPQEEDELELVPGDYI----YVSPEELDsssDGWVEGTSWLTGCSGLLPENYTE 58

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.

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                ....*....|....*....|....*....|....*....|....*....|....*...
gi 17647155 542 RVKATYGYAKEDVDELSFEIGDLIRVIEYDDPEdqeegWLMGQKEGTNekGLFPANFT 599
Cdd:cd11816   1 RCVARFDFEGEQEDELSFSEGDVITLKEYVGEE-----WAKGELNGKI--GIFPLNFV 51