ADF homology domain of drebrin and actin-binding protein 1 (abp1); Actin depolymerization factor/cofilin-like domains (ADF domains) are present in a family of essential eukaryotic actin regulatory proteins. Many of these proteins enhance the turnover rate of actin and interact with actin monomers as well as actin filaments. Abp1 and drebrin (developmentally regulated brain protein) are multidomain proteins with an N-terminal ADF homology domain and one or more C-terminal SH3 domains. They have been shown to interact with polymeric F-actin, but not with monomeric G-actin, and do not appear to promote the disassembly of actin filaments. Drebrin rather stabilizes actin filaments by inducing changes in the helical twist and may promote or interfere with the interactions of other proteins with actin filaments.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13786198   3 VNLSRNGPALQEAYVRVVTEKSPTDWALFTYEGNSNDIRVAGTGEGGLEELVEELNSGKVMYAFCRVKDPNSGLPKFVLI 82
Cdd:cd11281   1 IDLSTNSPEILAAYEDVVDGKSSTDWALFTYEGKSNDLKVADTGDGGLEELVEEFSDGKVQYGFARVKDPNSGLPKFVLI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13786198  83 NWTGEGVNDVRKGACANHVSTMANFLKGAHVTINARAEEDVEPECIMEKVAKASGA 138
Cdd:cd11281  81 NWCGEGVPDARKGSFASHVAAVANFLKGAHVQINARSEDDLDEDAILKKVSKASGA 136

ADF homology domain of drebrin and actin-binding protein 1 (abp1); Actin depolymerization factor/cofilin-like domains (ADF domains) are present in a family of essential eukaryotic actin regulatory proteins. Many of these proteins enhance the turnover rate of actin and interact with actin monomers as well as actin filaments. Abp1 and drebrin (developmentally regulated brain protein) are multidomain proteins with an N-terminal ADF homology domain and one or more C-terminal SH3 domains. They have been shown to interact with polymeric F-actin, but not with monomeric G-actin, and do not appear to promote the disassembly of actin filaments. Drebrin rather stabilizes actin filaments by inducing changes in the helical twist and may promote or interfere with the interactions of other proteins with actin filaments.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13786198   3 VNLSRNGPALQEAYVRVVTEKSPTDWALFTYEGNSNDIRVAGTGEGGLEELVEELNSGKVMYAFCRVKDPNSGLPKFVLI 82
Cdd:cd11281   1 IDLSTNSPEILAAYEDVVDGKSSTDWALFTYEGKSNDLKVADTGDGGLEELVEEFSDGKVQYGFARVKDPNSGLPKFVLI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13786198  83 NWTGEGVNDVRKGACANHVSTMANFLKGAHVTINARAEEDVEPECIMEKVAKASGA 138
Cdd:cd11281  81 NWCGEGVPDARKGSFASHVAAVANFLKGAHVQINARSEDDLDEDAILKKVSKASGA 136

Cofilin/tropomyosin-type actin-binding protein; Severs actin filaments and binds to actin monomers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13786198    12 LQEAYVRVVTEKSpTDWALFTYEGNSNDIRVAGTGEGGLEELVEEL--NSGKVMYAFCRVK---DPNSGLPKFVLINWTG 86
Cdd:pfam00241   1 CKEAYQELRSDKK-TNWIIFKIDDDKEEIVVEETGEGGLSYDEFLEelPDDEPRYAVYRFEythDDGSKRSKLVFITWCP 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 13786198    87 EGVNDVRKGACANHVSTMANFLKGAHVTINARAEEDVEPECIME 130
Cdd:pfam00241  80 DGAPIKRKMLYASSKAALKRELKGIHVEIQATDPSELTEEEILE 123

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 13786198    379 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHFGMFPANYVE 430
Cdd:smart00326   5 VRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56

ADF homology domain of drebrin and actin-binding protein 1 (abp1); Actin depolymerization factor/cofilin-like domains (ADF domains) are present in a family of essential eukaryotic actin regulatory proteins. Many of these proteins enhance the turnover rate of actin and interact with actin monomers as well as actin filaments. Abp1 and drebrin (developmentally regulated brain protein) are multidomain proteins with an N-terminal ADF homology domain and one or more C-terminal SH3 domains. They have been shown to interact with polymeric F-actin, but not with monomeric G-actin, and do not appear to promote the disassembly of actin filaments. Drebrin rather stabilizes actin filaments by inducing changes in the helical twist and may promote or interfere with the interactions of other proteins with actin filaments.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13786198   3 VNLSRNGPALQEAYVRVVTEKSPTDWALFTYEGNSNDIRVAGTGEGGLEELVEELNSGKVMYAFCRVKDPNSGLPKFVLI 82
Cdd:cd11281   1 IDLSTNSPEILAAYEDVVDGKSSTDWALFTYEGKSNDLKVADTGDGGLEELVEEFSDGKVQYGFARVKDPNSGLPKFVLI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13786198  83 NWTGEGVNDVRKGACANHVSTMANFLKGAHVTINARAEEDVEPECIMEKVAKASGA 138
Cdd:cd11281  81 NWCGEGVPDARKGSFASHVAAVANFLKGAHVQINARSEDDLDEDAILKKVSKASGA 136

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        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 13786198 378 CARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHFGMFPANYVEL 431
Cdd:cd11819   1 RAKALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAKGQKGLFPANYVEL 54

Actin depolymerization factor/cofilin- and gelsolin-like domains; Actin depolymerization factor/cofilin-like domains are present in a family of essential eukaryotic actin regulatory proteins; these proteins enhance the turnover rate of actin and interact with actin monomers as well as actin filaments.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13786198  27 DWALFTYEGNSNDIRVAGTGEGGLEELVEELNSGKVMYAFCRVKDPNSG--LPKFVLINWTGEGVNDVRKGACANHVSTM 104
Cdd:cd00013   1 DWVLFKVDAKKEEIVVGSTGAGFLDEFLEELPEDDPRYAFYRFKYPHSDdkRSKFVFISWIPDGVSIKQKMVYATNKQTL 80

                        90
                ....*....|....*..
gi 13786198 105 ANFLKGAHVTINARAEE 121
Cdd:cd00013  81 KEALFGLAVPVQIRDGD 97

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 13786198 377 LCARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGpDGHFGMFPANYVEL 431
Cdd:cd12073   1 ICAVALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTC-HGHRGLFPANYVEL 54

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 13786198    379 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHFGMFPANYVE 430
Cdd:smart00326   5 VRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 13786198 379 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGpDGHFGMFPANYVEL 431
Cdd:cd11961   2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGEC-HGSRGLFPSNYVEL 53

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 13786198 376 GLCARALYDYQAADDTEISFDPENLITGIEVIDEGWWRG-YGPDGHFGMFPANYVELI 432
Cdd:cd11933   1 GKSFRAMYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGtVQRTGKTGMLPANYVEAI 58

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 13786198 379 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRG-YGpDGHFGMFPANYVE 430
Cdd:cd11825   2 VKALYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGdYG-GKKQKWFPANYVE 53

Coactosin-like members of the ADF homology domain family; Actin depolymerization factor/cofilin-like domains (ADF domains) are present in a family of essential eukaryotic actin regulatory proteins. Many of these proteins enhance the turnover rate of actin and interact with actin monomers as well as actin filaments. The function of coactosins is not well understood. They appear to interfere with the capping of actin filaments in Dictyostelium, and may not be able to bind monomeric globular actin. A role for coactosins as chaperones stabilizing 5-lipoxygenase (5LO) has been suggested; 5LO plays a crucial role in leukotriene synthesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13786198  11 ALQEAYVRVVTEKSPTDWALFTYEGnSNDIRVAGTGEGGLEELVEELNSGKVMYAFCRV--KDPNSGLPKFVLINWTGEG 88
Cdd:cd11282   1 EIREAYNDVRSDVSDTNWVLLGYES-SNTLVLRGSGSGGIDELKAQLPDDEVLFGYVRItlGDGESKRSKFVFITWIGEN 79

                        90       100       110
                ....*....|....*....|....*....|....*
gi 13786198  89 VNDVRKGACANHVSTMANFLKGAHVTINARAEEDV 123
Cdd:cd11282  80 VSVLRRAKVSVHKGDVKEVLSPFHVELTASSKDEL 114

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGhFGMFPANYV 429
Cdd:cd11964   4 RAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQG-TGLFPSNFV 52

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHfGMFPANYV 429
Cdd:cd11820   4 RALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGE-GLFPANFV 52

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 13786198 378 CARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVELI 432
Cdd:cd11803   2 CCRALYDFEPENEGELGFKEGDIITLTNQIDENWYEGM-VNGQSGFFPVNYVEVL 55

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDE-GWWRGYgPDGHFGMFPANYVE 430
Cdd:cd11843   3 RALYDYEGQESDELSFKAGDILTKLEEEDEqGWCKGR-LDGRVGLYPANYVE 53

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVEL 431
Cdd:cd11840   3 IALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGE-LNGQTGLFPSNYVEP 53

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGhFGMFPANYV 429
Cdd:cd11963   5 RALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRG-VGLFPSNFV 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDE-GWWRGYGPDGHFGMFPANYVE 430
Cdd:cd11998   4 RALYDYDGQEQDELSFKAGDELTKLEDEDEqGWCKGRLDSGQVGLYPANYVE 55

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVE 430
Cdd:cd11826   3 VALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGV-LNGVTGLFPGNYVE 52

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 13786198 379 ARALYDYQAADDTEISFDPENLITGIEVIDE-GWWRGYgPDGHFGMFPANYVEL 431
Cdd:cd11882   2 ARALYACKAEDESELSFEPGQIITNVQPSDEpGWLEGT-LNGRTGLIPENYVEF 54

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

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                ....*....|....*....|....*....|....*....|....*....|....
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRG-YGPDGHFgMFPANYVELI 432
Cdd:cd11970   7 KALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGdYGGKKQL-WFPSNYVEEI 59

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....
gi 13786198 379 ARALYDYQAADDT-EISFDPENLI-----TGIEVIDEGWWRGYGPDGHFGMFPANYVEL 431
Cdd:cd11771   2 CRALYDFTPENPEmELSLKKGDIVavlskTDPLGRDSEWWKGRTRDGRIGWFPSNYVEV 60

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.

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13786198 376 GLCARALYDYQAADDTEISFDPENLITGIEVIDE-GWWRGYGPDGHFGMFPANYVE 430
Cdd:cd11999   1 GVRVRAVYDYTGQEPDELSFKAGEELLKVEDEDEqGWCKGVTDGGAVGLYPANYVE 56

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

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                ....*....|....*....|....*....|....*....|....*....|..
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRG-YGPDGHFgMFPANYVE 430
Cdd:cd11969   3 KALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGdYGGKVQH-YFPSNYVE 53

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

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                ....*....|....*....|....*....|....*....|....*....|...
gi 13786198 378 CARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVE 430
Cdd:cd11873   1 EVIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGT-LNGKRGMFPDNFVK 52

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.

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                ....*....|....*....|....*....|....*....|....*....|....*
gi 13786198 379 ARALYDYQAADDTEISFDPENLITGI--EVIDEGWWRGYgPDGHFGMFPANYVEL 431
Cdd:cd11875   2 ARVLFDYEAENEDELTLREGDIVTILskDCEDKGWWKGE-LNGKRGVFPDNFVEP 55

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

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gi 13786198 379 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGyGPDGHFGMFPANY 428
Cdd:cd11818   2 ARALYDFTGENEDELSFKAGDIITELESIDEEWMSG-ELRGKSGIFPKNF 50

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

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                ....*....|....*....|....*....|....*....|....*....|...
gi 13786198 379 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRgYGPDGHFGMFPANYVEL 431
Cdd:cd11824   2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWT-VERNGQKGLVPGTYLEK 53

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 13786198 381 ALYDYQAADDTEISFDPENLITGIEVID-EGWwrGYGP-DGHFGMFPANY 428
Cdd:cd11778   4 ALYDYEAQGDDEISIRVGDRIAVIRGDDgSGW--TYGEiNGVKGLFPTSY 51

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

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                ....*....|....*....|....*....|....*....|....*....
gi 13786198 381 ALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDgHFGMFPANYV 429
Cdd:cd11833   4 ALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIED-RVGFFPANFV 51

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                ....*....|....*....|....*....|....*....|....*....|....
gi 13786198 379 ARALYDYQAADDTEISF-DPENLITGIEVIDEGWWRGYGPDGHFGMFPANYVEL 431
Cdd:cd11896   2 ARALYSFQSENKEEINIqENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 55

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

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                ....*....|....*....|....*....|....*....|....*....|..
gi 13786198 379 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPdGHFGMFPANYVE 430
Cdd:cd11766   2 AVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECN-GQVGWFPSNYVT 52

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

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                ....*....|....*....|....*....|....*....|....*....
gi 13786198 381 ALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGPDGHFGMFPANYV 429
Cdd:cd11812   4 ALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLVNGQQGYFPANYV 52

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

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                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 13786198 378 CARALYDYQAADDTEISFDPENLItgiEVI--------DEGWWRGYGPDgHFGMFPANYV 429
Cdd:cd11876   1 LWTALFDYDARGEDELTLRRGQPV---EVLskdaavsgDEGWWTGKIGD-KVGIFPSNYV 56

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

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                ....*....|....*....|....*....|....*....|....*....|...
gi 13786198 379 ARALYDYQAADDTEISFDPENLITGIEViDEGWWRGYGPDGHFGMFPANYVEL 431
Cdd:cd11837   2 ATALYPWRAKKENHLSFAKGDIITVLEQ-QEMWWFGELEGGEEGWFPKSYVKE 53

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.

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                ....*....|....*....|....*....|....*....|....*....|...
gi 13786198 379 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYVEL 431
Cdd:cd11874   2 CKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGK-LNGKVGVFPSNFVKE 53

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

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                ....*....|....*....|....*....|....*....|....*....|..
gi 13786198 380 RALYDYQAADDTEISFDPENLITGIEVIDEGWWRGY-GPDGHFGMFPANYVE 430
Cdd:cd11780   3 RALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGTsERTGLFGTFPGNYVA 54

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

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                ....*....|....*....|....*....|....*....|....*....|..
gi 13786198 381 ALYDYQAADDTEISFDPENLITGIEVIDEGWWRGYGpDGHFGMFPANYVELI 432
Cdd:cd11971   4 AIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVC-NGVTGLFPGNYVESI 54

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 13786198 383 YDYQAADDTEISFDPENLITGIEVIDEGWWRGYgPDGHFGMFPANYV 429
Cdd:cd12052   6 FDYKAQHEDELTITVGDIITKIKKDDGGWWEGE-IKGRRGLFPDNFV 51

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

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13786198 378 CARALYDYQAADDTEISFDPENLITGI--EVIDEGWWRGYgPDGHFGMFPANYVEL 431
Cdd:cd12142   1 YCRVLFDYNPVAPDELALKKGDVIEVIskETEDEGWWEGE-LNGRRGFFPDNFVMP 55

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

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13786198 379 ARALYDYQAADDTEISFDPENLITGIEVIDEGWWR------GYGPDGHFGMFPANY 428
Cdd:cd11773   2 YKALYDYEPQTEDELTIQEDDILYLLEKSDDDWWKvklkvnSSDDDEPVGLVPATY 57