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 6320086   13 KVKARYGWSGQTKGDLGFLEGDIMEVTRIA-GSWFYGKLLRNkKCSGYFPHNFV 65
Cdd:cd11889   1 KVKAVYSWAGETEGDLGFLEGDLIEVLSIGdGSWWSGKLRRN-GAEGIFPSNFV 53

Cytokinesis protein 3, contains TGc (transglutaminase/protease-like) domain [Cell cycle control, cell division, chromosome partitioning];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320086  415 PQDSIYNGLNTNEVKGNTKPGLVDVELAELNIEYIDKMTWKRCIRDGTMTLDSwaqTTFSARYSTVLEKLRGIYIFCTEM 494
Cdd:COG5279  39 LYELAVLLFALLEGNSLAAFLKDAISSSTIYALKDEEGLLTEKATIADESKDD---DYIITPGMSDYEKVRAIHDWIVDN 115

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320086  495 FALtDDNGTSDFSAEPQNLEKILYRKH--CTPYELtwLFKKLANSLGITCEIVIGFLKTPSAInwefKYNHCWLRILVNK 572
Cdd:COG5279 116 IEY-DYEAYNSGKSDSHSAYGALKNGKgvCEGYAK--LFKLLCNKAGIECYIVTGYARGSGGE----SGNHAWNAVKIDG 188

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 6320086  573 EWRFIDVILGNvtnpiheFVNNRKIKKAENSYFLMAPLEMIYTHIP 618
Cdd:COG5279 189 KWYLVDATWDD-------GVPDNGGGDVNYDYFLLSDEEFAKDHLP 227

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 6320086   13 KVKARYGWSGQTKGDLGFLEGDIMEVTRIA-GSWFYGKLLRNkKCSGYFPHNFV 65
Cdd:cd11889   1 KVKAVYSWAGETEGDLGFLEGDLIEVLSIGdGSWWSGKLRRN-GAEGIFPSNFV 53

Cytokinesis protein 3, contains TGc (transglutaminase/protease-like) domain [Cell cycle control, cell division, chromosome partitioning];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320086  415 PQDSIYNGLNTNEVKGNTKPGLVDVELAELNIEYIDKMTWKRCIRDGTMTLDSwaqTTFSARYSTVLEKLRGIYIFCTEM 494
Cdd:COG5279  39 LYELAVLLFALLEGNSLAAFLKDAISSSTIYALKDEEGLLTEKATIADESKDD---DYIITPGMSDYEKVRAIHDWIVDN 115

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320086  495 FALtDDNGTSDFSAEPQNLEKILYRKH--CTPYELtwLFKKLANSLGITCEIVIGFLKTPSAInwefKYNHCWLRILVNK 572
Cdd:COG5279 116 IEY-DYEAYNSGKSDSHSAYGALKNGKgvCEGYAK--LFKLLCNKAGIECYIVTGYARGSGGE----SGNHAWNAVKIDG 188

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 6320086  573 EWRFIDVILGNvtnpiheFVNNRKIKKAENSYFLMAPLEMIYTHIP 618
Cdd:COG5279 189 KWYLVDATWDD-------GVPDNGGGDVNYDYFLLSDEEFAKDHLP 227

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 6320086     15 KARYGWSGQTKGDLGFLEGDIMEVT-RIAGSWFYGKLLRNKKcsGYFPH 62
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLeKSEDGWWKGRNKGGKE--GLIPS 47

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 6320086   13 KVKARYGWSGQTKGDLGFLEGDIMEVTRIA-GSWFYGKLLRNkKCSGYFPHNFV 65
Cdd:cd11889   1 KVKAVYSWAGETEGDLGFLEGDLIEVLSIGdGSWWSGKLRRN-GAEGIFPSNFV 53

Cytokinesis protein 3, contains TGc (transglutaminase/protease-like) domain [Cell cycle control, cell division, chromosome partitioning];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320086  415 PQDSIYNGLNTNEVKGNTKPGLVDVELAELNIEYIDKMTWKRCIRDGTMTLDSwaqTTFSARYSTVLEKLRGIYIFCTEM 494
Cdd:COG5279  39 LYELAVLLFALLEGNSLAAFLKDAISSSTIYALKDEEGLLTEKATIADESKDD---DYIITPGMSDYEKVRAIHDWIVDN 115

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320086  495 FALtDDNGTSDFSAEPQNLEKILYRKH--CTPYELtwLFKKLANSLGITCEIVIGFLKTPSAInwefKYNHCWLRILVNK 572
Cdd:COG5279 116 IEY-DYEAYNSGKSDSHSAYGALKNGKgvCEGYAK--LFKLLCNKAGIECYIVTGYARGSGGE----SGNHAWNAVKIDG 188

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 6320086  573 EWRFIDVILGNvtnpiheFVNNRKIKKAENSYFLMAPLEMIYTHIP 618
Cdd:COG5279 189 KWYLVDATWDD-------GVPDNGGGDVNYDYFLLSDEEFAKDHLP 227

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6320086   11 PFKVKARYGWSGQTKGDLGFLEGDIMEVTRIA-GSWFYGKLLRNK--KCSGYFPHNFV 65
Cdd:cd11887   1 PFKVKALYPYESDHEDDLNFDVGQLITVTEEEdADWYFGEYVDSNgnTKEGIFPKNFV 58

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 6320086   13 KVKARYGWSGQTKGDLGFLEGDIMEVTR-IAGSWFYGKLlrNKKcSGYFPHNFV 65
Cdd:cd11877   1 LVRAKFNFEGTNEDELSFDKGDIITVTQvVEGGWWEGTL--NGK-TGWFPSNYV 51

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 6320086   14 VKARYGWSGQTKGDLGFLEGDIMEVTRIA-GSWFYGKLlrNKKcSGYFPHNFV 65
Cdd:cd12060   4 VKARFNFKQTNEDELSVCKGDIIYVTRVEeGGWWEGTL--NGK-TGWFPSNYV 53

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 6320086   16 ARYGWSGQTKGDLGFLEGDIMEVTRIAGSWFYGKLlrnKKCSGYFPHNFV 65
Cdd:cd11992   4 ALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSI---EDRTGIFPSNYV 50

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 6320086   13 KVKARYGWSGQTKGDLGFLEGDIMEVTRIAGS-WFYGKlLRNKKcsGYFPHNFV 65
Cdd:cd11827   1 QCKALYAYDAQDTDELSFNEGDIIEILKEDPSgWWTGR-LRGKE--GLFPGNYV 51

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 6320086   15 KARYGWSGQTKGDLGFLEGDIMEVTR-IAGSWFYGKLlrnKKCSGYFPHNFV 65
Cdd:cd11927   4 KALYNYEGKEPGDLKFSKGDIIILRRqVDENWYHGEV---NGIHGFFPTNFV 52

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6320086   13 KVKARYGWSGQTKGDLGFLEGDIMEVT-RIAGSWFYGKlLRNKKcsGYFPHNFVI 66
Cdd:cd11805   1 RVQALYDFNPQEPGELEFRRGDIITVLdSSDPDWWKGE-LRGRV--GIFPANYVQ 52

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 6320086   15 KARYGWSGQTKGDLGFLEGDIMEVTR-IAGSWFYGKLlrnKKCSGYFPHNFV 65
Cdd:cd11928   4 KALYSYEGKEPGDLKFNKGDIIILRRkVDENWYHGEL---NGCHGFLPASYI 52

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 6320086   16 ARYGWSGQTKGDLGFLEGDIMEVTRIAGSWFYGKLlrnKKCSGYFPHNFV 65
Cdd:cd11991   4 AMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTV---GDKTGVFPSNYV 50

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 6320086   13 KVKARYGWSGQTKGDLGFLEGD-IMEVTRIAGSWFYGKLLRNKKcSGYFPHNFV 65
Cdd:cd11789   1 RYRAMYDYAAADDDEVSFQEGDvIINVEIIDDGWMEGTVQRTGQ-SGMLPANYV 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 6320086   13 KVKARYGWSGQTKGDLGFLEGDIMEVT-RIAGSWFYGKLLRNKkcsGYFPHNFV 65
Cdd:cd11826   1 KVVALYDYTADKDDELSFQEGDIIYVTkKNDDGWYEGVLNGVT---GLFPGNYV 51

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 6320086   14 VKARYGWSGQTKGDLGFLEGDIMEVTRIAGSWFYGKLLRNKKcSGYFPHNFV 65
Cdd:cd12004   2 VVALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARSLTTKK-EGFIPSNYV 52

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6320086   13 KVKARYGWSGQTKGDLGFLEGDIMEVTR--IAGSWFYGKLLRNKKcsGYFPHNFV 65
Cdd:cd11763   1 KVRALYDFDSQPSGELSLRAGEVLTITRqdVGDGWLEGRNSRGEV--GLFPSSYV 53

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 6320086   14 VKARYGWSGQTKGDLGFLEGDIMEV-TRIAGSWFYGKlLRNKkcSGYFPHNFV 65
Cdd:cd11950   2 VRALYDFEALEDDELGFNSGDVIEVlDSSNPSWWKGR-LHGK--LGLFPANYV 51

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 6320086   15 KARYGWSGQTKGDLGFLEGDIMEVTRIAG-SWFYGKLlrnKKCSGYFPHNFV 65
Cdd:cd11816   3 VARFDFEGEQEDELSFSEGDVITLKEYVGeEWAKGEL---NGKIGIFPLNFV 51