N-terminal (or first) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. The N-terminal SH3 domain increases the affinity of p67phox for the oxidase complex. 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 194383822 163 AHRVLFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFNGQKGLVPCNYLEPV 216
Cdd:cd11871    1 PHRVLYEFVPETKEELQVLPGNIVFVLKKGTDNWATVVFNGKKGLVPCNFLEPV 54

Lipoprotein NlpI, contains TPR repeats [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822   5 EAISLWNEGVLAADKKDWKGALDAFSAVQ--DP-HSRICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLY 81
Cdd:COG4785   72 LAQLYYERGVAYDSLGDYDLAIADFDQALelDPdLAEAYNNRGLAYLLLGDYDAALEDFDRALELDPDYAYAYLNRGIAL 151

                         90
                 ....*....|....*..
gi 194383822  82 YQTEKYDLAIKDLKEAL 98
Cdd:COG4785  152 YYLGRYELAIADLEKAL 168

N-terminal (or first) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. The N-terminal SH3 domain increases the affinity of p67phox for the oxidase complex. 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 194383822 163 AHRVLFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFNGQKGLVPCNYLEPV 216
Cdd:cd11871    1 PHRVLYEFVPETKEELQVLPGNIVFVLKKGTDNWATVVFNGKKGLVPCNFLEPV 54

PB1 domain; Phox and Bem1p domain, present in many eukaryotic cytoplasmic signalling proteins. The domain adopts a beta-grasp fold, similar to that found in ubiquitin and Ras-binding domains. A motif, variously termed OPR, PC and AID, represents the most conserved region of the majority of PB1 domains, and is necessary for PB1 domain function. This function is the formation of PB1 domain heterodimers, although not all PB1 domain pairs associate.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822   270 PYTLKVHYK-YTVVMKTQPGLPYSQVRDMVSKKLELRLEHTKLSYRPRDSNELVPLSEDSMKDAWGQVK---NYCLTLWC 345
Cdd:smart00666   1 TVDVKLRYGgETRRLSVPRDISFEDLRSKVAKRFGLDNQSFTLKYQDEDGDLVSLTSDEDLEEAIEEYDslgSKKLRLHV 80

                   .
gi 194383822   346 E 346
Cdd:smart00666  81 F 81

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
                   ....*....|....*....|....*....|....*....|.
gi 194383822   380 QVEALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:smart00326   4 QVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGR 44

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
                  ....*....|....*....|....*....|....*...
gi 194383822  383 ALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:pfam00018   2 ALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKG 39

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 194383822  165 RVLFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFN-GQKGLVPC 210
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKgGKEGLIPS 47

Tetratricopeptide repeats; Repeats present in 4 or more copies in proteins. Contain a minimum of 34 amino acids each and self-associate via a "knobs and holes" mechanism.

                           10        20
                   ....*....|....*....|....*...
gi 194383822    71 AVAYFQRGMLYYQTEKYDLAIKDLKEAL 98
Cdd:smart00028   1 AEALYNLGNAYLKLGDYDEALEYYEKAL 28

N-terminal (or first) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. The N-terminal SH3 domain increases the affinity of p67phox for the oxidase complex. 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 194383822 163 AHRVLFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFNGQKGLVPCNYLEPV 216
Cdd:cd11871    1 PHRVLYEFVPETKEELQVLPGNIVFVLKKGTDNWATVVFNGKKGLVPCNFLEPV 54

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. 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 194383822 380 QVEALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:cd11870    1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDG 41

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. 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 194383822 380 QVEALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:cd12047    1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDG 41

PB1 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822  270 PYTLKVHYKYTVV--MKTQPGLPYSQVRDMVSKKLELRLEHTKLSYRPRDsNELVPLSEDS-MKDAWGQVKNY---CLTL 343
Cdd:pfam00564   1 TVRLKLRYGGGIRrfLSVSRGISFEELRALVEQRFGLDDVDFKLKYPDED-GDLVSLTSDEdLEEALEEARSLgskSLRL 79

                  ....*
gi 194383822  344 WCENT 348
Cdd:pfam00564  80 HVFPT 84

Lipoprotein NlpI, contains TPR repeats [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822   5 EAISLWNEGVLAADKKDWKGALDAFSAVQ--DP-HSRICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLY 81
Cdd:COG4785   72 LAQLYYERGVAYDSLGDYDLAIADFDQALelDPdLAEAYNNRGLAYLLLGDYDAALEDFDRALELDPDYAYAYLNRGIAL 151

                         90
                 ....*....|....*..
gi 194383822  82 YQTEKYDLAIKDLKEAL 98
Cdd:COG4785  152 YYLGRYELAIADLEKAL 168

Tetratricopeptide (TPR) repeat [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822   5 EAISLWNEGVLAADKKDWKGALDAFS-AVQ-DP-HSRICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLY 81
Cdd:COG0457    7 DAEAYNNLGLAYRRLGRYEEAIEDYEkALElDPdDAEALYNLGLAYLRLGRYEEALADYEQALELDPDDAEALNNLGLAL 86

                         90
                 ....*....|....*..
gi 194383822  82 YQTEKYDLAIKDLKEAL 98
Cdd:COG0457   87 QALGRYEEALEDYDKAL 103

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 194383822 165 RVLFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFNGQKGLVPCNYLE 214
Cdd:cd11824    3 SVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLE 52

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 194383822   160 EGEAHRVLFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFN-GQKGLVPCNYLE 214
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56

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
                 ....*....|....*....|....*....|....*...
gi 194383822 383 ALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:cd11803    5 ALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNG 42

Lipoprotein NlpI, contains TPR repeats [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822  10 WNEGVLAADKKDWKGALDAFSAVQDP--HSRICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLYYQTEKY 87
Cdd:COG4785   44 LALALAAAALAAAALAAERIDRALALpdLAQLYYERGVAYDSLGDYDLAIADFDQALELDPDLAEAYNNRGLAYLLLGDY 123

                         90
                 ....*....|.
gi 194383822  88 DLAIKDLKEAL 98
Cdd:COG4785  124 DAALEDFDRAL 134

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH 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
                 ....*....|....*....|....*....|....*...
gi 194383822 380 QVEALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGE 417
Cdd:cd11793    1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGE 38

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
                 ....*....|....*....|....*....|....*....
gi 194383822 382 EALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:cd11928    4 KALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNG 42

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
                 ....*....|....*....|....*....|....*....|.
gi 194383822 380 QVEALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:cd11805    1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRG 41

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. 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
                 ....*....|....*....|....*....|....*....
gi 194383822 380 QVEALFSYEATQPEDLEFQEGDIILVLSKVN--EEWLEG 416
Cdd:cd11842    1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDsqNDWWTG 39

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 194383822 380 QVEALFSYEATQPEDLEFQEGDIILVLSKVNEE--WLEGECKG 420
Cdd:cd11875    1 KARVLFDYEAENEDELTLREGDIVTILSKDCEDkgWWKGELNG 43

Lipopolysaccharide biosynthesis regulator YciM/LapB, contains six TPR domains and a C-terminal metal-binding domain [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822  15 LAADKKDWKGALDAF---SAVQDPHSRICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLYYQTEKYDLAI 91
Cdd:COG2956  119 IYEQEGDWEKAIEVLerlLKLGPENAHAYCELAELYLEQGDYDEAIEALEKALKLDPDCARALLLLAELYLEQGDYEEAI 198

                 ....*....
gi 194383822  92 KDLKEALIQ 100
Cdd:COG2956  199 AALERALEQ 207

Predicted O-linked N-acetylglucosamine transferase, SPINDLY family [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822   5 EAISLWNEGVLAADKKDWKGALDAFS---AVQDPHSRICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLY 81
Cdd:COG3914  111 NAEALFNLGNLLLALGRLEEALAALRralALNPDFAEAYLNLGEALRRLGRLEEAIAALRRALELDPDNAEALNNLGNAL 190

                         90
                 ....*....|....*..
gi 194383822  82 YQTEKYDLAIKDLKEAL 98
Cdd:COG3914  191 QDLGRLEEAIAAYRRAL 207

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains 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
                 ....*....|....*....|....*....|....*....|.
gi 194383822 380 QVEALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:cd11823    1 RCKALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNG 41

Flp pilus assembly protein TadD, contains TPR repeats [Intracellular trafficking, secretion, and vesicular transport, Extracellular structures];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822   5 EAISLWNEGVLAADKKDWKGALDAFS-AVQ-DP-HSRICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLY 81
Cdd:COG5010   53 AFAIESPSDNLYNKLGDFEESLALLEqALQlDPnNPELYYNLALLYSRSGDKDEAKEYYEKALALSPDNPNAYSNLAALL 132

                         90
                 ....*....|....*..
gi 194383822  82 YQTEKYDLAIKDLKEAL 98
Cdd:COG5010  133 LSLGQDDEAKAALQRAL 149

Cytochrome c-type biogenesis protein CcmH/NrfG [Energy production and conversion, Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822  13 GVLAADKKDWKGALDAFS-AVQ-DP-HSRICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLYYQTEKYDL 89
Cdd:COG4235   24 GRAYLRLGRYDEALAAYEkALRlDPdNADALLDLAEALLAAGDTEEAEELLERALALDPDNPEALYLLGLAAFQQGDYAE 103

                 ....*....
gi 194383822  90 AIKDLKEAL 98
Cdd:COG4235  104 AIAAWQKLL 112

First Src homology 3 domain (or SH3A) 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 first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, 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
                 ....*....|....*....|....*....|....*....|
gi 194383822 383 ALFSYEATQPEDLEFQEGDIILVLSKVNEE--WLEGECKG 420
Cdd:cd11836    4 ALYAFEARNPDEISFQPGDIIQVDESQVAEpgWLAGELKG 43

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
                 ....*....|....*....|....*....|....*....
gi 194383822 382 EALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:cd11927    4 KALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNG 42

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
                 ....*....|....*....|....*....|....*..
gi 194383822 381 VEALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGE 417
Cdd:cd11887    4 VKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGE 40

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

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 194383822  383 ALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:pfam07653   4 VIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGG 41

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 194383822 165 RVLFGFVPETKEELQVMPGNIVFVLKKGNDNW--ATVMFNGQKGLVPCNYLEP 215
Cdd:cd11780    3 RALYSYTPQNEDELELREGDIVYVMEKCDDGWfvGTSERTGLFGTFPGNYVAR 55

Fourth 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 194383822 381 VEALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:cd11817    2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNG 41

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 194383822 167 LFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFNGQKGLVPCNYLEPV 216
Cdd:cd11971    5 IYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVESI 54

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains 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 194383822 165 RVLFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFNGQKGLVPCNYLE 214
Cdd:cd11823    3 KALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVE 52

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. 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 194383822 380 QVEALFSYEATQPEDLEFQEGDIILVLSKVNEEWLEGECKG 420
Cdd:cd11869    1 RAEALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRG 41

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. 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 194383822 168 FGFVPETKEELQVMPGNIVFVL----KKGNDNWATVMFNGQKGLVPCNYL 213
Cdd:cd11941    6 YPFTARSKHEVSLQAGQPVTVLephdKKGSPEWSLVEVNGQRGYVPSSYL 55

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 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. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. 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 194383822 164 HRVLFGFVPETKEELQVMPGNIVFVLKKGNDNW--ATVMFNGQKGLVPCNYLEP 215
Cdd:cd11785    2 YRVIVPYPPQSEAELELKEGDIVFVHKKREDGWfkGTLQRTGKTGLFPGSFVES 55

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 194383822 167 LFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFNGQKGLVPCNYLEPV 216
Cdd:cd11972    8 IYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVESI 57

Second 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 second 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 194383822 165 RVLFGFVPETKEELQVMPGNIVFVLKKGNDNWATVMFNGQKGLVPCNYLE 214
Cdd:cd11782    3 RAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQ 52

Lipopolysaccharide biosynthesis regulator YciM/LapB, contains six TPR domains and a C-terminal metal-binding domain [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822  13 GVLAADKKDWKGALDAFSAV--QDPHS-RICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLYYQTEKYDL 89
Cdd:COG2956  151 AELYLEQGDYDEAIEALEKAlkLDPDCaRALLLLAELYLEQGDYEEAIAALERALEQDPDYLPALPRLAELYEKLGDPEE 230

                 ....*....
gi 194383822  90 AIKDLKEAL 98
Cdd:COG2956  231 ALELLRKAL 239

Outer membrane protein chaperone/metalloprotease BepA/YfgC, contains M48 and TPR domains [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194383822  13 GVLAADKKDWKGALDAFSAV--QDP-HSRICFNIGCMYTILKNMTEAEKAFTRSINRDKHLAVAYFQRGMLYYQTEKYDL 89
Cdd:COG4783   45 GEILLQLGDLDEAIVLLHEAleLDPdEPEARLNLGLALLKAGDYDEALALLEKALKLDPEHPEAYLRLARAYRALGRPDE 124

                 ....*....
gi 194383822  90 AIKDLKEAL 98
Cdd:COG4783  125 AIAALEKAL 133

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They 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). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. 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
                 ....*....|....*....|....*....|.
gi 194383822 383 ALFSYEATQPEDLEFQEGDIILVLSKVNEEW 413
Cdd:cd11845    4 ALYDYEARTDDDLSFKKGDRLQILDDSDGDW 34