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 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKESdqeVKGIVPATYLEW 432
Cdd:cd11824    2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNG---QKGLVPGTYLEK 53

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 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKESdqeVKGIVPATYLEW 432
Cdd:cd11824    2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNG---QKGLVPGTYLEK 53

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 630972160  380 VVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKESdqeVKGIVPATYLE 431
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTG---RTGLVPANYVE 49

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 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKESdqeVKGIVPATYLEW 432
Cdd:cd11824    2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNG---QKGLVPGTYLEK 53

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. 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 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKESDQevkGIVPATYLE 431
Cdd:cd11856    2 YVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKE---GWVPASYLE 52

First Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the first SH3 domain of Tks5. 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 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKESDQevkGIVPATYLE 431
Cdd:cd12074    2 YVVVSNYEKQENSEISLQAGEVVDVIEKNESGWWFVSTAEEQ---GWVPATYLE 52

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. 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 630972160 379 RVVYEFVSESEHELSVEAGETVRVVGALEG-GWAIVTKESDQEvkGIVPATYLE 431
Cdd:cd11911    3 TALYDFDGTSEGTLSMEEGEILLVLEEDGGdGWTRVRKNNGDE--GYVPTSYIE 54

First 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 first 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 630972160 379 RVVYEFVSESEHELSVEAGETVRVVGALEG-GWAIVTKESDQEvkGIVPATYLE 431
Cdd:cd11912    3 KVLYDYTASGDDEVSISEGEEVTVLEPDDGsGWTKVRNGSGEE--GLVPTSYIE 54

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 630972160  380 VVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKESdqeVKGIVPATYLE 431
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTG---RTGLVPANYVE 49

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions 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 630972160 379 RVVYEFVSESEHELSVEAGETVRV----VGALEGGWAIVTkeSDQEVKGIVPATY 429
Cdd:cd11864    3 RAEYDFVAESEDELSFRAGDKLRLapkeLQPRVRGWLLAT--VDGQKIGLVPANY 55

Src homology 3 domain of Srms Protein Tyrosine Kinase; Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (Srms) is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. Src kinases in general 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, Srms 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. 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 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGAlEGGWAIVTKESDQEVKGIVPATYL 430
Cdd:cd11846    2 FTALYDFTARSTHELSVEQGDKLCVIEE-EGDYIFARKLTGNPESGLVPASYV 53

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. 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 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKESDQevKGIVPATYLE 431
Cdd:cd11770    2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAENSKGN--RGLVPKTYLK 53

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 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKesdQEVKGIVPATYLE 431
Cdd:cd11871    2 HRVLYEFVPETKEELQVLPGNIVFVLKKGTDNWATVVF---NGKKGLVPCNFLE 52

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR 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 630972160 379 RVVYEFVSESEHE-LSVEAGETVRVVGALEGGWAIVTKESdqeVKGIVPATYL 430
Cdd:cd11829    3 RTLYAFTGEQHQQgLSFEAGELIRVLQAPDGGWWEGEKDG---LRGWFPASYV 52

Third 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. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. 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 630972160 379 RVVYEFVSESEHELSVEAGETVRVVGALEGG-WAIVtKESDQEVKGIVPATYLE 431
Cdd:cd11775    4 KVLYDFDAQSDDELTVKEGDVVYILDDKKSKdWWMV-ENVSTGKEGVVPASYIE 56

Src Homology 3 domain of Formin Binding Protein 17; Formin Binding Protein 17 (FBP17), also called FormiN Binding Protein 1 (FNBP1), is involved in dynamin-mediated endocytosis. It is recruited to clathrin-coated pits late in the endocytosis process and may play a role in the invagination and scission steps. FBP17 binds in vivo to tankyrase, a protein involved in telomere maintenance and mitogen activated protein kinase (MAPK) signaling. It contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of the related protein, CIP4, associates with Gapex-5, a Rab31 GEF. 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 630972160 376 GVYRVVYEFVSESEHELSVEAGETVRVVGALEG-GWAIVTKESDQEvkGIVPATYLE 431
Cdd:cd12071    1 GTCKALYPFEGQNEGTISVAEGEMLYVIEEDKGdGWTRIRRNEDEE--GYVPTSYIE 55

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. 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 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTKESDqevKGIVPATYLE 431
Cdd:cd12021    2 YRAIADYEKSSKSEMALKTGDVVEVVEKSENGWWFCQLKAK---RGWVPASYLE 52

Src Homology 3 domain of Sorting nexin 9; Sorting nexin 9 (SNX9), also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX9 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 630972160 379 RVVYEFVSES-EHELSVEAGETVRVVGALEGGWAIVTKESDQEVkGIVPATYLE 431
Cdd:cd11898    3 RVLYDFAAEPgNNELTVKEGEIITVTNPNVGGGWIEAKNSQGER-GLVPTDYVE 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 630972160 377 VYRVVYEFVSESEHELSVEAGETVRVVGALEGGWAIVTK----ESDQEVKGIVPATY 429
Cdd:cd11773    1 VYKALYDYEPQTEDELTIQEDDILYLLEKSDDDWWKVKLkvnsSDDDEPVGLVPATY 57

DNA polymerase III subunits gamma and tau; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 630972160  45 AKPAQSPALTRVSSNPLSQSSDESKlVSPAVADPSSPSEDPSAILTLAPPK---PGPADTLYPSPSGGFVPSPEEGQDWR 121
Cdd:PRK07764 630 AGAAAAPAEASAAPAPGVAAPEHHP-KHVAVPDASDGGDGWPAKAGGAAPAappPAPAPAAPAAPAGAAPAQPAPAPAAT 708

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 630972160 122 LKPPPARKEWGETPRDRFEASKRlsptasrpgsldlQGAAGAVPPSPSRSDRDQRPGSLSSQSAGGGAGSRLSPTAPTRP 201
Cdd:PRK07764 709 PPAGQADDPAAQPPQAAQGASAP-------------SPAADDPVPLPPEPDDPPDPAGAPAQPPPPPAPAPAAAPAAAPP 775

                 ....*...
gi 630972160 202 PSIPPSQE 209
Cdd:PRK07764 776 PSPPSEEE 783

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 630972160 377 VYRVVYEFVSESEHELSVEAGETVRVVGALEGGWaivTKESDQEVKGIVPATYLE 431
Cdd:cd11772    1 VFRALYDYEAQHPDELSFEEGDLLYISDKSDPNW---WKATCGGKTGLIPSNYVE 52

First 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 first 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 630972160 379 RVVYEFVSESEHELSVEAGETVRVVGALEGGWaiVTKESDQEVkGIVPATYLE 431
Cdd:cd11781    3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNW--YEGEHNGRV-GIFPASYVE 52

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 630972160   58 SNPLSQSSDESKLVSPAVADPSSPSEDPSAILTLAPPKPGPADTLYPSP---SGGFVPSPEEGQDWRLKPPPARKEWGET 134
Cdd:PHA03247 2578 SEPAVTSRARRPDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPpppSPSPAANEPDPHPPPTVPPPERPRDDPA 2657

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 630972160  135 PR--------DRFEASKRLSPTASRPGSLDLQGAAGAV------PPSPSRSDRDQRPGSLSSQSAGGGAGSRLSPTAPTR 200
Cdd:PHA03247 2658 PGrvsrprraRRLGRAAQASSPPQRPRRRAARPTVGSLtsladpPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPA 2737

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 630972160  201 PPSIPPSQETAslIADASSASLSRRSSQASQYAGSPRMRPLSSASSLSRRGTAASSKDASPASPSAR 267
Cdd:PHA03247 2738 APAPPAVPAGP--ATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPW 2802

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 630972160 378 YRVVYEFVSESEHELSVEAGETVRV-VGALEGGWaIVTKESDQEVkGIVPATYLE 431
Cdd:cd11763    2 VRALYDFDSQPSGELSLRAGEVLTItRQDVGDGW-LEGRNSRGEV-GLFPSSYVE 54

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 630972160 378 YRVVYEFVSESEHELSVEAGETVRVVGALEG--GWAIVTKesdQEVKGIVPATYLE 431
Cdd:cd11836    2 YRALYAFEARNPDEISFQPGDIIQVDESQVAepGWLAGEL---KGKTGWFPANYVE 54

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 630972160   37 RSADVVMLAKPAQSPALTRVSSNPLSQSSDESKLVSPAVADPSSPSEDP-SAILTLAPP-KPGPADTLYPSPSGGFVPSP 114
Cdd:PHA03247  249 RGDIAAPAPPPVVGEGADRAPETARGATGPPPPPEAAAPNGAAAPPDGVwGAALAGAPLaLPAPPDPPPPAPAGDAEEED 328

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 630972160  115 EEGQDWRLKPPPARkewgetPRDRFEA--SKRLSPTASRPGSLDLQGAAGAVPPSPSRSDRDQRPGSLSSQSAGGGAGSR 192
Cdd:PHA03247  329 DEDGAMEVVSPLPR------PRQHYPLgfPKRRRPTWTPPSSLEDLSAGRHHPKRASLPTRKRRSARHAATPFARGPGGD 402

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 630972160  193 LSPTAPTRPPSIPPSQETASLIADASSASLSRRSSQASQYAGSPRMRPLSSASSLSRRGTAASSKDASPASPSARKRR 270
Cdd:PHA03247  403 DQTRPAAPVPASVPTPAPTPVPASAPPPPATPLPSAEPGSDDGPAPPPERQPPAPATEPAPDDPDDATRKALDALRER 480

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
                 ....*....|....*....|....*....|....
gi 630972160 377 VYRVVYEFVSESEHELSVEAGETVRVVGALEGGW 410
Cdd:cd11877    1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGW 34