RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619  34 AIRELIDTEVSYLHTLRLCTSDIRGHLQQL---PPGDLDILFSNIDDIIQVSSRFLhglQETACKEEKQAHLIGNLFLEF 110
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPlseSEEEIKTIFSNIEEIYELHRQLL---LEELLKEWISIQRIGDIFLKF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619 111 QEELEqVYKVYCANYDQALllvKAYQKEPELQKEIQGIIEAAVPQAGPSGLSF--LLVIPLQRITKYPLLLQKILENTPA 188
Cdd:pfam00621  78 APGFK-VYSTYCSNYPKAL---KLLKKLLKKNPKFRAFLEELEANPECRGLDLnsFLIKPVQRIPRYPLLLKELLKHTPP 153

                         170       180
                  ....*....|....*....|...
gi 2025113619 189 DASAHPVLQRATSALQDVNSNIN 211
Cdd:pfam00621 154 DHPDYEDLKKALEAIKEVAKQIN 176

First 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 2025113619 510 IYQVTSNINGTGTLDLTLPRGQIVALLQNKDTKGNNSRWLVDTGGHRGYVPAGK 563
Cdd:cd11799     1 IYQVMSNVSGTRDLDLTLTRGEIVAVLQEADTKGNTGRWLVDAGGKRGYVPASK 54

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619  34 AIRELIDTEVSYLHTLRLCTSDIRGHLQQL---PPGDLDILFSNIDDIIQVSSRFLhglQETACKEEKQAHLIGNLFLEF 110
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPlseSEEEIKTIFSNIEEIYELHRQLL---LEELLKEWISIQRIGDIFLKF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619 111 QEELEqVYKVYCANYDQALllvKAYQKEPELQKEIQGIIEAAVPQAGPSGLSF--LLVIPLQRITKYPLLLQKILENTPA 188
Cdd:pfam00621  78 APGFK-VYSTYCSNYPKAL---KLLKKLLKKNPKFRAFLEELEANPECRGLDLnsFLIKPVQRIPRYPLLLKELLKHTPP 153

                         170       180
                  ....*....|....*....|...
gi 2025113619 189 DASAHPVLQRATSALQDVNSNIN 211
Cdd:pfam00621 154 DHPDYEDLKKALEAIKEVAKQIN 176

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619  31 QRLAIRELIDTEVSYLHTLRLCTSDIRGHLQQ----LPPGDLDILFSNIDDIIQVSSRFLHGLQETACKEEKQAHLIGNL 106
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKellpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRIGDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619 107 FLEFQEELeQVYKVYCANYDQALLLVKAYQKEpelQKEIQGIIEAAVPQAGPSGLSFLLVIPLQRITKYPLLLQKILENT 186
Cdd:cd00160    81 FLKLAPFF-KIYSEYCSNHPDALELLKKLKKF---NKFFQEFLEKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156

                         170       180
                  ....*....|....*....|....*
gi 2025113619 187 PADASAHPVLQRATSALQDVNSNIN 211
Cdd:cd00160   157 PDGHEDREDLKKALEAIKEVASQVN 181

First 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 2025113619 510 IYQVTSNINGTGTLDLTLPRGQIVALLQNKDTKGNNSRWLVDTGGHRGYVPAGK 563
Cdd:cd11799     1 IYQVMSNVSGTRDLDLTLTRGEIVAVLQEADTKGNTGRWLVDAGGKRGYVPASK 54

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2025113619 610 AVYPFVARSTHELSLQAGQPVTILEaqdkKGNPEWSLVEANGQRGYVPSNFLA 662
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIE----ESEDGWWEGINTGRTGLVPANYVE 49

BAR domain; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different protein families. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysin, endophilin, BRAP and Nadrin. BAR domains are also frequently found alongside domains that determine lipid specificity, like pfam00169 and pfam00787 domains in beta centaurins and sorting nexins respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619 243 LSKKTTRLSQLLKQEAGLVPRTE-DKEFDDLEERFQWVSLCVTELKSNVAAYMDNLEAFLCfrpHERNLDIP-------- 313
Cdd:pfam03114   1 LKKQFNRASQLLGEKVGGAEKTKlDEDFEELERRFDTTEKEIKKLQKDTKGYLQPNPGARA---KQTVLEQPeellaesm 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619 314 -------------GGAAEQY-CSLARDLQLQAflQFKQRLTGLVWQPLCSLARALVGPQNLIKKRLDKLLDF-------- 371
Cdd:pfam03114  78 ieagkdlgedssfGKALEDYgEALKRLAQLLE--QLDDRVETNFLDPLRNLLKEFKEIQKHRKKLERKRLDYdaaktrvk 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619 372 --ERVEEKLLDVGSVTYEE-EAARHTYQALNSLIVAELPQFNHLVMQWLGQILRTFVVLQRDL---ADQVLRRAESSMAL 445
Cdd:pfam03114 156 kaKKKKSSKAKDESQAEEElRKAQAKFEESNEQLKALLPNLLSLEVEFVVNQLVAFVEAQLDFhrqCYQLLEQLQQQLGK 235

Uncharacterized conserved protein YgiM, contains N-terminal SH3 domain, DUF1202 family [General function prediction only];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2025113619 623 SLQAGQPVTILEAQDkkgnpEWSLVE-ANGQRGYVPSNFLARTPSPT 668
Cdd:COG3103    29 TLPKGEKVTVLGRSG-----GWYKVRySNGKTGWVSSRYLTVTPSAR 70

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619  34 AIRELIDTEVSYLHTLRLCTSDIRGHLQQL---PPGDLDILFSNIDDIIQVSSRFLhglQETACKEEKQAHLIGNLFLEF 110
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPlseSEEEIKTIFSNIEEIYELHRQLL---LEELLKEWISIQRIGDIFLKF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619 111 QEELEqVYKVYCANYDQALllvKAYQKEPELQKEIQGIIEAAVPQAGPSGLSF--LLVIPLQRITKYPLLLQKILENTPA 188
Cdd:pfam00621  78 APGFK-VYSTYCSNYPKAL---KLLKKLLKKNPKFRAFLEELEANPECRGLDLnsFLIKPVQRIPRYPLLLKELLKHTPP 153

                         170       180
                  ....*....|....*....|...
gi 2025113619 189 DASAHPVLQRATSALQDVNSNIN 211
Cdd:pfam00621 154 DHPDYEDLKKALEAIKEVAKQIN 176

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619  31 QRLAIRELIDTEVSYLHTLRLCTSDIRGHLQQ----LPPGDLDILFSNIDDIIQVSSRFLHGLQETACKEEKQAHLIGNL 106
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKellpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRIGDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619 107 FLEFQEELeQVYKVYCANYDQALLLVKAYQKEpelQKEIQGIIEAAVPQAGPSGLSFLLVIPLQRITKYPLLLQKILENT 186
Cdd:cd00160    81 FLKLAPFF-KIYSEYCSNHPDALELLKKLKKF---NKFFQEFLEKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156

                         170       180
                  ....*....|....*....|....*
gi 2025113619 187 PADASAHPVLQRATSALQDVNSNIN 211
Cdd:cd00160   157 PDGHEDREDLKKALEAIKEVASQVN 181

First 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 2025113619 510 IYQVTSNINGTGTLDLTLPRGQIVALLQNKDTKGNNSRWLVDTGGHRGYVPAGK 563
Cdd:cd11799     1 IYQVMSNVSGTRDLDLTLTRGEIVAVLQEADTKGNTGRWLVDAGGKRGYVPASK 54

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. 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 2025113619 610 AVYPFVARSTHELSLQAGQPVTILEAQDKKGNPEWSLVEANGQRGYVPSNFLAR 663
Cdd:cd12141     4 AVYTFKARSPNELSVSANQRVRILEFSDLTGNKEWWLAEANGQKGYVPSNYIRK 57

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 2025113619 607 QVVAVYPFVARSTHELSLQAGQPVTILEaqdkKGNPEWSLVEANGQRGYVPSNFL 661
Cdd:cd11856     1 SYVAIADYEAQGDDEISLQEGEVVEVLE----KNDSGWWYVRKGDKEGWVPASYL 51

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 2025113619 607 QVVAVYPFVARSTHELSLQAGQPVTILEaqdkKGNPEWSLVE-ANGQRGYVPSNF 660
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLE----KDDDGWWEGElNGGREGLFPANY 51

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2025113619 607 QVVAVYPFVARSTHELSLQAGQPVTILeaqdKKGNPEWSLVE--ANGQRGYVPSNF 660
Cdd:cd11845     1 IYVALYDYEARTDDDLSFKKGDRLQIL----DDSDGDWWLARhlSTGKEGYIPSNY 52

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. 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 2025113619 607 QVVAVYPFVARSTHELSLQAGQPVTILeaqDKKGNPEWSLVEANGQRGYVPSNFLA 662
Cdd:cd11768     1 IVVALYDFQPIEPGDLPLEKGEEYVVL---DDSNEHWWRARDKNGNEGYIPSNYVT 53

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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2025113619 609 VAVYPFVARSTHELSLQAGQPVTILEaqdkKGNPEWSLVE-ANGQRGYVPS 658
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLE----KSEDGWWKGRnKGGKEGLIPS 47

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 2025113619 609 VAVYPFVARSTHELSLQAGQPVTILEaqdkKGNPEWSLVEANGQRGYVPSNFL 661
Cdd:cd11824     3 SVLYDYTAQEDDELSISKGDVVAVIE----KGEDGWWTVERNGQKGLVPGTYL 51

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 2025113619 607 QVVAVYPFVARSTHELSLQAGQPVTILeaqDKKGNPEWSLVE--ANGQRGYVPSNFL 661
Cdd:cd11775     2 RGKVLYDFDAQSDDELTVKEGDVVYIL---DDKKSKDWWMVEnvSTGKEGVVPASYI 55

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. 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 2025113619 608 VVAVYPFVARSTHELSLQAGQPVTILEAQDKkgnpEWSLVEANGQRGYVPSNFLAR 663
Cdd:cd11808     2 VVALYDYQEKSPREVSMKKGDILTLLNSSNK----DWWKVEVNDRQGFVPAAYVKK 53

The Bin/Amphiphysin/Rvs (BAR) domain of Saccharomyces cerevisiae Reduced viability upon starvation protein 161 and similar proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of fungal proteins with similarity to Saccharomyces cerevisiae Reduced viability upon starvation protein 161 (Rvs161p) and Schizosaccharomyces pombe Hob3 (homolog of Bin3). S. cerevisiae Rvs161p plays a role in regulating cell polarity, actin cytoskeleton polarization, vesicle trafficking, endocytosis, bud formation, and the mating response. It forms a heterodimer with another BAR domain protein Rvs167p. Rvs161p and Rvs167p share common functions but are not interchangeable. Their BAR domains cannot be replaced with each other and the overexpression of one cannot suppress the mutant phenotypes of the other. S. pombe Hob3 is important in regulating filamentous actin localization and may be required in activating Cdc42 and recruiting it to cell division sites. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2025113619 258 AGLVPRTEDKEFDDLEERFQWVSLCVTELKSNVAAYMDNL-----------EAFLCFRPHERNLDiPGGAAEQYCSLARD 326
Cdd:cd07591     2 TGQVERTVDREFEFEERRYRTMEKASTKLQKEAKGYLDSLraltssqariaETISSFYGDAGDKD-GAMLSQEYKQAVEE 80

                          90       100       110       120       130       140       150       160
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gi 2025113619 327 LQLQAFLQFKQRLTGLVWQPLCSLARALVGPQNLIKKRLDKLLDFERVE---EKLLD--------VGSVTYEEEAARHTY 395
Cdd:cd07591    81 LDAETVKELDGPYRQTVLDPIGRFNSYFPEINEAIKKRNHKLLDYDAARakvRKLIDkpsedptkLPRAEKELDEAKEVY 160

                         170       180       190
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gi 2025113619 396 QALNSLIVAELPQFNHLVMQWLGQILRTFVVLQ 428
Cdd:cd07591   161 ETLNDQLKTELPQLVDLRIPYLDPSFEAFVKIQ 193

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. 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 2025113619 608 VVAVYPFVARSTHELSLQAGQPVTILEAQDkkgNPEWSLVEANGQRGYVPSNFL 661
Cdd:cd11906     3 VVALYDYTPMNAQDLQLRKGEEYVILEESN---LPWWRARDKNGREGYIPSNYV 53

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

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 2025113619 610 AVYPFVARSTHELSLQAGQPVTILEAQDKkgnpEWSLVEANGQRGYVPSNF 660
Cdd:cd11818     4 ALYDFTGENEDELSFKAGDIITELESIDE----EWMSGELRGKSGIFPKNF 50

First Src homology 3 domain (or SH3A) 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 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.

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gi 2025113619 610 AVYPFVARSTHELSLQAGQPVTILEAQdkKGNPEWSLVEANGQRGYVPSNFLAR 663
Cdd:cd11987     4 ALYPFEARSHDEITIQPGDIVMVDESQ--TGEPGWLGGELKGKTGWFPANYAEK 55

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.

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gi 2025113619 608 VVAVYPFVARSTHELSLQAGQPVTILEaqdkKGNPEWSLVEANGQRGYVPSNFLA 662
Cdd:pfam07653   2 GRVIFDYVGTDKNGLTLKKGDVVKVLG----KDNDGWWEGETGGRVGLVPSTAVE 52

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 2025113619 610 AVYPFVARSTHELSLQAGQPVTILEAQDkkGNPEWSLVEANGQRGYVPSNF 660
Cdd:cd11836     4 ALYAFEARNPDEISFQPGDIIQVDESQV--AEPGWLAGELKGKTGWFPANY 52

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2025113619 608 VVAVYPFVARSTHELSLQAGQPVTILeaqdKKGNPEWSLVEANGQRGYVPSNFLA 662
Cdd:cd11806     2 YVAIADFVATDDSQLSFESGDKLLVL----RKPSVDWWWAEHNGCCGYIPASHLH 52

Fifth Src homology 3 domain (or SH3E) 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 fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2025113619 607 QVVAVYPFVARSTHELSLQAGQPVTILEAQDkkgnPEWSLVEANGQRGYVPSNFL 661
Cdd:cd11995     2 QVIGMYDYTAQNDDELAFSKGQIINVLNKED----PDWWKGELNGQVGLFPSNYV 52

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.

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gi 2025113619 609 VAVYPFVARSTHELSLQAGQPVTILEAQDKKGNPEWSLVEANGQR-GYVPSNF 660
Cdd:cd11864     3 RAEYDFVAESEDELSFRAGDKLRLAPKELQPRVRGWLLATVDGQKiGLVPANY 55

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. 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 2025113619 608 VVAVYPFVARSTHELSLQAGQPVTILEAQDKKgNPEWSLVEANGQRGYVPSNFL 661
Cdd:cd11954     3 VYALWDYEAQNADELSFQEGDAITILRRKDDS-ETEWWWARLNDKEGYVPKNLL 55

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.

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gi 2025113619 607 QVVAVYPFVARSTHELSLQAGQPVTILEAQDKkgnpEWSLVEANGQRGYVPSNF 660
Cdd:cd11823     1 RCKALYSYTANREDELSLQPGDIIEVHEKQDD----GWWLGELNGKKGIFPATY 50

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. 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 2025113619 609 VAVYPFVARSTHELSLQAGQPVTILeaqDKKGNPEWSLVEANGQRGYVPSNFL 661
Cdd:cd11830     3 KARYDFCARDMRELSLKEGDVVKIY---NKKGQQGWWRGEINGRIGWFPSTYV 52

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

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gi 2025113619 608 VVAVYPFVARSTHELSLQAGQPVTILEaqdkKGNPEWSLVE-ANGQRGYVPSNFL 661
Cdd:cd11812     2 VVALYDYTANRSDELTIHRGDIIRVLY----KDNDNWWFGSlVNGQQGYFPANYV 52