RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 369 MDGKEPIYTLPA--IISKKEEMYLNEAGFNFVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNTTFSPK--SPPDMDID 444
Cdd:cd04374     1 MDGKEPVYHSPGrlQSEVEGEAQLDDIGFKFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGLDPKtsTPGDVDLD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 445 IELWDNKTITSGLKNYLRCLAEPLMTYKLHKDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQ 524
Cdd:cd04374    81 NSEWEIKTITSALKTYLRNLPEPLMTYELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKK 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1734342263 525 NLMTISNLGVIFGPTLMRAQEETVAAMMNIKFQNIVVEILIEH 567
Cdd:cd04374   161 NLMTVSNLGVVFGPTLLRPQEETVAAIMDIKFQNIVVEILIEN 203

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1734342263 800 QAQAMYSCKAEHSHELSFPQGAIFSNVHPSVEPGWLKATYEGRTGLVPENYVVFL 854
Cdd:cd12066     1 QAKAMYSCKAEHSHELSFPQGAIFSNVYPSVEPGWLKATYEGKTGLVPENYVVFL 55

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 369 MDGKEPIYTLPA--IISKKEEMYLNEAGFNFVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNTTFSPK--SPPDMDID 444
Cdd:cd04374     1 MDGKEPVYHSPGrlQSEVEGEAQLDDIGFKFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGLDPKtsTPGDVDLD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 445 IELWDNKTITSGLKNYLRCLAEPLMTYKLHKDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQ 524
Cdd:cd04374    81 NSEWEIKTITSALKTYLRNLPEPLMTYELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKK 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1734342263 525 NLMTISNLGVIFGPTLMRAQEETVAAMMNIKFQNIVVEILIEH 567
Cdd:cd04374   161 NLMTVSNLGVVFGPTLLRPQEETVAAIMDIKFQNIVVEILIEN 203

GTPase Regulator Associated with Focal adhesion and related proteins Pleckstrin homology (PH) domain; This hierarchy contains GRAF family members: OPHN1/oligophrenin1, GRAF1 (also called ARHGAP26/Rho GTPase activating protein 26), GRAF2 (also called ARHGAP10/ARHGAP42), AK057372, and LOC129897, all of which are members of the APPL family. OPHN1 is a RhoGAP involved in X-linked mental retardation, epilepsy, rostral ventricular enlargement, and cerebellar hypoplasia. Affected individuals have morphological abnormalities of their brain with enlargement of the cerebral ventricles and cerebellar hypoplasia. OPHN1 negatively regulates RhoA, Cdc42, and Rac1 in neuronal and non-neuronal cells. GRAF1 sculpts the endocytic membranes of the CLIC/GEEC (clathrin-independent carriers/GPI-enriched early endosomal compartments) endocytic pathway. It strongly interacts with dynamin and inhibition of dynamin abolishes CLIC/GEEC endocytosis. GRAF2, GRAF3 and oligophrenin are likely to play similar roles during clathrin-independent endocytic events. GRAF1 mutations are linked to leukaemia. All members are composed of a N-terminal BAR-PH domain, followed by a RhoGAP domain, a proline rich region, and a C-terminal SH3 domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 267 TMEGYLYVQEKRPLGFTWTKHYCTYDKGSKMFTMSVSDVKASGKmnglvTGSPEMFKLKSCIRRKTDSIDKRFCFDIEVV 346
Cdd:cd01249     1 TKEGYLYLQEKKPLGSTWTKHYCTYRKESKMFTMIPYNQQSSGK-----LGTTEVVTLKSCVRRKTDSIDRRFCFDIEVV 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 1734342263 347 ERHGIITLQAFSEANRKLWLEAMDGKEPIY 376
Cdd:cd01249    76 DRPTVLTLQALSEEDRKLWLEAMDGKEPIY 105

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 397 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNttfSPKSPPDMDIDIELWDNKTITSGLKNYLRCLAEPLMTYKLHKD 476
Cdd:pfam00620   3 IVRKCVEYLEKRGLDTEGIFRVSGSASRIKELRE---AFDRGPDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734342263 477 FIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMR 542
Cdd:pfam00620  80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLR 145

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 1734342263  797 GSVQAQAMYSCKAEHSHELSFPQGAIFSnVHPSVEPGWLKATYE-GRTGLVPENYV 851
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIIT-VLEKSDDGWWKGRLGrGKEGLFPSNYV 55

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263  267 TMEGYLYVQEKRPLGfTWTKHYCTYDKGSKMFTMSVSDVKASGKmnglvtgsPEMFKLKSCIRR---KTDSIDKRFCFDI 343
Cdd:smart00233   2 IKEGWLYKKSGGGKK-SWKKRYFVLFNSTLLYYKSKKDKKSYKP--------KGSIDLSGCTVReapDPDSSKKPHCFEI 72

                           90       100
                   ....*....|....*....|....*.
gi 1734342263  344 EVVERHgIITLQAFSEANRKLWLEAM 369
Cdd:smart00233  73 KTSDRK-TLLLQAESEEEREKWVEAL 97

The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin1-like Rho GTPase Activating Proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of Rho and Rac GTPase activating proteins (GAPs) with similarity to oligophrenin1 (OPHN1). Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and a Rho GAP domain. Some members contain a C-terminal SH3 domain. Vertebrates harbor at least three Rho GAPs in this subfamily including OPHN1, GTPase Regulator Associated with Focal adhesion kinase (GRAF), GRAF2, and an uncharacterized protein called GAP10-like. OPHN1, GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. In addition, OPHN1 is active towards Rac. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domains of OPHN1 and GRAF directly interact with their Rho GAP domains and inhibit their activity. The autoinhibited proteins are able to bind membranes and tubulate liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domains can occur simultaneously.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263  19 RERLQCHEIELERTNKFIKELLKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 98
Cdd:cd07602     1 RENLHEHEAELERTNKAIKELIKECKNLISATKNLSKAQRSFAQTLQNFKFECIGETQTDDEIEIAESLKEFGRLIETVE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263  99 EERRRLIQNANDVLIAPLEKFRKEQIGAAKDGKKKFDKESEKYYSILDKHLNLSAKKKESHLQEADSQIGREHQNFYEAS 178
Cdd:cd07602    81 DERDRMLENAEEQLIEPLEKFRKEQIGGAKEEKKKFDKETEKFCSSLEKHLNLSTKKKENQLQEADAQLDMERRNFHQAS 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1734342263 179 LEYVFKIQEVQEKKKFEFVEPLLSFLQGLFTFYHEGYELAQEFAPYK 225
Cdd:cd07602   161 LEYVFKLQEVQERKKFEFVETLLSFMYGWLTFYHQGHEVAKDFKPYL 207

The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion kinase; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. GTPase Regulator Associated with Focal adhesion kinase (GRAF), also called Rho GTPase activating protein 26 (ARHGAP26), is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263  19 RERLQCHEIELERTNKFIKELLKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 98
Cdd:cd07636     1 RERLKSHEAELDKTNKFIKELIKDGKSLIAALKNLSSAKRKFADSLNEFKFQCIGDAETDDEICIARSLQEFAAVLRNLE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263  99 EERRRLIQNANDVLIAPLEKFRKEQIGAAKDGKKKFDKESEKYYSILDKHLNLSAKKKESHLQEADSQIGREHQNFYEAS 178
Cdd:cd07636    81 DERTRMIENASEVLITPLEKFRKEQIGAAKEAKKKYDKETEKYCAVLEKHLNLSSKKKESQLHEADSQVDLVRQHFYEVS 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1734342263 179 LEYVFKIQEVQEKKKFEFVEPLLSFLQGLFTFYHEGYELAQEFAPYK 225
Cdd:cd07636   161 LEYVFKVQEVQERKMFEFVEPLLAFLQGLFTFYHHGYELAKDFSDFK 207

The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. GTPase Regulator Associated with Focal adhesion kinase 2 (GRAF2), also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA which regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle and also interacts with PKNbeta, which is a target of Rho. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263  19 RERLQCHEIELERTNKFIKELLKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 98
Cdd:cd07635     1 RERIRAHEAELERTNRFIKELLKDGKNLIAATKSLSAAQRKFAHSLRDFKFEFIGDAETDDERCIDASLQEFSNFLKNLE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263  99 EERRRLIQNANDVLIAPLEKFRKEQIGAAKDGKKKFDKESEKYYSILDKHLNLSAKKKESHLQEADSQIGREHQNFYEAS 178
Cdd:cd07635    81 EQREIMALNVTETLIKPLERFRKEQLGAVKEEKKKFDKETEKNYSLLEKHLNLSAKKKEPQLQEADVQVEQNRQHFYELS 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1734342263 179 LEYVFKIQEVQEKKKFEFVEPLLSFLQGLFTFYHEGYELAQEFAPYK 225
Cdd:cd07635   161 LEYVCKLQEIQERKKFECVEPMLSFFQGVFTFYHQGYELAKDFNHYK 207

GTPase Regulator Associated with Focal adhesion and related proteins Pleckstrin homology (PH) domain; This hierarchy contains GRAF family members: OPHN1/oligophrenin1, GRAF1 (also called ARHGAP26/Rho GTPase activating protein 26), GRAF2 (also called ARHGAP10/ARHGAP42), AK057372, and LOC129897, all of which are members of the APPL family. OPHN1 is a RhoGAP involved in X-linked mental retardation, epilepsy, rostral ventricular enlargement, and cerebellar hypoplasia. Affected individuals have morphological abnormalities of their brain with enlargement of the cerebral ventricles and cerebellar hypoplasia. OPHN1 negatively regulates RhoA, Cdc42, and Rac1 in neuronal and non-neuronal cells. GRAF1 sculpts the endocytic membranes of the CLIC/GEEC (clathrin-independent carriers/GPI-enriched early endosomal compartments) endocytic pathway. It strongly interacts with dynamin and inhibition of dynamin abolishes CLIC/GEEC endocytosis. GRAF2, GRAF3 and oligophrenin are likely to play similar roles during clathrin-independent endocytic events. GRAF1 mutations are linked to leukaemia. All members are composed of a N-terminal BAR-PH domain, followed by a RhoGAP domain, a proline rich region, and a C-terminal SH3 domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 267 TMEGYLYVQEKRPLGFTWTKHYCTYDKGSKMFTMSVSDVKASGKmnglvTGSPEMFKLKSCIRRKTDSIDKRFCFDIEVV 346
Cdd:cd01249     1 TKEGYLYLQEKKPLGSTWTKHYCTYRKESKMFTMIPYNQQSSGK-----LGTTEVVTLKSCVRRKTDSIDRRFCFDIEVV 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 1734342263 347 ERHGIITLQAFSEANRKLWLEAMDGKEPIY 376
Cdd:cd01249    76 DRPTVLTLQALSEEDRKLWLEAMDGKEPIY 105

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 397 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNTtFSPKSPPDmdiDIELWDNKTITSGLKNYLRCLAEPLMTYKLHKD 476
Cdd:cd00159     3 IIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKK-FDRGEDID---DLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 477 FIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMRAQEETVAAMMNIKF 556
Cdd:cd00159    79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                         170
                  ....*....|.
gi 1734342263 557 QNIVVEILIEH 567
Cdd:cd00159   159 LNEIVEFLIEN 169

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 397 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNttfSPKSPPDMDIDIELWDNKTITSGLKNYLRCLAEPLMTYKLHKD 476
Cdd:pfam00620   3 IVRKCVEYLEKRGLDTEGIFRVSGSASRIKELRE---AFDRGPDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734342263 477 FIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMR 542
Cdd:pfam00620  80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLR 145

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1734342263 800 QAQAMYSCKAEHSHELSFPQGAIFSNVHPSVEPGWLKATYEGRTGLVPENYVVFL 854
Cdd:cd12066     1 QAKAMYSCKAEHSHELSFPQGAIFSNVYPSVEPGWLKATYEGKTGLVPENYVVFL 55

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 397 FVRKCIQAVEMRGITILGLYRIGGVN---SKVQKLMNttfspKSPPDMDIDIELW-DNKTITSGLKNYLRCLAEPLMTYK 472
Cdd:cd04395    21 IVEVCCNIVEARGLETVGIYRVPGNNaaiSALQEELN-----RGGFDIDLQDPRWrDVNVVSSLLKSFFRKLPEPLFTNE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 473 LHKDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMRAQEETVAAMM 552
Cdd:cd04395    96 LYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNMETMV 175

                         170       180
                  ....*....|....*....|.
gi 1734342263 553 -NIKFQNIVVEILIEHYEKIF 572
Cdd:cd04395   176 tHMPDQCKIVETLIQHYDWFF 196

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 397 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNTTFSPKSPPDM-DIDIElwdnkTITSGLKNYLRCLAEPLMTYKLHK 475
Cdd:cd04382    20 LIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLsKVDIH-----VICGCLKDFLRSLKEPLITFALWK 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 476 DFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSlHSQQNLMTISNLGVIFGPTLM---RAQEETVAAMM 552
Cdd:cd04382    95 EFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVA-QSPECKMDINNLARVFGPTIVgysVPNPDPMTILQ 173

                         170
                  ....*....|....
gi 1734342263 553 NIKFQNIVVEILIE 566
Cdd:cd04382   174 DTVRQPRVVERLLE 187

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 398 VRKCIQAVEMRGITILGLYRIGG---VNSKVQKLMNTtfspksppDMDIDIELWDNKTITSG-LKNYLRCLAEPLMTYKL 473
Cdd:cd04404    27 VRETVEYLQAHALTTEGIFRRSAntqVVKEVQQKYNM--------GEPVDFDQYEDVHLPAViLKTFLRELPEPLLTFDL 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 474 HkDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMRA--QEETVAAM 551
Cdd:cd04404    99 Y-DDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAkdASMSLSAI 177

                         170       180
                  ....*....|....*....|.
gi 1734342263 552 MNIkfqNIVVEILIEHYEKIF 572
Cdd:cd04404   178 NPI---NTFTKFLLDHQDEIF 195

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 398 VRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNT--------TFSPKSPPDmdidielwdnktITSGLKNYLRCLAEPLM 469
Cdd:cd04378    20 IKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAfengkdlvELSELSPHD------------ISSVLKLFLRQLPEPLI 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 470 TYKLHKDFIIAVK--------------SDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVI 535
Cdd:cd04378    88 LFRLYNDFIALAKeiqrdteedkapntPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIV 167

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1734342263 536 FGPTLMR----AQEETVAAMMNIKFQNIVVEILIEH 567
Cdd:cd04378   168 FGPTLIRprpgDADVSLSSLVDYGYQARLVEFLITN 203

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 385 KEEMYLNeAGFNF---VRKCIQAVEMRGItILGLYRIGGVNSKVQKLmNTTFSPKSPPDMDIDIELWDNKTITSGLKNYL 461
Cdd:cd04384     7 LTEHLLN-SGQDVpqvLKSCTEFIEKHGI-VDGIYRLSGIASNIQRL-RHEFDSEQIPDLTKDVYIQDIHSVSSLCKLYF 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 462 RCLAEPLMTYKLHKDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLM 541
Cdd:cd04384    84 RELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLL 163

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1734342263 542 RAQE------ETVAAMMNIKFQNIVVEILIEH 567
Cdd:cd04384   164 RSKQiesacfSGTAAFMEVRIQSVVVEFILNH 195

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 397 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNttfspKSPPDMDIDIELWDN--KTITSGLKNYLRCLAEPLMTYKLH 474
Cdd:cd04373    18 FLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQK-----QFDQDHNLDLVSKDFtvNAVAGALKSFFSELPDPLIPYSMH 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734342263 475 KDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMRAQEETVAAMMNI 554
Cdd:cd04373    93 LELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMRPDFTSMEALSAT 172

                         170
                  ....*....|.
gi 1734342263 555 KFQNIVVEILI 565
Cdd:cd04373   173 RIYQTIIETFI 183