The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991   2 EEKKKFDKETEKNYSLIDKHLTLSARKKDSHLQEADLQVEQNRQHFYELSLEYVCKLQEIQERKKFEFVEPMLSFFQGMF 81
Cdd:cd07635   111 EEKKKFDKETEKNYSLLEKHLNLSAKKKEPQLQEADVQVEQNRQHFYELSLEYVCKLQEIQERKKFECVEPMLSFFQGVF 190

                          90
                  ....*....|....*..
gi 1039790991  82 TFYHQGHELSKDFNHYK 98
Cdd:cd07635   191 TFYHQGYELAKDFNHYK 207

Src Homology 3 domain of 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. It 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 is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 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 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 1039790991 605 KARAVYPCEAEHSSELSFEIGAIFEDVQTSREPGWLEGTLNGKRGLIPQNYVKL 658
Cdd:cd12065     1 KAKAVYPCEAEHSSELSFEVGAIFEDVTLSREPGWLEGTLNGKRGLIPENYVEI 54

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 1039790991   2 EEKKKFDKETEKNYSLIDKHLTLSARKKDSHLQEADLQVEQNRQHFYELSLEYVCKLQEIQERKKFEFVEPMLSFFQGMF 81
Cdd:cd07635   111 EEKKKFDKETEKNYSLLEKHLNLSAKKKEPQLQEADVQVEQNRQHFYELSLEYVCKLQEIQERKKFECVEPMLSFFQGVF 190

                          90
                  ....*....|....*..
gi 1039790991  82 TFYHQGHELSKDFNHYK 98
Cdd:cd07635   191 TFYHQGYELAKDFNHYK 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 1039790991 140 TAEGYLYVQEKRPapFGSSWVKHYCMYRKTAKKFNMIPFEHRSGGKLGDGEAFFLKECTKRHMDSTDRRFCFDIEAADRP 219
Cdd:cd01249     1 TKEGYLYLQEKKP--LGSTWTKHYCTYRKESKMFTMIPYNQQSSGKLGTTEVVTLKSCVRRKTDSIDRRFCFDIEVVDRP 78

                          90       100
                  ....*....|....*....|....*.
gi 1039790991 220 GvPLTVQAFSEEERKQWLEALGGKEA 245
Cdd:cd01249    79 T-VLTLQALSEEDRKLWLEAMDGKEP 103

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991 271 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMLmDVKMCNELDLEnsaDWEVKTVTSALKQYLRSLPEPLMTYELHR 350
Cdd:pfam00620   3 IVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAF-DRGPDVDLDLE---EEDVHVVASLLKLFLRELPEPLLTFELYE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1039790991 351 DFIVPAKSGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQ 419
Cdd:pfam00620  79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

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 1039790991  604 RKARAVYPCEAEHSSELSFEIGAIFEDVQTSrEPGWLEGTLN-GKRGLIPQNYVK 657
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITVLEKS-DDGWWKGRLGrGKEGLFPSNYVE 56

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 1039790991  142 EGYLYVQEKRpapFGSSWVKHYCMYRKTAkkfnMIPFEHRSGGKLGD-GEAFFLKECTKRHMDSTD---RRFCFDIEAAD 217
Cdd:smart00233   4 EGWLYKKSGG---GKKSWKKRYFVLFNST----LLYYKSKKDKKSYKpKGSIDLSGCTVREAPDPDsskKPHCFEIKTSD 76

                           90       100
                   ....*....|....*....|...
gi 1039790991  218 RpgVPLTVQAFSEEERKQWLEAL 240
Cdd:smart00233  77 R--KTLLLQAESEEEREKWVEAL 97

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991  452 DTTFAEPTCLSASPPNAPPRQSKRQGQRTKRPVAVYNLCLELEEGDSPS-----PLKEDPPSSSQDSLSTPS----PTTS 522
Cdd:PHA03247  2754 PARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWdpadpPAAVLAPAAALPPAASPAgplpPPTS 2833

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039790991  523 AAHGPPGLDGNHLAADGGSCGDATATTPSQTRPSMVQwlNMQSPTTPSSNP----AGTPPSPRMSPFPLSP 589
Cdd:PHA03247  2834 AQPTAPPPPPGPPPPSLPLGGSVAPGGDVRRRPPSRS--PAAKPAAPARPPvrrlARPAVSRSTESFALPP 2902

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 1039790991   2 EEKKKFDKETEKNYSLIDKHLTLSARKKDSHLQEADLQVEQNRQHFYELSLEYVCKLQEIQERKKFEFVEPMLSFFQGMF 81
Cdd:cd07635   111 EEKKKFDKETEKNYSLLEKHLNLSAKKKEPQLQEADVQVEQNRQHFYELSLEYVCKLQEIQERKKFECVEPMLSFFQGVF 190

                          90
                  ....*....|....*..
gi 1039790991  82 TFYHQGHELSKDFNHYK 98
Cdd:cd07635   191 TFYHQGYELAKDFNHYK 207

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 1039790991   2 EEKKKFDKETEKNYSLIDKHLTLSARKKDSHLQEADLQVEQNRQHFYELSLEYVCKLQEIQERKKFEFVEPMLSFFQGMF 81
Cdd:cd07602   111 EEKKKFDKETEKFCSSLEKHLNLSTKKKENQLQEADAQLDMERRNFHQASLEYVFKLQEVQERKKFEFVETLLSFMYGWL 190

                          90
                  ....*....|....*..
gi 1039790991  82 TFYHQGHELSKDFNHYK 98
Cdd:cd07602   191 TFYHQGHEVAKDFKPYL 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 1039790991 140 TAEGYLYVQEKRPapFGSSWVKHYCMYRKTAKKFNMIPFEHRSGGKLGDGEAFFLKECTKRHMDSTDRRFCFDIEAADRP 219
Cdd:cd01249     1 TKEGYLYLQEKKP--LGSTWTKHYCTYRKESKMFTMIPYNQQSSGKLGTTEVVTLKSCVRRKTDSIDRRFCFDIEVVDRP 78

                          90       100
                  ....*....|....*....|....*.
gi 1039790991 220 GvPLTVQAFSEEERKQWLEALGGKEA 245
Cdd:cd01249    79 T-VLTLQALSEEDRKLWLEAMDGKEP 103

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 1039790991   2 EEKKKFDKETEKNYSLIDKHLTLSARKKDSHLQEADLQVEQNRQHFYELSLEYVCKLQEIQERKKFEFVEPMLSFFQGMF 81
Cdd:cd07636   111 EAKKKYDKETEKYCAVLEKHLNLSSKKKESQLHEADSQVDLVRQHFYEVSLEYVFKVQEVQERKMFEFVEPLLAFLQGLF 190

                          90
                  ....*....|....*..
gi 1039790991  82 TFYHQGHELSKDFNHYK 98
Cdd:cd07636   191 TFYHHGYELAKDFSDFK 207

The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This group is composed of uncharacterized proteins called Rho GTPase activating protein (GAP) 10-like. GAP10-like may be a GAP with activity towards RhoA and Cdc42. Similar 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. 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 the related proteins GRAF and OPHN1, directly interact with their Rho GAP domains and inhibit theiractivity. The autoinhibited proteins are 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 1039790991   2 EEKKKFDKETEKNYSLIDKHLTLSARKKDSHLQEADLQVEQNRQHFYELSLEYVCKLQEIQERKKFEFVEPMLSFFQGMF 81
Cdd:cd07634   111 DGKKKFDKESEKYYSILEKHLNLSAKKKESHLQRADTQIDREHQNFYEASLEYVFKIQEVQEKKKFEFVEPLLAFLQGLF 190

                          90
                  ....*....|....*..
gi 1039790991  82 TFYHQGHELSKDFNHYK 98
Cdd:cd07634   191 TFYHEGYELAQEFAPYK 207

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. 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 1039790991 271 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSmLMDVKMCNeLDLENSADWE--VKTVTSALKQYLRSLPEPLMTYEL 348
Cdd:cd04398    19 IVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKE-LFDKDPLN-VLLISPEDYEsdIHSVASLLKLFFRELPEPLLTKAL 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991 349 HRDFIVPAKSGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQEETVAaimD 428
Cdd:cd04398    97 SREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLMNAAPDNAA---D 173

                         170
                  ....*....|....*....
gi 1039790991 429 LKFQNIVVEILIENHEKIF 447
Cdd:cd04398   174 MSFQSRVIETLLDNAYQIF 192

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. 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 1039790991 271 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSML----MDVKMCneldlenSADWEVKTVTSALKQYLRSLPEPLMTY 346
Cdd:cd04385    18 IVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFrkdaRSVQLR-------EGEYTVHDVADVLKRFLRDLPDPLLTS 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991 347 ELHRDFIVPAKSGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQEETVAAI 426
Cdd:cd04385    91 ELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQT 170

                         170
                  ....*....|....*..
gi 1039790991 427 MdlkfQNI-VVEILIEN 442
Cdd:cd04385   171 S----HEVkVIEDLIDN 183

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 1039790991 271 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMLMDVKMCNELDLENSADwevktVTSALKQYLRSLPEPLMTYELHR 350
Cdd:cd04378    19 IIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHD-----ISSVLKLFLRQLPEPLILFRLYN 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991 351 DFIVPAK--------------SGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLM 416
Cdd:cd04378    94 DFIALAKeiqrdteedkapntPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIVFGPTLI 173

                         170       180       190
                  ....*....|....*....|....*....|
gi 1039790991 417 RP----QEETVAAIMDLKFQNIVVEILIEN 442
Cdd:cd04378   174 RPrpgdADVSLSSLVDYGYQARLVEFLITN 203

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 1039790991 271 ILRKCISAVETRGINDQGLYRVVGVS---SKVQRLLSMLMDvkmcnELDLENSADWEVKTVTSALKQYLRSLPEPLMTYE 347
Cdd:cd04395    21 IVEVCCNIVEARGLETVGIYRVPGNNaaiSALQEELNRGGF-----DIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991 348 LHRDFIVPAKSGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQEETVA-AI 426
Cdd:cd04395    96 LYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNMEtMV 175

                         170       180
                  ....*....|....*....|.
gi 1039790991 427 MDLKFQNIVVEILIENHEKIF 447
Cdd:cd04395   176 THMPDQCKIVETLIQHYDWFF 196

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 1039790991 271 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMlmdVKMCNELDLENSADWEVKTVTsaLKQYLRSLPEPLMTYELHr 350
Cdd:cd04404    26 VVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQK---YNMGEPVDFDQYEDVHLPAVI--LKTFLRELPEPLLTFDLY- 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991 351 DFIVPAKSGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLM--RPQEETVAAIMD 428
Cdd:cd04404   100 DDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLwaKDASMSLSAINP 179

                         170
                  ....*....|....*....
gi 1039790991 429 LkfqNIVVEILIENHEKIF 447
Cdd:cd04404   180 I---NTFTKFLLDHQDEIF 195

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. 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 1039790991 270 TILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMLMDVKmcNELDLEnsaDWEVKTVTSALKQYLRSLPEPLMTYELH 349
Cdd:cd04377    17 LVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDP--DSVNLE---DYPIHVITSVLKQWLRELPEPLMTFELY 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991 350 RDFIVPAKSGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQEETVA--AIM 427
Cdd:cd04377    92 ENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRCPDTADPlqSLQ 171

                         170
                  ....*....|....
gi 1039790991 428 DLKFQNIVVEILIE 441
Cdd:cd04377   172 DVSKTTTCVETLIK 185

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 1039790991 271 ILRKCISAVETRGINDqGLYRVVGVSSKVQRLLSMLmDVKMCNELDLENSADwEVKTVTSALKQYLRSLPEPLMTYELHR 350
Cdd:cd04384    21 VLKSCTEFIEKHGIVD-GIYRLSGIASNIQRLRHEF-DSEQIPDLTKDVYIQ-DIHSVSSLCKLYFRELPNPLLTYQLYE 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991 351 DFIVPAKSGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQE------ETVA 424
Cdd:cd04384    98 KFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSKQiesacfSGTA 177

                         170
                  ....*....|....*...
gi 1039790991 425 AIMDLKFQNIVVEILIEN 442
Cdd:cd04384   178 AFMEVRIQSVVVEFILNH 195

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 1039790991 275 CISAVETRGINDQGLYRVVGVSSKVQRLLSMLMDVKMCNELdlensADWEVKTVTSALKQYLRSLPEPLMTYELHRDFIV 354
Cdd:cd04382    24 CVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNL-----SKVDIHVICGCLKDFLRSLKEPLITFALWKEFME 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039790991 355 PAKSGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSShSKQNLMTVANLGVVFGPTLM---RPQEETVAAIMDLKF 431
Cdd:cd04382    99 AAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVgysVPNPDPMTILQDTVR 177

                         170
                  ....*....|
gi 1039790991 432 QNIVVEILIE 441
Cdd:cd04382   178 QPRVVERLLE 187

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). 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 1039790991 271 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMLmDVKMCNELDLENSADweVKTVTSALKQYLRSLPEPLMTYELHR 350
Cdd:cd04387    19 IVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAF-DTNNKDVSVMLSEMD--VNAIAGTLKLYFRELPEPLFTDELYP 95

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039790991 351 DFIVPAKSGSPESRVNAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQEETV 423
Cdd:cd04387    96 NFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKES 168

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. 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 1039790991 271 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLlsmlmdvkmCNELDL---ENSADWEVKTV---TSALKQYLRSLPEPLM 344
Cdd:cd04391    25 IFQKLINKLEERGLETEGILRIPGSAQRVKFL---------CQELEAkfyEGTFLWDQVKQhdaASLLKLFIRELPQPLL 95