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 1958747298   1 MALSVTETLIKPLEKFRKEQLGAVKEEKKKFDKETERNYSLIDKHLTLSARKKDTHLQEADLQVEQNRQHFYELSLEYVC 80
Cdd:cd07635    86 MALNVTETLIKPLERFRKEQLGAVKEEKKKFDKETEKNYSLLEKHLNLSAKKKEPQLQEADVQVEQNRQHFYELSLEYVC 165

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958747298  81 KLQEIQERKKFEFVEPMLSFFQGMFTFYHQGHELSKDFNHYK 122
Cdd:cd07635   166 KLQEIQERKKFECVEPMLSFFQGVFTFYHQGYELAKDFNHYK 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 1958747298 666 KARAVYPCEAEHSSELSFEIGAIFEDVQTSREPGWLEGTLNGKRGLIPQNYVKL 719
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 1958747298   1 MALSVTETLIKPLEKFRKEQLGAVKEEKKKFDKETERNYSLIDKHLTLSARKKDTHLQEADLQVEQNRQHFYELSLEYVC 80
Cdd:cd07635    86 MALNVTETLIKPLERFRKEQLGAVKEEKKKFDKETEKNYSLLEKHLNLSAKKKEPQLQEADVQVEQNRQHFYELSLEYVC 165

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958747298  81 KLQEIQERKKFEFVEPMLSFFQGMFTFYHQGHELSKDFNHYK 122
Cdd:cd07635   166 KLQEIQERKKFECVEPMLSFFQGVFTFYHQGYELAKDFNHYK 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 1958747298 164 TAEGYLYVQEKRPapFGSSWVKHYCMYRKTAKKFNMIPFEHRSGGKLGDGEAFFLKECTKRHIDSTDRRFCFDIEAADRP 243
Cdd:cd01249     1 TKEGYLYLQEKKP--LGSTWTKHYCTYRKESKMFTMIPYNQQSSGKLGTTEVVTLKSCVRRKTDSIDRRFCFDIEVVDRP 78

                          90       100
                  ....*....|....*....|....*.
gi 1958747298 244 GvPLTVQAFSEEERKQWLEALGGKEA 269
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 1958747298 295 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMLmDVKTCNELDLEnstDWEVKTVTSALKQYLRSLPEPLMTYELHR 374
Cdd:pfam00620   3 IVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAF-DRGPDVDLDLE---EEDVHVVASLLKLFLRELPEPLLTFELYE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958747298 375 DFIVPAKSGSPESRVSAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQ 443
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 1958747298  665 RKARAVYPCEAEHSSELSFEIGAIFEDVQTSrEPGWLEGTLN-GKRGLIPQNYVK 718
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 1958747298  166 EGYLYVQEKRpapFGSSWVKHYCMYRKTAkkfnMIPFEHRSGGKLGD-GEAFFLKECTKRHIDSTD---RRFCFDIEAAD 241
Cdd:smart00233   4 EGWLYKKSGG---GKKSWKKRYFVLFNST----LLYYKSKKDKKSYKpKGSIDLSGCTVREAPDPDsskKPHCFEIKTSD 76

                           90       100
                   ....*....|....*....|...
gi 1958747298  242 RpgVPLTVQAFSEEERKQWLEAL 264
Cdd:smart00233  77 R--KTLLLQAESEEEREKWVEAL 97

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298  476 DTTFAEPTCLSASPPNAPPRQSKRQGQRTKRPVAVYNLCLELEEGDSPS-----PLKEDPPSSSQDSLSTPS----PTTS 546
Cdd:PHA03247  2754 PARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWdpadpPAAVLAPAAALPPAASPAgplpPPTS 2833

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958747298  547 AAHGPPGPDGNHLAADRGNCGDATATTPSQTRPSMVQwlNMQSPTTPSSNP----AGTPPSPRMSPFPLSP 613
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 1958747298   1 MALSVTETLIKPLEKFRKEQLGAVKEEKKKFDKETERNYSLIDKHLTLSARKKDTHLQEADLQVEQNRQHFYELSLEYVC 80
Cdd:cd07635    86 MALNVTETLIKPLERFRKEQLGAVKEEKKKFDKETEKNYSLLEKHLNLSAKKKEPQLQEADVQVEQNRQHFYELSLEYVC 165

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958747298  81 KLQEIQERKKFEFVEPMLSFFQGMFTFYHQGHELSKDFNHYK 122
Cdd:cd07635   166 KLQEIQERKKFECVEPMLSFFQGVFTFYHQGYELAKDFNHYK 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 1958747298   1 MALSVTETLIKPLEKFRKEQLGAVKEEKKKFDKETERNYSLIDKHLTLSARKKDTHLQEADLQVEQNRQHFYELSLEYVC 80
Cdd:cd07602    86 MLENAEEQLIEPLEKFRKEQIGGAKEEKKKFDKETEKFCSSLEKHLNLSTKKKENQLQEADAQLDMERRNFHQASLEYVF 165

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958747298  81 KLQEIQERKKFEFVEPMLSFFQGMFTFYHQGHELSKDFNHYK 122
Cdd:cd07602   166 KLQEVQERKKFEFVETLLSFMYGWLTFYHQGHEVAKDFKPYL 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 1958747298 164 TAEGYLYVQEKRPapFGSSWVKHYCMYRKTAKKFNMIPFEHRSGGKLGDGEAFFLKECTKRHIDSTDRRFCFDIEAADRP 243
Cdd:cd01249     1 TKEGYLYLQEKKP--LGSTWTKHYCTYRKESKMFTMIPYNQQSSGKLGTTEVVTLKSCVRRKTDSIDRRFCFDIEVVDRP 78

                          90       100
                  ....*....|....*....|....*.
gi 1958747298 244 GvPLTVQAFSEEERKQWLEALGGKEA 269
Cdd:cd01249    79 T-VLTLQALSEEDRKLWLEAMDGKEP 103

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298   7 ETLIKPLEKFRKEQLGAVKEEKKKFDKETERNYSLIDKHLTLSARKKDTHLQEADLQVEQNRQHFYELSLEYVCKLQEIQ 86
Cdd:pfam16746  99 RTIIKPLENFRKEDLKEVKELKKKFDKASEKLDAALEKNAQLSKKKKPSELEEADNELAATRKCFHHASLDYVLQINELQ 178

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298  87 ERKKFEFVEPMLSFFQGMFTFYHQGHELSKDFNHYKTELQINIQNTRnrfEGTRSEVEEL 146
Cdd:pfam16746 179 ERKKFEILEPLLSFMHAQFTFFHQGYELFKDLEPFMKDLQAQLQQTR---EDTREEKEEL 235

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. 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 1958747298 296 LRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMlmdVKTCNELDLENSTDWEVKTVTSALKQYLRSLPEPLMTYELHRD 375
Cdd:cd04403    20 VRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFA---VDHDEKLDLDDSKWEDIHVITGALKLFFRELPEPLFPYSLFND 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298 376 FIVPAKSGSPESRVSAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQEETVAAIMDLKF 455
Cdd:cd04403    97 FVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLRPEQETGNIAVHMVY 176

                         170
                  ....*....|.
gi 1958747298 456 QNIVVEILIEN 466
Cdd:cd04403   177 QNQIVELILLE 187

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 1958747298 295 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSmLMDVKTCNeLDLENSTDWE--VKTVTSALKQYLRSLPEPLMTYEL 372
Cdd:cd04398    19 IVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKE-LFDKDPLN-VLLISPEDYEsdIHSVASLLKLFFRELPEPLLTKAL 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298 373 HRDFIVPAKSGSPESRVSAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQEETVAaimD 452
Cdd:cd04398    97 SREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLMNAAPDNAA---D 173

                         170
                  ....*....|....*....
gi 1958747298 453 LKFQNIVVEILIENHEKIF 471
Cdd:cd04398   174 MSFQSRVIETLLDNAYQIF 192

The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin-1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Oligophrenin-1 (OPHN1) is a GTPase activating protein (GAP) with activity towards RhoA, Rac, and Cdc42, that is expressed in developing spinal cord and in adult brain areas with high plasticity. It plays a role in regulating the actin cystoskeleton as well as morphology changes in axons and dendrites, and may also function in modulating neuronal connectivity. Mutations in the OPHN1 gene causes X-linked mental retardation associated with cerebellar hypoplasia, lateral ventricle enlargement and epilepsy. OPHN1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and a Rho GAP domain. 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 1958747298   1 MALSVTETLIKPLEKFRKEQLGAVKEEKKKFDKETERNYSLIDKHLTLSARKKDTHLQEADLQVEQNRQHFYELSLEYVC 80
Cdd:cd07633    86 MVQNASDLLIKPLENFRKEQIGFTKERKKKFEKDSEKFYSLLDRHVNLSSKKKESQLQEADLQVDKERQNFYESSLEYVY 165

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958747298  81 KLQEIQERKKFEFVEPMLSFFQGMFTFYHQGHELSKDFNHYK 122
Cdd:cd07633   166 QIQEVQESKKFDVVEPVLAFLHSLFTSNNLTVELTQDFLPYK 207

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 1958747298 295 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMLMDVKTCNELDLENSTDwevktVTSALKQYLRSLPEPLMTYELHR 374
Cdd:cd04378    19 IIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHD-----ISSVLKLFLRQLPEPLILFRLYN 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298 375 DFIVPAK--------------SGSPESRVSAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLM 440
Cdd:cd04378    94 DFIALAKeiqrdteedkapntPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIVFGPTLI 173

                         170       180       190
                  ....*....|....*....|....*....|
gi 1958747298 441 RP----QEETVAAIMDLKFQNIVVEILIEN 466
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 1958747298 295 ILRKCISAVETRGINDQGLYRVVGVS---SKVQRLLSMLMDvktcnELDLENSTDWEVKTVTSALKQYLRSLPEPLMTYE 371
Cdd:cd04395    21 IVEVCCNIVEARGLETVGIYRVPGNNaaiSALQEELNRGGF-----DIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298 372 LHRDFIVPAKSGSPESRVSAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQEETVA-AI 450
Cdd:cd04395    96 LYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNMEtMV 175

                         170       180
                  ....*....|....*....|.
gi 1958747298 451 MDLKFQNIVVEILIENHEKIF 471
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 1958747298 295 ILRKCISAVETRGINDQGLYRV---VGVSSKVQRLLSMLMDVktcnelDLENSTDWEVKTVTsaLKQYLRSLPEPLMTYE 371
Cdd:cd04404    26 VVRETVEYLQAHALTTEGIFRRsanTQVVKEVQQKYNMGEPV------DFDQYEDVHLPAVI--LKTFLRELPEPLLTFD 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298 372 LHrDFIVPAKSGSPESRVSAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLM--RPQEETVAA 449
Cdd:cd04404    98 LY-DDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLwaKDASMSLSA 176

                         170       180
                  ....*....|....*....|..
gi 1958747298 450 IMDLkfqNIVVEILIENHEKIF 471
Cdd:cd04404   177 INPI---NTFTKFLLDHQDEIF 195

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. 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 1958747298 295 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMLMDVKTCNELDLENSTDwevktVTSALKQYLRSLPEPLMTYELHR 374
Cdd:cd04409    19 IIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELSELSPHD-----ISNVLKLYLRQLPEPLILFRLYN 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298 375 DFIVPAKSG------------------SPESRVSAIHF----LVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLG 432
Cdd:cd04409    94 EFIGLAKESqhvnetqeakknsdkkwpNMCTELNRILLkskdLLRQLPAPNYNTLQFLIVHLHRVSEQAEENKMSASNLG 173

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1958747298 433 VVFGPTLMRPQ----EETVAAIMDLKFQNIVVEILI 464
Cdd:cd04409   174 IIFGPTLIRPRptdaTVSLSSLVDYPHQARLVELLI 209

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 1958747298 299 CISAVETRGINDQGLYRVVGVSSKVQRLLSMLMDVKTCNELdleNSTDweVKTVTSALKQYLRSLPEPLMTYELHRDFIV 378
Cdd:cd04382    24 CVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNL---SKVD--IHVICGCLKDFLRSLKEPLITFALWKEFME 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298 379 PAKSGSPESRVSAIHFLVHKLPEKNKEMLDILVKHLTNVSShSKQNLMTVANLGVVFGPTLM---RPQEETVAAIMDLKF 455
Cdd:cd04382    99 AAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVgysVPNPDPMTILQDTVR 177

                         170
                  ....*....|
gi 1958747298 456 QNIVVEILIE 465
Cdd:cd04382   178 QPRVVERLLE 187

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). 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. 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 1958747298 289 DKMGFTILRkCISAVETRGINDQGLYRVVGVSSKVQRLLSMLMDVKTCNELDLENSTDwevktVTSALKQYLRSLPEPLM 368
Cdd:cd04408    14 EEVPFVVVR-CTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLSGHSPHD-----ITSVLKHFLKELPEPVL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958747298 369 TYELHRDFIVPAKS---------GSPESRVSAIHF---LVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFG 436
Cdd:cd04408    88 PFQLYDDFIALAKElqrdsekaaESPSIVENIIRSlkeLLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFG 167

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1958747298 437 PTLMRP---QEETVAAIMDLKFQNIVVEILIEN 466
Cdd:cd04408   168 PTLLRPlvgGDVSMICLLDTGYQAQLVEFLISN 200

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 1958747298 295 ILRKCISAVETRGINDQGLYRVVGVSSKVQRLLSMLmdvKTCNELDLENSTDWEVKTVTSALKQYLRSLPEPLMTYELHR 374
Cdd:cd04387    19 IVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAF---DTNNKDVSVMLSEMDVNAIAGTLKLYFRELPEPLFTDELYP 95

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958747298 375 DFIVPAKSGSPESRVSAIHFLVHKLPEKNKEMLDILVKHLTNVSSHSKQNLMTVANLGVVFGPTLMRPQEETV 447
Cdd:cd04387    96 NFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKES 168