Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. 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 1622845618 324 EKSGLLNMTKIAQGGRKLRKNWGPSWVVLTGNSLVFYREPPPTApssGWGPAGSRPESSVDLRGAALAHGRHLSSRRNVL 403
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAA---KSGNPYSKPESSVDLRGASIEWAKEKSSRKNVF 77

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1622845618 404 HIRTVPGHEFLLQSDHETELRAWHRALRTVIER 436
Cdd:cd13233    78 QISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. 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 1622845618 324 EKSGLLNMTKIAQGGRKLRKNWGPSWVVLTGNSLVFYREPPPTApssGWGPAGSRPESSVDLRGAALAHGRHLSSRRNVL 403
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAA---KSGNPYSKPESSVDLRGASIEWAKEKSSRKNVF 77

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1622845618 404 HIRTVPGHEFLLQSDHETELRAWHRALRTVIER 436
Cdd:cd13233    78 QISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; Rho GTPase-activating proteins (RhoGAPs or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP9 functions as a GAP for Rac and Cdc42, but not for RhoA. It negatively regulates cell migration and adhesion. It also acts as a docking protein for the MAP kinases Erk2 and p38alpha, and may facilitate cross-talk between the Rho GTPase and MAPK pathways to control actin remodeling. It contains SH3, WW, Pleckstin homology (PH), and RhoGAP domains. 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 1622845618  26 QLCALYAFTYTGADGRQVSLAEGDRFLLLRKTNSDWWLARRLEAPSTSRPIFVPAAY 82
Cdd:cd12143     1 QLCALYAYQYTGADGRQVSIAEGERFLLLRKTNSDWWQVRRLEAPSTSRPLFVPATY 57

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622845618 323 VEKSGLLnMTKiaqgGRKLRKNWGPSWVVLTGNSLVFYREPPptapssgwGPAGSRPESSVDLRGAALAHGRHLSS--RR 400
Cdd:pfam00169   1 VVKEGWL-LKK----GGGKKKSWKKRYFVLFDGSLLYYKDDK--------SGKSKEPKGSISLSGCEVVEVVASDSpkRK 67

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1622845618 401 NVLHIRTV---PGHEFLLQSDHETELRAWHRALRTVIE 435
Cdd:pfam00169  68 FCFELRTGertGKRTYLLQAESEEERKDWIKAIQSAIR 105

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1622845618  29 ALYAFTYTGADgrQVSLAEGDRFLLLRKTNSDWWLARRleapsTSRPIFVPAAY 82
Cdd:pfam14604   1 ALYPYEPKDDD--ELSLQRGDVITVIEESEDGWWEGIN-----TGRTGLVPANY 47

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. 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 1622845618 324 EKSGLLNMTKIAQGGRKLRKNWGPSWVVLTGNSLVFYREPPPTApssGWGPAGSRPESSVDLRGAALAHGRHLSSRRNVL 403
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAA---KSGNPYSKPESSVDLRGASIEWAKEKSSRKNVF 77

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1622845618 404 HIRTVPGHEFLLQSDHETELRAWHRALRTVIER 436
Cdd:cd13233    78 QISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; Rho GTPase-activating proteins (RhoGAPs or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP9 functions as a GAP for Rac and Cdc42, but not for RhoA. It negatively regulates cell migration and adhesion. It also acts as a docking protein for the MAP kinases Erk2 and p38alpha, and may facilitate cross-talk between the Rho GTPase and MAPK pathways to control actin remodeling. It contains SH3, WW, Pleckstin homology (PH), and RhoGAP domains. 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 1622845618  26 QLCALYAFTYTGADGRQVSLAEGDRFLLLRKTNSDWWLARRLEAPSTSRPIFVPAAY 82
Cdd:cd12143     1 QLCALYAYQYTGADGRQVSIAEGERFLLLRKTNSDWWQVRRLEAPSTSRPLFVPATY 57

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 1622845618 543 DLDSTEWDDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNRDTLRYLLEHLCRVIA 622
Cdd:cd00159    43 DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQ 122

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1622845618 623 HSDKNRMTPHNLGIVFGPTLFRPEQETSDPAAHALYPGQLVQLMLTN 669
Cdd:cd00159   123 NSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKKLNEIVEFLIEN 169

Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; This subfamily is composed of Rho GTPase-activating proteins including mammalian ARHGAP9, and vertebrate ARHGAPs 12 and 27. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP9 functions as a GAP for Rac and Cdc42, but not for RhoA. It negatively regulates cell migration and adhesion. It also acts as a docking protein for the MAP kinases Erk2 and p38alpha, and may facilitate cross-talk between the Rho GTPase and MAPK pathways to control actin remodeling. ARHGAP27, also called CAMGAP1, shows GAP activity towards Rac1 and Cdc42. It binds the adaptor protein CIN85 and may play a role in clathrin-mediated endocytosis. ARHGAP12 has been shown to display GAP activity towards Rac1. It plays a role in regulating HFG-driven cell growth and invasiveness. ARHGAPs in this subfamily contain SH3, WW, Pleckstin homology (PH), and RhoGAP domains. 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 1622845618  26 QLCALYAFTYTGADGRQVSLAEGDRFLLLRKTNSDWWLARRleaPSTSRPIFVPAAY 82
Cdd:cd11888     1 YVVVLYPFEYTGKDGRKVSIKEGERFLLLKKSNDDWWQVRR---PGDSKPFYVPAQY 54

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 1622845618 553 HVVTGALKLFLRELPQPLVPPLLLPHFrAALA---------------LSESEQCLSQIQELIGSMPKPNRDTLRYLLEHL 617
Cdd:cd04378    69 HDISSVLKLFLRQLPEPLILFRLYNDF-IALAkeiqrdteedkapntPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHL 147

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622845618 618 CRVIAHSDKNRMTPHNLGIVFGPTLFRPEQETSDPAAHAL----YPGQLVQLMLTN 669
Cdd:cd04378   148 YRVAEQFEENKMSPNNLGIVFGPTLIRPRPGDADVSLSSLvdygYQARLVEFLITN 203

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. 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 1622845618 534 EQPGQEGRLDL-DSTEWDDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESE-QCLSQIQELIGSMPKPNRDTLR 611
Cdd:cd04400    59 ERFNTEYDVDLfSSSLYPDVHTVAGLLKLYLRELPTLILGGELHNDFKRLVEENHDRsQRALELKDLVSQLPQANYDLLY 138

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622845618 612 YLLEHLCRVIAHSDKNRMTPHNLGIVFGPTLFrpeqetsdpaahalYPGQLVQLMLTNFTSLF 674
Cdd:cd04400   139 VLFSFLRKIIEHSDVNKMNLRNVCIVFSPTLN--------------IPAGIFVLFLTDFDCIF 187

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 1622845618 550 DDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNRDTLRYLLEHLCRVIAHSDKNRM 629
Cdd:cd04385    67 YTVHDVADVLKRFLRDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQM 146

                          90       100
                  ....*....|....*....|....*..
gi 1622845618 630 TPHNLGIVFGPTLFRPEQETSDPAAHA 656
Cdd:cd04385   147 SVHNLALVFGPTLFQTDEHSVGQTSHE 173

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 1622845618 592 LSQIQELIGSMPKPNRDTLRYLLEHLCRVIAHSDKNRMTPHNLGIVFGPTLFRPEQETSDPAAHAL--YPGQ--LVQLML 667
Cdd:cd04409   130 LLKSKDLLRQLPAPNYNTLQFLIVHLHRVSEQAEENKMSASNLGIIFGPTLIRPRPTDATVSLSSLvdYPHQarLVELLI 209

                  .
gi 1622845618 668 T 668
Cdd:cd04409   210 T 210

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 1622845618 543 DLDSTEWDD--IHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNRDTLRYLLEHLCRV 620
Cdd:cd04377    56 DPDSVNLEDypIHVITSVLKQWLRELPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRV 135

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1622845618 621 IAHSDKNRMTPHNLGIVFGPTLFRpEQETSDP 652
Cdd:cd04377   136 ALQEEVNRMSANALAIVFAPCILR-CPDTADP 166

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 1622845618 538 QEGRLDLDSTEWDdIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNRDTLRYLLEHL 617
Cdd:cd04373    55 QDHNLDLVSKDFT-VNAVAGALKSFFSELPDPLIPYSMHLELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHL 133

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1622845618 618 CRVIAHSDKNRMTPHNLGIVFGPTLFRPEQETSDpaahALYPGQLVQLMLTNF 670
Cdd:cd04373   134 NKVSQNSKVNLMTSENLSICFWPTLMRPDFTSME----ALSATRIYQTIIETF 182

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 1622845618 542 LDLDSTEWDDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQcLSQIQELIGSMPKPNRDTLRYLLEHLCRVI 621
Cdd:cd04404    65 EPVDFDQYEDVHLPAVILKTFLRELPEPLLTFDLYDDIVGFLNVDKEER-VERVKQLLQTLPEENYQVLKYLIKFLVQVS 143

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622845618 622 AHSDKNRMTPHNLGIVFGPTLFRPeqetSDPAA--HALYP-GQLVQLMLTNFTSLF 674
Cdd:cd04404   144 AHSDQNKMTNSNLAVVFGPNLLWA----KDASMslSAINPiNTFTKFLLDHQDEIF 195

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 1622845618 511 QSLQERGLLReravtsdgryvfpeQPGQEGRL-----DLDST------EWDDIHV--VTGALKLFLRELPQPLVPPLLLP 577
Cdd:cd04391    36 RGLETEGILR--------------IPGSAQRVkflcqELEAKfyegtfLWDQVKQhdAASLLKLFIRELPQPLLTVEYLP 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622845618 578 HFRAALALSESEQCLSQIQELIGSMPKPNRDTLRYLLEHLCRVIAHSDKNRMTPHNLGIVFGPTLFRP----------EQ 647
Cdd:cd04391   102 AFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMIMAPNLFPPrgkhskdnesLQ 181

                         170       180
                  ....*....|....*....|..
gi 1622845618 648 ETSDPAAHAlypGQLVQLMLTN 669
Cdd:cd04391   182 EEVNMAAGC---ANIMRLLIRY 200

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. 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 1622845618 510 LQSLQERGLLR---ERAVTSDGRYVFpeQPGQEGRLDLDSTEwdDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALS 586
Cdd:cd04383    31 LYGLQHQGIFRvsgSQVEVNDIKNAF--ERGEDPLADDQNDH--DINSVAGVLKLYFRGLENPLFPKERFEDLMSCVKLE 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622845618 587 ESEQCLSQIQELIGSMPKPNRDTLRYL---LEHLCRviaHSDKNRMTPHNLGIVFGPTLFrPEQETSDPAAHALYPGQLV 663
Cdd:cd04383   107 NPTERVHQIREILSTLPRSVIIVMRYLfafLNHLSQ---FSDENMMDPYNLAICFGPTLM-PVPEGQDQVSCQAHVNELI 182

                  ....*.
gi 1622845618 664 QLMLTN 669
Cdd:cd04383   183 KTIIIH 188

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. 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 1622845618 543 DLDSTEWDDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALAL---SESEQCLSQIQELIGSMPKPNRDTLRYLLEHLCR 619
Cdd:cd04379    64 ELSEELYPDINVITGVLKDYLRELPEPLITPQLYEMVLEALAValpNDVQTNTHLTLSIIDCLPLSAKATLLLLLDHLSL 143

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1622845618 620 VIAHSDKNRMTPHNLGIVFGPTLFRPEQETSDPAA 654
Cdd:cd04379   144 VLSNSERNKMTPQNLAVCFGPVLMFCSQEFSRYGI 178

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. 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 1622845618 537 GQEGRLDLDSTewddIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQcLSQIQELIGSMPKPNRDTLRYLLEH 616
Cdd:cd04376    50 GIDVVLDENHS----VHDVAALLKEFFRDMPDPLLPRELYTAFIGTALLEPDEQ-LEALQLLIYLLPPCNCDTLHRLLKF 124

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622845618 617 LCRVIAHSDK-----------NRMTPHNLGIVFGPTLFRPEQ-------ETSDPAAHALYPGQLVQLMLTNFTSLF 674
Cdd:cd04376   125 LHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHKQKsgerefvQASLRIEESTAIINVVQTMIDNYEELF 200

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a 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 up several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622845618 509 PLQSLQERGLLRERAVTSDGRYV-FPEQPG--QEG--------------RLDLDSTE------WDDIHVVTGALKLFLRE 565
Cdd:cd04393     6 PLQELQQAGQPENGVPAVVRHIVeYLEQHGleQEGlfrvngnaetvewlRQRLDSGEevdlskEADVCSAASLLRLFLQE 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622845618 566 LPQPLVPPLLLPHFRAALA--LSESEQClSQIQELIGSMPKPNRDTLRYLLEHLCRVIAHSDKNRMTPHNLGIVFGPTLF 643
Cdd:cd04393    86 LPEGLIPASLQIRLMQLYQdyNGEDEFG-RKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFGPDVF 164

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622845618 323 VEKSGLLnMTKiaqgGRKLRKNWGPSWVVLTGNSLVFYREPPptapssgwGPAGSRPESSVDLRGAALAHGRHLSS--RR 400
Cdd:pfam00169   1 VVKEGWL-LKK----GGGKKKSWKKRYFVLFDGSLLYYKDDK--------SGKSKEPKGSISLSGCEVVEVVASDSpkRK 67

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1622845618 401 NVLHIRTV---PGHEFLLQSDHETELRAWHRALRTVIE 435
Cdd:pfam00169  68 FCFELRTGertGKRTYLLQAESEEERKDWIKAIQSAIR 105

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP 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 1622845618 543 DLDSTEWDD--IHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNRDTLRYLLEHLCRV 620
Cdd:cd04406    56 DANSVNLDDynIHVIASVFKQWLRDLPNPLMTFELYEEFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRI 135

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1622845618 621 IAHSDKNRMTPHNLGIVFGPTLFRPEqETSDP 652
Cdd:cd04406   136 ALQEETNRMSANALAIVFAPCILRCP-DTTDP 166

Pleckstrin homology (PH) 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 1622845618 338 GRKLRKNWGPSWVVLTGNSLVFYREPPptapssgwgPAGSRPESSVDLRGAALAHGRHLSSRRNVLHIRTVPGHEFLLQS 417
Cdd:cd00821     9 GGGGLKSWKKRWFVLFEGVLLYYKSKK---------DSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRTYYLQA 79

                          90
                  ....*....|...
gi 1622845618 418 DHETELRAWHRAL 430
Cdd:cd00821    80 DSEEERQEWLKAL 92

RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP19-like proteins. The function of ArhGAP19 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 1622845618 542 LDLDSTEWDdIHVVTGALKLFLRELPQPLVPPLllpHFRAALALSE---------------SEQCLSQIQELIGSMPKPN 606
Cdd:cd04392    52 LDLESGGFH-AHDCATVLKGFLGELPEPLLTHA---HYPAHLQIADlcqfdekgnktsapdKERLLEALQLLLLLLPEEN 127

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1622845618 607 RDTLRYLLEHLCRVIAHSDKNRMTPHNLGIVFGPTLFRPEQET 649
Cdd:cd04392   128 RNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHLICPRNLT 170

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. 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 1622845618 551 DIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNRDTLRYLLEHLCRVIAHSDKNRMT 630
Cdd:cd04381    70 EPPTVASLLKQYLRELPEPLLTKELMPRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMN 149

                          90
                  ....*....|..
gi 1622845618 631 PHNLGIVFGPTL 642
Cdd:cd04381   150 IQNISIVLSPTV 161