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 568914445  89 EKEGYLQKAKIADGGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 168
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 568914445 169 TVSGNEFLLQSDIDFLILDWFQAIKNAIDR 198
Cdd:cd13233   81 TVTGTEFLLQSDNDTEIREWFDAIKAVIQR 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 568914445  89 EKEGYLQKAKIADGGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 168
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 568914445 169 TVSGNEFLLQSDIDFLILDWFQAIKNAIDR 198
Cdd:cd13233   81 TVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914445   298 STVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWeDIHVVTGALKMFFRELSEPLFPYSF 377
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90
                   ....*....|
gi 568914445   378 FERFVEAIRS 387
Cdd:smart00324  80 YEEFIEAAKL 89

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914445   88 VEKEGYLQKAkiadgGKKLRKNWSTSWIVLSGRKIEFYKDSKqqalpNMKTRHNVESVDLCGAHIEW--AKEKSSRKSVF 165
Cdd:pfam00169   1 VVKEGWLLKK-----GGGKKKSWKKRYFVLFDGSLLYYKDDK-----SGKSKEPKGSISLSGCEVVEvvASDSPKRKFCF 70

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568914445  166 QITTVS---GNEFLLQSDIDFLILDWFQAIKNAI 196
Cdd:pfam00169  71 ELRTGErtgKRTYLLQAESEEERKDWIKAIQSAI 104

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 568914445  89 EKEGYLQKAKIADGGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 168
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 568914445 169 TVSGNEFLLQSDIDFLILDWFQAIKNAIDR 198
Cdd:cd13233   81 TVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914445   298 STVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWeDIHVVTGALKMFFRELSEPLFPYSF 377
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90
                   ....*....|
gi 568914445   378 FERFVEAIRS 387
Cdd:smart00324  80 YEEFIEAAKL 89

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 568914445 301 PWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEklNLDDSQWEDIHVVTGALKMFFRELSEPLFPYSFFER 380
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                 ....*..
gi 568914445 381 FVEAIRS 387
Cdd:cd00159   79 FIELAKI 85

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 568914445 300 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQWEDIHVVTGALKMFFRELSEPLFPYSFF 378
Cdd:cd04395   18 VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgFDIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNELY 97

                 ....*...
gi 568914445 379 ERFVEAIR 386
Cdd:cd04395   98 PDFIEANR 105

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) 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 568914445 285 FGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQWEDIHVVTGALKM 363
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80

                         90       100
                 ....*....|....*....|....*
gi 568914445 364 FFRELSEPLFPYSFFERFVEAIRST 388
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKIS 105

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 568914445 285 FGSHLHTVCEREHST--VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKL-NLDDSQWEDIHVVTGAL 361
Cdd:cd04379    1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 568914445 362 KMFFRELSEPLFPYSFFERFVEAIrsTRVLP 392
Cdd:cd04379   81 KDYLRELPEPLITPQLYEMVLEAL--AVALP 109

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 568914445 300 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRfivnqeEKL-----NLDDSQwEDIHVVTGALKMFFRELSEPLFP 374
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALK------EKFlrgktVPNLSK-VDIHVICGCLKDFLRSLKEPLIT 89

                         90
                 ....*....|..
gi 568914445 375 YSFFERFVEAIR 386
Cdd:cd04382   90 FALWKEFMEAAE 101

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 568914445 296 EHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQwedIHVVTGALKMFFRELSEPLFP 374
Cdd:cd04377   11 EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDpDSVNLEDYP---IHVITSVLKQWLRELPEPLMT 87

                         90
                 ....*....|.
gi 568914445 375 YSFFERFVEAI 385
Cdd:cd04377   88 FELYENFLRAM 98

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. 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 568914445  91 EGYLQ-KAKIADGGKK-LRKNWSTSWIVLSGRKIEFYKDSKQQALPNmkTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 168
Cdd:cd10571    2 EGFLErKHEWESGGKKaSNRSWKNVYTVLRGQELSFYKDQKAAKSGI--TYAAEPPLNLYNAVCEVASDYTKKKHVFRLK 79

                         90       100
                 ....*....|....*....|....*..
gi 568914445 169 TVSGNEFLLQSDIDFLILDWFQAIKNA 195
Cdd:cd10571   80 LSDGAEFLFQAKDEEEMNQWVKKISFA 106

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 568914445 300 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKL-RFIVNQEEKLNLDDSQWEDIhvvTGALKMFFRELSEPLFPYSFF 378
Cdd:cd04408   16 VPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLcQAFENGRDLVDLSGHSPHDI---TSVLKHFLKELPEPVLPFQLY 92

                 ....
gi 568914445 379 ERFV 382
Cdd:cd04408   93 DDFI 96

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 568914445 283 QIFGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWEDIHVVTGALK 362
Cdd:cd04383    1 KLFNGSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLK 80

                         90       100
                 ....*....|....*....|....*
gi 568914445 363 MFFRELSEPLFPYSFFERFVEAIRS 387
Cdd:cd04383   81 LYFRGLENPLFPKERFEDLMSCVKL 105

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 568914445 284 IFGSHLHTVCEREH-----STVPWFVKQCIEAVEKRGLDVDGIYRVSGnlaTIQKLRFIVNQ-EEKLNLDDSQWEDIHV- 356
Cdd:cd04391    1 LFGVPLSTLLERDQkkvpgSKVPLIFQKLINKLEERGLETEGILRIPG---SAQRVKFLCQElEAKFYEGTFLWDQVKQh 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568914445 357 -VTGALKMFFRELSEPLFPYSFFERFveaiRSTRVLPVPALIFSELHCL 404
Cdd:cd04391   78 dAASLLKLFIRELPQPLLTVEYLPAF----YSVQGLPSKKDQLQALNLL 122

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 568914445 284 IFGSHLHTVCEREH-----STVPWFVKQCIEAVEK-RGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNL-DDSQWEDIHV 356
Cdd:cd04400    1 IFGSPLEEAVELSShkyngRDLPSVVYRCIEYLDKnRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLfSSSLYPDVHT 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568914445 357 VTGALKMFFRELSEPLFPYSFFERFvEAIRSTRVLPVP-ALIFSEL 401
Cdd:cd04400   81 VAGLLKLYLRELPTLILGGELHNDF-KRLVEENHDRSQrALELKDL 125

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. 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 568914445 296 EHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQwedIHVVTGALKMFFRELSEPLFP 374
Cdd:cd04407   11 NKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADpENVKLENYP---IHAITGLLKQWLRELPEPLMT 87

                         90
                 ....*....|.
gi 568914445 375 YSFFERFVEAI 385
Cdd:cd04407   88 FAQYNDFLRAV 98

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 568914445 285 FGSHLHTVCEREHStVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSqweDIHVVTGALKM 363
Cdd:cd04406    1 FGVELSRLTSEDRS-VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDaNSVNLDDY---NIHVIASVFKQ 76

                         90       100
                 ....*....|....*....|..
gi 568914445 364 FFRELSEPLFPYSFFERFVEAI 385
Cdd:cd04406   77 WLRDLPNPLMTFELYEEFLRAM 98

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 568914445 300 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQweDIHVVTGALKMFFRELSEPLFPYSFFE 379
Cdd:cd04376    9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENH--SVHDVAALLKEFFRDMPDPLLPRELYT 86

                 ....*
gi 568914445 380 RFVEA 384
Cdd:cd04376   87 AFIGT 91

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 568914445    88 VEKEGYLQKAkiadgGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKtrhnvESVDLCGAHIEWAKEKSS--RKSVF 165
Cdd:smart00233   1 VIKEGWLYKK-----SGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPK-----GSIDLSGCTVREAPDPDSskKPHCF 70

                           90       100       110
                   ....*....|....*....|....*....|..
gi 568914445   166 QITTVSGNEFLLQSDIDFLILDWFQAIKNAID 197
Cdd:smart00233  71 EIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A 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 568914445 284 IFGSHLH-----TVCEREHstVPWFVKQCIEAVEKRgLDVDGIYRVSGNLATIQKLRFIVNQEEKLnLDDSQWEDihvVT 358
Cdd:cd04394    1 VFGVPLHslphsTVPEYGN--VPKFLVDACTFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGEAC-LSSALPCD---VA 73

                         90       100
                 ....*....|....*....|....*.
gi 568914445 359 GALKMFFRELSEPLFPYSFFERFVEA 384
Cdd:cd04394   74 GLLKQFFRELPEPLLPYDLHEALLKA 99

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568914445 304 VKQCIEAVEKRgLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWEdIHVVTGALKMFFRELSEPL 372
Cdd:cd04392   13 IYQLIEYLEKN-LRVEGLFRKPGNSARQQELRDLLNSGTDLDLESGGFH-AHDCATVLKGFLGELPEPL 79

RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal LRG1-like proteins. Yeast Lrg1p is required for efficient cell fusion, and mother-daughter cell separation, possibly through acting as a RhoGAP specifically regulating 1,3-beta-glucan synthesis. 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 568914445 285 FGSHLHTVCERE--HST---------VPWFVKQCIEAVEKRGLDVDGIYRVSGNlatIQKLRFIVNQEEKLNLDDSQWED 353
Cdd:cd04397    1 FGVPLEILVEKFgaDSTlgvgpgklrIPALIDDIISAMRQMDMSVEGVFRKNGN---IRRLKELTEEIDKNPTEVPDLSK 77

                         90       100       110
                 ....*....|....*....|....*....|...
gi 568914445 354 IHVVTGA--LKMFFRELSEPLFPYSFFERFVEA 384
Cdd:cd04397   78 ENPVQLAalLKKFLRELPDPLLTFKLYRLWISS 110

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 568914445  90 KEGYLQKAkiadgGKKLRKNWSTSWIVLSGRKIEFYKDSKqqalpnMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQITT 169
Cdd:cd00821    1 KEGYLLKR-----GGGGLKSWKKRWFVLFEGVLLYYKSKK------DSSYKPKGSIPLSGILEVEEVSPKERPHCFELVT 69

                         90       100
                 ....*....|....*....|...
gi 568914445 170 VSGNEFLLQSDIDFLILDWFQAI 192
Cdd:cd00821   70 PDGRTYYLQADSEEERQEWLKAL 92

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. 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 568914445 284 IFGSHLHTVCEreHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDsqwEDIHVVTGALKM 363
Cdd:cd04402    1 LFGQPLSNICE--DDNLPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVEVDLKA---EPVLLLASVLKD 75

                         90       100
                 ....*....|....*....|..
gi 568914445 364 FFRELSEPLFPYSFFERFVEAI 385
Cdd:cd04402   76 FLRNIPGSLLSSDLYEEWMSAL 97

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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 568914445  88 VEKEGYLQKAKiadggkKLRKNWSTSWIVLSGRKIEFYKD---SKQQALPNMKTRHNVE---SVDLCGAH---IEWAKEK 158
Cdd:cd13378    3 VLKAGWLKKQR------SIMKNWQQRWFVLRGDQLFYYKDeeeTKPQGCISLQGSQVNElppNPEEPGKHlfeILPGGAG 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 568914445 159 SSRKsvfqiTTVSGNEFLL----QSDIDflilDWFQAIKNAI 196
Cdd:cd13378   77 DREK-----VPMNHEAFLLmansQSDME----DWVKAIRRVI 109

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. 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 568914445  90 KEGYLQKAKIADGGkklrknWSTSWIVLSGRKIEFYKDSKQQALPNMKtrhnvESVDL--CGAHIEwakEKSSRKSVFQI 167
Cdd:cd13275    1 KKGWLMKQGSRQGE------WSKHWFVLRGAALKYYRDPSAEEAGELD-----GVIDLssCTEVTE---LPVSRNYGFQV 66

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568914445 168 TTVSGNEFLLQSDIDFLILDWFQAIKNAIdRLPKNPS 204
Cdd:cd13275   67 KTWDGKVYVLSAMTSGIRTNWIQALRKAA-GLPSPPA 102

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. 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 568914445  83 LEHPMVEKEGYLQKAkiadgGKKlRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVdlcgAHIEWAKekssRK 162
Cdd:cd13298    1 FEFDRVLKSGYLLKR-----SRK-TKNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLAV----APLKDKK----RK 66