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 2077850559 280 FGSHLHLVCEHEKSTVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEKLNLDDSQWEDIHVVTGALKMF 359
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 360 FRELPEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPTL 439
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170       180
                  ....*....|....*....|....*..
gi 2077850559 440 LRPEKETGNMAVHMLYQNQIVELMLSE 466
Cdd:cd04403   161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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 2077850559 280 FGSHLHLVCEHEKSTVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEKLNLDDSQWEDIHVVTGALKMF 359
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 360 FRELPEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPTL 439
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170       180
                  ....*....|....*....|....*..
gi 2077850559 440 LRPEKETGNMAVHMLYQNQIVELMLSE 466
Cdd:cd04403   161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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 2077850559  83 EKEGYLLKAKIADGGKKLRKNWSTSWIVLTARKMEFYKESKQPALANLKPGYKPECVDLCGARIEWTSEKSSRKNVFQIT 162
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 2077850559 163 TVSGNEFLLQSDIDFLILDWFHAIKNAIDR 192
Cdd:cd13233    81 TVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

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 2077850559   82 VEKEGYLLKAkiadgGKKLRKNWSTSWIVLTARKMEFYKESKQPALANLKpgykpECVDLCGARIEWTSEKSS--RKNVF 159
Cdd:smart00233   1 VIKEGWLYKK-----SGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPK-----GSIDLSGCTVREAPDPDSskKPHCF 70

                           90       100       110
                   ....*....|....*....|....*....|..
gi 2077850559  160 QITTVSGNEFLLQSDIDFLILDWFHAIKNAID 191
Cdd:smart00233  71 EIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102

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 2077850559 280 FGSHLHLVCEHEKSTVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEKLNLDDSQWEDIHVVTGALKMF 359
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 360 FRELPEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPTL 439
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170       180
                  ....*....|....*....|....*..
gi 2077850559 440 LRPEKETGNMAVHMLYQNQIVELMLSE 466
Cdd:cd04403   161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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 2077850559  83 EKEGYLLKAKIADGGKKLRKNWSTSWIVLTARKMEFYKESKQPALANLKPGYKPECVDLCGARIEWTSEKSSRKNVFQIT 162
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 2077850559 163 TVSGNEFLLQSDIDFLILDWFHAIKNAIDR 192
Cdd:cd13233    81 TVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

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 2077850559 296 PQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEklNLDDSQWEDIHVVTGALKMFFRELPEPLFPYCFFEQ 375
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 376 FVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPTLLRPEKETGNMAVHMLY 455
Cdd:cd00159    79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                         170
                  ....*....|.
gi 2077850559 456 QNQIVELMLSE 466
Cdd:cd00159   159 LNEIVEFLIEN 169

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 2077850559 280 FGSHLHLVCEHEKSTVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLR--FVVNQEEKLNLDDSQWE-DIHVVTGAL 356
Cdd:cd04398     1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKelFDKDPLNVLLISPEDYEsDIHSVASLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 357 KMFFRELPEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFG 436
Cdd:cd04398    81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 2077850559 437 PTLLrpeKETGNMAVHMLYQNQIVELMLSEYSKIF 471
Cdd:cd04398   161 PTLM---NAAPDNAADMSFQSRVIETLLDNAYQIF 192

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 2077850559 280 FGSHLHLVCEHEKSTVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEKLNLDDSQWEDIHVVTGALKMF 359
Cdd:cd04387     1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 360 FRELPEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPTL 439
Cdd:cd04387    81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                         170       180
                  ....*....|....*....|....
gi 2077850559 440 LRPEKETGNMAVHMLYQNQIVELM 463
Cdd:cd04387   161 LRPSEKESKIPTNTMTDSWSLEVM 184

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 2077850559 293 STVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEKLNLDDSQWEdIHVVTGALKMFFRELPEPLFPYCF 372
Cdd:cd04373    13 KPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDLVSKDFT-VNAVAGALKSFFSELPDPLIPYSM 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2077850559 373 FEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPTLLRPEKET 446
Cdd:cd04373    92 HLELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMRPDFTS 165

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. 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 2077850559 278 QIFGSHL--HLVCEHEKSTVPqfVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVN-QEEKLNLDDsQWEDIHVVTG 354
Cdd:cd04386     3 PVFGTPLeeHLKRTGREIALP--IEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDaGTFSLPLDE-FYSDPHAVAS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 355 ALKMFFRELPEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIV 434
Cdd:cd04386    80 ALKSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIV 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 2077850559 435 FGPTLL--RPEKETGNMAVHM-LYQNQIVELMLSEYSKIF 471
Cdd:cd04386   160 LAPNLLwaKNEGSLAEMAAGTsVHVVAIVELIISHADWFF 199

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 279 IFGSHLHLVCEHEKSTVPQFVRLCIKAVEKRGLdVDGIYRVSGNLATIQKLR--FVVNQEEKLNLDDSQwEDIHVVTGAL 356
Cdd:cd04384     2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRheFDSEQIPDLTKDVYI-QDIHSVSSLC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 357 KMFFRELPEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFG 436
Cdd:cd04384    80 KLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWA 159

                         170       180
                  ....*....|....*....|....*...
gi 2077850559 437 PTLLRPEK-ETG---NMAVHMLYQNQIV 460
Cdd:cd04384   160 PNLLRSKQiESAcfsGTAAFMEVRIQSV 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 2077850559 295 VPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKL-RFVVNQEEKLNLDDSQWEDIhvvTGALKMFFRELPEPLFPYCFF 373
Cdd:cd04408    16 VPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLcQAFENGRDLVDLSGHSPHDI---TSVLKHFLKELPEPVLPFQLY 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 374 EQFVEAIKIQDNATR------------IKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPTLLR 441
Cdd:cd04408    93 DDFIALAKELQRDSEkaaespsiveniIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFGPTLLR 172

                         170       180
                  ....*....|....*....|....*...
gi 2077850559 442 PeKETGNMAVHML----YQNQIVELMLS 465
Cdd:cd04408   173 P-LVGGDVSMICLldtgYQAQLVEFLIS 199

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 2077850559 292 KSTVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKL--------RFVVNQEEKLNLDDsqwedihvVTGALKMFFREL 363
Cdd:cd04385    12 DNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLleafrkdaRSVQLREGEYTVHD--------VADVLKRFLRDL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 364 PEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPTLLRPE 443
Cdd:cd04385    84 PDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTD 163

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 2077850559 280 FGSHLHLVCEHEKST--VPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEKL-NLDDSQWEDIHVVTGAL 356
Cdd:cd04379     1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 357 KMFFRELPEPLFPYCFFEQFVEAIKI---QDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGI 433
Cdd:cd04379    81 KDYLRELPEPLITPQLYEMVLEALAValpNDVQTNTHLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                         170
                  ....*....|....
gi 2077850559 434 VFGPTLLRPEKETG 447
Cdd:cd04379   161 CFGPVLMFCSQEFS 174

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 2077850559 279 IFGSHLHLVCE---HE--KSTVPQFVRLCIKAVEK-RGLDVDGIYRVSGNLATIQKLRFVVNQEEKLNL-DDSQWEDIHV 351
Cdd:cd04400     1 IFGSPLEEAVElssHKynGRDLPSVVYRCIEYLDKnRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLfSSSLYPDVHT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 352 VTGALKMFFRELPEPLFPYCFFEQFVEAIKIQ-DNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQS 430
Cdd:cd04400    81 VAGLLKLYLRELPTLILGGELHNDFKRLVEENhDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRN 160

                  ....*....
gi 2077850559 431 LGIVFGPTL 439
Cdd:cd04400   161 VCIVFSPTL 169

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 2077850559 280 FGSHLHLVCE----HEKSTVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEKLNLDDSqweDIHVVTGA 355
Cdd:cd04381     1 FGASLSLAVErsrcHDGIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESPNLEEY---EPPTVASL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 356 LKMFFRELPEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVF 435
Cdd:cd04381    78 LKQYLRELPEPLLTKELMPRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVL 157

                  ....
gi 2077850559 436 GPTL 439
Cdd:cd04381   158 SPTV 161

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 2077850559 279 IFGSHLHLVCEheKSTVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEKLNLDDsqwEDIHVVTGALKM 358
Cdd:cd04402     1 LFGQPLSNICE--DDNLPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVEVDLKA---EPVLLLASVLKD 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 359 FFRELPEPLFPYCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPT 438
Cdd:cd04402    76 FLRNIPGSLLSSDLYEEWMSALDQENEEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPS 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 2077850559 439 LLRP------EKETGNMAVhmlyqnQIVELMLSEYSKIFGSE 474
Cdd:cd04402   156 LLWPpasselQNEDLKKVT------SLVQFLIENCQEIFGED 191

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 2077850559 290 HEKStVPQFVRLCIKAVEKRGLDVDGIYRVSGNLATIQKLRFVVNQEEKLNLDDSQweDIHVVTGALKMFFRELPEPLFP 369
Cdd:cd04376     5 IARQ-VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENH--SVHDVAALLKEFFRDMPDPLLP 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 370 YCFFEQFVEAIKIQdNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAA---------KESV--NLMSTQSLGIVFGPT 438
Cdd:cd04376    82 RELYTAFIGTALLE-PDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEhaadsidedGQEVsgNKMTSLNLATIFGPN 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 2077850559 439 LLRPEK----ETGNMAVHM---LYQNQIVELMLSEYSKIF 471
Cdd:cd04376   161 LLHKQKsgerEFVQASLRIeesTAIINVVQTMIDNYEELF 200

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 2077850559 293 STVPQFVRLCIKAVEKRGLDVDGIYRVSGnlaTIQKLRFVVNQ-EEKLNLDDSQWEDIHV--VTGALKMFFRELPEPLFP 369
Cdd:cd04391    20 SKVPLIFQKLINKLEERGLETEGILRIPG---SAQRVKFLCQElEAKFYEGTFLWDQVKQhdAASLLKLFIRELPQPLLT 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077850559 370 YCFFEQFVEAIKIQDNATRIKSIRNLVKKLPRPNYDTMKILFEHLKKIAAKESVNLMSTQSLGIVFGPTLLRPE----KE 445
Cdd:cd04391    97 VEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMIMAPNLFPPRgkhsKD 176

                         170       180
                  ....*....|....*....|...
gi 2077850559 446 TGNMAVHMLYQN---QIVELMLS 465
Cdd:cd04391   177 NESLQEEVNMAAgcaNIMRLLIR 199