Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229  25 LKEGSVQLTSlsTLLSHHRYFFLYHETLIISKQKGACSYKLKEKLRLEKVWIASSNTAD---------SFLIGWPFTNYL 95
Cdd:cd13319   4 LLEGPVQLTR--GLQTQERHLFLFSDVLVVAKPKSKNSFKLKHKIRLSELWLASCVDEVcegsksadkSFVLGWPTTNFV 81

                        90
                ....*....|....*.
gi 17510229  96 VHFRNTEEKDEWFELL 111
Cdd:cd13319  82 ATFSSQEEKDLWLSFL 97

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 17510229    264 PQPIMTIVDHLRMDGFDAEGIFRKSPKQSTFKELKCELDKGVVPD--FHKYNTHVLASILKEYLRSIPGKILLSGNYELW 341
Cdd:smart00324   4 PIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDldLSEYDVHDVAGLLKLFLRELPEPLITYELYEEF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229    342 mREIADEPNTEKKVSCCRALLSHLPTSHSILLANVLKLLNKIS-NSPSSKMNASSLSVCLAPSFLESPDPMEGGKKIPP- 419
Cdd:smart00324  84 -IEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAeHSEENKMTARNLAIVFGPTLLRPPDGEVASLKDIRh 162

                          170
                   ....*....|..
gi 17510229    420 ---LIEFLISHA 428
Cdd:smart00324 163 qntVIEFLIENA 174

RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. 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 17510229  25 LKEGSVQLTSlsTLLSHHRYFFLYHETLIISKQKGACSYKLKEKLRLEKVWIASSNTAD---------SFLIGWPFTNYL 95
Cdd:cd13319   4 LLEGPVQLTR--GLQTQERHLFLFSDVLVVAKPKSKNSFKLKHKIRLSELWLASCVDEVcegsksadkSFVLGWPTTNFV 81

                        90
                ....*....|....*.
gi 17510229  96 VHFRNTEEKDEWFELL 111
Cdd:cd13319  82 ATFSSQEEKDLWLSFL 97

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 17510229    264 PQPIMTIVDHLRMDGFDAEGIFRKSPKQSTFKELKCELDKGVVPD--FHKYNTHVLASILKEYLRSIPGKILLSGNYELW 341
Cdd:smart00324   4 PIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDldLSEYDVHDVAGLLKLFLRELPEPLITYELYEEF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229    342 mREIADEPNTEKKVSCCRALLSHLPTSHSILLANVLKLLNKIS-NSPSSKMNASSLSVCLAPSFLESPDPMEGGKKIPP- 419
Cdd:smart00324  84 -IEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAeHSEENKMTARNLAIVFGPTLLRPPDGEVASLKDIRh 162

                          170
                   ....*....|..
gi 17510229    420 ---LIEFLISHA 428
Cdd:smart00324 163 qntVIEFLIENA 174

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 17510229 264 PQPIMTIVDHLRMDGFDAEGIFRKSPKQSTFKELKCELDKGVVPDFH-KYNTHVLASILKEYLRSIPGKILLSGNYELWM 342
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLeDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229 343 rEIADEPNTEKKVSCCRALLSHLPTSHSILLANVLKLLNKIS-NSPSSKMNASSLSVCLAPSFLESPDPMEGG----KKI 417
Cdd:cd00159  81 -ELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISqNSEVNKMTASNLAIVFAPTLLRPPDSDDELlediKKL 159

                       170
                ....*....|
gi 17510229 418 PPLIEFLISH 427
Cdd:cd00159 160 NEIVEFLIEN 169

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 17510229 266 PIMTIVDHLRMDGFDAEGIFRKSPKQSTFKELKCELDKGVV--PDFHKYN-THVLASILKEYLRSIPGKILLSGNYELWM 342
Cdd:cd04386  23 PIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFslPLDEFYSdPHAVASALKSYLRELPDPLLTYNLYEDWV 102

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229 343 rEIADEPNTEKKVSCCRALLSHLPTSHSILLANVLKLLNKIS-NSPSSKMNASSLSVCLAPSFLESP-------DPMEGG 414
Cdd:cd04386 103 -QAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAqKSDENKMSPSNIAIVLAPNLLWAKnegslaeMAAGTS 181

                       170       180
                ....*....|....*....|
gi 17510229 415 KKIPPLIEFLISHAAQVMPG 434
Cdd:cd04386 182 VHVVAIVELIISHADWFFPG 201

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 17510229 262 TPPQPIMTIVDHLRMDGFDAEGIFRKSPKQSTFKELKCELDKGvvPD---FHKYNTHVLASILKEYLRSIPGKILLSGNY 338
Cdd:cd04377  14 SVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTD--PDsvnLEDYPIHVITSVLKQWLRELPEPLMTFELY 91

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17510229 339 ELWMReIADEPNTEKKVSCCRALLSHLPTSHSILLANVLKLLNKIS-NSPSSKMNASSLSVCLAPSFLESPD 409
Cdd:cd04377  92 ENFLR-AMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVAlQEEVNRMSANALAIVFAPCILRCPD 162

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 17510229 264 PQPIM--TIVDHLRMDGFDAEGIFRKSPKQSTFKELKCELDKGvvPD---FHKYNTHVLASILKEYLRSIPGKILLSGNY 338
Cdd:cd04407  14 SVPIVleKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQAD--PEnvkLENYPIHAITGLLKQWLRELPEPLMTFAQY 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229 339 ELWMREIaDEPNTEKKVSCCRALLSHLPTS-HSILLANVLKLLNKISNSPSSKMNASSLSVCLAPSFLESPD------PM 411
Cdd:cd04407  92 NDFLRAV-ELPEKQEQLQAIYRVLEQLPTAnHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDssdpltSM 170

                       170
                ....*....|....
gi 17510229 412 EGGKKIPPLIEFLI 425
Cdd:cd04407 171 KDVAKTTTCVEMLI 184

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 17510229 264 PQPIMTIVDHLRMDGFDAEGIFRKSPKQSTFKELKCELDKGVVP-DFHKYNTHVLASILKEYLRSIPGKILLSGNYELWM 342
Cdd:cd04406  16 PLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSvNLDDYNIHVIASVFKQWLRDLPNPLMTFELYEEFL 95

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17510229 343 REIADEPNTEkKVSCCRALLSHLPTSHSILLANVLKLLNKIS-NSPSSKMNASSLSVCLAPSFLESPD 409
Cdd:cd04406  96 RAMGLQERRE-TVRGVYSVIDQLSRTHLNTLERLIFHLVRIAlQEETNRMSANALAIVFAPCILRCPD 162

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 17510229 256 KGLNGPTPPQPIMTIVDHLRMDGFDAEGIFRKSPKQSTFKELKCELDKGVVPDFHKY-NTHVLASILKEYLRSIPGKILL 334
Cdd:cd04393  13 AGQPENGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSKEaDVCSAASLLRLFLQELPEGLIP 92

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17510229 335 SGNYELWMREIADEPNTEKKVSCCRALLSHLPTSHSILLANVLKLLNKI-SNSPSSKMNASSLSVCLAPS-FLESPDP 410
Cdd:cd04393  93 ASLQIRLMQLYQDYNGEDEFGRKLRDLLQQLPPVNYSLLKFLCHFLSNVaSQHHENRMTAENLAAVFGPDvFHVYTDV 170

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 17510229 278 GFDAEGIFRKSPKQSTFKELKCELDKG-VVPDFHKYNTHVLASILKEYLRSIPGKILlsgNYELW---MR--EIADEPNT 351
Cdd:cd04382  32 GLTEEGLYRVSGSEREVKALKEKFLRGkTVPNLSKVDIHVICGCLKDFLRSLKEPLI---TFALWkefMEaaEILDEDNS 108

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17510229 352 EKKVscCRALlSHLPTSHSILLANVLKLLNKISNSPSSKMNASSLSVCLAPSFL----ESPDPME 412
Cdd:cd04382 109 RAAL--YQAI-SELPQPNRDTLAFLILHLQRVAQSPECKMDINNLARVFGPTIVgysvPNPDPMT 170

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) 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 17510229 274 LRMDGFDAEGIFRKSPKQSTFKELKCELDKGVVPDFHKYNTHVLASILKEYLRSIPGKILLSGNYElwmREIADEPNTEK 353
Cdd:cd04389  33 LALGGFQTEGIFRVPGDIDEVNELKLRVDQWDYPLSGLEDPHVPASLLKLWLRELEEPLIPDALYQ---QCISASEDPDK 109

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17510229 354 KVsccrALLSHLPTSHSILLANVLKLLN---KISNSPSSKMNASSLSVCLAPSFL--ESPDP 410
Cdd:cd04389 110 AV----EIVQKLPIINRLVLCYLINFLQvfaQPENVAHTKMDVSNLAMVFAPNILrcTSDDP 167

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 17510229 282 EGIFRKSPKQSTFKELKCELDKGVVPDFHKYN----THVLASILKEYLRSIPGKILLSGNYELWMREIADEPNTEKKVSc 357
Cdd:cd04384  36 DGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVyiqdIHSVSSLCKLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEK- 114

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 17510229 358 CRALLSHLPTSHSILLANVLKLLNKISNSPS-SKMNASSLSVCLAPSFLESPdPMEGG 414
Cdd:cd04384 115 IHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSiTNMHAKNLAIVWAPNLLRSK-QIESA 171

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. 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 17510229 273 HLRMDGFDAEGIFRKSPKQSTFKELKCELDKGvvPDFHK------YNTHVLASILKEYLRSIPGKILLSGNYELWMREIA 346
Cdd:cd04396  42 YLKENATEVEGIFRVAGSSKRIRELQLIFSTP--PDYGKsfdwdgYTVHDAASVLRRYLNNLPEPLVPLDLYEEFRNPLR 119

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229 347 DEPNT----------------EKKVSCCRALLSHLPTSHSILLANVLKLLNKI-SNSPSSKMNASSLSVCLAPSFLESP- 408
Cdd:cd04396 120 KRPRIlqymkgrineplntdiDQAIKEYRDLITRLPNLNRQLLLYLLDLLAVFaRNSDKNLMTASNLAAIFQPGILSHPd 199

                       170       180
                ....*....|....*....|..
gi 17510229 409 -DPMEGGKKIPPL-IEFLISHA 428
Cdd:cd04396 200 hEMDPKEYKLSRLvVEFLIEHQ 221

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 17510229 281 AEGIFRKSPKQSTFKELKCELDKGVVPDFH--KYNTHVLASILKEYLRSIPGKILLSGNYELWMReIAD----------- 347
Cdd:cd04392  26 VEGLFRKPGNSARQQELRDLLNSGTDLDLEsgGFHAHDCATVLKGFLGELPEPLLTHAHYPAHLQ-IADlcqfdekgnkt 104

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229 348 -EPNTEKKVSCCRALLSHLPTSHSILLANVLKLLNK-ISNSPSSKMNASSLSVCLAPSF-----LESPDPMEGGKKIPPL 420
Cdd:cd04392 105 sAPDKERLLEALQLLLLLLPEENRNLLKLILDLLYQtAKHEDKNKMSADNLALLFTPHLicprnLTPEDLHENAQKLNSI 184

                ....*..
gi 17510229 421 IEFLISH 427
Cdd:cd04392 185 VTFMIKH 191

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 17510229 278 GFDAEGIFRKSPKQSTFKELKCELDK-GVVPDF--HKY-NTHVLASILKEYLRSIPGKILLSGNYELWMrEIADEPNTEK 353
Cdd:cd04372  31 GLQSEGLYRVSGFAEEIEDVKMAFDRdGEKADIsaTVYpDINVITGALKLYFRDLPIPVITYDTYPKFI-DAAKISNPDE 109

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17510229 354 KVSCCRALLSHLPTSHSILLANVLKLLNKIS-NSPSSKMNASSLSVCLAPSFLESPD 409
Cdd:cd04372 110 RLEAVHEALMLLPPAHYETLRYLMEHLKRVTlHEKDNKMNAENLGIVFGPTLMRPPE 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 17510229  26 KEGSVQLTSLSTLLS-HHRYFFLYHETLIISKQKGACSYKLKEKLRLEKVWIASSNTADS----FLIGWPFT-NYLVHFR 99
Cdd:cd00821   1 KEGYLLKRGGGGLKSwKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPKErphcFELVTPDGrTYYLQAD 80

                        90
                ....*....|..
gi 17510229 100 NTEEKDEWFELL 111
Cdd:cd00821  81 SEEERQEWLKAL 92

Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. 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.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. 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 kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229  24 PLKEGSVQLTSLSTLLSHHRYFFLYHETLIISKQKGACSYKLKEKLRLE--KVWIASSNTADSFLIGWPFTNYLVH---- 97
Cdd:cd01223  19 LQIDGELKIKSHEDQKKKDRYAFLFDKVLLICKSLRGDQYEYKEIINLSeyRIEDDPSRRTLKRDKRWSYQFLLVHkqgk 98

                        90
                ....*....|....*...
gi 17510229  98 ------FRNTEEKDEWFE 109
Cdd:cd01223  99 taytlyAKTEELKKKWME 116

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. 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 17510229 264 PQPIMTIVDHLRMDGFDAEGIFRKSPKQSTFKELKCELDKGVVPDFHKYNTHVLASILKEYLRSIPGKILLSGNYELWMR 343
Cdd:cd04388  16 PPLLIKLVEAIEKKGLESSTLYRTQSSSSLTELRQILDCDAASVDLEQFDVAALADALKRYLLDLPNPVIPAPVYSEMIS 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229 344 EIADEPNTEKKVSCCRALLS--HLPTSHSILLANVLKLLNKIS-NSPSSKMNASSLSVCLAPSFLESPDPMEGGKKIPP- 419
Cdd:cd04388  96 RAQEVQSSDEYAQLLRKLIRspNLPHQYWLTLQYLLKHFFRLCqSSSKNLLSARALAEIFSPLLFRFQPASSDSPEFHIr 175

                ....*..
gi 17510229 420 LIEFLIS 426
Cdd:cd04388 176 IIEVLIT 182

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 17510229 282 EGIFRKSPKQSTFKELKCELDKGV-VPDFHKYNTHVLASILKEYLRSIPGKILLSGNYELWM---REI--------ADEP 349
Cdd:cd04409  35 KGIYRVNGAKSRVEKLCQAFENGKdLVELSELSPHDISNVLKLYLRQLPEPLILFRLYNEFIglaKESqhvnetqeAKKN 114

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17510229 350 NTEKKVSCC----------RALLSHLPTSHSILLANVLKLLNKISN-SPSSKMNASSLSVCLAPSFLEsPDPMEGGKKIP 418
Cdd:cd04409 115 SDKKWPNMCtelnrillksKDLLRQLPAPNYNTLQFLIVHLHRVSEqAEENKMSASNLGIIFGPTLIR-PRPTDATVSLS 193

                       170
                ....*....|....
gi 17510229 419 PLIEFliSHAAQVM 432
Cdd:cd04409 194 SLVDY--PHQARLV 205