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 82546845 1008 FGVKIAVVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKLY 1087
Cdd:cd04387    1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845 1088 FRELPEPLFTDEFYPNFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLATVFGPTL 1167
Cdd:cd04387   81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 82546845 1168 LRPSEKESKLPANpsqpiTMTDSWSLEVMSQVQVLLYFLQL 1208
Cdd:cd04387  161 LRPSEKESKIPTN-----TMTDSWSLEVMSQVQVLLYFLQL 196

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845    502 VLSGILASEETYLSHLEALL-----LPMKPLKAaattsqpvlTSQQIETIFFKVPELYEIHKEFYdgLFPRVQQWSHQQR 576
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVevflpPNSKPLSE---------SEEEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQR 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845    577 VGDLFQKLASQLGVYRAFVDNYGVAMEMAEKCCQANAQFAEISENLRARSNkdakdpTTKNSLETLLYKPVDRVTRSTLV 656
Cdd:pfam00621   70 IGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPE------CRGLDLNSFLIKPVQRIPRYPLL 143

                          170       180       190
                   ....*....|....*....|....*....|...
gi 82546845    657 LHDLLKHTPASHPDHPLLQDALRISQNFLSSIN 689
Cdd:pfam00621  144 LKELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845  913 LNVIVHSATGFKQSSNLYCTLEVDSFGYFVNKAKTRVYRDTAEPNWNE-------------------------------- 960
Cdd:cd08686    1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEefeielegsqtlrilcyekcyskvkldgegtd 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 82546845  961 ---------LDPQALQDRDWQRTVIAMNGIEVKLSVKF 989
Cdd:cd08686   81 aimgkgqiqLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

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 82546845 1008 FGVKIAVVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKLY 1087
Cdd:cd04387    1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845 1088 FRELPEPLFTDEFYPNFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLATVFGPTL 1167
Cdd:cd04387   81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 82546845 1168 LRPSEKESKLPANpsqpiTMTDSWSLEVMSQVQVLLYFLQL 1208
Cdd:cd04387  161 LRPSEKESKIPTN-----TMTDSWSLEVMSQVQVLLYFLQL 196

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 82546845    1023 VPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDvNNKDVSVMMSEMDVNAIAGTLKLYFRELPEPLFTDEFYP 1102
Cdd:smart00324    3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845    1103 NFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLATVFGPTLLRPSEKESKLPANPS 1182
Cdd:smart00324   82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKDIR 161

                    ....
gi 82546845    1183 QPIT 1186
Cdd:smart00324  162 HQNT 165

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845    502 VLSGILASEETYLSHLEALL-----LPMKPLKAaattsqpvlTSQQIETIFFKVPELYEIHKEFYdgLFPRVQQWSHQQR 576
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVevflpPNSKPLSE---------SEEEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQR 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845    577 VGDLFQKLASQLGVYRAFVDNYGVAMEMAEKCCQANAQFAEISENLRARSNkdakdpTTKNSLETLLYKPVDRVTRSTLV 656
Cdd:pfam00621   70 IGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPE------CRGLDLNSFLIKPVQRIPRYPLL 143

                          170       180       190
                   ....*....|....*....|....*....|...
gi 82546845    657 LHDLLKHTPASHPDHPLLQDALRISQNFLSSIN 689
Cdd:pfam00621  144 LKELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176

Bcr-Abl oncoprotein oligomerization domain; The Bcr-Abl oncoprotein oligomerization domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerization domain is essential for the oncogenicity of the Bcr-Abl protein.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 82546845      3 DPVGFAEAWKAQFPDSEPPRMELRSVGDIEQELERCKASIRRLEQEVNQERFRMIYLQTLLAKEKKSYDRQRW 75
Cdd:pfam09036    1 EPAGFERHWRAEFPEGQVPKMELGSVEDIEQELERCKASLRRLQQELNEEKFKVIYLQTLLARERKSYDRQRW 73

C2 domain in the Active BCR (Breakpoint cluster region) Related protein; The ABR protein is similar to the breakpoint cluster region protein. It has homology to guanine nucleotide exchange proteins and GTPase-activating proteins (GAPs). ABR is expressed primarily in the brain, but also includes non-neuronal tissues such as the heart. It has been associated with human diseases such as Miller-Dieker syndrome in which mental retardation and malformations of the heart are present. ABR contains a RhoGEF domain and a PH-like domain upstream of its C2 domain and a RhoGAP domain downstream of this domain. A few members also contain a Bcr-Abl oncoprotein oligomerization domain at the very N-terminal end. Splice variants of ABR have been identified. ABR is found in a wide variety of organisms including chimpanzee, dog, mouse, rat, fruit fly, and mosquito. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845  913 LNVIVHSATGFKQSSNLYCTLEVDSFGYFVNKAKTRVYRDTAEPNWNE-------------------------------- 960
Cdd:cd08686    1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEefeielegsqtlrilcyekcyskvkldgegtd 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 82546845  961 ---------LDPQALQDRDWQRTVIAMNGIEVKLSVKF 989
Cdd:cd08686   81 aimgkgqiqLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

PH domain; This entry contains a PH domain found in RhoGEF proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 82546845    707 RQLLKDSFMVELVEGAR------KLRHVFLFTDLLLCTKLKKQSG------GKTQQYDCKWYIPLTDLSFQMVD 768
Cdd:pfam19057   11 RYLIRQDDVVETVYNERgevlksKERRLFLLNDLLVCVTVNSKSGsdfgslPGGEKYKLKWSVPLSDVEVVESG 84

N-terminal domain of Kruppel-like factor 14; Kruppel-like factor 14 (KLF14; also known as Krueppel-like factor 14 or basic transcription element-binding protein 5/BTEB5) is a protein that in humans is encoded by the KLF14 gene. KLF14 regulates the transcription of various genes, including TGFbetaRII (the type II receptor for TGFbeta). KLF14 is expressed in many tissues, lacks introns, and is subject to parent-specific expression. It also appears to be a master regulator of gene expression in adipose tissue. KLF14 is associated with coronary artery disease, hypercholesterolemia, and type 2 diabetes. KLF9, KLF10, KLF11, KLF13, KLF14, and KLF16 share a conserved alpha-helical motif AA/VXXL that mediates their binding to Sin3A and their activities as transcriptional repressors. KLF14 belongs to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF14.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 82546845   90 PRASASRPQPA----PADGADPPPAEEPEARPDGEGSPGK-ARPGTARRPGAAASGERDDRGPP 148
Cdd:cd21576  107 PRASSGSSDPArgssPTLGSEPAPASGEDAVSGPESSFGApAIPSAPAAPGAPAVSGEVPGGAP 170

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 82546845 1008 FGVKIAVVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKLY 1087
Cdd:cd04387    1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845 1088 FRELPEPLFTDEFYPNFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLATVFGPTL 1167
Cdd:cd04387   81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 82546845 1168 LRPSEKESKLPANpsqpiTMTDSWSLEVMSQVQVLLYFLQL 1208
Cdd:cd04387  161 LRPSEKESKIPTN-----TMTDSWSLEVMSQVQVLLYFLQL 196

Active breakpoint cluster region-related protein pleckstrin homology (PH) domain; The ABR protein contains multiple domains including a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. It is related to a slightly larger protein, BCR, which is structurally similar, but has an additional N-terminal kinase domain. ABR has GAP activity for both Rac and Cdc42. It promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. It is highly enriched in the brain and found to a lesser extent in heart, lung and muscle. 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 82546845  684 FLSSINEEITPRRQSMTVKKGEHRQLLKDSFMVELVEGARKLRHVFLFTDLLLCTKLKKQSGGKTQQYDCKWYIPLTDLS 763
Cdd:cd13366    1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845  764 FQMVDELEAVPNIPLVPDEELDALKIKISQIKNDIQREKRANKG-SKATERLKKKLSEQESLLLLMSPSMAFRVHSRNGK 842
Cdd:cd13366   81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                        170       180
                 ....*....|....*....|....*
gi 82546845  843 SYTFLISSDYERAEWRENIREQQKK 867
Cdd:cd13366  161 SYLFLLSSDYERSEWREAIQKLQKK 185

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 82546845    1023 VPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDvNNKDVSVMMSEMDVNAIAGTLKLYFRELPEPLFTDEFYP 1102
Cdd:smart00324    3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845    1103 NFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLATVFGPTLLRPSEKESKLPANPS 1182
Cdd:smart00324   82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKDIR 161

                    ....
gi 82546845    1183 QPIT 1186
Cdd:smart00324  162 HQNT 165

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 82546845 1024 PYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVsvMMSEMDVNAIAGTLKLYFRELPEPLFTDEFYPN 1103
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDID--DLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 82546845 1104 FAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLATVFGPTLLRPSEKESKL 1177
Cdd:cd00159   79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDEL 152

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 82546845 1008 FGVKIAVVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMS---EMDVNAIAGTL 1084
Cdd:cd04398    1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLISPedyESDIHSVASLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845 1085 KLYFRELPEPLFTDEFYPNFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLATVFG 1164
Cdd:cd04398   81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160

                 ....
gi 82546845 1165 PTLL 1168
Cdd:cd04398  161 PTLM 164

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 82546845 1007 VFGVKIA-VVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAafDVNNKDVSVMMSE---MDVNAIAG 1082
Cdd:cd04395    1 TFGVPLDdCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQE--ELNRGGFDIDLQDprwRDVNVVSS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845 1083 TLKLYFRELPEPLFTDEFYPNFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLATV 1162
Cdd:cd04395   79 LLKSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIV 158

                        170
                 ....*....|
gi 82546845 1163 FGPTLLRPSE 1172
Cdd:cd04395  159 FGPTLVRTSD 168

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845  499 RKWVLSGILASEETYLSHLEALLLP-MKPLKAaattSQPVLTSQQIETIFFKVPELYEIHKEFYDGLFPRVQQW-SHQQR 576
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVfLKPLDK----ELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWdKSGPR 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845  577 VGDLFQKLASQLGVYRAFVDNYGVAMEMAEKCCQANAQFAEISENLRARSNKdakdpttkNSLETLLYKPVDRVTRSTLV 656
Cdd:cd00160   77 IGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESECGR--------LKLESLLLKPVQRLTKYPLL 148

                        170       180       190
                 ....*....|....*....|....*....|...
gi 82546845  657 LHDLLKHTPASHPDHPLLQDALRISQNFLSSIN 689
Cdd:cd00160  149 LKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845     502 VLSGILASEETYLSHLEALL-LPMKPLKAaattSQPVLTSQQIETIFFKVPELYEIHKEFYDGLFPRVQQWSH-QQRVGD 579
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVeVFLKPLKK----ELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDsVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845     580 LFQKLASQLGVYRAFVDNYGVAMEMAEKCcQANAQFAEISENLRARSNKDAKDpttknsLETLLYKPVDRVTRSTLVLHD 659
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLT------LESLLLKPVQRLTKYPLLLKE 149

                           170       180       190
                    ....*....|....*....|....*....|.
gi 82546845     660 LLKHTPASHPDHPLLQDALRISQNFLSSINE 690
Cdd:smart00325  150 LLKHTPEDHEDREDLKKALKAIKELANQVNE 180

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 82546845 1008 FGVKIAVVTKRERSK--VPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEM-DVNAIAGTL 1084
Cdd:cd04379    1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYpDINVITGVL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845 1085 KLYFRELPEPLFTDEFYPNFAEGIAL---SDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLAT 1161
Cdd:cd04379   81 KDYLRELPEPLITPQLYEMVLEALAValpNDVQTNTHLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 82546845 1162 VFGPTLLRPSEKESKLPANPSQpiTMTDSWSLEVMSQVQVLLYFLQL 1208
Cdd:cd04379  161 CFGPVLMFCSQEFSRYGISPTS--KMAAVSTVDFKQHIEVLHYLLQI 205

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 82546845 1023 VPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFdVNNKDVSvMMSEMDVNAIAGTLKLYFRELPEPLFTDEFYP 1102
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKF-LRGKTVP-NLSKVDIHVICGCLKDFLRSLKEPLITFALWK 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845 1103 NFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAvNKMSLHNLATVFGPTLLrpsekeSKLPANPS 1182
Cdd:cd04382   95 EFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFGPTIV------GYSVPNPD 167

                        170       180
                 ....*....|....*....|
gi 82546845 1183 QPITMTDswsleVMSQVQVL 1202
Cdd:cd04382  168 PMTILQD-----TVRQPRVV 182

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 82546845 1007 VFGVKIAVVTKRERSKVPYIVRQCVEEIERRGMEEvGIYRVSGVATDIQALKAAFDVNN-KDVSVMMSEMDVNAIAGTLK 1085
Cdd:cd04384    2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVD-GIYRLSGIASNIQRLRHEFDSEQiPDLTKDVYIQDIHSVSSLCK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845 1086 LYFRELPEPLFTDEFYPNFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKEAVNKMSLHNLATVFGP 1165
Cdd:cd04384   81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                        170
                 ....*....|
gi 82546845 1166 TLLRPSEKES 1175
Cdd:cd04384  161 NLLRSKQIES 170

Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 22 and 9. BCR is a GTPase-activating protein (GAP) for RAC1 (primarily) and CDC42. The Dbl region of BCR has the most RhoGEF activity for Cdc42, and less activity towards Rac and Rho. Since BCR possesses both GAP and GEF activities, it may function to temporally regulate the activity of these GTPases. It also displays serine/threonine kinase activity. The BCR protein contains multiple domains including an N-terminal kinase domain, a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. This hierarchy is composed of arthropod BCRs. 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 82546845  707 RQLLKDSFMVELVEGARKLRHVFLFTDLLLCTKLKKqSGGKTQQYDCKWYIPLTDLSfqMVDELEAVPNIPLVPDEEldA 786
Cdd:cd13368   22 RRLVKNSFIVELADGHRKLRHLFLFNDVIACAKYKS-SGRTRITFELKWFIPLNDVT--ILEEEAPAPKESSPPNIE--Q 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82546845  787 LKIKISQIKNDIQREKRANkgSKATERLKKKLSEQESLLLLMSPSMAFRVHSRNGKSYTFLISSDYERAEWRENIREQQK 866
Cdd:cd13368   97 LKSNACQVRDQLADRSRAS--TSGSDKIRKKLADLEAQLVLASPNLVFRIGNKNNKTYTFFLSSEFERTQWIEAILTLQQ 174

                 ..
gi 82546845  867 KC 868
Cdd:cd13368  175 TC 176

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 82546845 1008 FGVKIAVVTKRERS----KVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFdvnNKDVSVMMSEMDVNAIAGT 1083
Cdd:cd04381    1 FGASLSLAVERSRChdgiDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAY---NRRESPNLEEYEPPTVASL 77