Rho (Ras homology) subfamily of Ras-like small GTPases; Members of this subfamily of Ras-like small GTPases include Cdc42 and Rac, as well as Rho isoforms.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880     16 LVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFDIS 95
Cdd:smart00174   1 LVVVGDGAVGKTCLLIVYTTNAFPEDYVPTVFENYSADVEVDGKPVELGLWDTAGQEDYDRLRPLSYPDTDVFLICFSVD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880     96 RPETMDSALKKWRTEILDYCPSTRVLLIGCKTDLRTDLSTLMELSHQKQAPISYEQGCAIAKQLGAEIYLEGSAFTSEtS 175
Cdd:smart00174  81 SPASFENVKEKWYPEVKHFCPNVPIILVGTKLDLRNDKSTLEELSKKKQEPVTYEQGQALAKRIGAVKYLECSALTQE-G 159

                          170
                   ....*....|....*
gi 27369880    176 IHSIFRTASMVCLNK 190
Cdd:smart00174 160 VREVFEEAIRAALNK 174

small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this model include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.This model recognizes a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880    15 KLVLVGDVQCGKTAMLQVLAK-DCYPETYVPTVFENYTACLETEE-QRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCF 92
Cdd:TIGR00231   3 KIVIVGHPNVGKSTLLNSLLGnKGSITEYYPGTTRNYVTTVIEEDgKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVF 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 27369880    93 DI-SRPETMDSALKKWRTEILDYCPS-TRVLLIGCKTDLRT 131
Cdd:TIGR00231  83 DIvILVLDVEEILEKQTKEIIHHADSgVPIILVGNKIDLKD 123

Rho family GTPase subfamily Rnd includes Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8; The Rnd subfamily contains Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8. These novel Rho family proteins have substantial structural differences compared to other Rho members, including N- and C-terminal extensions relative to other Rhos. Rnd3/RhoE is farnesylated at the C-terminal prenylation site, unlike most other Rho proteins that are geranylgeranylated. In addition, Rnd members are unable to hydrolyze GTP and are resistant to GAP activity. They are believed to exist only in the GTP-bound conformation, and are antagonists of RhoA activity. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  13 RCKLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCF 92
Cdd:cd04131   1 RCKIVLVGDSQCGKTALLQVFAKDSFPENYVPTVFENYTASFEVDKQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLICF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  93 DISRPETMDSALKKWRTEILDYCPSTRVLLIGCKTDLRTDLSTLMELSHQKQAPISYEQGCAIAKQLGAEIYLEGSAFTS 172
Cdd:cd04131  81 DISRPETLDSVLKKWKGEVREFCPNTPVLLVGCKSDLRTDLSTLTELSNKRQIPVSHEQGRNLAKQIGAAAYVECSAKTS 160

                       170
                ....*....|....*.
gi 27369880 173 ETSIHSIFRTASMVCL 188
Cdd:cd04131 161 ENSVRDVFEMATLACL 176

Rnd3/RhoE/Rho8 GTPases; Rnd3/RhoE/Rho8 subfamily. Rnd3/RhoE/Rho8 is a member of the novel Rho subfamily Rnd, together with Rnd1/Rho6 and Rnd2/Rho7. Rnd3/RhoE is known to bind the serine-threonine kinase ROCK I. Unphosphorylated Rnd3/RhoE associates primarily with membranes, but ROCK I-phosphorylated Rnd3/RhoE localizes in the cytosol. Phosphorylation of Rnd3/RhoE correlates with its activity in disrupting RhoA-induced stress fibers and inhibiting Ras-induced fibroblast transformation. In cells that lack stress fibers, such as macrophages and monocytes, Rnd3/RhoE induces a redistribution of actin, causing morphological changes in the cell. In addition, Rnd3/RhoE has been shown to inhibit cell cycle progression in G1 phase at a point upstream of the pRb family pocket protein checkpoint. Rnd3/RhoE has also been shown to inhibit Ras- and Raf-induced fibroblast transformation. In mammary epithelial tumor cells, Rnd3/RhoE regulates the assembly of the apical junction complex and tight junction formation. Rnd3/RhoE is underexpressed in prostate cancer cells both in vitro and in vivo; re-expression of Rnd3/RhoE suppresses cell cycle progression and increases apoptosis, suggesting it may play a role in tumor suppression. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  12 VRCKLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLC 91
Cdd:cd04172   4 VKCKIVVVGDSQCGKTALLHVFAKDCFPENYVPTVFENYTASFEIDTQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLIC 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  92 FDISRPETMDSALKKWRTEILDYCPSTRVLLIGCKTDLRTDLSTLMELSHQKQAPISYEQGCAIAKQLGAEIYLEGSAFT 171
Cdd:cd04172  84 FDISRPETLDSVLKKWKGEIQEFCPNTKMLLVGCKSDLRTDVSTLVELSNHRQTPVSYDQGANMAKQIGAATYIECSALQ 163

                       170
                ....*....|....*....
gi 27369880 172 SETSIHSIFRTASMVCLNK 190
Cdd:cd04172 164 SENSVRDIFHVATLACVNK 182

Ras homology family (Rho) of small guanosine triphosphatases (GTPases); Members of the Rho (Ras homology) family include RhoA, Cdc42, Rac, Rnd, Wrch1, RhoBTB, and Rop. There are 22 human Rho family members identified currently. These proteins are all involved in the reorganization of the actin cytoskeleton in response to external stimuli. They also have roles in cell transformation by Ras in cytokinesis, in focal adhesion formation and in the stimulation of stress-activated kinase. These various functions are controlled through distinct effector proteins and mediated through a GTP-binding/GTPase cycle involving three classes of regulating proteins: GAPs (GTPase-activating proteins), GEFs (guanine nucleotide exchange factors), and GDIs (guanine nucleotide dissociation inhibitors). Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Since crystal structures often lack C-terminal residues, this feature is not available for annotation in many of the CDs in the hierarchy.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  14 CKLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFD 93
Cdd:cd00157   1 IKIVVVGDGAVGKTCLLISYTTNKFPTEYVPTVFDNYSANVTVDGKQVNLGLWDTAGQEEYDRLRPLSYPQTDVFLLCFS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  94 ISRPETMDSALKKWRTEILDYCPSTRVLLIGCKTDLRTDLSTLMELShQKQAPISYEQGCAIAKQLGAEIYLEGSAFTSE 173
Cdd:cd00157  81 VDSPSSFENVKTKWYPEIKHYCPNVPIILVGTKIDLRDDGNTLKKLE-KKQKPITPEEGEKLAKEIGAVKYMECSALTQE 159

                       170
                ....*....|
gi 27369880 174 tSIHSIFRTA 183
Cdd:cd00157 160 -GLKEVFDEA 168

Ras homology family 4 (Rho4) of small guanosine triphosphatases (GTPases)-like; Rho4 is a GTPase that controls septum degradation by regulating secretion of Eng1 or Agn1 during cytokinesis. Rho4 also plays a role in cell morphogenesis. Rho4 regulates septation and cell morphology by controlling the actin cytoskeleton and cytoplasmic microtubules. The localization of Rho4 is modulated by Rdi1, which may function as a GDI, and by Rga9, which is believed to function as a GAP. In S. pombe, both Rho4 deletion and Rho4 overexpression result in a defective cell wall, suggesting a role for Rho4 in maintaining cell wall integrity. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  15 KLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTACLETEEQR-VELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFD 93
Cdd:cd04132   5 KIVVVGDGGCGKTCLLMVYAQGSFPEEYVPTVFENYVTTLQVPNGKiIELALWDTAGQEDYDRLRPLSYPDVDVILICYS 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  94 ISRPETMDSALKKWRTEILDYCPSTRVLLIGCKTDLRTDLSTLMELSHQKQAPISYEQGCAIAKQLGAEIYLEGSAFTSE 173
Cdd:cd04132  85 VDNPTSLDNVEDKWYPEVNHFCPGTPIVLVGLKTDLRKDKNSVSKLRAQGLEPVTPEQGESVAKSIGAVAYIECSAKLME 164

                       170       180
                ....*....|....*....|
gi 27369880 174 tSIHSIFRTASMVCLNKSSP 193
Cdd:cd04132 165 -NVDEVFDAAINVALSKSGR 183

Ras homolog family, member G (RhoG) of small guanosine triphosphatases (GTPases); RhoG is a GTPase with high sequence similarity to members of the Rac subfamily, including the regions involved in effector recognition and binding. However, RhoG does not bind to known Rac1 and Cdc42 effectors, including proteins containing a Cdc42/Rac interacting binding (CRIB) motif. Instead, RhoG interacts directly with Elmo, an upstream regulator of Rac1, in a GTP-dependent manner and forms a ternary complex with Dock180 to induce activation of Rac1. The RhoG-Elmo-Dock180 pathway is required for activation of Rac1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor. Thus RhoG activates Rac1 through Elmo and Dock180 to control cell morphology. RhoG has also been shown to play a role in caveolar trafficking and has a novel role in signaling the neutrophil respiratory burst stimulated by G protein-coupled receptor (GPCR) agonists. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  15 KLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFDI 94
Cdd:cd01875   5 KCVVVGDGAVGKTCLLICYTTNAFPKEYIPTVFDNYSAQTAVDGRTVSLNLWDTAGQEEYDRLRTLSYPQTNVFIICFSI 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  95 SRPETMDSALKKWRTEILDYCPSTRVLLIGCKTDLRTDLSTLMELSHQKQAPISYEQGCAIAKQLGAEIYLEGSAFTSEt 174
Cdd:cd01875  85 ASPSSYENVRHKWHPEVCHHCPNVPILLVGTKKDLRNDADTLKKLKEQGQAPITPQQGGALAKQIHAVKYLECSALNQD- 163

                       170       180
                ....*....|....*....|...
gi 27369880 175 SIHSIFRTASMVCLNkssPVPPK 197
Cdd:cd01875 164 GVKEVFAEAVRAVLN---PTPIK 183

Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)-like consists of Rac1, Rac2 and Rac3; The Rac1-like subfamily consists of Rac1, Rac2, and Rac3 proteins, plus the splice variant Rac1b that contains a 19-residue insertion near switch II relative to Rac1. While Rac1 is ubiquitously expressed, Rac2 and Rac3 are largely restricted to hematopoietic and neural tissues respectively. Rac1 stimulates the formation of actin lamellipodia and membrane ruffles. It also plays a role in cell-matrix adhesion and cell anoikis. In intestinal epithelial cells, Rac1 is an important regulator of migration and mediates apoptosis. Rac1 is also essential for RhoA-regulated actin stress fiber and focal adhesion complex formation. In leukocytes, Rac1 and Rac2 have distinct roles in regulating cell morphology, migration, and invasion, but are not essential for macrophage migration or chemotaxis. Rac3 has biochemical properties that are closely related to Rac1, such as effector interaction, nucleotide binding, and hydrolysis; Rac2 has a slower nucleotide association and is more efficiently activated by the RacGEF Tiam1. Both Rac1 and Rac3 have been implicated in the regulation of cell migration and invasion in human metastatic breast cancer. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  15 KLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFDI 94
Cdd:cd01871   3 KCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTDVFLICFSL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  95 SRPETMDSALKKWRTEILDYCPSTRVLLIGCKTDLRTDLSTLMELSHQKQAPISYEQGCAIAKQLGAEIYLEGSAFTsET 174
Cdd:cd01871  83 VSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLRDDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALT-QR 161

                ....*....
gi 27369880 175 SIHSIFRTA 183
Cdd:cd01871 162 GLKTVFDEA 170

Rho GTPase TC10 (Tc10); TC10 is a Rho family protein that has been shown to induce microspike formation and neurite outgrowth in vitro. Its expression changes dramatically after peripheral nerve injury, suggesting an important role in promoting axonal outgrowth and regeneration. TC10 regulates translocation of insulin-stimulated GLUT4 in adipocytes and has also been shown to bind directly to Golgi COPI coat proteins. GTP-bound TC10 in vitro can bind numerous potential effectors. Depending on its subcellular localization and distinct functional domains, TC10 can differentially regulate two types of filamentous actin in adipocytes. TC10 mRNAs are highly expressed in three types of mouse muscle tissues: leg skeletal muscle, cardiac muscle, and uterus; they were also present in brain, with higher levels in adults than in newborns. TC10 has also been shown to play a role in regulating the expression of cystic fibrosis transmembrane conductance regulator (CFTR) through interactions with CFTR-associated ligand (CAL). The GTP-bound form of TC10 directs the trafficking of CFTR from the juxtanuclear region to the secretory pathway toward the plasma membrane, away from CAL-mediated DFTR degradation in the lysosome. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  15 KLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFDI 94
Cdd:cd04135   2 KCVVVGDGAVGKTCLLMSYANDAFPEEYVPTVFDHYAVSVTVGGKQYLLGLYDTAGQEDYDRLRPLSYPMTDVFLICFSV 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  95 SRPETMDSALKKWRTEILDYCPSTRVLLIGCKTDLRTDLSTLMELSHQKQAPISYEQGCAIAKQLGAEIYLEGSAFTsET 174
Cdd:cd04135  82 VNPASFQNVKEEWVPELKEYAPNVPYLLIGTQIDLRDDPKTLARLNDMKEKPITVEQGQKLAKEIGACCYVECSALT-QK 160

                       170
                ....*....|....
gi 27369880 175 SIHSIFRTASMVCL 188
Cdd:cd04135 161 GLKTVFDEAIIAIL 174

Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See pfam00009 pfam00025, pfam00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880    15 KLVLVGDVQCGKTAMLQVLAKDCYPETYVPTV-FENYTACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFD 93
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIgVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880    94 ISRPETMDSAlKKWRTEILDYCP-STRVLLIGCKTDLRTdlstlmelshqkQAPISYEQGCAIAKQLGAeIYLEGSAFTS 172
Cdd:pfam00071  81 ITSRDSFENV-KKWVEEILRHADeNVPIVLVGNKCDLED------------QRVVSTEEGEALAKELGL-PFMETSAKTN 146

                         170
                  ....*....|.
gi 27369880   173 EtSIHSIFRTA 183
Cdd:pfam00071 147 E-NVEEAFEEL 156

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  14 CKLVLVGDVQCGKTAMLQVLAKDCYPETYVPTV---FENYTacLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLL 90
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIgvdFKSKT--IEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  91 CFDISRPETMDSaLKKWRTEILDYCPSTRV-LLIGCKTDLRtdlstlmelsHQKQapISYEQGCAIAKQLGAEiYLEGSA 169
Cdd:cd00154  79 VYDVTNRESFEN-LDKWLNELKEYAPPNIPiILVGNKSDLE----------DERQ--VSTEEAQQFAKENGLL-FFETSA 144

                       170
                ....*....|....*
gi 27369880 170 FTSEtSIHSIFRTAS 184
Cdd:cd00154 145 KTGE-NVDEAFESLA 158

RhoBTB protein is an atypical member of the Rho family of small GTPases; Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila, and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase domain, a proline rich region, a tandem of two BTB (Broad-Complex, Tramtrack, and Bric a brac) domains, and a C-terminal region of unknown function. RhoBTB proteins may act as docking points for multiple components participating in signal transduction cascades. RhoBTB genes appeared upregulated in some cancer cell lines, suggesting a participation of RhoBTB proteins in the pathogenesis of particular tumors. Note that the Dictyostelium RacA GTPase domain is more closely related to Rac proteins than to RhoBTB proteins, where RacA actually belongs. Thus, the Dictyostelium RacA is not included here. Most Rho proteins contain a lipid modification site at the C-terminus; however, RhoBTB is one of few Rho subfamilies that lack this feature.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  15 KLVLVGDVQCGKTAMlqVLAKDCYPE--------TYVPTVF--ENYTACLETEEQR--------VELSLWDTSGSpyYDN 76
Cdd:cd01873   4 KCVVVGDNAVGKTRL--ICARACNKTltqyqllaTHVPTVWaiDQYRVCQEVLERSrdvvdgvsVSLRLWDTFGD--HDK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  77 VRPLCYSDSDAVLLCFDISRPETMDSALKKWRTEILDYCPSTRVLLIGCKTDLR-TDLSTLMELSHQKQAPISY------ 149
Cdd:cd01873  80 DRRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRyADLDEVNRARRPLARPIKNadilpp 159

                       170       180       190
                ....*....|....*....|....*....|....
gi 27369880 150 EQGCAIAKQLGAEiYLEGSAFTSEtSIHSIFRTA 183
Cdd:cd01873 160 ETGRAVAKELGIP-YYETSVVTQF-GVKDVFDNA 191

small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this model include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.This model recognizes a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880    15 KLVLVGDVQCGKTAMLQVLAK-DCYPETYVPTVFENYTACLETEE-QRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCF 92
Cdd:TIGR00231   3 KIVIVGHPNVGKSTLLNSLLGnKGSITEYYPGTTRNYVTTVIEEDgKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVF 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 27369880    93 DI-SRPETMDSALKKWRTEILDYCPS-TRVLLIGCKTDLRT 131
Cdd:TIGR00231  83 DIvILVLDVEEILEKQTKEIIHHADSgVPIILVGNKIDLKD 123

Rab GTPase family 19 (Rab19); Rab19 subfamily. Rab19 proteins are associated with Golgi stacks. Similarity analysis indicated that Rab41 is closely related to Rab19. However, the function of these Rabs is not yet characterized. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  15 KLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTA-CLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFD 93
Cdd:cd01864   5 KIILIGDSNVGKTCVVQRFKSGTFSERQGNTIGVDFTMkTLEIQGKRVKLQIWDTAGQERFRTITQSYYRSANGAIIAYD 84

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27369880  94 ISRPETMDSaLKKWRTEILDYCPSTRV-LLIGCKTDLrtdlstlmelshQKQAPISYEQGCAIAKQLGAEIYLEGSA 169
Cdd:cd01864  85 ITRRSSFES-VPHWIEEVEKYGASNVVlLLIGNKCDL------------EEQREVLFEEACTLAEHYGILAVLETSA 148

Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways through the Golgi and from endosomes to the Golgi. Rab6A of mammals is implicated in retrograde transport through the Golgi stack, and is also required for a slow, COPI-independent, retrograde transport pathway from the Golgi to the endoplasmic reticulum (ER). This pathway may allow Golgi residents to be recycled through the ER for scrutiny by ER quality-control systems. Yeast Ypt6p, the homolog of the mammalian Rab6 GTPase, is not essential for cell viability. Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER trafficking. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  14 CKLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENY-TACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCF 92
Cdd:cd01861   1 HKLVFLGDQSVGKTSIITRFMYDTFDNQYQATIGIDFlSKTMYVDDKTVRLQLWDTAGQERFRSLIPSYIRDSSVAVVVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  93 DISRPETMDSaLKKWRTEILDYCPS-TRVLLIGCKTDlrtdlstlmeLSHQKQapISYEQGCAIAKQLGAeIYLEGSAFT 171
Cdd:cd01861  81 DITNRQSFDN-TDKWIDDVRDERGNdVIIVLVGNKTD----------LSDKRQ--VSTEEGEKKAKENNA-MFIETSAKA 146

                       170
                ....*....|
gi 27369880 172 SeTSIHSIFR 181
Cdd:cd01861 147 G-HNVKQLFK 155

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  15 KLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENY-TACLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFD 93
Cdd:cd01865   3 KLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFkVKTVYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILMYD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  94 ISRPETMDsALKKWRTEILDYC-PSTRVLLIGCKTDLrtdlstlmelshQKQAPISYEQGCAIAKQLGAEiYLEGSAfTS 172
Cdd:cd01865  83 ITNEESFN-AVQDWSTQIKTYSwDNAQVILVGNKCDM------------EDERVVSAERGRQLADQLGFE-FFEASA-KE 147

                       170
                ....*....|....*.
gi 27369880 173 ETSIHSIF-RTASMVC 187
Cdd:cd01865 148 NINVKQVFeRLVDIIC 163

Rab GTPase families 8, 10, 13 (Rab8, Rab10, Rab13); Rab8/Sec4/Ypt2 are known or suspected to be involved in post-Golgi transport to the plasma membrane. It is likely that these Rabs have functions that are specific to the mammalian lineage and have no orthologs in plants. Rab8 modulates polarized membrane transport through reorganization of actin and microtubules, induces the formation of new surface extensions, and has an important role in directed membrane transport to cell surfaces. The Ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the Ypt/Rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian Rab8. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  15 KLVLVGDVQCGKTAMLQVLAKDCYPETYVPTV---FENYTacLETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLC 91
Cdd:cd01867   5 KLLLIGDSGVGKSCLLLRFSEDSFNPSFISTIgidFKIRT--IELDGKKIKLQIWDTAGQERFRTITTSYYRGAMGIILV 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  92 FDISRPETMDSaLKKWRTEILDYC-PSTRVLLIGCKTDlrtdlstlmeLSHQKQapISYEQGCAIAKQLGAEiYLEGSAF 170
Cdd:cd01867  83 YDITDEKSFEN-IKNWMRNIDEHAsEDVERMLVGNKCD----------MEEKRV--VSKEEGEALAREYGIK-FLETSAK 148

                       170
                ....*....|..
gi 27369880 171 TSeTSIHSIFRT 182
Cdd:cd01867 149 AN-INVEEAFLT 159

Rab GTPase family 2 (Rab2); Rab2 is localized on cis-Golgi membranes and interacts with Golgi matrix proteins. Rab2 is also implicated in the maturation of vesicular tubular clusters (VTCs), which are microtubule-associated intermediates in transport between the ER and Golgi apparatus. In plants, Rab2 regulates vesicle trafficking between the ER and the Golgi bodies and is important to pollen tube growth. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369880  15 KLVLVGDVQCGKTAMLQVLAKDCYPETYVPTVFENYTACL-ETEEQRVELSLWDTSGSPYYDNVRPLCYSDSDAVLLCFD 93
Cdd:cd01866   6 KYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMiTIDGKQIKLQIWDTAGQESFRSITRSYYRGAAGALLVYD 85