Ras homology family A (RhoA)-like includes RhoA, RhoB and RhoC; The RhoA subfamily consists of RhoA, RhoB, and RhoC. RhoA promotes the formation of stress fibers and focal adhesions, regulating cell shape, attachment, and motility. RhoA can bind to multiple effector proteins, thereby triggering different downstream responses. In many cell types, RhoA mediates local assembly of the contractile ring, which is necessary for cytokinesis. RhoA is vital for muscle contraction; in vascular smooth muscle cells, RhoA plays a key role in cell contraction, differentiation, migration, and proliferation. RhoA activities appear to be elaborately regulated in a time- and space-dependent manner to control cytoskeletal changes. 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. RhoA and RhoC are observed only in geranylgeranylated forms; however, RhoB can be present in palmitoylated, farnesylated, and geranylgeranylated forms. RhoA and RhoC are highly relevant for tumor progression and invasiveness; however, RhoB has recently been suggested to be a tumor suppressor. 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 19549710   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd01870   1 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  85 SVDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKMKQEPVKPQEGRAMAEKINAFAYLECSAKSK 164
Cdd:cd01870  81 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTIRELAKMKQEPVKPEEGRAMAEKIGAFGYLECSAKTK 160

                       170
                ....*....|....*
gi 19549710 165 EGVRDVFETATRAAL 179
Cdd:cd01870 161 EGVREVFEMATRAAL 175

Ras homology family A (RhoA)-like includes RhoA, RhoB and RhoC; The RhoA subfamily consists of RhoA, RhoB, and RhoC. RhoA promotes the formation of stress fibers and focal adhesions, regulating cell shape, attachment, and motility. RhoA can bind to multiple effector proteins, thereby triggering different downstream responses. In many cell types, RhoA mediates local assembly of the contractile ring, which is necessary for cytokinesis. RhoA is vital for muscle contraction; in vascular smooth muscle cells, RhoA plays a key role in cell contraction, differentiation, migration, and proliferation. RhoA activities appear to be elaborately regulated in a time- and space-dependent manner to control cytoskeletal changes. 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. RhoA and RhoC are observed only in geranylgeranylated forms; however, RhoB can be present in palmitoylated, farnesylated, and geranylgeranylated forms. RhoA and RhoC are highly relevant for tumor progression and invasiveness; however, RhoB has recently been suggested to be a tumor suppressor. 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 19549710   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd01870   1 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  85 SVDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKMKQEPVKPQEGRAMAEKINAFAYLECSAKSK 164
Cdd:cd01870  81 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTIRELAKMKQEPVKPEEGRAMAEKIGAFGYLECSAKTK 160

                       170
                ....*....|....*
gi 19549710 165 EGVRDVFETATRAAL 179
Cdd:cd01870 161 EGVREVFEMATRAAL 175

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 19549710     7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTV-FENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFS 85
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIgVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710    86 VDSPDSLENIPeKWTPEVKHFCP-NVPIILVGNKKDLRNdpntirdlakmkQEPVKPQEGRAMAEKINAFaYLECSAKSK 164
Cdd:pfam00071  81 ITSRDSFENVK-KWVEEILRHADeNVPIVLVGNKCDLED------------QRVVSTEEGEALAKELGLP-FMETSAKTN 146

                         170
                  ....*....|....*.
gi 19549710   165 EGVRDVFETATRAALQ 180
Cdd:pfam00071 147 ENVEEAFEELAREILK 162

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710   4 IRKKLVIVGDGACGKTCLLIVFSKDQF-PEVYVPTV-FENYVADIEVDGKQVELALWDTAGQEDYDRLRPL---SYPDTD 78
Cdd:COG1100   2 GEKKIVVVGTGGVGKTSLVNRLVGDIFsLEKYLSTNgVTIDKKELKLDGLDVDLVIWDTPGQDEFRETRQFyarQLTGAS 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  79 VILMCFSVDSPDSLENIPEkWTPEVKHFCPNVPIILVGNKKDLRNDpntirdlakmkQEPVKPQEGRAMAEKINAFAYLE 158
Cdd:COG1100  82 LYLFVVDGTREETLQSLYE-LLESLRRLGKKSPIILVLNKIDLYDE-----------EEIEDEERLKEALSEDNIVEVVA 149

                       170       180
                ....*....|....*....|..
gi 19549710 159 CSAKSKEGVRDVFETATRAALQ 180
Cdd:COG1100 150 TSAKTGEGVEELFAALAEILRG 171

Ras homology family A (RhoA)-like includes RhoA, RhoB and RhoC; The RhoA subfamily consists of RhoA, RhoB, and RhoC. RhoA promotes the formation of stress fibers and focal adhesions, regulating cell shape, attachment, and motility. RhoA can bind to multiple effector proteins, thereby triggering different downstream responses. In many cell types, RhoA mediates local assembly of the contractile ring, which is necessary for cytokinesis. RhoA is vital for muscle contraction; in vascular smooth muscle cells, RhoA plays a key role in cell contraction, differentiation, migration, and proliferation. RhoA activities appear to be elaborately regulated in a time- and space-dependent manner to control cytoskeletal changes. 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. RhoA and RhoC are observed only in geranylgeranylated forms; however, RhoB can be present in palmitoylated, farnesylated, and geranylgeranylated forms. RhoA and RhoC are highly relevant for tumor progression and invasiveness; however, RhoB has recently been suggested to be a tumor suppressor. 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 19549710   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd01870   1 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  85 SVDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKMKQEPVKPQEGRAMAEKINAFAYLECSAKSK 164
Cdd:cd01870  81 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTIRELAKMKQEPVKPEEGRAMAEKIGAFGYLECSAKTK 160

                       170
                ....*....|....*
gi 19549710 165 EGVRDVFETATRAAL 179
Cdd:cd01870 161 EGVREVFEMATRAAL 175

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 19549710   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSV 86
Cdd:cd00157   2 KIVVVGDGAVGKTCLLISYTTNKFPTEYVPTVFDNYSANVTVDGKQVNLGLWDTAGQEEYDRLRPLSYPQTDVFLLCFSV 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  87 DSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKmKQEPVKPQEGRAMAEKINAFAYLECSAKSKEG 166
Cdd:cd00157  82 DSPSSFENVKTKWYPEIKHYCPNVPIILVGTKIDLRDDGNTLKKLEK-KQKPITPEEGEKLAKEIGAVKYMECSALTQEG 160

                       170
                ....*....|.
gi 19549710 167 VRDVFETATRA 177
Cdd:cd00157 161 LKEVFDEAIRA 171

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 19549710   1 MTTIrkKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVI 80
Cdd:cd01875   1 MQSI--KCVVVGDGAVGKTCLLICYTTNAFPKEYIPTVFDNYSAQTAVDGRTVSLNLWDTAGQEEYDRLRTLSYPQTNVF 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  81 LMCFSVDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKMKQEPVKPQEGRAMAEKINAFAYLECS 160
Cdd:cd01875  79 IICFSIASPSSYENVRHKWHPEVCHHCPNVPILLVGTKKDLRNDADTLKKLKEQGQAPITPQQGGALAKQIHAVKYLECS 158

                       170       180       190
                ....*....|....*....|....*....|...
gi 19549710 161 AKSKEGVRDVFETATRAALQVKKRKKTR-CLLL 192
Cdd:cd01875 159 ALNQDGVKEVFAEAVRAVLNPTPIKDTKsCVLL 191

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 19549710   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd04131   1 RCKIVLVGDSQCGKTALLQVFAKDSFPENYVPTVFENYTASFEVDKQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLICF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  85 SVDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKMKQEPVKPQEGRAMAEKINAFAYLECSAKSK 164
Cdd:cd04131  81 DISRPETLDSVLKKWKGEVREFCPNTPVLLVGCKSDLRTDLSTLTELSNKRQIPVSHEQGRNLAKQIGAAAYVECSAKTS 160

                       170
                ....*....|....*.
gi 19549710 165 E-GVRDVFETATRAAL 179
Cdd:cd04131 161 EnSVRDVFEMATLACL 176

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 19549710     7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTV-FENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFS 85
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIgVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710    86 VDSPDSLENIPeKWTPEVKHFCP-NVPIILVGNKKDLRNdpntirdlakmkQEPVKPQEGRAMAEKINAFaYLECSAKSK 164
Cdd:pfam00071  81 ITSRDSFENVK-KWVEEILRHADeNVPIVLVGNKCDLED------------QRVVSTEEGEALAKELGLP-FMETSAKTN 146

                         170
                  ....*....|....*.
gi 19549710   165 EGVRDVFETATRAALQ 180
Cdd:pfam00071 147 ENVEEAFEELAREILK 162

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 19549710   3 TIRKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILM 82
Cdd:cd04172   3 NVKCKIVVVGDSQCGKTALLHVFAKDCFPENYVPTVFENYTASFEIDTQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLI 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  83 CFSVDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKMKQEPVKPQEGRAMAEKINAFAYLECSA- 161
Cdd:cd04172  83 CFDISRPETLDSVLKKWKGEIQEFCPNTKMLLVGCKSDLRTDVSTLVELSNHRQTPVSYDQGANMAKQIGAATYIECSAl 162

                       170
                ....*....|....*...
gi 19549710 162 KSKEGVRDVFETATRAAL 179
Cdd:cd04172 163 QSENSVRDIFHVATLACV 180

Rnd2/Rho7 GTPases; Rnd2/Rho7 is a member of the novel Rho subfamily Rnd, together with Rnd1/Rho6 and Rnd3/RhoE/Rho8. Rnd2/Rho7 is transiently expressed in radially migrating cells in the brain while they are within the subventricular zone of the hippocampus and cerebral cortex. These migrating cells typically develop into pyramidal neurons. Cells that exogenously expressed Rnd2/Rho7 failed to migrate to upper layers of the brain, suggesting that Rnd2/Rho7 plays a role in the radial migration and morphological changes of developing pyramidal neurons, and that Rnd2/Rho7 degradation is necessary for proper cellular migration. The Rnd2/Rho7 GEF Rapostlin is found primarily in the brain and together with Rnd2/Rho7 induces dendrite branching. Unlike Rnd1/Rho6 and Rnd3/RhoE/Rho8, which are RhoA antagonists, Rnd2/Rho7 binds the GEF Pragmin and significantly stimulates RhoA activity and Rho-A mediated cell contraction. Rnd2/Rho7 is also found to be expressed in spermatocytes and early spermatids, with male-germ-cell Rac GTPase-activating protein (MgcRacGAP), where it localizes to the Golgi-derived pro-acrosomal vesicle. 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 19549710   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd04173   1 RCKIVVVGDTQCGKTALLHVFAKDNYPESYVPTVFENYTASFEIDKHRIELNMWDTSGSSYYDNVRPLAYPDSDAVLICF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  85 SVDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKMKQEPVKPQEGRAMAEKINAFAYLECSAKSK 164
Cdd:cd04173  81 DISRPETLDSVLKKWQGETQEFCPNAKLVLVGCKLDMRTDLSTLRELSKQRLIPVTHEQGSLLARQLGAVAYVECSSRMS 160

                       170
                ....*....|....*.
gi 19549710 165 E-GVRDVFETATRAAL 179
Cdd:cd04173 161 EnSVRDVFHVTTLASV 176

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 19549710   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSV 86
Cdd:cd04135   2 KCVVVGDGAVGKTCLLMSYANDAFPEEYVPTVFDHYAVSVTVGGKQYLLGLYDTAGQEDYDRLRPLSYPMTDVFLICFSV 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  87 DSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKMKQEPVKPQEGRAMAEKINAFAYLECSAKSKEG 166
Cdd:cd04135  82 VNPASFQNVKEEWVPELKEYAPNVPYLLIGTQIDLRDDPKTLARLNDMKEKPITVEQGQKLAKEIGACCYVECSALTQKG 161

                       170
                ....*....|...
gi 19549710 167 VRDVFETATRAAL 179
Cdd:cd04135 162 LKTVFDEAIIAIL 174

Rho-related protein from plants (Rop)-like; The Rop (Rho-related protein from plants) subfamily plays a role in diverse cellular processes, including cytoskeletal organization, pollen and vegetative cell growth, hormone responses, stress responses, and pathogen resistance. Rops are able to regulate several downstream pathways to amplify a specific signal by acting as master switches early in the signaling cascade. They transmit a variety of extracellular and intracellular signals. Rops are involved in establishing cell polarity in root-hair development, root-hair elongation, pollen-tube growth, cell-shape formation, responses to hormones such as abscisic acid (ABA) and auxin, responses to abiotic stresses such as oxygen deprivation, and disease resistance and disease susceptibility. An individual Rop can have a unique function or an overlapping function shared with other Rop proteins; in addition, a given Rop-regulated function can be controlled by one or multiple Rop proteins. For example, Rop1, Rop3, and Rop5 are all involved in pollen-tube growth; Rop2 plays a role in response to low-oxygen environments, cell-morphology, and root-hair development; root-hair development is also regulated by Rop4 and Rop6; Rop6 is also responsible for ABA response, and ABA response is also regulated by Rop10. Plants retain some of the regulatory mechanisms that are shared by other members of the Rho family, but have also developed a number of unique modes for regulating Rops. Unique RhoGEFs have been identified that are exclusively active toward Rop proteins, such as those containing the domain PRONE (plant-specific Rop nucleotide exchanger). 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 19549710   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSV 86
Cdd:cd04133   3 KCVTVGDGAVGKTCMLISYTSNTFPTDYVPTVFDNFSANVVVDGNTVNLGLWDTAGQEDYNRLRPLSYRGADVFLLAFSL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  87 DSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDPNTIRDLAKMKqePVKPQEGRAMAEKINAFAYLECSAKSKEG 166
Cdd:cd04133  83 ISKASYENVLKKWIPELRHYAPGVPIVLVGTKLDLRDDKQFFADHPGAV--PITTAQGEELRKQIGAAAYIECSSKTQQN 160

                       170
                ....*....|...
gi 19549710 167 VRDVFETATRAAL 179
Cdd:cd04133 161 VKAVFDAAIKVVL 173

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 19549710     5 RKKLVIVGDGACGKTCLLIVFSKDQ-FPEVYVPTVFENYVAD-IEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILM 82
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGNKgSITEYYPGTTRNYVTTvIEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710    83 CFSVDSP-DSLENIPEKWTPEVKHFCP-NVPIILVGNKKDLRN---DPNTIRDLAKMKQEPVKPQEGRAMAEKINAFAYL 157
Cdd:TIGR00231  81 VFDIVILvLDVEEILEKQTKEIIHHADsGVPIILVGNKIDLKDadlKTHVASEFAKLNGEPIIPLSAETGKNIDSAFKIV 160

                  ..
gi 19549710   158 EC 159
Cdd:TIGR00231 161 EA 162

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Most Ras 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 Ras 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 19549710   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSV 86
Cdd:cd00876   1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIEDSYRKQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYSI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  87 DSPDSLENIPE--KWTPEVKHfCPNVPIILVGNKKDLrndpntirdlakMKQEPVKPQEGRAMAEKINAfAYLECSAKSK 164
Cdd:cd00876  81 TSRESFEEIKNirEQILRVKD-KEDVPIVLVGNKCDL------------ENERQVSTEEGEALAEEWGC-PFLETSAKTN 146

                       170
                ....*....|..
gi 19549710 165 EGVRDVFETATR 176
Cdd:cd00876 147 INIDELFNTLVR 158

Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. p21Ras couples receptor Tyr kinases and G protein receptors to protein kinase cascades

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710      7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSV 86
Cdd:smart00173   2 KLVVLGSGGVGKSALTIQFIQGHFVDDYDPTIEDSYRKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVYSI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710     87 DSPDSLENIPEKWTP--EVKHfCPNVPIILVGNKKDLRNdpntirdlakmkQEPVKPQEGRAMAEKINAfAYLECSAKSK 164
Cdd:smart00173  82 TDRQSFEEIKKFREQilRVKD-RDDVPIVLVGNKCDLES------------ERVVSTEEGKELARQWGC-PFLETSAKER 147

                          170       180
                   ....*....|....*....|
gi 19549710    165 EGVRDVFETATRaalQVKKR 184
Cdd:smart00173 148 VNVDEAFYDLVR---EIRKK 164

Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic transport and is expressed most highly in polarized epithelial cells. However, trypanosomal Rab, TbRAB18, is upregulated in the BSF (Blood Stream Form) stage and localized predominantly to elements of the Golgi complex. In human and mouse cells, Rab18 has been identified in lipid droplets, organelles that store neutral lipids. 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 19549710   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENY-VADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFS 85
Cdd:cd01863   2 KILLIGDSGVGKSSLLLRFTDDTFDEDLSSTIGVDFkVKTVTVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVYD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  86 VDSPDSLENIpEKWTPEVKHFC--PNVPIILVGNKKDLRNdpntirdlakmkqEPVKPQEGRAMAEKINAFaYLECSAKS 163
Cdd:cd01863  82 VTRRDTFDNL-DTWLNELDTYStnPDAVKMLVGNKIDKEN-------------REVTREEGQKFARKHNML-FIETSAKT 146

                ....*....
gi 19549710 164 KEGVRDVFE 172
Cdd:cd01863 147 RIGVQQAFE 155

Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The Rab5-related subfamily includes Rab5 and Rab22 of mammals, Ypt51/Ypt52/Ypt53 of yeast, and RabF of plants. The members of this subfamily are involved in endocytosis and endocytic-sorting pathways. In mammals, Rab5 GTPases localize to early endosomes and regulate fusion of clathrin-coated vesicles to early endosomes and fusion between early endosomes. In yeast, Ypt51p family members similarly regulate membrane trafficking through prevacuolar compartments. 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 19549710   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTV---FENYVadIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMC 83
Cdd:cd01860   3 KLVLLGDSSVGKSSIVLRFVKNEFSENQESTIgaaFLTQT--VNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  84 FSVDSPDSLENIpEKWTPEVK-HFCPNVPIILVGNKKDLRNdpntirdlakmkQEPVKPQEGRAMAEKINAFaYLECSAK 162
Cdd:cd01860  81 YDITSEESFEKA-KSWVKELQeHGPPNIVIALAGNKADLES------------KRQVSTEEAQEYADENGLL-FMETSAK 146

                       170
                ....*....|....*
gi 19549710 163 SKEGVRDVFETATRA 177
Cdd:cd01860 147 TGENVNELFTEIARK 161

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710   9 VIVGDGACGKTCLLIVFSKDQFPEV---YVPTVFENYVaDIEVDGKQVELALWDTAGQEDYDRLRP-----LSYPDTDVI 80
Cdd:cd00882   1 VVVGRGGVGKSSLLNALLGGEVGEVsdvPGTTRDPDVY-VKELDKGKVKLVLVDTPGLDEFGGLGReelarLLLRGADLI 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  81 LMCFSVDSPDSLENIpeKWTPEVKHFCPNVPIILVGNKKDLRNDpntirdlakmkqEPVKPQEGRAMAEKINAFAYLECS 160
Cdd:cd00882  80 LLVVDSTDRESEEDA--KLLILRRLRKEGIPIILVGNKIDLLEE------------REVEELLRLEELAKILGVPVFEVS 145

                       170
                ....*....|...
gi 19549710 161 AKSKEGVRDVFET 173
Cdd:cd00882 146 AKTGEGVDELFEK 158

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 19549710   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTV---FEnyVADIEVDGKQVELALWDTAGQEdydRLRPLS---YPDTDVI 80
Cdd:cd01867   5 KLLLIGDSGVGKSCLLLRFSEDSFNPSFISTIgidFK--IRTIELDGKKIKLQIWDTAGQE---RFRTITtsyYRGAMGI 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549710  81 LMCFSVDSPDSLENIpEKWTPEV-KHFCPNVPIILVGNKKDLRNDpntirdlakmkqEPVKPQEGRAMAEKINaFAYLEC 159
Cdd:cd01867  80 ILVYDITDEKSFENI-KNWMRNIdEHASEDVERMLVGNKCDMEEK------------RVVSKEEGEALAREYG-IKFLET 145

                       170       180
                ....*....|....*....|.
gi 19549710 160 SAKSKEGVRDVFETATRAALQ 180
Cdd:cd01867 146 SAKANINVEEAFLTLAKDILK 166