Mitochondrial Rho family 1 (Miro1), N-terminal; Miro1 subfamily. Miro (mitochondrial Rho) proteins have tandem GTP-binding domains separated by a linker region containing putative calcium-binding EF hand motifs. Genes encoding Miro-like proteins were found in several eukaryotic organisms. This CD represents the N-terminal GTPase domain of Miro proteins. These atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. Most Rho proteins contain a lipid modification site at the C-terminus; however, Miro is one of few Rho subfamilies that lack this feature.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404   3 RDVRILLLGEAQVGKTSLILSLVGEEFPEEVPPRAEEITIPADVTPEKVPTHIVDYSEAEQTDEELREEIHK-------- 74
Cdd:cd01893     1 KDVRIVLIGDEGVGKSSLIMSLVSEEFPENVPRVLPEITIPADVTPERVPTTIVDTSSRPQDRANLAAEIRKanviclvy 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  75 ----------IRTKWIPLVNGGTTqgpRVPIILVGNKSDLRSGSS----MEAVLPIMSQFPEIETCVECSAKNLRNISEL 140
Cdd:cd01893    81 svdrpstlerIRTKWLPLIRRLGV---KVPIILVGNKSDLRDGSSqaglEEEMLPIMNEFREIETCVECSAKTLINVSEV 157

                         170
                  ....*....|.
gi 1206271404 141 FYYAQKAVLHP 151
Cdd:cd01893   158 FYYAQKAVLHP 168

EF hand associated; This region typically appears on the C-terminus of EF hands in GTP-binding proteins such as Arht/Rhot (may be involved in mitochondrial homeostasis and apoptosis). The EF hand associated region is found in yeast, vertebrates and plants.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1206271404 323 W-GPELPRTV-RTEAGRLPLHGYLCQWTLVTYLDVRSCLGHLGYLGYPT-LCEQDQaHAITVTREKRLDQE 390
Cdd:pfam08355   1 WlEPDFPDTVvTNEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGdLGSQSQ-SAIKVTRPRKLDRK 70

Mitochondrial Rho family 1 (Miro1), N-terminal; Miro1 subfamily. Miro (mitochondrial Rho) proteins have tandem GTP-binding domains separated by a linker region containing putative calcium-binding EF hand motifs. Genes encoding Miro-like proteins were found in several eukaryotic organisms. This CD represents the N-terminal GTPase domain of Miro proteins. These atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. Most Rho proteins contain a lipid modification site at the C-terminus; however, Miro is one of few Rho subfamilies that lack this feature.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404   3 RDVRILLLGEAQVGKTSLILSLVGEEFPEEVPPRAEEITIPADVTPEKVPTHIVDYSEAEQTDEELREEIHK-------- 74
Cdd:cd01893     1 KDVRIVLIGDEGVGKSSLIMSLVSEEFPENVPRVLPEITIPADVTPERVPTTIVDTSSRPQDRANLAAEIRKanviclvy 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  75 ----------IRTKWIPLVNGGTTqgpRVPIILVGNKSDLRSGSS----MEAVLPIMSQFPEIETCVECSAKNLRNISEL 140
Cdd:cd01893    81 svdrpstlerIRTKWLPLIRRLGV---KVPIILVGNKSDLRDGSSqaglEEEMLPIMNEFREIETCVECSAKTLINVSEV 157

                         170
                  ....*....|.
gi 1206271404 141 FYYAQKAVLHP 151
Cdd:cd01893   158 FYYAQKAVLHP 168

EF hand associated; This region typically appears on the C-terminus of EF hands in GTP-binding proteins such as Arht/Rhot (may be involved in mitochondrial homeostasis and apoptosis). The EF hand associated region is found in yeast, vertebrates and plants.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1206271404 323 W-GPELPRTV-RTEAGRLPLHGYLCQWTLVTYLDVRSCLGHLGYLGYPT-LCEQDQaHAITVTREKRLDQE 390
Cdd:pfam08355   1 WlEPDFPDTVvTNEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGdLGSQSQ-SAIKVTRPRKLDRK 70

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404   2 RRDVRILLLGEAQVGKTSLILSLVGEEFPEEvppraeeitipadvtpEKVPTH--IVDYSEAEQTDEELR---------E 70
Cdd:COG1100     1 MGEKKIVVVGTGGVGKTSLVNRLVGDIFSLE----------------KYLSTNgvTIDKKELKLDGLDVDlviwdtpgqD 64

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  71 EIHKIRTKWIPLVNG-------------GTTQ------------GPRVPIILVGNKSDLRSGSSMEAVLPIMSQFPE--I 123
Cdd:COG1100    65 EFRETRQFYARQLTGaslylfvvdgtreETLQslyelleslrrlGKKSPIILVLNKIDLYDEEEIEDEERLKEALSEdnI 144

                         170
                  ....*....|....*...
gi 1206271404 124 ETCVECSAKNLRNISELF 141
Cdd:COG1100   145 VEVVATSAKTGEGVEELF 162

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 1206271404   4 DVRILLLGEAQVGKTSLILSLVG-EEFPEEVPPRAEEITIPADVT--PEKVPTHIVD------YSEAE-----QTDEELR 69
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGnKGSITEYYPGTTRNYVTTVIEedGKTYKFNLLDtagqedYDAIRrlyypQVERSLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  70 --------EEIHKIRTKWIPLVNGGTTQGprVPIILVGNKSDLRSGSSMEAV---LPIMSQFPEIETcvecSAKNLRNIS 138
Cdd:TIGR00231  81 vfdivilvLDVEEILEKQTKEIIHHADSG--VPIILVGNKIDLKDADLKTHVaseFAKLNGEPIIPL----SAETGKNID 154

                  ....*
gi 1206271404 139 ELFYY 143
Cdd:TIGR00231 155 SAFKI 159

Mitochondrial Rho family 1 (Miro1), N-terminal; Miro1 subfamily. Miro (mitochondrial Rho) proteins have tandem GTP-binding domains separated by a linker region containing putative calcium-binding EF hand motifs. Genes encoding Miro-like proteins were found in several eukaryotic organisms. This CD represents the N-terminal GTPase domain of Miro proteins. These atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. Most Rho proteins contain a lipid modification site at the C-terminus; however, Miro is one of few Rho subfamilies that lack this feature.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404   3 RDVRILLLGEAQVGKTSLILSLVGEEFPEEVPPRAEEITIPADVTPEKVPTHIVDYSEAEQTDEELREEIHK-------- 74
Cdd:cd01893     1 KDVRIVLIGDEGVGKSSLIMSLVSEEFPENVPRVLPEITIPADVTPERVPTTIVDTSSRPQDRANLAAEIRKanviclvy 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  75 ----------IRTKWIPLVNGGTTqgpRVPIILVGNKSDLRSGSS----MEAVLPIMSQFPEIETCVECSAKNLRNISEL 140
Cdd:cd01893    81 svdrpstlerIRTKWLPLIRRLGV---KVPIILVGNKSDLRDGSSqaglEEEMLPIMNEFREIETCVECSAKTLINVSEV 157

                         170
                  ....*....|.
gi 1206271404 141 FYYAQKAVLHP 151
Cdd:cd01893   158 FYYAQKAVLHP 168

EF hand associated; This region typically appears on the C-terminus of EF hands in GTP-binding proteins such as Arht/Rhot (may be involved in mitochondrial homeostasis and apoptosis). The EF hand associated region is found in yeast, vertebrates and plants.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1206271404 323 W-GPELPRTV-RTEAGRLPLHGYLCQWTLVTYLDVRSCLGHLGYLGYPT-LCEQDQaHAITVTREKRLDQE 390
Cdd:pfam08355   1 WlEPDFPDTVvTNEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGdLGSQSQ-SAIKVTRPRKLDRK 70

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 1206271404   6 RILLLGEAQVGKTSLILSLVGEEFPEEVPPRAEEI-TIPADVTPEKVPTHIVDYSEAEQ--------------------- 63
Cdd:cd00876     1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIEDSyRKQIVVDGETYTLDILDTAGQEEfsamrdqyirngdgfilvysi 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  64 TD-------EELREEIHKIRTKwiplvnggttqgPRVPIILVGNKSDL---RSGSSMEAvlpimSQFPEIETC--VECSA 131
Cdd:cd00876    81 TSresfeeiKNIREQILRVKDK------------EDVPIVLVGNKCDLeneRQVSTEEG-----EALAEEWGCpfLETSA 143

                         170
                  ....*....|..
gi 1206271404 132 KNLRNISELFYY 143
Cdd:cd00876   144 KTNINIDELFNT 155

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 1206271404   8 LLLGEAQVGKTSLILSLVGEEFPEEVPPR---AEEITIPADVTPEKVPTHIVD----------------YSEAEQTD--- 65
Cdd:cd00882     1 VVVGRGGVGKSSLLNALLGGEVGEVSDVPgttRDPDVYVKELDKGKVKLVLVDtpgldefgglgreelaRLLLRGADlil 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  66 ----EELREEIHKIRTKWIplvngGTTQGPRVPIILVGNKSDLRSGSSMEAVLP-IMSQFPEIETCVECSAKNLRNISEL 140
Cdd:cd00882    81 lvvdSTDRESEEDAKLLIL-----RRLRKEGIPIILVGNKIDLLEEREVEELLRlEELAKILGVPVFEVSAKTGEGVDEL 155

                  ....*.
gi 1206271404 141 FYYAQK 146
Cdd:cd00882   156 FEKLIE 161

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 1206271404   2 RRDVRILLLGEAQVGKTSLILSLVGEEFPEEVPPRAEEITIPADVTPEKVPTHIVDYSEAEQTD-EELR----------- 69
Cdd:cd04132     1 DLKVKIVVVGDGGCGKTCLLMVYAQGSFPEEYVPTVFENYVTTLQVPNGKIIELALWDTAGQEDyDRLRplsypdvdvil 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  70 --------EEIHKIRTKWIPLVNGGTtqgPRVPIILVGNKSDLRSGSSMEAVLPIMSQFP-----EIETC--------VE 128
Cdd:cd04132    81 icysvdnpTSLDNVEDKWYPEVNHFC---PGTPIVLVGLKTDLRKDKNSVSKLRAQGLEPvtpeqGESVAksigavayIE 157

                         170       180
                  ....*....|....*....|.
gi 1206271404 129 CSAKNLRNISELFYYAQKAVL 149
Cdd:cd04132   158 CSAKLMENVDEVFDAAINVAL 178

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 1206271404   5 VRILLLGEAQVGKTSLILSLVGEEFPEEVPPraeeiTIPADVTPEKVPT-------HIVDYSEAEQ-------------- 63
Cdd:cd00154     1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKS-----TIGVDFKSKTIEVdgkkvklQIWDTAGQERfrsitssyyrgahg 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  64 -------TDEELREEIhkirTKWIPLVNggTTQGPRVPIILVGNKSDLRSGS--SMEAVLPIMSQFpeIETCVECSAKNL 134
Cdd:cd00154    76 ailvydvTNRESFENL----DKWLNELK--EYAPPNIPIILVGNKSDLEDERqvSTEEAQQFAKEN--GLLFFETSAKTG 147

                         170
                  ....*....|
gi 1206271404 135 RNISELFYYA 144
Cdd:cd00154   148 ENVDEAFESL 157

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 1206271404   5 VRILLLGEAQVGKTSLILSLVGEEFPEE-VPPRAEEITIPADVTPEKVPTHIVDYSEAEQTDEeLR-------------- 69
Cdd:cd01875     4 IKCVVVGDGAVGKTCLLICYTTNAFPKEyIPTVFDNYSAQTAVDGRTVSLNLWDTAGQEEYDR-LRtlsypqtnvfiicf 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  70 -----EEIHKIRTKWIPLVnggTTQGPRVPIILVGNKSDLRSGSSMEAVLPIMSQFP-----------EIETC--VECSA 131
Cdd:cd01875    83 siaspSSYENVRHKWHPEV---CHHCPNVPILLVGTKKDLRNDADTLKKLKEQGQAPitpqqggalakQIHAVkyLECSA 159

                         170       180
                  ....*....|....*....|..
gi 1206271404 132 KNLRNISELFYYAQKAVLHPTA 153
Cdd:cd01875   160 LNQDGVKEVFAEAVRAVLNPTP 181

Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily consists of the highly homologous RalA and RalB. Ral proteins are believed to play a crucial role in tumorigenesis, metastasis, endocytosis, and actin cytoskeleton dynamics. Despite their high sequence similarity (>80% sequence identity), nonoverlapping and opposing functions have been assigned to RalA and RalBs in tumor migration. In human bladder and prostate cancer cells, RalB promotes migration while RalA inhibits it. A Ral-specific set of GEFs has been identified that are activated by Ras binding. This RalGEF activity is enhanced by Ras binding to another of its target proteins, phosphatidylinositol 3-kinase (PI3K). Ral effectors include RLIP76/RalBP1, a Rac/cdc42 GAP, and the exocyst (Sec6/8) complex, a heterooctomeric protein complex that is involved in tethering vesicles to specific sites on the plasma membrane prior to exocytosis. In rat kidney cells, RalB is required for functional assembly of the exocyst and for localizing the exocyst to the leading edge of migrating cells. In human cancer cells, RalA is required to support anchorage-independent proliferation and RalB is required to suppress apoptosis. RalA has been shown to localize to the plasma membrane while RalB is localized to the intracellular vesicles. 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 1206271404   5 VRILLLGEAQVGKTSLILSLVGEEFPEEVPP-----RAEEITipadVTPEKVPTHIVDYSEAEQ---------------- 63
Cdd:cd04139     1 HKVIMVGSGGVGKSALTLQFMYDEFVEDYEPtkadsYRKKVV----LDGEEVQLNILDTAGQEDyaairdnyfrsgegfl 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  64 -----TDEELREEIHKIRTKWIPLVNGgttqgPRVPIILVGNKSDL----RSGSSMEAVLPIMSQFPEIETcvecSAKNL 134
Cdd:cd04139    77 lvfsiTDMESFTALAEFREQILRVKED-----DNVPLLLVGNKCDLedkrQVSVEEAANLAEQWGVNYVET----SAKTR 147

                  ....*...
gi 1206271404 135 RNISELFY 142
Cdd:cd04139   148 ANVDKVFF 155

Ras homology family 2 (Rho2) of small guanosine triphosphatases (GTPases); Rho2 is a fungal GTPase that plays a role in cell morphogenesis, control of cell wall integrity, control of growth polarity, and maintenance of growth direction. Rho2 activates the protein kinase C homolog Pck2, and Pck2 controls Mok1, the major (1-3) alpha-D-glucan synthase. Together with Rho1 (RhoA), Rho2 regulates the construction of the cell wall. Unlike Rho1, Rho2 is not an essential protein, but its overexpression is lethal. 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 proper intracellular localization via membrane attachment. As with other Rho family GTPases, the GDP/GTP cycling is regulated by GEFs (guanine nucleotide exchange factors), GAPs (GTPase-activating proteins) and GDIs (guanine nucleotide dissociation inhibitors).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404   2 RRdvRILLLGEAQVGKTSLILSLVGEEFPEEVPPRAEEITIpADVTPEKVPTHIVDYSEAEQTD-EELR----------- 69
Cdd:cd04129     1 RR--KLVIVGDGACGKTSLLYVFTLGEFPEEYHPTVFENYV-TDCRVDGKPVQLALWDTAGQEEyERLRplsyskahvil 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  70 --------EEIHKIRTKWIPLVNggtTQGPRVPIILVGNKSDLRSGSSMEAVlPIMSQFPEIETC------------VEC 129
Cdd:cd04129    78 igfaidtpDSLENVRTKWIEEVR---RYCPNVPVILVGLKKDLRQEAVAKGN-YATDEFVPIQQAklvaraigakkyMEC 153

                         170       180
                  ....*....|....*....|
gi 1206271404 130 SAKNLRNISELFYYAQKAVL 149
Cdd:cd04129   154 SALTGEGVDDVFEAATRAAL 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 1206271404   4 DVRILLLGEAQVGKTSLILSLVG-EEFPEEVPPRAEEITIPADVT--PEKVPTHIVD------YSEAE-----QTDEELR 69
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGnKGSITEYYPGTTRNYVTTVIEedGKTYKFNLLDtagqedYDAIRrlyypQVERSLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  70 --------EEIHKIRTKWIPLVNGGTTQGprVPIILVGNKSDLRSGSSMEAV---LPIMSQFPEIETcvecSAKNLRNIS 138
Cdd:TIGR00231  81 vfdivilvLDVEEILEKQTKEIIHHADSG--VPIILVGNKIDLKDADLKTHVaseFAKLNGEPIIPL----SAETGKNID 154

                  ....*
gi 1206271404 139 ELFYY 143
Cdd:TIGR00231 155 SAFKI 159

Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small GTPases of the ARF, RAB, RAN, RAS, and SAR subfamilies. Others that could not be classified in this way are predicted to be members of the small GTPase superfamily without predictions of the subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404    3 RDVRILLLGEAQVGKTSLILSLVGEEFPEEVPPRAE-----EITIPADVtpekVPTHIVDYSEAEQ-------------- 63
Cdd:smart00010   1 REYKLVVLGGGGVGKSALTIQFVQGHFVDEYDPTIEdsyrkQIEIDGEV----CLLDILDTAGQEEfsamrdqymrtgeg 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404   64 -------TDEELREEIHKIRTKwIPLVNGGTtqgpRVPIILVGNKSDL---RSGSSMEAvLPIMSQFPeietC--VECSA 131
Cdd:smart00010  77 fllvysiTDRQSFEEIAKFREQ-ILRVKDRD----DVPIVLVGNKCDLeneRVVSTEEG-KELARQWG----CpfLETSA 146

                          170
                   ....*....|.
gi 1206271404  132 KNLRNISELFY 142
Cdd:smart00010 147 KERINVDEAFY 157

Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404    5 VRILLLGEAQVGKTSLILSLVGEEFPEEVPPraeeiTIPAD-------VTPEKVPTHIVD--------------YSEA-- 61
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKS-----TIGVDfktktieVDGKRVKLQIWDtagqerfrsitssyYRGAvg 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404   62 ---------EQTDEELREEIHKIRTKwiplvnggttQGPRVPIILVGNKSDL---RSGSSMEAvlpimSQFPEIETC--V 127
Cdd:smart00175  76 allvyditnRESFENLENWLKELREY----------ASPNVVIMLVGNKSDLeeqRQVSREEA-----EAFAEEHGLpfF 140

                          170
                   ....*....|....
gi 1206271404  128 ECSAKNLRNISELF 141
Cdd:smart00175 141 ETSAKTNTNVEEAF 154

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 1206271404   5 VRILLLGEAQVGKTSLILSLVGEEFPEEVPPraeeiTIPAD-------VTPEKVPTHIVDYSEAEQ-------------- 63
Cdd:cd01863     1 LKILLIGDSGVGKSSLLLRFTDDTFDEDLSS-----TIGVDfkvktvtVDGKKVKLAIWDTAGQERfrtltssyyrgaqg 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  64 ----TDEELREEIHKIRTkWIPLVNGGTTQgPRVPIILVGNKSDLrsgSSMEAVLPIMSQFPEIETC--VECSAKNLRNI 137
Cdd:cd01863    76 vilvYDVTRRDTFDNLDT-WLNELDTYSTN-PDAVKMLVGNKIDK---ENREVTREEGQKFARKHNMlfIETSAKTRIGV 150

                  ....
gi 1206271404 138 SELF 141
Cdd:cd01863   151 QQAF 154

Ras homolog enriched in striatum (Rhes) and activator of G-protein signaling 1 (Dexras1/AGS1); This subfamily includes Rhes (Ras homolog enriched in striatum) and Dexras1/AGS1 (activator of G-protein signaling 1). These proteins are homologous, but exhibit significant differences in tissue distribution and subcellular localization. Rhes is found primarily in the striatum of the brain, but is also expressed in other areas of the brain, such as the cerebral cortex, hippocampus, inferior colliculus, and cerebellum. Rhes expression is controlled by thyroid hormones. In rat PC12 cells, Rhes is farnesylated and localizes to the plasma membrane. Rhes binds and activates PI3K, and plays a role in coupling serpentine membrane receptors with heterotrimeric G-protein signaling. Rhes has recently been shown to be reduced under conditions of dopamine supersensitivity and may play a role in determining dopamine receptor sensitivity. Dexras1/AGS1 is a dexamethasone-induced Ras protein that is expressed primarily in the brain, with low expression levels in other tissues. Dexras1 localizes primarily to the cytoplasm, and is a critical regulator of the circadian master clock to photic and nonphotic input. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404   6 RILLLGEAQVGKTSLILSLVGEEFPEEVPPRAEEI-----TIPADVT-------------PEKVPTHI-----------V 56
Cdd:cd04143     2 RMVVLGASKVGKTAIVSRFLGGRFEEQYTPTIEDFhrklySIRGEVYqldildtsgnhpfPAMRRLSIltgdvfilvfsL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  57 DYSEAEQTDEELREEIhkIRTKWIPLVNggTTQGPRVPIILVGNKSDLRSgssmeavlPIMSQFPEIETCV--------- 127
Cdd:cd04143    82 DNRESFEEVCRLREQI--LETKSCLKNK--TKENVKIPMVICGNKADRDF--------PREVQRDEVEQLVggdencayf 149

                         170
                  ....*....|....*
gi 1206271404 128 ECSAKNLRNISELFY 142
Cdd:cd04143   150 EVSAKKNSNLDEMFR 164

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 1206271404   5 VRILLLGEAQVGKTSLILSLVGEEFPEE-VPPRAEEITIPADVTPEKVPTHIVDYSEAEQTDeELR-------------- 69
Cdd:cd04135     1 LKCVVVGDGAVGKTCLLMSYANDAFPEEyVPTVFDHYAVSVTVGGKQYLLGLYDTAGQEDYD-RLRplsypmtdvflicf 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  70 -----EEIHKIRTKWIPLVNggtTQGPRVPIILVGNKSDLRSGSSMEAVLPIMSQFP-----------EIETC--VECSA 131
Cdd:cd04135    80 svvnpASFQNVKEEWVPELK---EYAPNVPYLLIGTQIDLRDDPKTLARLNDMKEKPitveqgqklakEIGACcyVECSA 156

                         170
                  ....*....|....*...
gi 1206271404 132 KNLRNISELFYYAQKAVL 149
Cdd:cd04135   157 LTQKGLKTVFDEAIIAIL 174

Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They 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 that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF 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 1206271404   6 RILLLGEAQVGKTSLILSLVGEEFPEEVPPRAEEITIPADVTPEKVPT-HIVDYSEAEQ----TDEELR----------- 69
Cdd:cd04138     3 KLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLlDILDTAGQEEysamRDQYMRtgegflcvfai 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1206271404  70 ------EEIHKIRTKwIPLVNGGTTqgprVPIILVGNKSDLRSGS-SMEAVLPIMSQF--PEIETcvecSAKNLRNISEL 140
Cdd:cd04138    83 nsrksfEDIHTYREQ-IKRVKDSDD----VPMVLVGNKCDLAARTvSTRQGQDLAKSYgiPYIET----SAKTRQGVEEA 153

                  ..
gi 1206271404 141 FY 142
Cdd:cd04138   154 FY 155