Mitochondrial Rho family 2 (Miro2), C-terminal; Miro2 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 putative GTPase domain in the C terminus 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 31559891 428 QRNVFRCNVIGVKGCGKTGVLQSLLGRNLMrQKKIRDDHKSYYAINTVYVYGQEKYLLLHDISESEFLTEAETI----CD 503
Cdd:cd01892   1 QRNVFLCFVLGAKGSGKSALLQAFLGRSFS-QNAYSPTIKPRYAVNTVEVPGQEKYLILREVGEDEEAILLNDAelaaCD 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891 504 VVCLVYDVTNPKSFEYCARIFKQHFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMPPPQAFTCNTADaPSKDIF 583
Cdd:cd01892  80 VACLVYDSSDPNSFSYCAEVYKKYFMLGEIPCLFVAAKADLDEQQQRAEVQPDEFCRKLGLPPPLHFSSRLGD-SSNELF 158

                       170       180
                ....*....|....*....|..
gi 31559891 584 VKLTTMAMYPHVTQADLKSSTF 605
Cdd:cd01892 159 TKLATAAQYPHLSIPELESGKT 180

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 31559891   354 W-GPDVNNTVCTNERGWITYQGFLSQWTLTTYLDVQRCLEYLGYLGYSILTEQESQaSAITVTRDKKIDLQ 423
Cdd:pfam08355   1 WlEPDFPDTVVTNEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGDLGSQSQ-SAIKVTRPRKLDRK 70

Mitochondrial Rho family 2 (Miro2), C-terminal; Miro2 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 putative GTPase domain in the C terminus 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 31559891 428 QRNVFRCNVIGVKGCGKTGVLQSLLGRNLMrQKKIRDDHKSYYAINTVYVYGQEKYLLLHDISESEFLTEAETI----CD 503
Cdd:cd01892   1 QRNVFLCFVLGAKGSGKSALLQAFLGRSFS-QNAYSPTIKPRYAVNTVEVPGQEKYLILREVGEDEEAILLNDAelaaCD 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891 504 VVCLVYDVTNPKSFEYCARIFKQHFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMPPPQAFTCNTADaPSKDIF 583
Cdd:cd01892  80 VACLVYDSSDPNSFSYCAEVYKKYFMLGEIPCLFVAAKADLDEQQQRAEVQPDEFCRKLGLPPPLHFSSRLGD-SSNELF 158

                       170       180
                ....*....|....*....|..
gi 31559891 584 VKLTTMAMYPHVTQADLKSSTF 605
Cdd:cd01892 159 TKLATAAQYPHLSIPELESGKT 180

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 31559891   354 W-GPDVNNTVCTNERGWITYQGFLSQWTLTTYLDVQRCLEYLGYLGYSILTEQESQaSAITVTRDKKIDLQ 423
Cdd:pfam08355   1 WlEPDFPDTVVTNEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGDLGSQSQ-SAIKVTRPRKLDRK 70

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 31559891    19 RILLVGEPRVGKTSLIMSLVSEEFPEEVPPraeeiTIPADVTPERVPTH-------IVDYSEAEQSDEQLHQEISQANVI 91
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIP-----TIGVDFYTKTIEVDgktvklqIWDTAGQERFRALRPLYYRGADGF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891    92 CIVYAVNNKHSIDKVTsRWIPLINERTDKDsrLPLILVGNKSDL-----VEYSSMETI-----LPIMnqyteietcvECS 161
Cdd:pfam00071  76 LLVYDITSRDSFENVK-KWVEEILRHADEN--VPIVLVGNKCDLedqrvVSTEEGEALakelgLPFM----------ETS 142

                         170
                  ....*....|....*....
gi 31559891   162 AKNLKNISELFYYAQKAVL 180
Cdd:pfam00071 143 AKTNENVEEAFEELAREIL 161

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 31559891    17 DVRILLVGEPRVGKTSLIMSLV-SEEFPEEVPPRAEEITIPADVT--PERVPTHIVDYSEAEQSDEQLHQEISQANVICI 93
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLgNKGSITEYYPGTTRNYVTTVIEedGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891    94 VYAVNNKH-SIDKVTSRWIPLINERTDKDSrlPLILVGNKSDLVEYSSME---TILPIMNQYTEIETcvecSAKNLKNIS 169
Cdd:TIGR00231  81 VFDIVILVlDVEEILEKQTKEIIHHADSGV--PIILVGNKIDLKDADLKThvaSEFAKLNGEPIIPL----SAETGKNID 154

                  ....*
gi 31559891   170 ELFYY 174
Cdd:TIGR00231 155 SAFKI 159

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 31559891   479 GQEKYlllHDISESEFLTeaetiCDVVCLVYDVTNPKSFEYCARIFKQ--HFMDSRIPCLIVAAKSDLHEVKQehsISPT 556
Cdd:pfam00071  57 GQERF---RALRPLYYRG-----ADGFLLVYDITSRDSFENVKKWVEEilRHADENVPIVLVGNKCDLEDQRV---VSTE 125

                          90
                  ....*....|..
gi 31559891   557 D---FCRKHKMP 565
Cdd:pfam00071 126 EgeaLAKELGLP 137

Mitochondrial Rho family 2 (Miro2), C-terminal; Miro2 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 putative GTPase domain in the C terminus 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 31559891 428 QRNVFRCNVIGVKGCGKTGVLQSLLGRNLMrQKKIRDDHKSYYAINTVYVYGQEKYLLLHDISESEFLTEAETI----CD 503
Cdd:cd01892   1 QRNVFLCFVLGAKGSGKSALLQAFLGRSFS-QNAYSPTIKPRYAVNTVEVPGQEKYLILREVGEDEEAILLNDAelaaCD 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891 504 VVCLVYDVTNPKSFEYCARIFKQHFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMPPPQAFTCNTADaPSKDIF 583
Cdd:cd01892  80 VACLVYDSSDPNSFSYCAEVYKKYFMLGEIPCLFVAAKADLDEQQQRAEVQPDEFCRKLGLPPPLHFSSRLGD-SSNELF 158

                       170       180
                ....*....|....*....|..
gi 31559891 584 VKLTTMAMYPHVTQADLKSSTF 605
Cdd:cd01892 159 TKLATAAQYPHLSIPELESGKT 180

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 31559891   354 W-GPDVNNTVCTNERGWITYQGFLSQWTLTTYLDVQRCLEYLGYLGYSILTEQESQaSAITVTRDKKIDLQ 423
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 31559891  19 RILLVGEPRVGKTSLIMSLVSEEFPEEVPPRAEEI-TIPADVTPERVPTHIVDYSEAEQSDEQLHQEISQANVICIVYAV 97
Cdd:cd00876   1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIEDSyRKQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYSI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  98 NNKHSIDKVtSRWIPLINERTDKDsRLPLILVGNKSDLVEYSSMetilpimnQYTEIETCV--------ECSAKNLKNIS 169
Cdd:cd00876  81 TSRESFEEI-KNIREQILRVKDKE-DVPIVLVGNKCDLENERQV--------STEEGEALAeewgcpflETSAKTNINID 150

                ....*
gi 31559891 170 ELFYY 174
Cdd:cd00876 151 ELFNT 155

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 31559891     20 ILLVGEPRVGKTSLIMSLVSEEFPEE-VPPRAEEITipADVTPERVPTHIVDYSEAEQSD-EQLhQEIS--QANVICIVY 95
Cdd:smart00174   1 LVVVGDGAVGKTCLLIVYTTNAFPEDyVPTVFENYS--ADVEVDGKPVELGLWDTAGQEDyDRL-RPLSypDTDVFLICF 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891     96 AVNNKHSIDKVTSRWIPLINERTDKdsrLPLILVGNKSDLVEYSSMETILPIMNQ--YTEIETC-----------VECSA 162
Cdd:smart00174  78 SVDSPASFENVKEKWYPEVKHFCPN---VPIILVGTKLDLRNDKSTLEELSKKKQepVTYEQGQalakrigavkyLECSA 154

                          170       180
                   ....*....|....*....|
gi 31559891    163 KNLKNISELFYYAQKAVLHP 182
Cdd:smart00174 155 LTQEGVREVFEEAIRAALNK 174

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 31559891  18 VRILLVGEPRVGKTSLIMSLVSEEFPEEVPPRAEEITIpADVT--PERVPTHIVDYSEAEQSDE--QLHQeiSQANVICI 93
Cdd:cd00157   1 IKIVVVGDGAVGKTCLLISYTTNKFPTEYVPTVFDNYS-ANVTvdGKQVNLGLWDTAGQEEYDRlrPLSY--PQTDVFLL 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  94 VYAVNNKHSIDKVTSRWIPLINERTdkdSRLPLILVGNKSDLVEYSSMETILPIMN---QYTEIETC---------VECS 161
Cdd:cd00157  78 CFSVDSPSSFENVKTKWYPEIKHYC---PNVPIILVGTKIDLRDDGNTLKKLEKKQkpiTPEEGEKLakeigavkyMECS 154

                       170
                ....*....|.
gi 31559891 162 AKNLKNISELF 172
Cdd:cd00157 155 ALTQEGLKEVF 165

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 31559891  16 KDVRILLVGEPRVGKTSLIMSLVSEEFPEE-VPPRAEEITIPADVTPERVPTHIVDYSEAEQSDEQLHQEISQANVICIV 94
Cdd:cd01875   2 QSIKCVVVGDGAVGKTCLLICYTTNAFPKEyIPTVFDNYSAQTAVDGRTVSLNLWDTAGQEEYDRLRTLSYPQTNVFIIC 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  95 YAVNNKHSIDKVTSRWIPlinERTDKDSRLPLILVGNKSDL------VEYSSMETILPIMNQY-----TEIETC--VECS 161
Cdd:cd01875  82 FSIASPSSYENVRHKWHP---EVCHHCPNVPILLVGTKKDLrndadtLKKLKEQGQAPITPQQggalaKQIHAVkyLECS 158

                       170       180
                ....*....|....*....|..
gi 31559891 162 AKNLKNISELFYYAQKAVLHPT 183
Cdd:cd01875 159 ALNQDGVKEVFAEAVRAVLNPT 180

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  15 KKDVRILLVGEPRVGKTSLIMSLVSEEFPEE--VPPRA---EEITIPADVTPERVptHIVD---YSEAEQSDEQLHQEIS 86
Cdd:COG1100   1 MGEKKIVVVGTGGVGKTSLVNRLVGDIFSLEkyLSTNGvtiDKKELKLDGLDVDL--VIWDtpgQDEFRETRQFYARQLT 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  87 QANVICIVYAVNNKHSIDKVTSrWIPLInERTDKDSrlPLILVGNKSDLVEYSSMETILPIMNQYTE--IETCVECSAKN 164
Cdd:COG1100  79 GASLYLFVVDGTREETLQSLYE-LLESL-RRLGKKS--PIILVLNKIDLYDEEEIEDEERLKEALSEdnIVEVVATSAKT 154

                ....*...
gi 31559891 165 LKNISELF 172
Cdd:COG1100 155 GEGVEELF 162

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 31559891  19 RILLVGEPRVGKTSLIMSLVSEEFPEEVPPRAEEITIpADVTPERVPTHIVDYSEAEQSD-EQLHQ-EISQANVICIVYA 96
Cdd:cd04129   3 KLVIVGDGACGKTSLLYVFTLGEFPEEYHPTVFENYV-TDCRVDGKPVQLALWDTAGQEEyERLRPlSYSKAHVILIGFA 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  97 VNNKHSIDKVTSRWIPLINERTDKdsrLPLILVGNKSDL-VEYSSMETilPIMNQYTEIETC------------VECSAK 163
Cdd:cd04129  82 IDTPDSLENVRTKWIEEVRRYCPN---VPVILVGLKKDLrQEAVAKGN--YATDEFVPIQQAklvaraigakkyMECSAL 156

                       170
                ....*....|....*..
gi 31559891 164 NLKNISELFYYAQKAVL 180
Cdd:cd04129 157 TGEGVDDVFEAATRAAL 173

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 31559891  18 VRILLVGEPRVGKTSLIMSLVSEEFPEEVPP-----RAEEITipadVTPERVPTHIVDYSEAEQSDEQLHQEISQANVIC 92
Cdd:cd04139   1 HKVIMVGSGGVGKSALTLQFMYDEFVEDYEPtkadsYRKKVV----LDGEEVQLNILDTAGQEDYAAIRDNYFRSGEGFL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  93 IVYAVNNKHSIDKVTSRWIPLIneRTDKDSRLPLILVGNKSDLVEYSSMetilPIMNQYTEIETC----VECSAKNLKNI 168
Cdd:cd04139  77 LVFSITDMESFTALAEFREQIL--RVKEDDNVPLLLVGNKCDLEDKRQV----SVEEAANLAEQWgvnyVETSAKTRANV 150

                ....*
gi 31559891 169 SELFY 173
Cdd:cd04139 151 DKVFF 155

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 31559891  19 RILLVGEPRVGKTSLIMSLVSEEFPEE-VPPRAEEITIPADVTPERVPTHIVDYSEAEQSDEQLHQEISQANVICIVYAV 97
Cdd:cd04131   3 KIVLVGDSQCGKTALLQVFAKDSFPENyVPTVFENYTASFEVDKQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLICFDI 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  98 NNKHSIDKVTSRWIPlinERTDKDSRLPLILVGNKSDL-------VEYSSMETILPIMNQYTEI------ETCVECSAKN 164
Cdd:cd04131  83 SRPETLDSVLKKWKG---EVREFCPNTPVLLVGCKSDLrtdlstlTELSNKRQIPVSHEQGRNLakqigaAAYVECSAKT 159

                       170
                ....*....|....*..
gi 31559891 165 LKN-ISELFYYAQKAVL 180
Cdd:cd04131 160 SENsVRDVFEMATLACL 176

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 31559891 436 VIGVKGCGKTGVLQSLLGRNLmrqKKIRDDHKSYYAINT--VYVYGQEKYLLLHD---ISESEFLTEAETI------CDV 504
Cdd:cd00882   2 VVGRGGVGKSSLLNALLGGEV---GEVSDVPGTTRDPDVyvKELDKGKVKLVLVDtpgLDEFGGLGREELArlllrgADL 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891 505 VCLVYDVTNPKSFEYCARIFKQHFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMPPPQAFTCNT 574
Cdd:cd00882  79 ILLVVDSTDRESEEDAKLLILRRLRKEGIPIILVGNKIDLLEEREVEELLRLEELAKILGVPVFEVSAKT 148

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 31559891  18 VRILLVGEPRVGKTSLIMSLVSEEFPEEVPPraeeiTIPAD-------VTPERVPTHIVDYSEAEQSDEQLHQEISQANV 90
Cdd:cd01863   1 LKILLIGDSGVGKSSLLLRFTDDTFDEDLSS-----TIGVDfkvktvtVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQG 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  91 ICIVYAVNNKHSIDKVtSRWIPLINERTDKDSrLPLILVGNKSDLveySSMETILPIMNQYTEIETC--VECSAKNLKNI 168
Cdd:cd01863  76 VILVYDVTRRDTFDNL-DTWLNELDTYSTNPD-AVKMLVGNKIDK---ENREVTREEGQKFARKHNMlfIETSAKTRIGV 150

                ....
gi 31559891 169 SELF 172
Cdd:cd01863 151 QQAF 154

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 31559891  19 RILLVGEPRVGKTSLIMSLVSEEFPEE-VPPRAEEITIPADVTPERVPTHIVDYSEAEQSDEQLHQEISQANVICIVYAV 97
Cdd:cd04172   7 KIVVVGDSQCGKTALLHVFAKDCFPENyVPTVFENYTASFEIDTQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLICFDI 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  98 NNKHSIDKVTSRWIPLINERTDKDSrlpLILVGNKSDL-------VEYSSmETILPI-------MNQYTEIETCVECSAK 163
Cdd:cd04172  87 SRPETLDSVLKKWKGEIQEFCPNTK---MLLVGCKSDLrtdvstlVELSN-HRQTPVsydqganMAKQIGAATYIECSAL 162

                       170
                ....*....|....*.
gi 31559891 164 NLKN-ISELFYYAQKA 178
Cdd:cd04172 163 QSENsVRDIFHVATLA 178

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 31559891  19 RILLVGEPRVGKTSLIMSLVSEEFPEEVPPraeeiTIPADVTpervpTHIVDYseaEQSDEQLH------QE-------- 84
Cdd:cd01861   2 KLVFLGDQSVGKTSIITRFMYDTFDNQYQA-----TIGIDFL-----SKTMYV---DDKTVRLQlwdtagQErfrslips 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  85 -ISQANVICIVYAVNNKHSIDKVTsRWIPLINERTDKDSRLplILVGNKSDL-----VEYSSMETILPIMNQYTeIETcv 158
Cdd:cd01861  69 yIRDSSVAVVVYDITNRQSFDNTD-KWIDDVRDERGNDVII--VLVGNKTDLsdkrqVSTEEGEKKAKENNAMF-IET-- 142

                       170
                ....*....|....
gi 31559891 159 ecSAKNLKNISELF 172
Cdd:cd01861 143 --SAKAGHNVKQLF 154

Rem, Rem2, Rad, Gem/Kir (RGK) subfamily of Ras GTPases; RGK subfamily. The RGK (Rem, Rem2, Rad, Gem/Kir) subfamily of Ras GTPases are expressed in a tissue-specific manner and are dynamically regulated by transcriptional and posttranscriptional mechanisms in response to environmental cues. RGK proteins bind to the beta subunit of L-type calcium channels, causing functional down-regulation of these voltage-dependent calcium channels, and either termination of calcium-dependent secretion or modulation of electrical conduction and contractile function. Inhibition of L-type calcium channels by Rem2 may provide a mechanism for modulating calcium-triggered exocytosis in hormone-secreting cells, and has been proposed to influence the secretion of insulin in pancreatic beta cells. RGK proteins also interact with and inhibit the Rho/Rho kinase pathway to modulate remodeling of the cytoskeleton. Two characteristics of RGK proteins cited in the literature are N-terminal and C-terminal extensions beyond the GTPase domain typical of Ras superfamily members. The N-terminal extension is not conserved among family members; the C-terminal extension is reported to be conserved among the family and lack the CaaX prenylation motif typical of membrane-associated Ras proteins. However, a putative CaaX motif has been identified in the alignment of the C-terminal residues of this CD.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31559891  19 RILLVGEPRVGKTSLIMSLVSEEFpEEVPPRAE-----EITIPADVtpERVPTHIVDYSEAEQSDeQLHQEISQ-ANVIC 92
Cdd:cd04148   2 RVVLLGDSGVGKSSLANIFTAGVY-EDSAYEASgddtyERTVSVDG--EEATLVVYDHWEQEDGM-WLEDSCMQvGDAYV 77