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 20070266  81 YRVVLLGDPGVGKTSLASLF-AGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEklDKSWSQESCLQGGSAYVI 159
Cdd:cd04148   1 YRVVLLGDSGVGKSSLANIFtAGVYEDSAYEASGDDTYERTVSVDGEEATLVVYDHWEQE--DGMWLEDSCMQVGDAYVI 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 160 VYSIADRGSFESASELRIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELFEGV 239
Cdd:cd04148  79 VYSVTDRSSFEKASELRIQLRRARQAEDIPIILVGNKSDLVRSREVSVQEGRACAVVFDCKFIETSAALQHNVDELFEGI 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 20070266 240 VRQLRLRRRDSAAKE--PPAPRRPASLAQRARRFLARLTARSARRRALKARSKSCHNLAVL 298
Cdd:cd04148 159 VRQVRLRRDSKEKNTrrMASRKRRESITKKAKRFLSKIVAKNNKGMAFKQKSKSCHDLSVL 219

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 20070266  81 YRVVLLGDPGVGKTSLASLF-AGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEklDKSWSQESCLQGGSAYVI 159
Cdd:cd04148   1 YRVVLLGDSGVGKSSLANIFtAGVYEDSAYEASGDDTYERTVSVDGEEATLVVYDHWEQE--DGMWLEDSCMQVGDAYVI 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 160 VYSIADRGSFESASELRIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELFEGV 239
Cdd:cd04148  79 VYSVTDRSSFEKASELRIQLRRARQAEDIPIILVGNKSDLVRSREVSVQEGRACAVVFDCKFIETSAALQHNVDELFEGI 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 20070266 240 VRQLRLRRRDSAAKE--PPAPRRPASLAQRARRFLARLTARSARRRALKARSKSCHNLAVL 298
Cdd:cd04148 159 VRQVRLRRDSKEKNTrrMASRKRRESITKKAKRFLSKIVAKNNKGMAFKQKSKSCHDLSVL 219

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 20070266    82 RVVLLGDPGVGKTSLASLFAGKQERDLHE-QLGEDVYERTLTVDGEDTTLVVVDTweAekldkswSQE-------SCLQG 153
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIpTIGVDFYTKTIEVDGKTVKLQIWDT--A-------GQErfralrpLYYRG 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266   154 GSAYVIVYSIADRGSFESASELRIQLRRtHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVA 233
Cdd:pfam00071  72 ADGFLLVYDITSRDSFENVKKWVEEILR-HADENVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTNENVE 150

                  ....
gi 20070266   234 ELFE 237
Cdd:pfam00071 151 EAFE 154

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266  82 RVVLLGDPGVGKTSLASLFAGkQERDLHEQL---GEDVYERTLTVDGEDTTLVVVDT---WEAEKLDKSWSQEscLQGGS 155
Cdd:COG1100   5 KIVVVGTGGVGKTSLVNRLVG-DIFSLEKYLstnGVTIDKKELKLDGLDVDLVIWDTpgqDEFRETRQFYARQ--LTGAS 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 156 AYVIVYSIADRGSFESASELRIQLRRThqADHVPIILVGNKADLARCREVSVEEG--RACAVVFDCKFIETSATLQHNVA 233
Cdd:COG1100  82 LYLFVVDGTREETLQSLYELLESLRRL--GKKSPIILVLNKIDLYDEEEIEDEERlkEALSEDNIVEVVATSAKTGEGVE 159

                ....
gi 20070266 234 ELFE 237
Cdd:COG1100 160 ELFA 163

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 20070266  81 YRVVLLGDPGVGKTSLASLF-AGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEklDKSWSQESCLQGGSAYVI 159
Cdd:cd04148   1 YRVVLLGDSGVGKSSLANIFtAGVYEDSAYEASGDDTYERTVSVDGEEATLVVYDHWEQE--DGMWLEDSCMQVGDAYVI 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 160 VYSIADRGSFESASELRIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELFEGV 239
Cdd:cd04148  79 VYSVTDRSSFEKASELRIQLRRARQAEDIPIILVGNKSDLVRSREVSVQEGRACAVVFDCKFIETSAALQHNVDELFEGI 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 20070266 240 VRQLRLRRRDSAAKE--PPAPRRPASLAQRARRFLARLTARSARRRALKARSKSCHNLAVL 298
Cdd:cd04148 159 VRQVRLRRDSKEKNTrrMASRKRRESITKKAKRFLSKIVAKNNKGMAFKQKSKSCHDLSVL 219

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 20070266     81 YRVVLLGDPGVGKTSLASLFAGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTweAEKLDKSWSQESCLQGGSAYVIV 160
Cdd:smart00010   3 YKLVVLGGGGVGKSALTIQFVQGHFVDEYDPTIEDSYRKQIEIDGEVCLLDILDT--AGQEEFSAMRDQYMRTGEGFLLV 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 20070266    161 YSIADRGSFESASELRIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELFE 237
Cdd:smart00010  81 YSITDRQSFEEIAKFREQILRVKDRDDVPIVLVGNKCDLENERVVSTEEGKELARQWGCPFLETSAKERINVDEAFY 157

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 20070266    82 RVVLLGDPGVGKTSLASLFAGKQERDLHE-QLGEDVYERTLTVDGEDTTLVVVDTweAekldkswSQE-------SCLQG 153
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIpTIGVDFYTKTIEVDGKTVKLQIWDT--A-------GQErfralrpLYYRG 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266   154 GSAYVIVYSIADRGSFESASELRIQLRRtHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVA 233
Cdd:pfam00071  72 ADGFLLVYDITSRDSFENVKKWVEEILR-HADENVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTNENVE 150

                  ....
gi 20070266   234 ELFE 237
Cdd:pfam00071 151 EAFE 154

Ras Homolog Enriched in Brain (RheB) is a small GTPase; Rheb (Ras Homolog Enriched in Brain) subfamily. Rheb was initially identified in rat brain, where its expression is elevated by seizures or by long-term potentiation. It is expressed ubiquitously, with elevated levels in muscle and brain. Rheb functions as an important mediator between the tuberous sclerosis complex proteins, TSC1 and TSC2, and the mammalian target of rapamycin (TOR) kinase to stimulate cell growth. TOR kinase regulates cell growth by controlling nutrient availability, growth factors, and the energy status of the cell. TSC1 and TSC2 form a dimeric complex that has tumor suppressor activity, and TSC2 is a GTPase activating protein (GAP) for Rheb. The TSC1/TSC2 complex inhibits the activation of TOR kinase through Rheb. Rheb has also been shown to induce the formation of large cytoplasmic vacuoles in a process that is dependent on the GTPase cycle of Rheb, but independent of the TOR kinase, suggesting Rheb plays a role in endocytic trafficking that leads to cell growth and cell-cycle progression. 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 20070266  82 RVVLLGDPGVGKTSLASLFAGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTweAEKLDKSWSQESCLQGGSAYVIVY 161
Cdd:cd04137   3 KIAVLGSRSVGKSSLTVQFVEGHFVESYYPTIENTFSKIITYKGQEYHLEIVDT--AGQDEYSILPQKYSIGIHGYILVY 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 20070266 162 SIADRGSFESASELRIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELFE 237
Cdd:cd04137  81 SVTSRKSFEVVKVIYDKILDMLGKESVPIVLVGNKSDLHMERQVSAEEGKKLAESWGAAFLESSAKENENVEEAFE 156

Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap subfamily of the Ras family. It consists of Rap2a, Rap2b, and Rap2c. Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton. In human platelets, Rap2 was shown to interact with the cytoskeleton by binding the actin filaments. In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway. The Rap2 interacting protein 9 (RPIP9) is highly expressed in human breast carcinomas and correlates with a poor prognosis, suggesting a role for Rap2 in breast cancer oncogenesis. Rap2b, but not Rap2a, Rap2c, Rap1a, or Rap1b, is expressed in human red blood cells, where it is believed to be involved in vesiculation. A number of additional effector proteins for Rap2 have been identified, including the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. 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 20070266  81 YRVVLLGDPGVGKTSLASLFAGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEKLdkSWSQESCLQGGSAYVIV 160
Cdd:cd04176   2 YKVVVLGSGGVGKSALTVQFVSGTFIEKYDPTIEDFYRKEIEVDSSPSVLEILDTAGTEQF--ASMRDLYIKNGQGFIVV 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 20070266 161 YSIADRGSFESASELRIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELF 236
Cdd:cd04176  80 YSLVNQQTFQDIKPMRDQIVRVKGYEKVPIILVGNKVDLESEREVSSAEGRALAEEWGCPFMETSAKSKTMVNELF 155

Rap-like family consists of Rap1, Rap2 and RSR1; The Rap subfamily consists of the Rap1, Rap2, and RSR1. Rap subfamily proteins perform different cellular functions, depending on the isoform and its subcellular localization. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and microsomal membrane of the pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. Rap1 localizes in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap2 is involved in multiple functions, including activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton and activation of the Wnt/beta-catenin signaling pathway in embryonic Xenopus. A number of effector proteins for Rap2 have been identified, including isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK), and the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. RSR1 is the fungal homolog of Rap1 and Rap2. In budding yeasts, it is involved in selecting a site for bud growth, which directs the establishment of cell polarization. The Rho family GTPase Cdc42 and its GEF, Cdc24, then establish an axis of polarized growth. It is believed that Cdc42 interacts directly with RSR1 in vivo. In filamentous fungi such as Ashbya gossypii, RSR1 is a key regulator of polar growth in the hypha. 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 20070266  81 YRVVLLGDPGVGKTSLASLFAGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEKLdkSWSQESCLQGGSAYVIV 160
Cdd:cd04136   2 YKLVVLGSGGVGKSALTVQFVQGIFVDKYDPTIEDSYRKQIEVDCQQCMLEILDTAGTEQF--TAMRDLYIKNGQGFALV 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 20070266 161 YSIADRGSFESASELRIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVF-DCKFIETSATLQHNVAELF 236
Cdd:cd04136  80 YSITAQQSFNDLQDLREQILRVKDTEDVPMILVGNKCDLEDERVVSKEEGQNLARQWgNCPFLETSAKSKINVDEIF 156

Rat sarcoma (Ras) family 2 of small guanosine triphosphatases (GTPases); The Ras2 subfamily, found exclusively in fungi, was first identified in Ustilago maydis. In U. maydis, Ras2 is regulated by Sql2, a protein that is homologous to GEFs (guanine nucleotide exchange factors) of the CDC25 family. Ras2 has been shown to induce filamentous growth, but the signaling cascade through which Ras2 and Sql2 regulate cell morphology is not known. 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 20070266  82 RVVLLGDPGVGKTSLASLFAGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEK---LDKSWSQEsclqgGSAYV 158
Cdd:cd04144   1 KLVVLGDGGVGKTALTIQLCLNHFVETYDPTIEDSYRKQVVVDGQPCMLEVLDTAGQEEytaLRDQWIRE-----GEGFI 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 159 IVYSIADRGSFESASELRIQLRRT-HQADH-VPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELF 236
Cdd:cd04144  76 LVYSITSRSTFERVERFREQIQRVkDESAAdVPIMIVGNKCDKVYEREVSTEEGAALARRLGCEFIEASAKTNVNVERAF 155

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266     81 YRVVLLGDPGVGKTSLASLFAGKQERDLHEQ-LGEDVYERTLTVDGEDTTLVVVDTweAekldkswSQESCLQGGSAY-- 157
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKStIGVDFKTKTIEVDGKRVKLQIWDT--A-------GQERFRSITSSYyr 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266    158 -----VIVYSIADRGSFESASELRIQLRrTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNV 232
Cdd:smart00175  72 gavgaLLVYDITNRESFENLENWLKELR-EYASPNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSAKTNTNV 150

                   ....*
gi 20070266    233 AELFE 237
Cdd:smart00175 151 EEAFE 155

A Ras homolog member I (ARHI); ARHI (A Ras homolog member I) is a member of the Ras family with several unique structural and functional properties. ARHI is expressed in normal human ovarian and breast tissue, but its expression is decreased or eliminated in breast and ovarian cancer. ARHI contains an N-terminal extension of 34 residues (human) that is required to retain its tumor suppressive activity. Unlike most other Ras family members, ARHI is maintained in the constitutively active (GTP-bound) state in resting cells and has modest GTPase activity. ARHI inhibits STAT3 (signal transducers and activators of transcription 3), a latent transcription factor whose abnormal activation plays a critical role in oncogenesis. 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 20070266  81 YRVVLLGDPGVGKTSLASLFAGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEKLDKSwsQESCLQGGSAYVIV 160
Cdd:cd04140   2 YRVVVFGAGGVGKSSLVLRFVKGTFRESYIPTIEDTYRQVISCSKSICTLQITDTTGSHQFPAM--QRLSISKGHAFILV 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 20070266 161 YSIADRGSFESASELRIQLRRTHQAD--HVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELFE 237
Cdd:cd04140  80 YSITSKQSLEELKPIYELICEIKGNNleKIPIMLVGNKCDESPSREVSSSEGAALARTWNCAFMETSAKTNHNVQELFQ 158

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 20070266  81 YRVVLLGDPGVGKTSLASLFAGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTweAEKLDKSWSQESCLQGGSAYVIV 160
Cdd:cd04139   1 HKVIMVGSGGVGKSALTLQFMYDEFVEDYEPTKADSYRKKVVLDGEEVQLNILDT--AGQEDYAAIRDNYFRSGEGFLLV 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 20070266 161 YSIADRGSFESASELRIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELF 236
Cdd:cd04139  79 FSITDMESFTALAEFREQILRVKEDDNVPLLLVGNKCDLEDKRQVSVEEAANLAEQWGVNYVETSAKTRANVDKVF 154

RSR1/Bud1p family GTPase; RSR1/Bud1p is a member of the Rap subfamily of the Ras family that is found in fungi. In budding yeasts, RSR1 is involved in selecting a site for bud growth on the cell cortex, which directs the establishment of cell polarization. The Rho family GTPase cdc42 and its GEF, cdc24, then establish an axis of polarized growth by organizing the actin cytoskeleton and secretory apparatus at the bud site. It is believed that cdc42 interacts directly with RSR1 in vivo. In filamentous fungi, polar growth occurs at the tips of hypha and at novel growth sites along the extending hypha. In Ashbya gossypii, RSR1 is a key regulator of hyphal growth, localizing at the tip region and regulating in apical polarization of the actin cytoskeleton. 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 20070266  81 YRVVLLGDPGVGKTSLASLFAGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEKLdkSWSQESCLQGGSAYVIV 160
Cdd:cd04177   2 YKIVVLGAGGVGKSALTVQFVQNVFIESYDPTIEDSYRKQVEIDGRQCDLEILDTAGTEQF--TAMRELYIKSGQGFLLV 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 20070266 161 YSIADRGSFESASELRIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVF-DCKFIETSATLQHNVAELF 236
Cdd:cd04177  80 YSVTSEASLNELGELREQVLRIKDSDNVPMVLVGNKADLEDDRQVSREDGVSLSQQWgNVPFYETSARKRTNVDEVF 156

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266  80 LYRVVLLGDPGVGKTSLASLFAGKQERDLHE-QLGEDVYERTLTVDGEDTTLVVVDTWEAEKLdKSWSQeSCLQGGSAYV 158
Cdd:cd01866   4 LFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDlTIGVEFGARMITIDGKQIKLQIWDTAGQESF-RSITR-SYYRGAAGAL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 159 IVYSIADRGSFEsasELRIQLR--RTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVAELF 236
Cdd:cd01866  82 LVYDITRRETFN---HLTSWLEdaRQHSNSNMTIMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKTASNVEEAF 158

Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kD (TIP47). Rab9 is a key mediator of vesicular transport from late endosomes to the trans-Golgi network (TGN) by redirecting the MPRs. Rab9 has been identified as a key component for the replication of several viruses, including HIV1, Ebola, Marburg, and measles, making it a potential target for inhibiting a variety of viruses. 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 20070266  80 LYRVVLLGDPGVGKTSLASLF-AGKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEKLdKSWsQESCLQGGSAYV 158
Cdd:cd04116   5 LLKVILLGDGGVGKSSLMNRYvTNKFDTQLFHTIGVEFLNKDLEVDGHFVTLQIWDTAGQERF-RSL-RTPFYRGSDCCL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 159 IVYSIADRGSFESASELR---IQLRRTHQADHVPIILVGNKADLARcREVSVEEGRA-CAVVFDCKFIETSATLQHNVAE 234
Cdd:cd04116  83 LTFSVDDSQSFQNLSNWKkefIYYADVKEPESFPFVILGNKIDIPE-RQVSTEEAQAwCRDNGDYPYFETSAKDATNVAA 161

                ...
gi 20070266 235 LFE 237
Cdd:cd04116 162 AFE 164

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 20070266  84 VLLGDPGVGKTSLASLFAGKQ----ERDLHEQLGEDVYerTLTVDGEDTTLVVVDT---WEAEKLDKSWSQESCLQGGSA 156
Cdd:cd00882   1 VVVGRGGVGKSSLLNALLGGEvgevSDVPGTTRDPDVY--VKELDKGKVKLVLVDTpglDEFGGLGREELARLLLRGADL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 157 YVIVYSIADRGSFESASELRIQLRRTHQadhVPIILVGNKADL-ARCREVSVEEGRACAVVFDCKFIETSATLQHNVAEL 235
Cdd:cd00882  79 ILLVVDSTDRESEEDAKLLILRRLRKEG---IPIILVGNKIDLlEEREVEELLRLEELAKILGVPVFEVSAKTGEGVDEL 155

                ..
gi 20070266 236 FE 237
Cdd:cd00882 156 FE 157

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 20070266  81 YRVVLLGDPGVGKTSLASLFA-GKQERDLHEQLGEDVYERTLTVDGEDTTLVVVDTWEAEKLDKSWSqeSCLQGGSAYVI 159
Cdd:cd01863   1 LKILLIGDSGVGKSSLLLRFTdDTFDEDLSSTIGVDFKVKTVTVDGKKVKLAIWDTAGQERFRTLTS--SYYRGAQGVIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 160 VYSIADRGSFES----ASELRIQLRRthqaDHVPIILVGNKADLARcREVSVEEGRACAVVFDCKFIETSATLQHNVAEL 235
Cdd:cd01863  79 VYDVTRRDTFDNldtwLNELDTYSTN----PDAVKMLVGNKIDKEN-REVTREEGQKFARKHNMLFIETSAKTRIGVQQA 153

                ..
gi 20070266 236 FE 237
Cdd:cd01863 154 FE 155

Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, with conflicting data reported. Rab21 has been reported to localize in the ER in human intestinal epithelial cells, with partial colocalization with alpha-glucosidase, a late endosomal/lysosomal marker. More recently, Rab21 was shown to colocalize with and affect the morphology of early endosomes. In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate phagocytosis. 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 20070266  81 YRVVLLGDPGVGKTSLAS-----LFAGKQERDLHEQLgedvYERTLTVDGEDTTLVVVDTWEAEK---LDKSWSQESclQ 152
Cdd:cd04123   1 FKVVLLGEGRVGKTSLVLryvenKFNEKHESTTQASF----FQKTVNIGGKRIDLAIWDTAGQERyhaLGPIYYRDA--D 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 153 GGsayVIVYSIADRGSFESASELRIQLRRTHQaDHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNV 232
Cdd:cd04123  75 GA---ILVYDITDADSFQKVKKWIKELKQMRG-NNISLVIVGNKIDLERQRVVSKSEAEEYAKSVGAKHFETSAKTGKGI 150

                ....*.
gi 20070266 233 AELFEG 238
Cdd:cd04123 151 EELFLS 156

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266  80 LYRVVLLGDPGVGKTSLASLFAGKQERDLHEQ-LGEDVYERTLTVDGEDTTLVVVDTWEAEKLdKSWSQeSCLQGGSAYV 158
Cdd:cd01864   3 LFKIILIGDSNVGKTCVVQRFKSGTFSERQGNtIGVDFTMKTLEIQGKRVKLQIWDTAGQERF-RTITQ-SYYRSANGAI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20070266 159 IVYSIADRGSFESASELrIQLRRTHQADHVPIILVGNKADLARCREVSVEEGRACAVVFDCKF-IETSATLQHNVAELFE 237
Cdd:cd01864  81 IAYDITRRSSFESVPHW-IEEVEKYGASNVVLLLIGNKCDLEEQREVLFEEACTLAEHYGILAvLETSAKESSNVEEAFL 159