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 1371977098    4 TYRVAVLGARGVGKSAIVRQFLYNEFSEVCVPT---TTRRLylpaVVMNGHVHDLQILD------FppiSAFPvntlqew 74
Cdd:smart00010   2 EYKLVVLGGGGVGKSALTIQFVQGHFVDEYDPTiedSYRKQ----IEIDGEVCLLDILDtagqeeF---SAMR------- 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098   75 aDACcrgLRSVHAYILVYDICCFDSFEYVKTIRQQILetRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKtWKCG 154
Cdd:smart00010  68 -DQY---MRTGEGFLLVYSITDRQSFEEIAKFREQIL--RVKDRDDVPIVLVGNKCDLENERVVSTEEGKELARQ-WGCP 140

                          170       180
                   ....*....|....*....|...
gi 1371977098  155 YVECSAKYNWHILLLFSELLKSV 177
Cdd:smart00010 141 FLETSAKERINVDEAFYDLVREI 163

Ras-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098   1 MVST-YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRlYLPAVVMNGHVHDLQILDfppisafpVNTLQEWADACC 79
Cdd:PTZ00369    1 MASTeYKLVVVGGGGVGKSALTIQFIQNHFIDEYDPTIEDS-YRKQCVIDEETCLLDILD--------TAGQEEYSAMRD 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  80 RGLRSVHAYILVYDICCFDSFEYVKTIRQQILetRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVrKTWKCGYVECS 159
Cdd:PTZ00369   72 QYMRTGQGFLCVYSITSRSSFEEIASFREQIL--RVKDKDRVPMILVGNKCDLDSERQVSTGEGQELA-KSFGIPFLETS 148

                         170
                  ....*....|....*...
gi 1371977098 160 AKYNWHILLLFSELLKSV 177
Cdd:PTZ00369  149 AKQRVNVDEAFYELVREI 166

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098   6 RVAVLGARGVGKSAIVRQFLYNEFSEVCVPTT------TRRLYLPavvmNGHVhDLQILDFPPISAFPVnTLQEWAdacc 79
Cdd:COG1100     5 KIVVVGTGGVGKTSLVNRLVGDIFSLEKYLSTngvtidKKELKLD----GLDV-DLVIWDTPGQDEFRE-TRQFYA---- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  80 RGLRSVHAYILVYD--ICcfDSFEYVKTIRQQILetRVIGTSetPIIIVGNKRDLQRGRVIPRWN-VSHLVRKTWKCGYV 156
Cdd:COG1100    75 RQLTGASLYLFVVDgtRE--ETLQSLYELLESLR--RLGKKS--PIILVLNKIDLYDEEEIEDEErLKEALSEDNIVEVV 148

                         170
                  ....*....|....*....
gi 1371977098 157 ECSAKYNWHILLLFSELLK 175
Cdd:COG1100   149 ATSAKTGEGVEELFAALAE 167

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 1371977098   6 RVAVLGARGVGKSAIVRQFLYNEFSEVCVPtTTRRLYLPAVVMNGHVHDLQILDFPPISAFPvnTLQEwadaccRGLRSV 85
Cdd:cd00876     1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDP-TIEDSYRKQIVVDGETYTLDILDTAGQEEFS--AMRD------QYIRNG 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  86 HAYILVYDICCFDSFEYVKTIRQQILetRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKtWKCGYVECSAKYNWH 165
Cdd:cd00876    72 DGFILVYSITSRESFEEIKNIREQIL--RVKDKEDVPIVLVGNKCDLENERQVSTEEGEALAEE-WGCPFLETSAKTNIN 148

                         170
                  ....*....|..
gi 1371977098 166 ILLLFSELLKSV 177
Cdd:cd00876   149 IDELFNTLVREI 160

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098    5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPT---TTRRLylpaVVMNGHVHDLQILD------FppiSAFPvntlqewa 75
Cdd:smart00173   1 YKLVVLGSGGVGKSALTIQFIQGHFVDDYDPTiedSYRKQ----IEIDGEVCLLDILDtagqeeF---SAMR-------- 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098   76 DACcrgLRSVHAYILVYDICCFDSFEYVKTIRQQILetRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKtWKCGY 155
Cdd:smart00173  66 DQY---MRTGEGFLLVYSITDRQSFEEIKKFREQIL--RVKDRDDVPIVLVGNKCDLESERVVSTEEGKELARQ-WGCPF 139

                          170       180
                   ....*....|....*....|
gi 1371977098  156 VECSAKYNWHILLLFSELLK 175
Cdd:smart00173 140 LETSAKERVNVDEAFYDLVR 159

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 1371977098   6 RVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRlYLPAVVMNGHVHDLQILD---------FPPISAFpvntlqewad 76
Cdd:cd04137     3 KIAVLGSRSVGKSSLTVQFVEGHFVESYYPTIENT-FSKIITYKGQEYHLEIVDtagqdeysiLPQKYSI---------- 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  77 accrglrSVHAYILVYDICCFDSFEYVKTIRQQILETrvIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKtWKCGYV 156
Cdd:cd04137    72 -------GIHGYILVYSVTSRKSFEVVKVIYDKILDM--LGKESVPIVLVGNKSDLHMERQVSAEEGKKLAES-WGAAFL 141

                         170       180
                  ....*....|....*....|.
gi 1371977098 157 ECSAKYNWHILLLFSELLKSV 177
Cdd:cd04137   142 ESSAKENENVEEAFELLIEEI 162

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 1371977098   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTT---RRLYlpavVMNGHVHDLQILDFPPISAFPVNtlqewadaccRG 81
Cdd:cd04143     1 YRMVVLGASKVGKTAIVSRFLGGRFEEQYTPTIEdfhRKLY----SIRGEVYQLDILDTSGNHPFPAM----------RR 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  82 LRSVHA--YILVYDICCFDSFEYVKTIRQQILETRVIGTSET------PIIIVGNKRDLQRGRVIPRWNVSHLVRKTWKC 153
Cdd:cd04143    67 LSILTGdvFILVFSLDNRESFEEVCRLREQILETKSCLKNKTkenvkiPMVICGNKADRDFPREVQRDEVEQLVGGDENC 146

                         170       180
                  ....*....|....*....|
gi 1371977098 154 GYVECSAKYNWHILLLFSEL 173
Cdd:cd04143   147 AYFEVSAKKNSNLDEMFRAL 166

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 1371977098   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTtRRLYLPAVVMNGHVHDLQILDFPPISAFPvnTLQEWADAccRGlrs 84
Cdd:cd04140     2 YRVVVFGAGGVGKSSLVLRFVKGTFRESYIPTI-EDTYRQVISCSKSICTLQITDTTGSHQFP--AMQRLSIS--KG--- 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  85 vHAYILVYDICCFDSFEYVKTIRQQILETRVIGTSETPIIIVGNKRDLQRGRVIPRwNVSHLVRKTWKCGYVECSAKYNW 164
Cdd:cd04140    74 -HAFILVYSITSKQSLEELKPIYELICEIKGNNLEKIPIMLVGNKCDESPSREVSS-SEGAALARTWNCAFMETSAKTNH 151

                         170
                  ....*....|
gi 1371977098 165 HILLLFSELL 174
Cdd:cd04140   152 NVQELFQELL 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098   8 AVLGARGVGKSAIVRQFLYNEFSEVC-VPTTTRRLYLPAVVMNGHVHDLQILDFPPISAFPVNTLQEWADACCRGlrsVH 86
Cdd:cd00882     1 VVVGRGGVGKSSLLNALLGGEVGEVSdVPGTTRDPDVYVKELDKGKVKLVLVDTPGLDEFGGLGREELARLLLRG---AD 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  87 AYILVYDICCFDSFEYVKTIRQQILETRvigtsETPIIIVGNKRDLQRGRVIPRWNVSHLVRKTWKCGYVECSAKYNWHI 166
Cdd:cd00882    78 LILLVVDSTDRESEEDAKLLILRRLRKE-----GIPIILVGNKIDLLEEREVEELLRLEELAKILGVPVFEVSAKTGEGV 152

                  ....*....
gi 1371977098 167 LLLFSELLK 175
Cdd:cd00882   153 DELFEKLIE 161

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 1371977098   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTtRRLYLPAVVMNGHVHDLQILDFPPISAFpvntlqewadACCRGL-- 82
Cdd:cd04136     2 YKLVVLGSGGVGKSALTVQFVQGIFVDKYDPTI-EDSYRKQIEVDCQQCMLEILDTAGTEQF----------TAMRDLyi 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  83 RSVHAYILVYDICCFDSFEYVKTIRQQILetRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKTWKCGYVECSAKY 162
Cdd:cd04136    71 KNGQGFALVYSITAQQSFNDLQDLREQIL--RVKDTEDVPMILVGNKCDLEDERVVSKEEGQNLARQWGNCPFLETSAKS 148

                         170
                  ....*....|....*
gi 1371977098 163 NWHILLLFSELLKSV 177
Cdd:cd04136   149 KINVDEIFYDLVRQI 163

Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap subfamily of the Ras family. It can be further divided into the Rap1a and Rap1b isoforms. In humans, Rap1a and Rap1b share 95% sequence homology, but are products of two different genes located on chromosomes 1 and 12, respectively. Rap1a is sometimes called smg p21 or Krev1 in the older literature. Rap1 proteins are believed to perform different cellular functions, depending on the isoform, its subcellular localization, and the effector proteins it binds. 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 the microsomal membrane of pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. High expression of Rap1 has been observed in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines; interestingly, in the SCCs, the active GTP-bound form localized to the nucleus, while the inactive GDP-bound form localized to the cytoplasm. 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. Rap1a, which is stimulated by T-cell receptor (TCR) activation, is a positive regulator of T cells by directing integrin activation and augmenting lymphocyte responses. In murine hippocampal neurons, Rap1b determines which neurite will become the axon and directs the recruitment of Cdc42, which is required for formation of dendrites and axons. In murine platelets, Rap1b is required for normal homeostasis in vivo and is involved in integrin activation. 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 1371977098   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRlYLPAVVMNGHVHDLQILDFPPISAFpvntlqewadACCRGL-- 82
Cdd:cd04175     2 YKLVVLGSGGVGKSALTVQFVQGIFVEKYDPTIEDS-YRKQVEVDGQQCMLEILDTAGTEQF----------TAMRDLym 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  83 RSVHAYILVYDICCFDSFEYVKTIRQQILetRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKtWKCGYVECSAKY 162
Cdd:cd04175    71 KNGQGFVLVYSITAQSTFNDLQDLREQIL--RVKDTEDVPMILVGNKCDLEDERVVGKEQGQNLARQ-WGCAFLETSAKA 147

                         170
                  ....*....|....*
gi 1371977098 163 NWHILLLFSELLKSV 177
Cdd:cd04175   148 KINVNEIFYDLVRQI 162

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 1371977098   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRLYLPAVVMNGHVHDLQILDFPPisafpvNTLQEWADACCrgLRS 84
Cdd:cd04148     1 YRVVLLGDSGVGKSSLANIFTAGVYEDSAYEASGDDTYERTVSVDGEEATLVVYDHWE------QEDGMWLEDSC--MQV 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1371977098  85 VHAYILVYDICCFDSFEYVKTIRQQILETRVigTSETPIIIVGNKRDLQRGRVIPRWNVSHLVrKTWKCGYVECSA 160
Cdd:cd04148    73 GDAYVIVYSVTDRSSFEKASELRIQLRRARQ--AEDIPIILVGNKSDLVRSREVSVQEGRACA-VVFDCKFIETSA 145

R-Ras2/TC21, M-Ras/R-Ras3; The M-Ras/R-Ras-like subfamily contains R-Ras2/TC21, M-Ras/R-Ras3, and related members of the Ras family. M-Ras is expressed in lympho-hematopoetic cells. It interacts with some of the known Ras effectors, but appears to also have its own effectors. Expression of mutated M-Ras leads to transformation of several types of cell lines, including hematopoietic cells, mammary epithelial cells, and fibroblasts. Overexpression of M-Ras is observed in carcinomas from breast, uterus, thyroid, stomach, colon, kidney, lung, and rectum. In addition, expression of a constitutively active M-Ras mutant in murine bone marrow induces a malignant mast cell leukemia that is distinct from the monocytic leukemia induced by H-Ras. TC21, along with H-Ras, has been shown to regulate the branching morphogenesis of ureteric bud cell branching in mice. 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 1371977098   4 TYRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRlYLPAVVMNGHVHDLQILDFPPISAFpvNTLQEwadaccRGLR 83
Cdd:cd04145     2 TYKLVVVGGGGVGKSALTIQFIQSYFVTDYDPTIEDS-YTKQCEIDGQWARLDILDTAGQEEF--SAMRE------QYMR 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  84 SVHAYILVYDICCFDSFEYVKTIRQQILetRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKtWKCGYVECSAKYN 163
Cdd:cd04145    73 TGEGFLLVFSVTDRGSFEEVDKFHTQIL--RVKDRDEFPMILVGNKADLEHQRQVSREEGQELARQ-LKIPYIETSAKDR 149

                         170
                  ....*....|....
gi 1371977098 164 WHILLLFSELLKSV 177
Cdd:cd04145   150 VNVDKAFHDLVRVI 163

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098    5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPT-----TTRRLYLPavvmnGHVHDLQILD------FPPI-SAFpvntlq 72
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTigvdfKTKTIEVD-----GKRVKLQIWDtagqerFRSItSSY------ 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098   73 ewadaccrgLRSVHAYILVYDICCFDSFEYVKTIRQQIletRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKTwK 152
Cdd:smart00175  70 ---------YRGAVGALLVYDITNRESFENLENWLKEL---REYASPNVVIMLVGNKSDLEEQRQVSREEAEAFAEEH-G 136

                          170       180
                   ....*....|....*....|....*
gi 1371977098  153 CGYVECSAKYNWHILLLFSELLKSV 177
Cdd:smart00175 137 LPFFETSAKTNTNVEEAFEELAREI 161

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 1371977098   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRLYLPAVVMNGHVHDLQILDfppisafpvnTL-QEWADAccrgL- 82
Cdd:cd04123     1 FKVVLLGEGRVGKTSLVLRYVENKFNEKHESTTQASFFQKTVNIGGKRIDLAIWD----------TAgQERYHA----Lg 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  83 ----RSVHAYILVYDICCFDSFEYVktiRQQILETRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVrKTWKCGYVEC 158
Cdd:cd04123    67 piyyRDADGAILVYDITDADSFQKV---KKWIKELKQMRGNNISLVIVGNKIDLERQRVVSKSEAEEYA-KSVGAKHFET 142

                         170
                  ....*....|....*....
gi 1371977098 159 SAKYNWHILLLFSELLKSV 177
Cdd:cd04123   143 SAKTGKGIEELFLSLAKRM 161

Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The Rab5-related subfamily includes Rab5 and Rab22 of mammals, Ypt51/Ypt52/Ypt53 of yeast, and RabF of plants. The members of this subfamily are involved in endocytosis and endocytic-sorting pathways. In mammals, Rab5 GTPases localize to early endosomes and regulate fusion of clathrin-coated vesicles to early endosomes and fusion between early endosomes. In yeast, Ypt51p family members similarly regulate membrane trafficking through prevacuolar compartments. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098   4 TYRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTtRRLYLPAVVM-NGHVHDLQILDfppisafpvnTL-QEWADACC-- 79
Cdd:cd01860     1 QFKLVLLGDSSVGKSSIVLRFVKNEFSENQESTI-GAAFLTQTVNlDDTTVKFEIWD----------TAgQERYRSLApm 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  80 --RGLRsvhAYILVYDICCFDSFEYVKTirqQILETRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKTwKCGYVE 157
Cdd:cd01860    70 yyRGAA---AAIVVYDITSEESFEKAKS---WVKELQEHGPPNIVIALAGNKADLESKRQVSTEEAQEYADEN-GLLFME 142

                         170
                  ....*....|....*.
gi 1371977098 158 CSAKYNWHILLLFSEL 173
Cdd:cd01860   143 TSAKTGENVNELFTEI 158

Rab GTPase family 30 (Rab30); Rab30 subfamily. Rab30 appears to be associated with the Golgi stack. It is expressed in a wide variety of tissue types and in humans maps to chromosome 11. 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 1371977098   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRLYLPAVVMNGHVHDLQILDFPPISAFPVNTLQEWadaccrglRS 84
Cdd:cd04114     8 FKIVLIGNAGVGKTCLVRRFTQGLFPPGQGATIGVDFMIKTVEIKGEKIKLQIWDTAGQERFRSITQSYY--------RS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  85 VHAYILVYDICCFDSF----EYVKTIrQQILETRVIGtsetpiIIVGNKRDLQRGRVIPRwNVSHLVRKTWKCGYVECSA 160
Cdd:cd04114    80 ANALILTYDITCEESFrclpEWLREI-EQYANNKVIT------ILVGNKIDLAERREVSQ-QRAEEFSDAQDMYYLETSA 151

                         170
                  ....*....|...
gi 1371977098 161 KYNWHILLLFSEL 173
Cdd:cd04114   152 KESDNVEKLFLDL 164

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 1371977098   6 RVAVLGARGVGKSAIVRQFLYNEFSEVcVPTTTRRLYLPAVVMNGHVhDLQILDFppiSAFPVNTlqEWADACCrglRSV 85
Cdd:cd01893     4 RIVLIGDEGVGKSSLIMSLVSEEFPEN-VPRVLPEITIPADVTPERV-PTTIVDT---SSRPQDR--ANLAAEI---RKA 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  86 HAYILVYDICCFDSFEYVKTIRqqILETRVIGTsETPIIIVGNKRDLQRGRVIPRW-NVSHLVRKTWK----CgyVECSA 160
Cdd:cd01893    74 NVICLVYSVDRPSTLERIRTKW--LPLIRRLGV-KVPIILVGNKSDLRDGSSQAGLeEEMLPIMNEFReietC--VECSA 148

                  .
gi 1371977098 161 K 161
Cdd:cd01893   149 K 149

Rab GTPase family 12 (Rab12); Rab12 was first identified in canine cells, where it was localized to the Golgi complex. The specific function of Rab12 remains unknown, and inconsistent results about its cellular localization have been reported. More recent studies have identified Rab12 associated with post-Golgi vesicles, or with other small vesicle-like structures but not with the Golgi complex. 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. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098   6 RVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRLYLPAVVMNGHVHDLQILDFPPISAFPVNTLQEWadaccrglRSV 85
Cdd:cd04120     2 QVIIIGSRGVGKTSLMERFTDDTFCEACKSTVGVDFKIKTVELRGKKIRLQIWDTAGQERFNSITSAYY--------RSA 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977098  86 HAYILVYDICCFDSFE----YVKTIRQQILEtrvigtsETPIIIVGNKRDLQRGRVIPRWNVSHLVRKTWKCGYVECSAK 161
Cdd:cd04120    74 KGIILVYDITKKETFDdlpkWMKMIDKYASE-------DAELLLVGNKLDCETDREITRQQGEKFAQQITGMRFCEASAK 146

                         170
                  ....*....|....*.
gi 1371977098 162 YNWHILLLFSELLKSV 177
Cdd:cd04120   147 DNFNVDEIFLKLVDDI 162