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 124248562   115 FKVMLVGESGVGKSTLAGTFggLQG--DSAHEPeNPEDTYERRIMVDKEEVTLVVYDIweqgdAG----GWLRDHCLQTG 188
Cdd:smart00173   1 YKLVVLGSGGVGKSALTIQF--IQGhfVDDYDP-TIEDSYRKQIEIDGEVCLLDILDT-----AGqeefSAMRDQYMRTG 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562   189 DAFLIVFSVTDRRSF---SKVPETLLRLRaGRphHDLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHN 265
Cdd:smart00173  73 EGFLLVYSITDRQSFeeiKKFREQILRVK-DR--DDVPIVLVGNKCDLESERVVSTEEGKELARQWGCPFLETSAKERVN 149

                          170
                   ....*....|...
gi 124248562   266 TRELFEGAVRQIR 278
Cdd:smart00173 150 VDEAFYDLVREIR 162

Ras-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 115 FKVMLVGESGVGKSTLAGTFGGLQGDSAHEPeNPEDTYERRIMVDKEEVTLVVYDIWEQGDAGGwLRDHCLQTGDAFLIV 194
Cdd:PTZ00369   6 YKLVVVGGGGVGKSALTIQFIQNHFIDEYDP-TIEDSYRKQCVIDEETCLLDILDTAGQEEYSA-MRDQYMRTGQGFLCV 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 195 FSVTDRRSFSKVP---ETLLRLRagrPHHDLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHNTRELFE 271
Cdd:PTZ00369  84 YSITSRSSFEEIAsfrEQILRVK---DKDRVPMILVGNKCDLDSERQVSTGEGQELAKSFGIPFLETSAKQRVNVDEAFY 160

                        170       180
                 ....*....|....*....|....*...
gi 124248562 272 GAVRQIRlrrgRNHAGGQRPDPGSPEGP 299
Cdd:PTZ00369 161 ELVREIR----KYLKEDMPSQKQKKKGG 184

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 124248562  114 IFKVMLVGESGVGKSTLAGTFGGLQGdSAHE--PENPEDTYERRIMVDKEEVTLVVYDIWEQgDAGGWLRDHCLQTGDAF 191
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGNKG-SITEyyPGTTRNYVTTVIEEDGKTYKFNLLDTAGQ-EDYDAIRRLYYPQVERS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562  192 LIVFSVTDRR-SFSKVPETLLRLRAGRPHHDLPVILVGNKSDLaRSREVSLEEGRHLAGTLSCKHIETSAALHHNTRELF 270
Cdd:TIGR00231  79 LRVFDIVILVlDVEEILEKQTKEIIHHADSGVPIILVGNKIDL-KDADLKTHVASEFAKLNGEPIIPLSAETGKNIDSAF 157

                  .
gi 124248562  271 E 271
Cdd:TIGR00231 158 K 158

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 124248562 116 KVMLVGESGVGKSTLAGTFGGLQGDSAHEPeNPEDTYERRIMVDKEEVTLVVYDIWEQgDAGGWLRDHCLQTGDAFLIVF 195
Cdd:cd00876    1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDP-TIEDSYRKQIVVDGETYTLDILDTAGQ-EEFSAMRDQYIRNGDGFILVY 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 196 SVTDRRSFSKVPETLLRLRAGRPHHDLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHNTRELFEGAVR 275
Cdd:cd00876   79 SITSRESFEEIKNIREQILRVKDKEDVPIVLVGNKCDLENERQVSTEEGEALAEEWGCPFLETSAKTNINIDELFNTLVR 158

                 ..
gi 124248562 276 QI 277
Cdd:cd00876  159 EI 160

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 124248562   115 FKVMLVGESGVGKSTLAGTFggLQG--DSAHEPeNPEDTYERRIMVDKEEVTLVVYDIweqgdAG----GWLRDHCLQTG 188
Cdd:smart00010   3 YKLVVLGGGGVGKSALTIQF--VQGhfVDEYDP-TIEDSYRKQIEIDGEVCLLDILDT-----AGqeefSAMRDQYMRTG 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562   189 DAFLIVFSVTDRRSF---SKVPETLLRLRaGRphHDLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHN 265
Cdd:smart00010  75 EGFLLVYSITDRQSFeeiAKFREQILRVK-DR--DDVPIVLVGNKCDLENERVVSTEEGKELARQWGCPFLETSAKERIN 151

                          170
                   ....*....|....*
gi 124248562   266 TRELFEGAVRQIRLR 280
Cdd:smart00010 152 VDEAFYDLVREIRKS 166

Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like families; RERG (Ras-related and Estrogen- Regulated Growth inhibitor) and Ras-like 11 are members of a novel subfamily of Ras that were identified based on their behavior in breast and prostate tumors, respectively. RERG expression was decreased or lost in a significant fraction of primary human breast tumors that lack estrogen receptor and are correlated with poor clinical prognosis. Elevated RERG expression correlated with favorable patient outcome in a breast tumor subtype that is positive for estrogen receptor expression. In contrast to most Ras proteins, RERG overexpression inhibited the growth of breast tumor cells in vitro and in vivo. RasL11 was found to be ubiquitously expressed in human tissue, but down-regulated in prostate tumors. Both RERG and RasL11 lack the C-terminal CaaX prenylation motif, where a = an aliphatic amino acid and X = any amino acid, and are localized primarily in the cytoplasm. Both are believed to have tumor suppressor activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 116 KVMLVGESGVGKSTLAGTFggLQ----GDSAHepeNPEDTYERRIMVDKEEVTLVVYD-IWEQGDAGGWLRDHCLQTGDA 190
Cdd:cd04146    1 KIAVLGASGVGKSALTVRF--LTkrfiGEYEP---NLESLYSRQVTIDGEQVSLEIQDtPGQQQNEDPESLERSLRWADG 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 191 FLIVFSVTDRRSFSKVPETLLRLRAGRPHH-DLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAAL-HHNTRE 268
Cdd:cd04146   76 FVLVYSITDRSSFDVVSQLLQLIREIKKRDgEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAEnYLEVQN 155

                        170
                 ....*....|
gi 124248562 269 LFEGAVRQIR 278
Cdd:cd04146  156 VFHELCREVR 165

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 124248562 115 FKVMLVGESGVGKSTLAGTFGGLQGDSAHEPeNPEDTYERRIMVDKEEVTLVVYDIWEQGDAGGwLRDHCLQTGDAFLIV 194
Cdd:cd04145    3 YKLVVVGGGGVGKSALTIQFIQSYFVTDYDP-TIEDSYTKQCEIDGQWARLDILDTAGQEEFSA-MREQYMRTGEGFLLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 195 FSVTDRRSFSKVP---ETLLRLRagrPHHDLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHNTRELFE 271
Cdd:cd04145   81 FSVTDRGSFEEVDkfhTQILRVK---DRDEFPMILVGNKADLEHQRQVSREEGQELARQLKIPYIETSAKDRVNVDKAFH 157

                 ....*..
gi 124248562 272 GAVRQIR 278
Cdd:cd04145  158 DLVRVIR 164

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 124248562 115 FKVMLVGESGVGKSTLAGTFGGLQGDSAHEPeNPEDTYERRIMVDKEEVTLVVYDIWEQGDAGGwLRDHCLQTGDAFLIV 194
Cdd:cd04139    1 HKVIMVGSGGVGKSALTLQFMYDEFVEDYEP-TKADSYRKKVVLDGEEVQLNILDTAGQEDYAA-IRDNYFRSGEGFLLV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 195 FSVTDRRSFSKVPEtlLRLRAGRPHHD--LPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHNTRELFEG 272
Cdd:cd04139   79 FSITDMESFTALAE--FREQILRVKEDdnVPLLLVGNKCDLEDKRQVSVEEAANLAEQWGVNYVETSAKTRANVDKVFFD 156

                 ....*.
gi 124248562 273 AVRQIR 278
Cdd:cd04139  157 LVREIR 162

Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active (GTP-bound) Ras interacts with several effector proteins that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 115 FKVMLVGESGVGKSTLagTFGGLQGDSAHEpENP--EDTYERRIMVDKEEVTLVVYDIWEQGDAGGwLRDHCLQTGDAFL 192
Cdd:cd04138    2 YKLVVVGAGGVGKSAL--TIQLIQNHFVDE-YDPtiEDSYRKQVVIDGETCLLDILDTAGQEEYSA-MRDQYMRTGEGFL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 193 IVFSVTDRRSFSKVP---ETLLRLragRPHHDLPVILVGNKSDLArSREVSLEEGRHLAGTLSCKHIETSAALHHNTREL 269
Cdd:cd04138   78 CVFAINSRKSFEDIHtyrEQIKRV---KDSDDVPMVLVGNKCDLA-ARTVSTRQGQDLAKSYGIPYIETSAKTRQGVEEA 153

                 ....*....
gi 124248562 270 FEGAVRQIR 278
Cdd:cd04138  154 FYTLVREIR 162

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 124248562 115 FKVMLVGESGVGKSTLAGTFggLQGDSAHE--PeNPEDTYERRIMVDKEEVTLVVYDIwEQGDAGGWLRDHCLQTGDAFL 192
Cdd:cd04140    2 YRVVVFGAGGVGKSSLVLRF--VKGTFRESyiP-TIEDTYRQVISCSKSICTLQITDT-TGSHQFPAMQRLSISKGHAFI 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 193 IVFSVTDRRSFSKVPE--TLLRLRAGRPHHDLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHNTRELF 270
Cdd:cd04140   78 LVYSITSKQSLEELKPiyELICEIKGNNLEKIPIMLVGNKCDESPSREVSSSEGAALARTWNCAFMETSAKTNHNVQELF 157

                 .
gi 124248562 271 E 271
Cdd:cd04140  158 Q 158

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 124248562 115 FKVMLVGESGVGKSTLAGTFggLQGDSAhEPENP--EDTYERRIMVDKEEVTLVVYDI--WEQGDAggwLRDHCLQTGDA 190
Cdd:cd04136    2 YKLVVLGSGGVGKSALTVQF--VQGIFV-DKYDPtiEDSYRKQIEVDCQQCMLEILDTagTEQFTA---MRDLYIKNGQG 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 191 FLIVFSVTDRRSFSKVP---ETLLRLRAgrpHHDLPVILVGNKSDLARSREVSLEEGRHLAGTL-SCKHIETSAALHHNT 266
Cdd:cd04136   76 FALVYSITAQQSFNDLQdlrEQILRVKD---TEDVPMILVGNKCDLEDERVVSKEEGQNLARQWgNCPFLETSAKSKINV 152

                        170
                 ....*....|.
gi 124248562 267 RELFEGAVRQI 277
Cdd:cd04136  153 DEIFYDLVRQI 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 124248562 115 FKVMLVGESGVGKSTLAGTFggLQGDSAhEPENP--EDTYERRIMVDKEEVTLVVYDI--WEQGDAggwLRDHCLQTGDA 190
Cdd:cd04175    2 YKLVVLGSGGVGKSALTVQF--VQGIFV-EKYDPtiEDSYRKQVEVDGQQCMLEILDTagTEQFTA---MRDLYMKNGQG 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 191 FLIVFSVTDRRSFSKVP---ETLLRLRagrPHHDLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHNTR 267
Cdd:cd04175   76 FVLVYSITAQSTFNDLQdlrEQILRVK---DTEDVPMILVGNKCDLEDERVVGKEQGQNLARQWGCAFLETSAKAKINVN 152

                        170
                 ....*....|
gi 124248562 268 ELFEGAVRQI 277
Cdd:cd04175  153 EIFYDLVRQI 162

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 124248562 119 LVGESGVGKSTLAGT-FGGLQGDSAHEPENPEDTYERRIMVDKEEVTLVVYDIWEQGDAGG----WLRDHCLQTGDAFLI 193
Cdd:cd00882    2 VVGRGGVGKSSLLNAlLGGEVGEVSDVPGTTRDPDVYVKELDKGKVKLVLVDTPGLDEFGGlgreELARLLLRGADLILL 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 124248562 194 VFSVTDRRSFSKVPETLLRLRAGrphHDLPVILVGNKSDLARSREVS-LEEGRHLAGTLSCKHIETSAALHHNTRELFE 271
Cdd:cd00882   82 VVDSTDRESEEDAKLLILRRLRK---EGIPIILVGNKIDLLEEREVEeLLRLEELAKILGVPVFEVSAKTGEGVDELFE 157

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 124248562 116 KVMLVGESGVGKSTLAgtfggLQGDSAHEPEN--P--EDTYERRIMVDKEEVTLVVYDIWEQgDAGGWLRDHCLQTGDAF 191
Cdd:cd04137    3 KIAVLGSRSVGKSSLT-----VQFVEGHFVESyyPtiENTFSKIITYKGQEYHLEIVDTAGQ-DEYSILPQKYSIGIHGY 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 192 LIVFSVTDRRSFSKVP---ETLLRLRaGRPHhdLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHNTRE 268
Cdd:cd04137   77 ILVYSVTSRKSFEVVKviyDKILDML-GKES--VPIVLVGNKSDLHMERQVSAEEGKKLAESWGAAFLESSAKENENVEE 153

                        170       180
                 ....*....|....*....|...
gi 124248562 269 LFEGAVRQIRLRRGRNHAGGQRP 291
Cdd:cd04137  154 AFELLIEEIEKVENPLPPGQKSK 176

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 124248562 115 FKVMLVGESGVGKSTLAGTFGGLQGDSAHEPENPEDTYERRIMVDKEEVTLvvyDIWeqgDAGGWLRDHCLQTG---DAF 191
Cdd:cd01861    1 HKLVFLGDQSVGKTSIITRFMYDTFDNQYQATIGIDFLSKTMYVDDKTVRL---QLW---DTAGQERFRSLIPSyirDSS 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 192 --LIVFSVTDRRSFSKVPE--TLLRLRAGrphHDLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETSAALHHNTR 267
Cdd:cd01861   75 vaVVVYDITNRQSFDNTDKwiDDVRDERG---NDVIIVLVGNKTDLSDKRQVSTEEGEKKAKENNAMFIETSAKAGHNVK 151

                 ....
gi 124248562 268 ELFE 271
Cdd:cd01861  152 QLFK 155

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 124248562 116 KVMLVGESGVGKSTL-----AGTFgglqgdsahePEN--P--EDTYERRIMVDKEEVTLVVYDIWEQGDAGGwLRDHCLQ 186
Cdd:cd00157    2 KIVVVGDGAVGKTCLlisytTNKF----------PTEyvPtvFDNYSANVTVDGKQVNLGLWDTAGQEEYDR-LRPLSYP 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 187 TGDAFLIVFSVTDRRSFSKV-----PEtlLRlragrpHH--DLPVILVGNKSDL-----------ARSREVSLEEGRHLA 248
Cdd:cd00157   71 QTDVFLLCFSVDSPSSFENVktkwyPE--IK------HYcpNVPIILVGTKIDLrddgntlkkleKKQKPITPEEGEKLA 142

                        170       180
                 ....*....|....*....|....*...
gi 124248562 249 GTLSC-KHIETSAALHHNTRELFEGAVR 275
Cdd:cd00157  143 KEIGAvKYMECSALTQEGLKEVFDEAIR 170

Rab GTPase families 8, 10, 13 (Rab8, Rab10, Rab13); Rab8/Sec4/Ypt2 are known or suspected to be involved in post-Golgi transport to the plasma membrane. It is likely that these Rabs have functions that are specific to the mammalian lineage and have no orthologs in plants. Rab8 modulates polarized membrane transport through reorganization of actin and microtubules, induces the formation of new surface extensions, and has an important role in directed membrane transport to cell surfaces. The Ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the Ypt/Rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian Rab8. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 112 DGIFKVMLVGESGVGKSTLAGTFgglqgdsAHEPENPE-------DTYERRIMVDKEEVTLvvyDIWeqgDAGGWLRDHC 184
Cdd:cd01867    1 DYLFKLLLIGDSGVGKSCLLLRF-------SEDSFNPSfistigiDFKIRTIELDGKKIKL---QIW---DTAGQERFRT 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124248562 185 LQT-----GDAFLIVFSVTDRRSFSKVpETLLRLRAGRPHHDLPVILVGNKSDLARSREVSLEEGRHLAGTLSCKHIETS 259
Cdd:cd01867   68 ITTsyyrgAMGIILVYDITDEKSFENI-KNWMRNIDEHASEDVERMLVGNKCDMEEKRVVSKEEGEALAREYGIKFLETS 146

                        170       180
                 ....*....|....*....|.
gi 124248562 260 AALHHNTRELFEGAVRQIRLR 280
Cdd:cd01867  147 AKANINVEEAFLTLAKDILKK 167