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 13376046   6 HLKYNEKSVSVTKALTVRFLTKRFIGEYASNFESIYKKHLCLERKQLNLEIYDPCSQTQ-KAKFSLTSELHWADGFVIVY 84
Cdd:cd04146   1 KIAVLGASGVGKSALTVRFLTKRFIGEYEPNLESLYSRQVTIDGEQVSLEIQDTPGQQQnEDPESLERSLRWADGFVLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046  85 DISDRSSFAFAKALIYRIREPQtshcKRAVESAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSAAEQSLEVEMM 164
Cdd:cd04146  81 SITDRSSFDVVSQLLQLIREIK----KRDGEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAENYLEVQNV 156

                       170
                ....*....|
gi 13376046 165 FIRIIKDILI 174
Cdd:cd04146 157 FHELCREVRR 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 13376046   6 HLKYNEKSVSVTKALTVRFLTKRFIGEYASNFESIYKKHLCLERKQLNLEIYDPCSQTQ-KAKFSLTSELHWADGFVIVY 84
Cdd:cd04146   1 KIAVLGASGVGKSALTVRFLTKRFIGEYEPNLESLYSRQVTIDGEQVSLEIQDTPGQQQnEDPESLERSLRWADGFVLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046  85 DISDRSSFAFAKALIYRIREPQtshcKRAVESAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSAAEQSLEVEMM 164
Cdd:cd04146  81 SITDRSSFDVVSQLLQLIREIK----KRDGEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAENYLEVQNV 156

                       170
                ....*....|
gi 13376046 165 FIRIIKDILI 174
Cdd:cd04146 157 FHELCREVRR 166

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 13376046    19 ALTVRFLTKRFIGEYAS--NFESiYKKHLCLERKQLNLEIYDPCSQTqkaKFSLTSELHW--ADGFVIVYDISDRSSFAF 94
Cdd:pfam00071  14 SLLIRFTQNKFPEEYIPtiGVDF-YTKTIEVDGKTVKLQIWDTAGQE---RFRALRPLYYrgADGFLLVYDITSRDSFEN 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13376046    95 AKALIYRIREpqtsHCKRAVesAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSaAEQSLEVEMMFIRIIKDIL 173
Cdd:pfam00071  90 VKKWVEEILR----HADENV--PIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETS-AKTNENVEEAFEELAREIL 161

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046  25 LTKRFIGEYASNFES-------IYKKHLCLERKQLNLEIYDPCSQTQKAKF--SLTSELHWADGFVIVYDISDRSSFAFA 95
Cdd:COG1100  19 LVNRLVGDIFSLEKYlstngvtIDKKELKLDGLDVDLVIWDTPGQDEFRETrqFYARQLTGASLYLFVVDGTREETLQSL 98

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13376046  96 KALIYRIREpqtshckRAVESAVFLVGNKRDLCHVREVGWEEGQKLAL--ENRCQFCELSAAEqSLEVEMMFIRIIK 170
Cdd:COG1100  99 YELLESLRR-------LGKKSPIILVLNKIDLYDEEEIEDEERLKEALseDNIVEVVATSAKT-GEGVEELFAALAE 167

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 13376046   6 HLKYNEKSVSVTKALTVRFLTKRFIGEYASNFESIYKKHLCLERKQLNLEIYDPCSQTQ-KAKFSLTSELHWADGFVIVY 84
Cdd:cd04146   1 KIAVLGASGVGKSALTVRFLTKRFIGEYEPNLESLYSRQVTIDGEQVSLEIQDTPGQQQnEDPESLERSLRWADGFVLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046  85 DISDRSSFAFAKALIYRIREPQtshcKRAVESAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSAAEQSLEVEMM 164
Cdd:cd04146  81 SITDRSSFDVVSQLLQLIREIK----KRDGEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAENYLEVQNV 156

                       170
                ....*....|
gi 13376046 165 FIRIIKDILI 174
Cdd:cd04146 157 FHELCREVRR 166

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 13376046     19 ALTVRFLTKRFIGEYASNFESIYKKHLCLERKQLNLEIYDPCSQTQkakFSLTSELHW--ADGFVIVYDISDRSSFAFAK 96
Cdd:smart00173  15 ALTIQFIQGHFVDDYDPTIEDSYRKQIEIDGEVCLLDILDTAGQEE---FSAMRDQYMrtGEGFLLVYSITDRQSFEEIK 91

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13376046     97 AL---IYRIrepqtshcKRAVESAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSAAEQSlEVEMMFIRIIKDI 172
Cdd:smart00173  92 KFreqILRV--------KDRDDVPIVLVGNKCDLESERVVSTEEGKELARQWGCPFLETSAKERV-NVDEAFYDLVREI 161

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 13376046    19 ALTVRFLTKRFIGEYAS--NFESiYKKHLCLERKQLNLEIYDPCSQTqkaKFSLTSELHW--ADGFVIVYDISDRSSFAF 94
Cdd:pfam00071  14 SLLIRFTQNKFPEEYIPtiGVDF-YTKTIEVDGKTVKLQIWDTAGQE---RFRALRPLYYrgADGFLLVYDITSRDSFEN 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13376046    95 AKALIYRIREpqtsHCKRAVesAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSaAEQSLEVEMMFIRIIKDIL 173
Cdd:pfam00071  90 VKKWVEEILR----HADENV--PIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETS-AKTNENVEEAFEELAREIL 161

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 13376046  38 ESIYKKHLCLERKQLNLEIYDPCSQtQKAKFSLTSELHWADGFVIVYDISDRSSFAFAKALIYRIREPQTSHckravESA 117
Cdd:cd04148  35 DDTYERTVSVDGEEATLVVYDHWEQ-EDGMWLEDSCMQVGDAYVIVYSVTDRSSFEKASELRIQLRRARQAE-----DIP 108

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046 118 VFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSAAEQSlEVEMMFIRIIKDIlinfKLKEKRRPSGSKSMAKlinnv 197
Cdd:cd04148 109 IILVGNKSDLVRSREVSVQEGRACAVVFDCKFIETSAALQH-NVDELFEGIVRQV----RLRRDSKEKNTRRMAS----- 178

                ....*...
gi 13376046 198 fGKRRKSV 205
Cdd:cd04148 179 -RKRRESI 185

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 13376046  19 ALTVRFLTKRFIGEYASNFESIYKKHLCLERKQLNLEIYDPCSQTQkakFSLTSELHWAD--GFVIVYDISDRSSFAFAK 96
Cdd:cd04136  16 ALTVQFVQGIFVDKYDPTIEDSYRKQIEVDCQQCMLEILDTAGTEQ---FTAMRDLYIKNgqGFALVYSITAQQSFNDLQ 92

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13376046  97 ALiyriREpQTSHCKRAVESAVFLVGNKRDLCHVREVGWEEGQKLALE-NRCQFCELSAAEQSLeVEMMFIRIIKDI 172
Cdd:cd04136  93 DL----RE-QILRVKDTEDVPMILVGNKCDLEDERVVSKEEGQNLARQwGNCPFLETSAKSKIN-VDEIFYDLVRQI 163

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 13376046  19 ALTVRFLTKRFIGEYASNFESIYKKHLCLERKQLNLEIYDPCSQTQkakFSLTSE--LHWADGFVIVYDISDRSSFAFAK 96
Cdd:cd04145  17 ALTIQFIQSYFVTDYDPTIEDSYTKQCEIDGQWARLDILDTAGQEE---FSAMREqyMRTGEGFLLVFSVTDRGSFEEVD 93

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13376046  97 ALiyrirEPQTSHCKRAVESAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSaAEQSLEVEMMF---IRIIK 170
Cdd:cd04145  94 KF-----HTQILRVKDRDEFPMILVGNKADLEHQRQVSREEGQELARQLKIPYIETS-AKDRVNVDKAFhdlVRVIR 164

Ras-like protein in all tissues (Rit), Ras-like protein in neurons (Rin) and Ras-related protein which interacts with calmodulin (Ric); Rit (Ras-like protein in all tissues), Rin (Ras-like protein in neurons) and Ric (Ras-related protein which interacts with calmodulin) form a subfamily with several unique structural and functional characteristics. These proteins all lack a the C-terminal CaaX lipid-binding motif typical of Ras family proteins, and Rin and Ric contain calmodulin-binding domains. Rin, which is expressed only in neurons, induces neurite outgrowth in rat pheochromocytoma cells through its association with calmodulin and its activation of endogenous Rac/cdc42. Rit, which is ubiquitously expressed in mammals, inhibits growth-factor withdrawl-mediated apoptosis and induces neurite extension in pheochromocytoma cells. Rit and Rin are both able to form a ternary complex with PAR6, a cell polarity-regulating protein, and Rac/cdc42. This ternary complex is proposed to have physiological function in processes such as tumorigenesis. Activated Ric is likely to signal in parallel with the Ras pathway or stimulate the Ras pathway at some upstream point, and binding of calmodulin to Ric may negatively regulate Ric activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046  19 ALTVRFLTKRFIGEYASNFESIYKKHLCLERKQLNLEIYDPCSQtqkAKFSLTSE--LHWADGFVIVYDISDRSSFAFA- 95
Cdd:cd04141  17 AVTMQFISHSFPDYHDPTIEDAYKTQARIDNEPALLDILDTAGQ---AEFTAMRDqyMRCGEGFIICYSVTDRHSFQEAs 93

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13376046  96 --KALIYRIRepqtshckRAVESAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSAA 155
Cdd:cd04141  94 efKELITRVR--------LTEDIPLVLVGNKVDLEQQRQVTTEEGRNLAREFNCPFFETSAA 147

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 13376046  13 SVSVTK-ALTVRFLTKRFIGEYASNFESIYKKHLCLERKQLNLEIYDPCSQTQkakFSLTSELHWAD--GFVIVYDISDR 89
Cdd:cd04137   9 SRSVGKsSLTVQFVEGHFVESYYPTIENTFSKIITYKGQEYHLEIVDTAGQDE---YSILPQKYSIGihGYILVYSVTSR 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046  90 SSFAFAKAliyrIREPQTSHCKrAVESAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSaAEQSLEVEMMFIRII 169
Cdd:cd04137  86 KSFEVVKV----IYDKILDMLG-KESVPIVLVGNKSDLHMERQVSAEEGKKLAESWGAAFLESS-AKENENVEEAFELLI 159

                ...
gi 13376046 170 KDI 172
Cdd:cd04137 160 EEI 162

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 13376046  47 LERKQLNLEIYDPCSQtQKAKFSLTSELHWADGFVIVYDISDRSSFAFAKALIYRIREpqtsHCKRAVESavFLVGNKRD 126
Cdd:cd01867  47 LDGKKIKLQIWDTAGQ-ERFRTITTSYYRGAMGIILVYDITDEKSFENIKNWMRNIDE----HASEDVER--MLVGNKCD 119

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 13376046 127 LCHVREVGWEEGQKLALENRCQFCELSAAEqSLEVEMMFIRIIKDIL 173
Cdd:cd01867 120 MEEKRVVSKEEGEALAREYGIKFLETSAKA-NINVEEAFLTLAKDIL 165

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 13376046  11 EKSVSVTKALTvRFLTKRFIGEYAS----NFESiykKHLCLERKQLNLEIYDPCSQTqkaKF-----SLTSELHWAdgfV 81
Cdd:cd01861   8 DQSVGKTSIIT-RFMYDTFDNQYQAtigiDFLS---KTMYVDDKTVRLQLWDTAGQE---RFrslipSYIRDSSVA---V 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046  82 IVYDISDRSSFAFAKALIYRIREpqtshcKRAVESAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSAAEqSLEV 161
Cdd:cd01861  78 VVYDITNRQSFDNTDKWIDDVRD------ERGNDVIIVLVGNKTDLSDKRQVSTEEGEKKAKENNAMFIETSAKA-GHNV 150

                       170
                ....*....|.
gi 13376046 162 EMMFIRIIKDI 172
Cdd:cd01861 151 KQLFKKIAQAL 161

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 13376046  19 ALTVRFLTKRFIGEYASNFESIYKKHLCLERKQLNLEIYDPCSQTQkakFSLTSELHW--ADGFVIVYDISDRSSFAFAK 96
Cdd:cd04177  16 ALTVQFVQNVFIESYDPTIEDSYRKQVEIDGRQCDLEILDTAGTEQ---FTAMRELYIksGQGFLLVYSVTSEASLNELG 92

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13376046  97 ALiyriREpQTSHCKRAVESAVFLVGNKRDLCHVREVGWEEGQKLALE-NRCQFCELSAAEQSlEVEMMFIRIIKDIL 173
Cdd:cd04177  93 EL----RE-QVLRIKDSDNVPMVLVGNKADLEDDRQVSREDGVSLSQQwGNVPFYETSARKRT-NVDEVFIDLVRQII 164

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. 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 13376046  20 LTVRFLTKRFIGEYASNFESIYK-KHLCLERKQLNLEIYDPCSQTqkaKF-SLTSELH-WADGFVIVYDISDRSSFAFAK 96
Cdd:cd01869  18 LLLRFADDTYTESYISTIGVDFKiRTIELDGKTVKLQIWDTAGQE---RFrTITSSYYrGAHGIIIVYDVTDQESFNNVK 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046  97 ALIYRIRepqtshcKRAVESAV-FLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSAAEqSLEVEMMFIRIIKDILIN 175
Cdd:cd01869  95 QWLQEID-------RYASENVNkLLVGNKCDLTDKKVVDYTEAKEFADELGIPFLETSAKN-ATNVEEAFMTMAREIKKR 166

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046   20 LTVRFLTKRF-------IG-EYASNFESIykkhlclERKQLNLEIYDpcSQTQKAKFSLT-SELHWADGFVIVYDISDRS 90
Cdd:PLN03108  22 LLLQFTDKRFqpvhdltIGvEFGARMITI-------DNKPIKLQIWD--TAGQESFRSITrSYYRGAAGALLVYDITRRE 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046   91 SFAFAKALIYRIREPQTSHCkravesAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSaAEQSLEVEMMFIRIIK 170
Cdd:PLN03108  93 TFNHLASWLEDARQHANANM------TIMLIGNKCDLAHRRAVSTEEGEQFAKEHGLIFMEAS-AKTAQNVEEAFIKTAA 165

                 ....*..
gi 13376046  171 DILINFK 177
Cdd:PLN03108 166 KIYKKIQ 172

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 13376046  50 KQLNLEIYDPCSQTqkaKF-SLT-SELHWADGFVIVYDISDRSSFAFAKALIYRIREPQTSHckraveSAVFLVGNKRDL 127
Cdd:cd01866  51 KQIKLQIWDTAGQE---SFrSITrSYYRGAAGALLVYDITRRETFNHLTSWLEDARQHSNSN------MTIMLIGNKCDL 121

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 13376046 128 CHVREVGWEEGQKLALENRCQFCELSAAEQSlEVEMMFIRIIKDILIN 175
Cdd:cd01866 122 ESRREVSYEEGEAFAREHGLIFMETSAKTAS-NVEEAFINTAKEIYDK 168

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 13376046  19 ALTVRFLTKRFIGEYASNFESIYK-KHLCLERKQLNLEIYDPCSQTqkaKF-SLTSELH-WADGFVIVYDISDRSSFAFA 95
Cdd:cd04120  15 SLMERFTDDTFCEACKSTVGVDFKiKTVELRGKKIRLQIWDTAGQE---RFnSITSAYYrSAKGIILVYDITKKETFDDL 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046  96 KALIYRIRepqtshcKRAVESA-VFLVGNKRDLCHVREVGWEEGQKLALE-NRCQFCELSAAEqSLEVEMMFIRIIKDIL 173
Cdd:cd04120  92 PKWMKMID-------KYASEDAeLLLVGNKLDCETDREITRQQGEKFAQQiTGMRFCEASAKD-NFNVDEIFLKLVDDIL 163

Rab GTPase family 14 (Rab14); Rab14 GTPases are localized to biosynthetic compartments, including the rough ER, the Golgi complex, and the trans-Golgi network, and to endosomal compartments, including early endosomal vacuoles and associated vesicles. Rab14 is believed to function in both the biosynthetic and recycling pathways between the Golgi and endosomal compartments. Rab14 has also been identified on GLUT4 vesicles, and has been suggested to help regulate GLUT4 translocation. In addition, Rab14 is believed to play a role in the regulation of 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 13376046  50 KQLNLEIYDPCSQtQKAKFSLTSELHWADGFVIVYDISDRSSFAFAKALIYRIREPQTSHckraveSAVFLVGNKRDLCH 129
Cdd:cd04122  49 QKIKLQIWDTAGQ-ERFRAVTRSYYRGAAGALMVYDITRRSTYNHLSSWLTDARNLTNPN------TVIFLIGNKADLEA 121

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 13376046 130 VREVGWEEGQKLALENRCQFCELSAAEQSlEVEMMFIRIIKDILIN 175
Cdd:cd04122 122 QRDVTYEEAKQFADENGLLFLECSAKTGE-NVEDAFLETAKKIYQN 166

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 13376046  25 LTKRFIGEYASNFESIY-------KKHLCLERKQLNLEIYDPCSQTQKAKFSLTSELHW----ADGFVIVYDISDRSSFA 93
Cdd:cd00882  13 LLNALLGGEVGEVSDVPgttrdpdVYVKELDKGKVKLVLVDTPGLDEFGGLGREELARLllrgADLILLVVDSTDRESEE 92

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13376046  94 FAKALIYRIrepqtshcKRAVESAVFLVGNKRDLC-HVREVGWEEGQKLALENRCQFCELSAAEQSLEVEmMFIRIIK 170
Cdd:cd00882  93 DAKLLILRR--------LRKEGIPIILVGNKIDLLeEREVEELLRLEELAKILGVPVFEVSAKTGEGVDE-LFEKLIE 161

Rab GTPase family 26 (Rab26); Rab26 subfamily. First identified in rat pancreatic acinar cells, Rab26 is believed to play a role in recruiting mature granules to the plasma membrane upon beta-adrenergic stimulation. Rab26 belongs to the Rab functional group III, which are considered key regulators of intracellular vesicle transport during exocytosis. 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 13376046  24 FLTKRFIGEYASNFESiykKHLCLERKQLNLEIYDPCSQTqkaKFSLTSELHWADG--FVIVYDISDRSSFAFAKALIYR 101
Cdd:cd04112  25 FLAGSFIATVGIQFTN---KVVTVDGVKVKLQIWDTAGQE---RFRSVTHAYYRDAhaLLLLYDVTNKSSFDNIRAWLTE 98

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376046 102 IREPQTShckravESAVFLVGNKRDLCHVREVGWEEGQKLALENRCQFCELSaAEQSLEVEMMFIRIIKDilinfkLKEK 181
Cdd:cd04112  99 ILEYAQS------DVVIMLLGNKADMSGERVVKREDGERLAKEYGVPFMETS-AKTGLNVELAFTAVAKE------LKHR 165

                       170       180
                ....*....|....*....|...
gi 13376046 182 RRPSGSKSMAKLINNVFGKRRKS 204
Cdd:cd04112 166 SVEQPDEPKFKIQDYVEKQKKSS 188