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 1062594154   1 MIVRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGGVQIQDSlpqvvDSLSKCVQWAEGFLLVYSITDYDSYL 80
Cdd:cd04146    15 LTVRFLTKRFIGEYEPNLESLYSRQVTIDGEQVSLEIQDTPGQQQNEDP-----ESLERSLRWADGFVLVYSITDRSSFD 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1062594154  81 SIRPLYQHIRKVHP-DSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEISTSENYEDVCDVFQHLCKEVSK 156
Cdd:cd04146    90 VVSQLLQLIREIKKrDGEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAENYLEVQNVFHELCREVRR 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 1062594154   1 MIVRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGGVQIQDSlpqvvDSLSKCVQWAEGFLLVYSITDYDSYL 80
Cdd:cd04146    15 LTVRFLTKRFIGEYEPNLESLYSRQVTIDGEQVSLEIQDTPGQQQNEDP-----ESLERSLRWADGFVLVYSITDRSSFD 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1062594154  81 SIRPLYQHIRKVHP-DSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEISTSENYEDVCDVFQHLCKEVSK 156
Cdd:cd04146    90 VVSQLLQLIREIKKrDGEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAENYLEVQNVFHELCREVRR 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 1062594154   3 VRFLTKRFIGDYEPNTG-KLYSRLVYVEGDQLSLQIQDTPGgvqiQDSlpqvVDSL-SKCVQWAEGFLLVYSITDYDSYL 80
Cdd:pfam00071  17 IRFTQNKFPEEYIPTIGvDFYTKTIEVDGKTVKLQIWDTAG----QER----FRALrPLYYRGADGFLLVYDITSRDSFE 88

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1062594154  81 SIRPLYQHIRKVHPDSkAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEIS--TSENYEdvcDVFQHLCKEV 154
Cdd:pfam00071  89 NVKKWVEEILRHADEN-VPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSakTNENVE---EAFEELAREI 160

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1062594154   6 LTKRFIGD------YEPNTG-KLYSRLVYVEGDQLSLQIQDTPGGVQIQDSLPQVVDSLSKcvqwAEGFLLVYSITDYDS 78
Cdd:COG1100    19 LVNRLVGDifslekYLSTNGvTIDKKELKLDGLDVDLVIWDTPGQDEFRETRQFYARQLTG----ASLYLFVVDGTREET 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1062594154  79 YLSIRPLYQHIRKVHPDSkaPVIIVGNKGDLLHARQVQTQDGIQ--LANELGSLFLEIS--TSENYEDV 143
Cdd:COG1100    95 LQSLYELLESLRRLGKKS--PIILVLNKIDLYDEEEIEDEERLKeaLSEDNIVEVVATSakTGEGVEEL 161

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 1062594154   1 MIVRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGGVQIQDSlpqvvDSLSKCVQWAEGFLLVYSITDYDSYL 80
Cdd:cd04146    15 LTVRFLTKRFIGEYEPNLESLYSRQVTIDGEQVSLEIQDTPGQQQNEDP-----ESLERSLRWADGFVLVYSITDRSSFD 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1062594154  81 SIRPLYQHIRKVHP-DSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEISTSENYEDVCDVFQHLCKEVSK 156
Cdd:cd04146    90 VVSQLLQLIREIKKrDGEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAENYLEVQNVFHELCREVRR 166

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 1062594154    1 MIVRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGgvqiQDSLPQVVDSLSKCvqwAEGFLLVYSITDYDSYL 80
Cdd:smart00010  18 LTIQFVQGHFVDEYDPTIEDSYRKQIEIDGEVCLLDILDTAG----QEEFSAMRDQYMRT---GEGFLLVYSITDRQSFE 90

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1062594154   81 SIRPLYQHIRKVHPDSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEISTSENyEDVCDVFQHLCKEVSKM 157
Cdd:smart00010  91 EIAKFREQILRVKDRDDVPIVLVGNKCDLENERVVSTEEGKELARQWGCPFLETSAKER-INVDEAFYDLVREIRKS 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 1062594154   3 VRFLTKRFIGDYEPNTG-KLYSRLVYVEGDQLSLQIQDTPGgvqiQDSlpqvVDSL-SKCVQWAEGFLLVYSITDYDSYL 80
Cdd:pfam00071  17 IRFTQNKFPEEYIPTIGvDFYTKTIEVDGKTVKLQIWDTAG----QER----FRALrPLYYRGADGFLLVYDITSRDSFE 88

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1062594154  81 SIRPLYQHIRKVHPDSkAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEIS--TSENYEdvcDVFQHLCKEV 154
Cdd:pfam00071  89 NVKKWVEEILRHADEN-VPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSakTNENVE---EAFEELAREI 160

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 1062594154   1 MIVRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGgvqiQDS---LPQvvdslsKCVQWAEGFLLVYSITDYD 77
Cdd:cd04137    17 LTVQFVEGHFVESYYPTIENTFSKIITYKGQEYHLEIVDTAG----QDEysiLPQ------KYSIGIHGYILVYSVTSRK 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1062594154  78 SYLSIRPLYQHIRKVHPDSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEISTSENyEDVCDVFQHLCKEVSKM 157
Cdd:cd04137    87 SFEVVKVIYDKILDMLGKESVPIVLVGNKSDLHMERQVSAEEGKKLAESWGAAFLESSAKEN-ENVEEAFELLIEEIEKV 165

                  ..
gi 1062594154 158 HG 159
Cdd:cd04137   166 EN 167

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 1062594154   3 VRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGgvqiQDSLPQVVDSlskCVQWAEGFLLVYSITDYDSYLSI 82
Cdd:cd04139    18 LQFMYDEFVEDYEPTKADSYRKKVVLDGEEVQLNILDTAG----QEDYAAIRDN---YFRSGEGFLLVFSITDMESFTAL 90

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1062594154  83 RPLYQHIRKVHPDSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEIS--TSENYEdvcDVFQHLCKEVSK 156
Cdd:cd04139    91 AEFREQILRVKEDDNVPLLLVGNKCDLEDKRQVSVEEAANLAEQWGVNYVETSakTRANVD---KVFFDLVREIRQ 163

Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap subfamily of the Ras family. It consists of Rap2a, Rap2b, and Rap2c. Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton. In human platelets, Rap2 was shown to interact with the cytoskeleton by binding the actin filaments. In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway. The Rap2 interacting protein 9 (RPIP9) is highly expressed in human breast carcinomas and correlates with a poor prognosis, suggesting a role for Rap2 in breast cancer oncogenesis. Rap2b, but not Rap2a, Rap2c, Rap1a, or Rap1b, is expressed in human red blood cells, where it is believed to be involved in vesiculation. A number of additional effector proteins for Rap2 have been identified, including the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1062594154   1 MIVRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGGVQIQdSLPQVVdslskcVQWAEGFLLVYSITDYDSYL 80
Cdd:cd04176    17 LTVQFVSGTFIEKYDPTIEDFYRKEIEVDSSPSVLEILDTAGTEQFA-SMRDLY------IKNGQGFIVVYSLVNQQTFQ 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1062594154  81 SIRPLYQHIRKVHPDSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEISTSEN 139
Cdd:cd04176    90 DIKPMRDQIVRVKGYEKVPIILVGNKVDLESEREVSSAEGRALAEEWGCPFMETSAKSK 148

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1062594154    2 IVRFLTKRFIGDYEPNTG-KLYSRLVYVEGDQLSLQIQDTPGgvqiQDSLPQVVDSLSKCvqwAEGFLLVYSITDYDSYL 80
Cdd:smart00175  17 LSRFTDGKFSEQYKSTIGvDFKTKTIEVDGKRVKLQIWDTAG----QERFRSITSSYYRG---AVGALLVYDITNRESFE 89

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1062594154   81 SIRPLYQHIRKvHPDSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEISTSENyEDVCDVFQHLCKEV 154
Cdd:smart00175  90 NLENWLKELRE-YASPNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSAKTN-TNVEEAFEELAREI 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 1062594154   3 VRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGgvqiqdsLPQVVDSLSKCVQWAEGFLLVYSITDYDSYLSI 82
Cdd:cd04177    19 VQFVQNVFIESYDPTIEDSYRKQVEIDGRQCDLEILDTAG-------TEQFTAMRELYIKSGQGFLLVYSVTSEASLNEL 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1062594154  83 RPLYQHIRKVHPDSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSL-FLEisTSENYE-DVCDVFQHLCKEV 154
Cdd:cd04177    92 GELREQVLRIKDSDNVPMVLVGNKADLEDDRQVSREDGVSLSQQWGNVpFYE--TSARKRtNVDEVFIDLVRQI 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 1062594154   3 VRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGGVQIQDSLPQVVDSlskcvqwAEGFLLVYSITDYDSYLSI 82
Cdd:cd04145    20 IQFIQSYFVTDYDPTIEDSYTKQCEIDGQWARLDILDTAGQEEFSAMREQYMRT-------GEGFLLVFSVTDRGSFEEV 92

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1062594154  83 RPLYQHIRKVHPDSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEIS 135
Cdd:cd04145    93 DKFHTQILRVKDRDEFPMILVGNKADLEHQRQVSREEGQELARQLKIPYIETS 145

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 1062594154   1 MIVRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGGVQIQdSLPQVvdSLSKcvqwAEGFLLVYSITDYDSYL 80
Cdd:cd04140    17 LVLRFVKGTFRESYIPTIEDTYRQVISCSKSICTLQITDTTGSHQFP-AMQRL--SISK----GHAFILVYSITSKQSLE 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1062594154  81 SIRPLYQHIRKVHPDS--KAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEISTSENYeDVCDVFQHL 150
Cdd:cd04140    90 ELKPIYELICEIKGNNleKIPIMLVGNKCDESPSREVSSSEGAALARTWNCAFMETSAKTNH-NVQELFQEL 160

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 1062594154   3 VRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGgvqiQDSLPQVVDSLSKCvqwAEGFLLVYSITDYDSYLSI 82
Cdd:cd04138    19 IQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG----QEEYSAMRDQYMRT---GEGFLCVFAINSRKSFEDI 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1062594154  83 RPLYQHIRKVHPDSKAPVIIVGNKGDlLHARQVQTQDGIQLANELGSLFLEIStSENYEDVCDVFQHLCKEV 154
Cdd:cd04138    92 HTYREQIKRVKDSDDVPMVLVGNKCD-LAARTVSTRQGQDLAKSYGIPYIETS-AKTRQGVEEAFYTLVREI 161

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 1062594154  24 RLVYVEGDQLSLQIQDTPGgvqiQDSLPQVVDSLSKcvqWAEGFLLVYSITDYDSYLSIRPLYQHIRKvHPDSKAPVIIV 103
Cdd:cd01867    43 RTIELDGKKIKLQIWDTAG----QERFRTITTSYYR---GAMGIILVYDITDEKSFENIKNWMRNIDE-HASEDVERMLV 114

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1062594154 104 GNKGDLLHARQVQTQDGIQLANELGSLFLEISTSENyEDVCDVFQHLCKEVSK 156
Cdd:cd01867   115 GNKCDMEEKRVVSKEEGEALAREYGIKFLETSAKAN-INVEEAFLTLAKDILK 166

Rab GTPase family 11 (Rab11)-like includes Rab11a, Rab11b, and Rab25; Rab11a, Rab11b, and Rab25 are closely related, evolutionary conserved Rab proteins that are differentially expressed. Rab11a is ubiquitously synthesized, Rab11b is enriched in brain and heart and Rab25 is only found in epithelia. Rab11/25 proteins seem to regulate recycling pathways from endosomes to the plasma membrane and to the trans-Golgi network. Furthermore, Rab11a is thought to function in the histamine-induced fusion of tubulovesicles containing H+, K+ ATPase with the plasma membrane in gastric parietal cells and in insulin-stimulated insertion of GLUT4 in the plasma membrane of cardiomyocytes. Overexpression of Rab25 has recently been observed in ovarian cancer and breast cancer, and has been correlated with worsened outcomes in both diseases. In addition, Rab25 overexpression has also been observed in prostate cancer, transitional cell carcinoma of the bladder, and invasive breast tumor cells. 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 1062594154  64 AEGFLLVYSITDYDSYLSIRPLYQHIRKvHPDSKAPVIIVGNKGDLLHARQVQTQDGIQLANELGSLFLEIS--TSENYE 141
Cdd:cd01868    76 AVGALLVYDITKKSTFENVERWLKELRD-HADSNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIETSalDGTNVE 154

                          90
                  ....*....|...
gi 1062594154 142 dvcDVFQHLCKEV 154
Cdd:cd01868   155 ---EAFKQLLTEI 164

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. 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 1062594154  24 RLVYVEGDQLSLQIQDTPGgvqiQDSLPQVVDSLSKCvqwAEGFLLVYSITDYDSYLSIRPLYQHIrKVHPDSKAPVIIV 103
Cdd:cd01865    41 KTVYRNDKRIKLQIWDTAG----QERYRTITTAYYRG---AMGFILMYDITNEESFNAVQDWSTQI-KTYSWDNAQVILV 112

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1062594154 104 GNKGDLLHARQVQTQDGIQLANELGSLFLEISTSENYeDVCDVFQHL 150
Cdd:cd01865   113 GNKCDMEDERVVSAERGRQLADQLGFEFFEASAKENI-NVKQVFERL 158

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 1062594154   1 MIVRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGgvqiQDSLPqVVDSLSkcVQWAEGFLLVYSITDYDSYL 80
Cdd:cd04143    16 IVSRFLGGRFEEQYTPTIEDFHRKLYSIRGEVYQLDILDTSG----NHPFP-AMRRLS--ILTGDVFILVFSLDNRESFE 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1062594154  81 SIRPLYQHI--------RKVHPDSKAPVIIVGNKGDLLHARQVQTQDGIQL-ANELGSLFLEISTSENYeDVCDVFQHLc 151
Cdd:cd04143    89 EVCRLREQIletksclkNKTKENVKIPMVICGNKADRDFPREVQRDEVEQLvGGDENCAYFEVSAKKNS-NLDEMFRAL- 166

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1062594154 152 kevSKMHGLSGE-----RRRASII---PRPRSPNMQDLKRRFKQA---LSPKVKAPS 197
Cdd:cd04143   167 ---FSLAKLPNEmspslHRKISVQygdALHKKSRGGSRKRKEGDAcgaVAPFARRPS 220

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 1062594154  24 RLVYVEGDQLSLQIQDTPGgvqiQDSLPQVVDSLSKcvqWAEGFLLVYSITDYDSYLSIRPLYQHIRKVHPDSKAPvIIV 103
Cdd:cd01869    42 RTIELDGKTVKLQIWDTAG----QERFRTITSSYYR---GAHGIIIVYDVTDQESFNNVKQWLQEIDRYASENVNK-LLV 113

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1062594154 104 GNKGDLLHARQVQTQDGIQLANELGSLFLEIS--TSENYED 142
Cdd:cd01869   114 GNKCDLTDKKVVDYTEAKEFADELGIPFLETSakNATNVEE 154

Wnt-1 responsive Cdc42 homolog (Wrch-1) is a Rho family GTPase similar to Cdc42; Wrch-1 (Wnt-1 responsive Cdc42 homolog) is a Rho family GTPase that shares significant sequence and functional similarity with Cdc42. Wrch-1 was first identified in mouse mammary epithelial cells, where its transcription is upregulated in Wnt-1 transformation. Wrch-1 contains N- and C-terminal extensions relative to cdc42, suggesting potential differences in cellular localization and function. The Wrch-1 N-terminal extension contains putative SH3 domain-binding motifs and has been shown to bind the SH3 domain-containing protein Grb2, which increases the level of active Wrch-1 in cells. Unlike Cdc42, which localizes to the cytosol and perinuclear membranes, Wrch-1 localizes extensively with the plasma membrane and endosomes. The membrane association, localization, and biological activity of Wrch-1 indicate an atypical model of regulation distinct from other Rho family GTPases. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1062594154   1 MIVRFLTKRFIGDYEPNTGKLYSRLVYVEGDQLSLQIQDTPGgvqiQDSLpqvvDSL-SKCVQWAEGFLLVYSITDYDSY 79
Cdd:cd04130    16 LIVSYTTNGYPTEYVPTAFDNFSVVVLVDGKPVRLQLCDTAG----QDEF----DKLrPLCYPDTDVFLLCFSVVNPSSF 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1062594154  80 LSIR-PLYQHIRKVHPdsKAPVIIVGNKGDL------------LHARQVQTQDGIQLANELGSL-FLEIS--TSENYEDV 143
Cdd:cd04130    88 QNISeKWIPEIRKHNP--KAPIILVGTQADLrtdvnvliqlarYGEKPVSQSRAKALAEKIGACeYIECSalTQKNLKEV 165

                  ..
gi 1062594154 144 CD 145
Cdd:cd04130   166 FD 167

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1062594154   6 LTKRFIGD------YEPNTG-KLYSRLVYVEGDQLSLQIQDTPGGVQIQDSLPQVVDSLSKcvqwAEGFLLVYSITDYDS 78
Cdd:COG1100    19 LVNRLVGDifslekYLSTNGvTIDKKELKLDGLDVDLVIWDTPGQDEFRETRQFYARQLTG----ASLYLFVVDGTREET 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1062594154  79 YLSIRPLYQHIRKVHPDSkaPVIIVGNKGDLLHARQVQTQDGIQ--LANELGSLFLEIS--TSENYEDV 143
Cdd:COG1100    95 LQSLYELLESLRRLGKKS--PIILVLNKIDLYDEEEIEDEERLKeaLSEDNIVEVVATSakTGEGVEEL 161