P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLTLPNGEPVPCLLLANKCDLSP--WAVSRDQIDRFSKENGFTG 78
Cdd:cd04107   66 MTRVYYKGAVGAIIVFDVTRPSTFEAVLKWKADLDSKVTLPNGEPIPALLLANKCDLKKerLAKDPEQMDQFCKENGFIG 145

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 208609966  79 WTETSVKENKNINEAMRVLIEKMMRNSTEDIMSLSTQ---GDYINLQTKSSSWSCC 131
Cdd:cd04107  146 WFETSAKENINIEEAMRFLVKNILKNDKGLQSPEPDEdnvIDLKQETTTSKSKSCC 201

Rab GTPase families 18 (Rab18) and 32 (Rab32); Rab38/Rab32 subfamily. Rab32 and Rab38 are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP). Rab38 has been shown to be melanocyte-specific. 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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLTLPNGEPVPCLLLANKCDLSP--WAVSRDQIDRFSKENGFTG 78
Cdd:cd04107   66 MTRVYYKGAVGAIIVFDVTRPSTFEAVLKWKADLDSKVTLPNGEPIPALLLANKCDLKKerLAKDPEQMDQFCKENGFIG 145

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 208609966  79 WTETSVKENKNINEAMRVLIEKMMRNSTEDIMSLSTQ---GDYINLQTKSSSWSCC 131
Cdd:cd04107  146 WFETSAKENINIEEAMRFLVKNILKNDKGLQSPEPDEdnvIDLKQETTTSKSKSCC 201

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 208609966    1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLtlpnGEPVPCLLLANKCDLSPW-AVSRDQIDRFSKENGFTgW 79
Cdd:pfam00071  64 LRPLYYRGADGFLLVYDITSRDSFENVKKWVEEILRHA----DENVPIVLVGNKCDLEDQrVVSTEEGEALAKELGLP-F 138

                          90       100
                  ....*....|....*....|....
gi 208609966   80 TETSVKENKNINEAMRVLIEKMMR 103
Cdd:pfam00071 139 METSAKTNENVEEAFEELAREILK 162

GTPase SAR1 family domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   7 RDASACVIMFDVTNATTFSNSQRWkqdldSKLTLPNGEPVPCLLLANKCDL-SPWAV-SRDQIDRFSKENGFTGWTETSV 84
Cdd:COG1100   78 TGASLYLFVVDGTREETLQSLYEL-----LESLRRLGKKSPIILVLNKIDLyDEEEIeDEERLKEALSEDNIVEVVATSA 152

                         90
                 ....*....|....*..
gi 208609966  85 KENKNINEAMRVLIEKM 101
Cdd:COG1100  153 KTGEGVEELFAALAEIL 169

Rab GTPase families 18 (Rab18) and 32 (Rab32); Rab38/Rab32 subfamily. Rab32 and Rab38 are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP). Rab38 has been shown to be melanocyte-specific. 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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLTLPNGEPVPCLLLANKCDLSP--WAVSRDQIDRFSKENGFTG 78
Cdd:cd04107   66 MTRVYYKGAVGAIIVFDVTRPSTFEAVLKWKADLDSKVTLPNGEPIPALLLANKCDLKKerLAKDPEQMDQFCKENGFIG 145

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 208609966  79 WTETSVKENKNINEAMRVLIEKMMRNSTEDIMSLSTQ---GDYINLQTKSSSWSCC 131
Cdd:cd04107  146 WFETSAKENINIEEAMRFLVKNILKNDKGLQSPEPDEdnvIDLKQETTTSKSKSCC 201

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966     1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLtlpnGEPVPCLLLANKCDL-SPWAVSRDQIDRFSKENGFTGW 79
Cdd:smart00175  65 ITSSYYRGAVGALLVYDITNRESFENLENWLKELREYA----SPNVVIMLVGNKSDLeEQRQVSREEAEAFAEEHGLPFF 140

                           90       100
                   ....*....|....*....|....*
gi 208609966    80 tETSVKENKNINEAMRVLIEKMMRN 104
Cdd:smart00175 141 -ETSAKTNTNVEEAFEELAREILKR 164

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   4 LYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLtlpNGEPVPClLLANKCDL-SPWAVSRDQIDRFSKENG--FtgwT 80
Cdd:cd01860   69 MYYRGAAAAIVVYDITSEESFEKAKSWVKELQEHG---PPNIVIA-LAGNKADLeSKRQVSTEEAQEYADENGllF---M 141

                         90
                 ....*....|..
gi 208609966  81 ETSVKENKNINE 92
Cdd:cd01860  142 ETSAKTGENVNE 153

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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRW----KQDLDSKLTLpngepvpcLLLANKCDL-SPWAVSRDQIDRFSKENG 75
Cdd:cd01866   69 ITRSYYRGAAGALLVYDITRRETFNHLTSWledaRQHSNSNMTI--------MLIGNKCDLeSRREVSYEEGEAFAREHG 140

                         90
                 ....*....|....*...
gi 208609966  76 FTgWTETSVKENKNINEA 93
Cdd:cd01866  141 LI-FMETSAKTASNVEEA 157

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRW----KQDLDSKLTLpngepvpcLLLANKCDLS-PWAVSRDQIDRFSKENG 75
Cdd:PLN03108  71 ITRSYYRGAAGALLVYDITRRETFNHLASWledaRQHANANMTI--------MLIGNKCDLAhRRAVSTEEGEQFAKEHG 142

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 208609966  76 FTgWTETSVKENKNINEAMRVLIEKMMRNSTEDIMSLSTQGDYINL-------------QTKSSSWSCC 131
Cdd:PLN03108 143 LI-FMEASAKTAQNVEEAFIKTAAKIYKKIQDGVFDVSNESYGIKVgygaipgasggrdGTSSQGGGCC 210

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 208609966   5 YYRDASACVIMFDVTNATTFSNSQRWKQDLDSKltlpNGEPVPCLLLANKCDLSP-WAVSRDQIDRFSKENGfTGWTETS 83
Cdd:cd01861   69 YIRDSSVAVVVYDITNRQSFDNTDKWIDDVRDE----RGNDVIIVLVGNKTDLSDkRQVSTEEGEKKAKENN-AMFIETS 143

                         90
                 ....*....|..
gi 208609966  84 VKENKNINEAMR 95
Cdd:cd01861  144 AKAGHNVKQLFK 155

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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLdskLTLPNGEPVPCLLLANKCDLSPW-AVSRDQIDRFSKENGfTGW 79
Cdd:cd00876   63 MRDQYIRNGDGFILVYSITSRESFEEIKNIREQI---LRVKDKEDVPIVLVGNKCDLENErQVSTEEGEALAEEWG-CPF 138

                         90
                 ....*....|....*....
gi 208609966  80 TETSVKENKNINEAMRVLI 98
Cdd:cd00876  139 LETSAKTNINIDELFNTLV 157

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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLTlpngEPVPCLLLANKCDL-SPWAVSRDQIDRFSKENGFTGW 79
Cdd:cd04120   65 ITSAYYRSAKGIILVYDITKKETFDDLPKWMKMIDKYAS----EDAELLLVGNKLDCeTDREITRQQGEKFAQQITGMRF 140

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 208609966  80 TETSVKENKNINEAMRVLIEKMMRNSTEDIMSLSTQGDYINLQ 122
Cdd:cd04120  141 CEASAKDNFNVDEIFLKLVDDILKKMPLDILRNELSNSILSLQ 183

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 208609966   2 TRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLTlpngEPVPCLLLANKCDLSP-WAVSRDQIDRFSKENGFtGWT 80
Cdd:cd01867   69 TTSYYRGAMGIILVYDITDEKSFENIKNWMRNIDEHAS----EDVERMLVGNKCDMEEkRVVSKEEGEALAREYGI-KFL 143

                         90
                 ....*....|...
gi 208609966  81 ETSVKENKNINEA 93
Cdd:cd01867  144 ETSAKANINVEEA 156

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 208609966   2 TRLYYRDASACVIMFDVTNATTFSNSQRWKQDL----DSKLTLpngepvpcLLLANKCDLSPW-AVSRDQIDRFSKENGF 76
Cdd:cd01868   69 TSAYYRGAVGALLVYDITKKSTFENVERWLKELrdhaDSNIVI--------MLVGNKSDLRHLrAVPTEEAKAFAEKNGL 140

                         90       100
                 ....*....|....*....|....
gi 208609966  77 tGWTETSVKENKNINEAMRVLIEK 100
Cdd:cd01868  141 -SFIETSALDGTNVEEAFKQLLTE 163

Rab GTPase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDL----DSKLTLpngepvpcLLLANKCDLSPW-AVSRDQIDRFSKENG 75
Cdd:PLN03110  77 ITSAYYRGAVGALLVYDITKRQTFDNVQRWLRELrdhaDSNIVI--------MMAGNKSDLNHLrSVAEEDGQALAEKEG 148

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 208609966  76 FTgWTETSVKENKNINEAMRV-------LIEKMMRNSTEDIMS--LSTQGDYINLQTKSSS--WSCC 131
Cdd:PLN03110 149 LS-FLETSALEATNVEKAFQTilleiyhIISKKALAAQEAAANsgLPGQGTTINVADTSGNnkRGCC 214

Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats. In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with N|PM-ALK, it may provide a target for cancer treatments. 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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSkltlpNGEPVPCLLLANKCDLSPWAV--SRDQiDRFSKENGFTg 78
Cdd:cd04110   71 ITSTYYRGTHGVIVVYDVTNGESFVNVKRWLQEIEQ-----NCDDVCKVLVGNKNDDPERKVveTEDA-YKFAGQMGIS- 143

                         90       100
                 ....*....|....*....|....*
gi 208609966  79 WTETSVKENKNINEAMRVLIEKMMR 103
Cdd:cd04110  144 LFETSAKENINVEEMFNCITELVLR 168

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. 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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQdlDSKLTLPNGEPVpCLLLANKCDL-SPWAVSRDQIDRFSKENGfTGW 79
Cdd:cd04111   68 ITRSYYRNSVGVLLVFDITNRESFEHVHDWLE--EARSHIQPHRPV-FILVGHKCDLeSQRQVTREEAEKLAKDLG-MKY 143

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 208609966  80 TETSVKENKNINEAMRVLiekmmrnsTEDIMSLSTQGDY 118
Cdd:cd04111  144 IETSARTGDNVEEAFELL--------TQEIYERIKRGEL 174

Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kD (TIP47). Rab9 is a key mediator of vesicular transport from late endosomes to the trans-Golgi network (TGN) by redirecting the MPRs. Rab9 has been identified as a key component for the replication of several viruses, including HIV1, Ebola, Marburg, and measles, making it a potential target for inhibiting a variety of viruses. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   5 YYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLTLPNGEPVPCLLLANKCDLSPWAVSRDQIDRFSKENGFTGWTETSV 84
Cdd:cd04116   74 FYRGSDCCLLTFSVDDSQSFQNLSNWKKEFIYYADVKEPESFPFVILGNKIDIPERQVSTEEAQAWCRDNGDYPYFETSA 153

                 ....*....
gi 208609966  85 KENKNINEA 93
Cdd:cd04116  154 KDATNVAAA 162

Rab GTPase family 33 includes Rab33A and Rab33B; Rab33B/Rab33A subfamily. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways. Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes. 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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLtLPNgePVPCLLLANKCDLSPWA-VSRDQIDRFSKENGFTGW 79
Cdd:cd04115   68 MVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQHS-LPN--EVPRILVGNKCDLREQIqVPTDLAQRFADAHSMPLF 144

                         90
                 ....*....|....
gi 208609966  80 tETSVK---ENKNI 90
Cdd:cd04115  145 -ETSAKdpsENDHV 157

Ras-related nuclear proteins (Ran)/TC4 family of small GTPases; Ran GTPase is involved in diverse biological functions, such as nuclear transport, spindle formation during mitosis, DNA replication, and cell division. Among the Ras superfamily, Ran is a unique small G protein. It does not have a lipid modification motif at the C-terminus to bind to the membrane, which is often observed within the Ras superfamily. Ran may therefore interact with a wide range of proteins in various intracellular locations. Like other GTPases, Ran exists in GTP- and GDP-bound conformations that interact differently with effectors. Conversion between these forms and the assembly or disassembly of effector complexes requires the interaction of regulator proteins. The intrinsic GTPase activity of Ran is very low, but it is greatly stimulated by a GTPase-activating protein (RanGAP1) located in the cytoplasm. By contrast, RCC1, a guanine nucleotide exchange factor that generates RanGTP, is bound to chromatin and confined to the nucleus. Ran itself is mobile and is actively imported into the nucleus by a mechanism involving NTF-2. Together with the compartmentalization of its regulators, this is thought to produce a relatively high concentration of RanGTP in the nucleus.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   5 YYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLtlpngEPVPCLLLANKCDLSPWAVSRDQIDRFSKENgfTGWTETSV 84
Cdd:cd00877   69 YYIQGQCAIIMFDVTSRVTYKNVPNWHRDLVRVC-----ENIPIVLCGNKVDIKDRKVKPKQITFHRKKN--LQYYEISA 141

                         90       100
                 ....*....|....*....|
gi 208609966  85 KENKNINEAMRVLIEKMMRN 104
Cdd:cd00877  142 KSNYNFEKPFLWLARKLLGN 161

GTP-binding nuclear protein Ran; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   5 YYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLtlpngEPVPCLLLANKCDLSPWAVSRDQIDRFSKENgfTGWTETSV 84
Cdd:PTZ00132  78 YYIKGQCAIIMFDVTSRITYKNVPNWHRDIVRVC-----ENIPIVLVGNKVDVKDRQVKARQITFHRKKN--LQYYDISA 150

                 ....*
gi 208609966  85 KENKN 89
Cdd:PTZ00132 151 KSNYN 155

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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKltlpNGEPVPCLLLANKCDL-SPWAVSRDQIDRFSKENGFTgW 79
Cdd:cd01865   66 ITTAYYRGAMGFILMYDITNEESFNAVQDWSTQIKTY----SWDNAQVILVGNKCDMeDERVVSAERGRQLADQLGFE-F 140

                         90       100
                 ....*....|....*....|
gi 208609966  80 TETSVKENKNINEAMRVLIE 99
Cdd:cd01865  141 FEASAKENINVKQVFERLVD 160

Rab GTPase-like family 4 (Rab-like4); RabL4 (Rab-like4) subfamily. RabL4s are novel proteins that have high sequence similarity with Rab family members, but display features that are distinct from Rabs, and have been termed Rab-like. As in other Rab-like proteins, RabL4 lacks a prenylation site at the C-terminus. The specific function of RabL4 remains unknown.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWkqdLDSKLTLPNGEPVPCLLLANKCDLSPWA-VSRDQIDRFSKENGFTgW 79
Cdd:cd04101   69 MVENVWEQPAVVCVVYDVTNEVSFNNCSRW---INRVRTHSHGLHTPGVLVGNKCDLTDRReVDAAQAQALAQANTLK-F 144

                         90
                 ....*....|...
gi 208609966  80 TETSVKENKNINE 92
Cdd:cd04101  145 YETSAKEGVGYEA 157

GTPase SAR1 family domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208609966   7 RDASACVIMFDVTNATTFSNSQRWkqdldSKLTLPNGEPVPCLLLANKCDL-SPWAV-SRDQIDRFSKENGFTGWTETSV 84
Cdd:COG1100   78 TGASLYLFVVDGTREETLQSLYEL-----LESLRRLGKKSPIILVLNKIDLyDEEEIeDEERLKEALSEDNIVEVVATSA 152

                         90
                 ....*....|....*..
gi 208609966  85 KENKNINEAMRVLIEKM 101
Cdd:COG1100  153 KTGEGVEELFAALAEIL 169

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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQrwkqDL-DSKLTLPNGEPVPCLLLANKCDL-SPWAVSRDQIDRFSKENGFTg 78
Cdd:cd04175   65 MRDLYMKNGQGFVLVYSITAQSTFNDLQ----DLrEQILRVKDTEDVPMILVGNKCDLeDERVVGKEQGQNLARQWGCA- 139

                         90       100
                 ....*....|....*....|....*
gi 208609966  79 WTETSVKENKNINEAMRVLIEKMMR 103
Cdd:cd04175  140 FLETSAKAKINVNEIFYDLVRQINR 164

Rab GTPase family 15 (Rab15); Rab15 colocalizes with the transferrin receptor in early endosome compartments, but not with late endosomal markers. It codistributes with Rab4 and Rab5 on early/sorting endosomes, and with Rab11 on pericentriolar recycling endosomes. It is believed to function as an inhibitory GTPase that regulates distinct steps in early endocytic 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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSklTLPNGepVPCLLLANKCDL-SPWAVSRDQIDRFSKENGFTgW 79
Cdd:cd04117   65 ITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDE--YAPEG--VQKILIGNKADEeQKRQVGDEQGNKLAKEYGMD-F 139

                         90       100
                 ....*....|....*....|....*
gi 208609966  80 TETSVKENKNINEAMRVLIEKMMRN 104
Cdd:cd04117  140 FETSACTNKNIKESFTRLTELVLQA 164

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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQD-LDSKLTLPNG--EP--VPCLLLANKCDL-SPWAVSRDQIDRFSKEN 74
Cdd:cd04143   64 MRRLSILTGDVFILVFSLDNRESFEEVCRLREQiLETKSCLKNKtkENvkIPMVICGNKADRdFPREVQRDEVEQLVGGD 143

                         90       100
                 ....*....|....*....|...
gi 208609966  75 GFTGWTETSVKENKNINEAMRVL 97
Cdd:cd04143  144 ENCAYFEVSAKKNSNLDEMFRAL 166

Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. 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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSNSQRWKQDLDSKLtlpnGEpVPCLLLANKCDLSPWA-VSRDQIDRFSKENGFTgW 79
Cdd:cd04106   67 ITKAYYRGAQACILVFSTTDRESFEAIESWKEKVEAEC----GD-IPMVLVQTKIDLLDQAvITNEEAEALAKRLQLP-L 140

                         90       100
                 ....*....|....*....|.
gi 208609966  80 TETSVKENKNINEAMRVLIEK 100
Cdd:cd04106  141 FRTSVKDDFNVTELFEYLAEK 161

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 208609966   1 MTRLYYRDASACVIMFDVTNATTFSN-SQRWKQDLdsKLTLPNgepVPCLLLANKCDL--------------SPwaVSRD 65
Cdd:cd00157   64 LRPLSYPQTDVFLLCFSVDSPSSFENvKTKWYPEI--KHYCPN---VPIILVGTKIDLrddgntlkklekkqKP--ITPE 136

                         90       100
                 ....*....|....*....|....*..
gi 208609966  66 QIDRFSKENGFTGWTETSVKENKNINE 92
Cdd:cd00157  137 EGEKLAKEIGAVKYMECSALTQEGLKE 163

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 208609966  44 EPVPCLLLANKCDLSPW-AVSRDQIDRFSKENGfTGWTETSVKENKNINEAMRVLIEKMMR 103
Cdd:cd04137  105 ESVPIVLVGNKSDLHMErQVSAEEGKKLAESWG-AAFLESSAKENENVEEAFELLIEEIEK 164