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 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDL 85
Cdd:cd01869    40 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDQESFNNVKQWLQEIDRYASENVNKLLVGNKCDL 119

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKR 132
Cdd:cd01869   120 TDKKVVDYTEAKEFADELGIPFLETSAKNATNVEEAFMTMAREIKKR 166

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 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDL 85
Cdd:cd01869    40 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDQESFNNVKQWLQEIDRYASENVNKLLVGNKCDL 119

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKR 132
Cdd:cd01869   120 TDKKVVDYTEAKEFADELGIPFLETSAKNATNVEEAFMTMAREIKKR 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 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDL 85
Cdd:pfam00071  37 YTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYDITSRDSFENVKKWVEEILRHADENVPIVLVGNKCDL 116

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKK 131
Cdd:pfam00071 117 EDQRVVSTEEGEALAKELGLPFMETSAKTNENVEEAFEELAREILK 162

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002269649  10 IELDGKTVKLQIWDTAGQERFRTITSSY---YRGAHGIIIVYDVTDMESFNNVKQWLSEIdRYASDSVCKLLVGNKCDLV 86
Cdd:COG1100    46 LKLDGLDVDLVIWDTPGQDEFRETRQFYarqLTGASLYLFVVDGTREETLQSLYELLESL-RRLGKKSPIILVLNKIDLY 124

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1002269649  87 DSKVVDTEE--AKAFAESLGISFLETSAKESINVEEAFLTMS 126
Cdd:COG1100   125 DEEEIEDEErlKEALSEDNIVEVVATSAKTGEGVEELFAALA 166

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 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDL 85
Cdd:cd01869    40 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDQESFNNVKQWLQEIDRYASENVNKLLVGNKCDL 119

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKR 132
Cdd:cd01869   120 TDKKVVDYTEAKEFADELGIPFLETSAKNATNVEEAFMTMAREIKKR 166

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002269649    6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDL 85
Cdd:smart00175  38 KTKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVYDITNRESFENLENWLKELREYASPNVVIMLVGNKSDL 117

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1002269649   86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKR 132
Cdd:smart00175 118 EEQRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEAFEELAREILKR 164

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. 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 mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. 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. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDL 85
Cdd:cd00154    38 KSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYAPPNIPIILVGNKSDL 117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSS 127
Cdd:cd00154   118 EDERQVSTEEAQQFAKENGLLFFETSAKTGENVDEAFESLAR 159

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 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRyASDSVCKLLVGNKCDL 85
Cdd:cd04110    44 KIRTVEINGERVKLQIWDTAGQERFRTITSTYYRGTHGVIVVYDVTNGESFVNVKRWLQEIEQ-NCDDVCKVLVGNKNDD 122

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKRMATQPAVERKPTVH 146
Cdd:cd04110   123 PERKVVETEDAYKFAGQMGISLFETSAKENINVEEMFNCITELVLRAKKDNLAKQQQQQQN 183

Rab GTPase family 19 (Rab19); Rab19 subfamily. Rab19 proteins are associated with Golgi stacks. Similarity analysis indicated that Rab41 is closely related to Rab19. However, the function of these Rabs is not yet characterized. 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 1002269649   7 IRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDLV 86
Cdd:cd01864    42 MKTLEIQGKRVKLQIWDTAGQERFRTITQSYYRSANGAIIAYDITRRSSFESVPHWIEEVEKYGASNVVLLLIGNKCDLE 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1002269649  87 DSKVVDTEEAKAFAESLGISF-LETSAKESINVEEAFLTMSSDI 129
Cdd:cd01864   122 EQREVLFEEACTLAEHYGILAvLETSAKESSNVEEAFLLMATEL 165

Rab GTPase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002269649   8 RTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDLVD 87
Cdd:PLN03110   52 RTLQVEGKTVKAQIWDTAGQERYRAITSAYYRGAVGALLVYDITKRQTFDNVQRWLRELRDHADSNIVIMMAGNKSDLNH 131

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1002269649  88 SKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDI-----KKRMATQPA 138
Cdd:PLN03110  132 LRSVAEEDGQALAEKEGLSFLETSALEATNVEKAFQTILLEIyhiisKKALAAQEA 187

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 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDL 85
Cdd:cd04120    38 KIKTVELRGKKIRLQIWDTAGQERFNSITSAYYRSAKGIILVYDITKKETFDDLPKWMKMIDKYASEDAELLLVGNKLDC 117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1002269649  86 VDSKVVDTEEAKAFAESL-GISFLETSAKESINVEEAFLTMSSDIKKRM 133
Cdd:cd04120   118 ETDREITRQQGEKFAQQItGMRFCEASAKDNFNVDEIFLKLVDDILKKM 166

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 1002269649   8 RTIEL-DGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCK-LLVGNKCDL 85
Cdd:cd04111    42 RLIEIePGVRIKLQLWDTAGQERFRSITRSYYRNSVGVLLVFDITNRESFEHVHDWLEEARSHIQPHRPVfILVGHKCDL 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKRM 133
Cdd:cd04111   122 ESQRQVTREEAEKLAKDLGMKYIETSARTGDNVEEAFELLTQEIYERI 169

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 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDL 85
Cdd:cd01865    39 KVKTVYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILMYDITNEESFNAVQDWSTQIKTYSWDNAQVILVGNKCDM 118

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAF 122
Cdd:cd01865   119 EDERVVSAERGRQLADQLGFEFFEASAKENINVKQVF 155

Rab GTPase family 4 (Rab4); Rab4 subfamily. Rab4 has been implicated in numerous functions within the cell. It helps regulate endocytosis through the sorting, recycling, and degradation of early endosomes. Mammalian Rab4 is involved in the regulation of many surface proteins including G-protein-coupled receptors, transferrin receptor, integrins, and surfactant protein A. Experimental data implicate Rab4 in regulation of the recycling of internalized receptors back to the plasma membrane. It is also believed to influence receptor-mediated antigen processing in B-lymphocytes, in calcium-dependent exocytosis in platelets, in alpha-amylase secretion in pancreatic cells, and in insulin-induced translocation of Glut4 from internal vesicles to the cell surface. Rab4 is known to share effector proteins with Rab5 and Rab11. 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 1002269649   8 RTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDLVD 87
Cdd:cd04113    40 RVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVYDITSRESFNALTNWLTDARTLASPDIVIILVGNKKDLED 119

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1002269649  88 SKVVDTEEAKAFAESLGISFLETSAKESINVEEAFL 123
Cdd:cd04113   120 DREVTFLEASRFAQENGLLFLETSALTGENVEEAFL 155

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 1002269649   9 TIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDLVDS 88
Cdd:cd01861    41 TMYVDDKTVRLQLWDTAGQERFRSLIPSYIRDSSVAVVVYDITNRQSFDNTDKWIDDVRDERGNDVIIVLVGNKTDLSDK 120

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1002269649  89 KVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDI 129
Cdd:cd01861   121 RQVSTEEGEKKAKENNAMFIETSAKAGHNVKQLFKKIAQAL 161

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQ-WLSEIDRYASDSVC-KLLVGNKC 83
Cdd:PLN03118   51 KIKQLTVGGKRLKLTIWDTAGQERFRTLTSSYYRNAQGIILVYDVTRRETFTNLSDvWGKEVELYSTNQDCvKMLVGNKV 130

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1002269649  84 DLVDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAF 122
Cdd:PLN03118  131 DRESERDVSREEGMALAKEHGCLFLECSAKTRENVEQCF 169

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 1002269649   8 RTIELDGKTVKLQIWDTAGQERFR-TITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYA-SDSVCKLLVGNKCDL 85
Cdd:cd04115    42 RTVEIDGERIKVQLWDTAGQERFRkSMVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQHSlPNEVPRILVGNKCDL 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAK---ESINVEEAFLTMSSDIK 130
Cdd:cd04115   122 REQIQVPTDLAQRFADAHSMPLFETSAKdpsENDHVEAIFMTLAHKLK 169

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 1002269649   6 KIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDSVCKLLVGNKCDL 85
Cdd:cd04117    38 KMKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADE 117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMS 126
Cdd:cd04117   118 EQKRQVGDEQGNKLAKEYGMDFFETSACTNKNIKESFTRLT 158

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 1002269649   10 IELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDR-YASDSVCKLLVGNKCDLVDS 88
Cdd:smart00010  43 IEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVYSITDRQSFEEIAKFREQILRvKDRDDVPIVLVGNKCDLENE 122

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1002269649   89 KVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKR 132
Cdd:smart00010 123 RVVSTEEGKELARQWGCPFLETSAKERINVDEAFYDLVREIRKS 166

Rab GTPase family 27a (Rab27a); The Rab27a subfamily consists of Rab27a and its highly homologous isoform, Rab27b. Unlike most Rab proteins whose functions remain poorly defined, Rab27a has many known functions. Rab27a has multiple effector proteins, and depending on which effector it binds, Rab27a has different functions as well as tissue distribution and/or cellular localization. Putative functions have been assigned to Rab27a when associated with the effector proteins Slp1, Slp2, Slp3, Slp4, Slp5, DmSlp, rabphilin, Dm/Ce-rabphilin, Slac2-a, Slac2-b, Slac2-c, Noc2, JFC1, and Munc13-4. Rab27a has been associated with several human diseases, including hemophagocytic syndrome (Griscelli syndrome or GS), Hermansky-Pudlak syndrome, and choroidermia. In the case of GS, a rare, autosomal recessive disease, a Rab27a mutation is directly responsible for the disorder. When Rab27a is localized to the secretory granules of pancreatic beta cells, it is believed to mediate glucose-stimulated insulin secretion, making it a potential target for diabetes therapy. When bound to JFC1 in prostate cells, Rab27a is believed to regulate the exocytosis of prostate- specific markers. 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 1002269649  14 GKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYA-SDSVCKLLVGNKCDLVDSKVVD 92
Cdd:cd04127    60 AFRVHLQLWDTAGQERFRSLTTAFFRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAyCENPDIVLIGNKADLPDQREVS 139

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1002269649  93 TEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKRM 133
Cdd:cd04127   140 ERQARELADKYGIPYFETSAATGQNVEKAVETLLDLIMKRM 180

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 1002269649   8 RTIELDGKT-VKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEID---RYAS-DSVCKLLVGNK 82
Cdd:cd04107    40 KVIEWDPNTvVRLQLWDIAGQERFGGMTRVYYKGAVGAIIVFDVTRPSTFEAVLKWKADLDskvTLPNgEPIPALLLANK 119

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1002269649  83 CDL-VDSKVVDTEEAKAFAESLG-ISFLETSAKESINVEEAF 122
Cdd:cd04107   120 CDLkKERLAKDPEQMDQFCKENGfIGWFETSAKENINIEEAM 161

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 1002269649  11 ELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYAS-DSVCKLLVGNKCDLVDSK 89
Cdd:cd04145    44 EIDGQWARLDILDTAGQEEFSAMREQYMRTGEGFLLVFSVTDRGSFEEVDKFHTQILRVKDrDEFPMILVGNKADLEHQR 123

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1002269649  90 VVDTEEAKAFAESLGISFLETSAKESINVEEAF 122
Cdd:cd04145   124 QVSREEGQELARQLKIPYIETSAKDRVNVDKAF 156

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 1002269649   4 FQKIrtIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEI-DRYASDSVCKLLVGNK 82
Cdd:cd04137    38 FSKI--ITYKGQEYHLEIVDTAGQDEYSILPQKYSIGIHGYILVYSVTSRKSFEVVKVIYDKIlDMLGKESVPIVLVGNK 115

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1002269649  83 CDLVDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKRMATQPAVERKPtvHIHM 149
Cdd:cd04137   116 SDLHMERQVSAEEGKKLAESWGAAFLESSAKENENVEEAFELLIEEIEKVENPLPPGQKSK--CSVM 180

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002269649  10 IELDGKTVKLQIWDTAGQERFRTITSSY---YRGAHGIIIVYDVTDMESFNNVKQWLSEIdRYASDSVCKLLVGNKCDLV 86
Cdd:COG1100    46 LKLDGLDVDLVIWDTPGQDEFRETRQFYarqLTGASLYLFVVDGTREETLQSLYELLESL-RRLGKKSPIILVLNKIDLY 124

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1002269649  87 DSKVVDTEE--AKAFAESLGISFLETSAKESINVEEAFLTMS 126
Cdd:COG1100   125 DEEEIEDEErlKEALSEDNIVEVVATSAKTGEGVEELFAALA 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 1002269649   8 RTIELD--GKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYASDsVCKLLVGNKCDL 85
Cdd:cd04106    40 KQIFLRqsDEDVRLMLWDTAGQEEFDAITKAYYRGAQACILVFSTTDRESFEAIESWKEKVEAECGD-IPMVLVQTKIDL 118

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1002269649  86 VDSKVVDTEEAKAFAESLGISFLETSAKESINVEEAF 122
Cdd:cd04106   119 LDQAVITNEEAEALAKRLQLPLFRTSVKDDFNVTELF 155

Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists primarily in the GTP-bound state, having a low intrinsic GTPase activity; it is not efficiently geranyl-geranylated at the C-terminus; it does not form a detectable complex with Rab GDP-dissociation inhibitors (GDIs); and it has recently been shown to undergo tyrosine phosphorylation when overexpressed in vitro. The specific function of Rab24 still remains unknown. It is found in a transport route between ER-cis-Golgi and late endocytic compartments. It is putatively involved in an autophagic pathway, possibly directing misfolded proteins in the ER to degradative pathways. 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 1002269649   8 RTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRyaSDSVCKL-LVGNKCDLV 86
Cdd:cd04118    41 KRMVVGERVVTLGIWDTAGSERYEAMSRIYYRGAKAAIVCYDLTDSSSFERAKFWVKELQN--LEEHCKIyLCGTKSDLI 118

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1002269649  87 DS----KVVDTEEAKAFAESLGISFLETSAKESINVEEAFLTMSSDIKKRMATQ 136
Cdd:cd04118   119 EQdrslRQVDFHDVQDFADEIKAQHFETSSKTGQNVDELFQKVAEDFVSRANNQ 172

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 1002269649   8 RTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDMESFNNVKQWLSEIDRYA----SDSVCKLLVGNKC 83
Cdd:cd04116    45 KDLEVDGHFVTLQIWDTAGQERFRSLRTPFYRGSDCCLLTFSVDDSQSFQNLSNWKKEFIYYAdvkePESFPFVILGNKI 124

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1002269649  84 DLVDSKvVDTEEAKAFAESLGIS-FLETSAKESINVEEAF 122
Cdd:cd04116   125 DIPERQ-VSTEEAQAWCRDNGDYpYFETSAKDATNVAAAF 163

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.