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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04115    68 MVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQHSLPNEVPRILVGNKCDLREQIQVPTDLAQRFADAHSMPLFETS 147

                          90       100
                  ....*....|....*....|...
gi 1720434768  81 AKDPKESQNVESIFMCLACRLKA 103
Cdd:cd04115   148 AKDPSENDHVEAIFMTLAHKLKS 170

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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04115    68 MVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQHSLPNEVPRILVGNKCDLREQIQVPTDLAQRFADAHSMPLFETS 147

                          90       100
                  ....*....|....*....|...
gi 1720434768  81 AKDPKESQNVESIFMCLACRLKA 103
Cdd:cd04115   148 AKDPSENDHVEAIFMTLAHKLKS 170

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 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAvPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAKDp 84
Cdd:pfam00071  68 YYRGADGFLLVYDITSRDSFENVKKWVEEILRHA-DENVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKT- 145

                          90
                  ....*....|....
gi 1720434768  85 keSQNVESIFMCLA 98
Cdd:pfam00071 146 --NENVEEAFEELA 157

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   7 RNVHAVVFVYDVTKMTSFTNLKMWIQECngHAVPPLVPKVLVGNKCDLR--EQIQVPSNLALKFADAHNMLLFETSAKDP 84
Cdd:COG1100    78 TGASLYLFVVDGTREETLQSLYELLESL--RRLGKKSPIILVLNKIDLYdeEEIEDEERLKEALSEDNIVEVVATSAKTG 155

                          90
                  ....*....|
gi 1720434768  85 KesqNVESIF 94
Cdd:COG1100   156 E---GVEELF 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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04115    68 MVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQHSLPNEVPRILVGNKCDLREQIQVPTDLAQRFADAHSMPLFETS 147

                          90       100
                  ....*....|....*....|...
gi 1720434768  81 AKDPKESQNVESIFMCLACRLKA 103
Cdd:cd04115   148 AKDPSENDHVEAIFMTLAHKLKS 170

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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAvPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd00154    65 ITSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYA-PPNIPIILVGNKSDLEDERQVSTEEAQQFAKENGLLFFETS 143

                          90
                  ....*....|....*...
gi 1720434768  81 AKDpkeSQNVESIFMCLA 98
Cdd:cd00154   144 AKT---GENVDEAFESLA 158

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 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAvPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAKDp 84
Cdd:cd01869    71 YYRGAHGIIIVYDVTDQESFNNVKQWLQEIDRYA-SENVNKLLVGNKCDLTDKKVVDYTEAKEFADELGIPFLETSAKN- 148

                          90
                  ....*....|....*...
gi 1720434768  85 keSQNVESIFMCLACRLK 102
Cdd:cd01869   149 --ATNVEEAFMTMAREIK 164

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 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPlVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAKDp 84
Cdd:cd01867    72 YYRGAMGIILVYDITDEKSFENIKNWMRNIDEHASED-VERMLVGNKCDMEEKRVVSKEEGEALAREYGIKFLETSAKA- 149

                          90       100
                  ....*....|....*....|
gi 1720434768  85 keSQNVESIFMCLACRLKAQ 104
Cdd:cd01867   150 --NINVEEAFLTLAKDILKK 167

Rab GTPase family 30 (Rab30); Rab30 subfamily. Rab30 appears to be associated with the Golgi stack. It is expressed in a wide variety of tissue types and in humans maps to chromosome 11. 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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04114    72 ITQSYYRSANALILTYDITCEESFRCLPEWLREIEQYANNKVI-TILVGNKIDLAERREVSQQRAEEFSDAQDMYYLETS 150

                          90       100
                  ....*....|....*....|.
gi 1720434768  81 AkdpKESQNVESIFMCLACRL 101
Cdd:cd04114   151 A---KESDNVEKLFLDLACRL 168

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 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLALKFADAHNML-LFETSAkd 83
Cdd:cd01864    72 YYRSANGAIIAYDITRRSSFESVPHWIEEVEKYGASNVV-LLLIGNKCDLEEQREVLFEEACTLAEHYGILaVLETSA-- 148

                          90
                  ....*....|....*...
gi 1720434768  84 pKESQNVESIFMCLACRL 101
Cdd:cd01864   149 -KESSNVEEAFLLMATEL 165

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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd00876    63 MRDQYIRNGDGFILVYSITSRESFEEIKNIREQILRVKDKEDVPIVLVGNKCDLENERQVSTEEGEALAEEWGCPFLETS 142

                          90
                  ....*....|....*...
gi 1720434768  81 AKDpkeSQNVESIFMCLA 98
Cdd:cd00876   143 AKT---NINIDELFNTLV 157

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 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAKDp 84
Cdd:cd01866    73 YYRGAAGALLVYDITRRETFNHLTSWLEDARQHSNSNMT-IMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKT- 150

                          90
                  ....*....|....
gi 1720434768  85 keSQNVESIFMCLA 98
Cdd:cd01866   151 --ASNVEEAFINTA 162

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 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHA-VPPLVpkVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAkd 83
Cdd:cd01861    69 YIRDSSVAVVVYDITNRQSFDNTDKWIDDVRDERgNDVII--VLVGNKTDLSDKRQVSTEEGEKKAKENNAMFIETSA-- 144

                          90
                  ....*....|.
gi 1720434768  84 pKESQNVESIF 94
Cdd:cd01861   145 -KAGHNVKQLF 154

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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04101    69 MVENVWEQPAVVCVVYDVTNEVSFNNCSRWINRVRTHSHGLHTPGVLVGNKCDLTDRREVDAAQAQALAQANTLKFYETS 148

                          90
                  ....*....|....*...
gi 1720434768  81 AkdpKESQNVESIFMCLA 98
Cdd:cd04101   149 A---KEGVGYEAPFLSLA 163

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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04113    65 VTRSYYRGAAGALLVYDITSRESFNALTNWLTDARTLASPDIV-IILVGNKKDLEDDREVTFLEASRFAQENGLLFLETS 143

                          90
                  ....*....|....*
gi 1720434768  81 AkdpKESQNVESIFM 95
Cdd:cd04113   144 A---LTGENVEEAFL 155

Rab GTPase family 14 (Rab14); Rab14 GTPases are localized to biosynthetic compartments, including the rough ER, the Golgi complex, and the trans-Golgi network, and to endosomal compartments, including early endosomal vacuoles and associated vesicles. Rab14 is believed to function in both the biosynthetic and recycling pathways between the Golgi and endosomal compartments. Rab14 has also been identified on GLUT4 vesicles, and has been suggested to help regulate GLUT4 translocation. In addition, Rab14 is believed to play a role in the regulation of phagocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAKDp 84
Cdd:cd04122    71 YYRGAAGALMVYDITRRSTYNHLSSWLTDARNLTNPNTV-IFLIGNKADLEAQRDVTYEEAKQFADENGLLFLECSAKT- 148

                          90
                  ....*....|.
gi 1720434768  85 keSQNVESIFM 95
Cdd:cd04122   149 --GENVEDAFL 157

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 1720434768    1 MVEHYYRNVHAVVFVYDVTKMTSFT---NLKMWIQECNGHAVpplVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLF 77
Cdd:smart00010  66 MRDQYMRTGEGFLLVYSITDRQSFEeiaKFREQILRVKDRDD---VPIVLVGNKCDLENERVVSTEEGKELARQWGCPFL 142

                           90
                   ....*....|....*..
gi 1720434768   78 ETSAkdpKESQNVESIF 94
Cdd:smart00010 143 ETSA---KERINVDEAF 156

Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily consists of the highly homologous RalA and RalB. Ral proteins are believed to play a crucial role in tumorigenesis, metastasis, endocytosis, and actin cytoskeleton dynamics. Despite their high sequence similarity (>80% sequence identity), nonoverlapping and opposing functions have been assigned to RalA and RalBs in tumor migration. In human bladder and prostate cancer cells, RalB promotes migration while RalA inhibits it. A Ral-specific set of GEFs has been identified that are activated by Ras binding. This RalGEF activity is enhanced by Ras binding to another of its target proteins, phosphatidylinositol 3-kinase (PI3K). Ral effectors include RLIP76/RalBP1, a Rac/cdc42 GAP, and the exocyst (Sec6/8) complex, a heterooctomeric protein complex that is involved in tethering vesicles to specific sites on the plasma membrane prior to exocytosis. In rat kidney cells, RalB is required for functional assembly of the exocyst and for localizing the exocyst to the leading edge of migrating cells. In human cancer cells, RalA is required to support anchorage-independent proliferation and RalB is required to suppress apoptosis. RalA has been shown to localize to the plasma membrane while RalB is localized to the intracellular vesicles. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   3 EHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAk 82
Cdd:cd04139    66 DNYFRSGEGFLLVFSITDMESFTALAEFREQILRVKEDDNVPLLLVGNKCDLEDKRQVSVEEAANLAEQWGVNYVETSA- 144

                          90
                  ....*....|....*.
gi 1720434768  83 dpKESQNVESIFMCLA 98
Cdd:cd04139   145 --KTRANVDKVFFDLV 158

Rab GTPase family 26 (Rab26); Rab26 subfamily. First identified in rat pancreatic acinar cells, Rab26 is believed to play a role in recruiting mature granules to the plasma membrane upon beta-adrenergic stimulation. Rab26 belongs to the Rab functional group III, which are considered key regulators of intracellular vesicle transport during exocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   2 VEH-YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04112    66 VTHaYYRDAHALLLLYDVTNKSSFDNIRAWLTEILEYAQSDVV-IMLLGNKADMSGERVVKREDGERLAKEYGVPFMETS 144

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720434768  81 AkdpKESQNVESIFMCLACRLKaqksllYRDAER-QQGKVQKLEFSQEANGKASC 134
Cdd:cd04112   145 A---KTGLNVELAFTAVAKELK------HRSVEQpDEPKFKIQDYVEKQKKSSGC 190

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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAvPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04117    65 ITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYA-PEGVQKILIGNKADEEQKRQVGDEQGNKLAKEYGMDFFETS 143

                          90
                  ....*....|
gi 1720434768  81 A---KDPKES 87
Cdd:cd04117   144 ActnKNIKES 153

Rab GTPase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAkdp 84
Cdd:PLN03110   81 YYRGAVGALLVYDITKRQTFDNVQRWLRELRDHADSNIV-IMMAGNKSDLNHLRSVAEEDGQALAEKEGLSFLETSA--- 156

                          90
                  ....*....|
gi 1720434768  85 KESQNVESIF 94
Cdd:PLN03110  157 LEATNVEKAF 166

Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMW----IQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04119    69 FYKDTQGVLLVYDVTDRQSFEALDSWlkemKQEGGPHGNMENIVVVVCANKIDLTKHRAVSEDEGRLWAESKGFKYFETS 148

                  .
gi 1720434768  81 A 81
Cdd:cd04119   149 A 149

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIqecNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNML-LFET 79
Cdd:cd00882    68 LARLLLRGADLILLVVDSTDRESEEDAKLLI---LRRLRKEGIPIILVGNKIDLLEEREVEELLRLEELAKILGVpVFEV 144

                          90
                  ....*....|....*....
gi 1720434768  80 SAKDPkesQNVESIFMCLA 98
Cdd:cd00882   145 SAKTG---EGVDELFEKLI 160

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 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLK------MWIQECNGHavpplvPKVLVGNKCDLREQIQVPSNLALKFADAHNM 74
Cdd:cd04145    66 MREQYMRTGEGFLLVFSVTDRGSFEEVDkfhtqiLRVKDRDEF------PMILVGNKADLEHQRQVSREEGQELARQLKI 139

                          90       100
                  ....*....|....*....|.
gi 1720434768  75 LLFETSAKDPKesqNVESIFM 95
Cdd:cd04145   140 PYIETSAKDRV---NVDKAFH 157

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 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPlVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAkdp 84
Cdd:cd01865    70 YYRGAMGFILMYDITNEESFNAVQDWSTQIKTYSWDN-AQVILVGNKCDMEDERVVSAERGRQLADQLGFEFFEASA--- 145

                          90
                  ....*....|
gi 1720434768  85 KESQNVESIF 94
Cdd:cd01865   146 KENINVKQVF 155

rab6; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:PTZ00099   45 LIPSYIRDSAAAIVVYDITNRQSFENTTKWIQDILNERGKDVI-IALVGNKTDLGDLRKVTYEEGMQKAQEYNTMFHETS 123

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720434768  81 AkdpKESQNVESIFMCLACRLKAQKSLLYRDAERQQGKVQKLEFSQEANGKASCPC 136
Cdd:PTZ00099  124 A---KAGHNIKVLFKKIAAKLPNLDNSNSNDANVVDIQLTNNSNANDKNMLSKCMC 176

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 1720434768   6 YRNVHAVVFVYDVTKMTSFTNLK-MWIQECNGHAvpPLVPKVLVGNKCDLREQIQVPSNLA-----LKFADAHNM----- 74
Cdd:cd00157    69 YPQTDVFLLCFSVDSPSSFENVKtKWYPEIKHYC--PNVPIILVGTKIDLRDDGNTLKKLEkkqkpITPEEGEKLakeig 146

                          90       100
                  ....*....|....*....|..
gi 1720434768  75 --LLFETSAKDpkeSQNVESIF 94
Cdd:cd00157   147 avKYMECSALT---QEGLKEVF 165

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 1720434768   9 VHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAkdpKESQ 88
Cdd:cd04137    73 IHGYILVYSVTSRKSFEVVKVIYDKILDMLGKESVPIVLVGNKSDLHMERQVSAEEGKKLAESWGAAFLESSA---KENE 149

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1720434768  89 NVESIFMclacrlkaqksLLYRDAERQQGkvqklefSQEANGKASC 134
Cdd:cd04137   150 NVEEAFE-----------LLIEEIEKVEN-------PLPPGQKSKC 177

Ras-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   1 MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:PTZ00369   69 MRDQYMRTGQGFLCVYSITSRSSFEEIASFREQILRVKDKDRVPMILVGNKCDLDSERQVSTGEGQELAKSFGIPFLETS 148

                          90
                  ....*....|....*..
gi 1720434768  81 AkdpKESQNVESIFMCL 97
Cdd:PTZ00369  149 A---KQRVNVDEAFYEL 162

Ras homology family 4 (Rho4) of small guanosine triphosphatases (GTPases)-like; Rho4 is a GTPase that controls septum degradation by regulating secretion of Eng1 or Agn1 during cytokinesis. Rho4 also plays a role in cell morphogenesis. Rho4 regulates septation and cell morphology by controlling the actin cytoskeleton and cytoplasmic microtubules. The localization of Rho4 is modulated by Rdi1, which may function as a GDI, and by Rga9, which is believed to function as a GAP. In S. pombe, both Rho4 deletion and Rho4 overexpression result in a defective cell wall, suggesting a role for Rho4 in maintaining cell wall integrity. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434768   6 YRNVHAVVFVYDVTKMTSFTNLK-MWIQECNGHAvpPLVPKVLVGNKCDLREQIQVPSNLALK------FADAHNM---- 74
Cdd:cd04132    73 YPDVDVILICYSVDNPTSLDNVEdKWYPEVNHFC--PGTPIVLVGLKTDLRKDKNSVSKLRAQglepvtPEQGESVaksi 150

                          90       100
                  ....*....|....*....|...
gi 1720434768  75 ---LLFETSAKDpkeSQNVESIF 94
Cdd:cd04132   151 gavAYIECSAKL---MENVDEVF 170

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 1720434768   5 YYRNVHAVVFVYDVTKMTSFTNLKMWIQ----ECNGhavpplVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETS 80
Cdd:cd04106    71 YYRGAQACILVFSTTDRESFEAIESWKEkveaECGD------IPMVLVQTKIDLLDQAVITNEEAEALAKRLQLPLFRTS 144

                          90
                  ....*....|....*...
gi 1720434768  81 AKDpkeSQNVESIFMCLA 98
Cdd:cd04106   145 VKD---DFNVTELFEYLA 159

Rat sarcoma (Ras) family 2 of small guanosine triphosphatases (GTPases); The Ras2 subfamily, found exclusively in fungi, was first identified in Ustilago maydis. In U. maydis, Ras2 is regulated by Sql2, a protein that is homologous to GEFs (guanine nucleotide exchange factors) of the CDC25 family. Ras2 has been shown to induce filamentous growth, but the signaling cascade through which Ras2 and Sql2 regulate cell morphology is not known. 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 1720434768  13 VFVYDVTKMTSFTNLKMWIQECN--GHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFETSAkdpKESQNV 90
Cdd:cd04144    75 ILVYSITSRSTFERVERFREQIQrvKDESAADVPIMIVGNKCDKVYEREVSTEEGAALARRLGCEFIEASA---KTNVNV 151

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1720434768  91 ESIFMCL--ACRLKAQKSLLYRDAERQQGKVQK 121
Cdd:cd04144   152 ERAFYTLvrALRQQRQGGQGPKGGPTKKKEKKK 184