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 1034590981   1 MGIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:cd01867    77 MGIILVYDITDEKSFENIKNWMRNIDEHASEDVERMLVGNKCDMEEKRVVSKEEGEALAREYGIKFLETSAKANINVEEA 156

                          90
                  ....*....|.
gi 1034590981  81 FFTLARDIMTK 91
Cdd:cd01867   157 FLTLAKDILKK 167

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 1034590981   1 MGIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:cd01867    77 MGIILVYDITDEKSFENIKNWMRNIDEHASEDVERMLVGNKCDMEEKRVVSKEEGEALAREYGIKFLETSAKANINVEEA 156

                          90
                  ....*....|.
gi 1034590981  81 FFTLARDIMTK 91
Cdd:cd01867   157 FLTLAKDILKK 167

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981    1 MGIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:smart00175  74 VGALLVYDITNRESFENLENWLKELREYASPNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEA 153

                           90
                   ....*....|.
gi 1034590981   81 FFTLARDIMTK 91
Cdd:smart00175 154 FEELAREILKR 164

small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this model include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.This model recognizes a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981   2 GIMLVYDITN-EKSFDNIKN-WIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEkLAIDYGIKFLETSAKSSANVEE 79
Cdd:TIGR00231  77 RSLRVFDIVIlVLDVEEILEkQTKEIIHHADSGVPIILVGNKIDLKDADLKTHVASE-FAKLNGEPIIPLSAETGKNIDS 155

                  ..
gi 1034590981  80 AF 81
Cdd:TIGR00231 156 AF 157

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 1034590981   1 MGIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:cd01867    77 MGIILVYDITDEKSFENIKNWMRNIDEHASEDVERMLVGNKCDMEEKRVVSKEEGEALAREYGIKFLETSAKANINVEEA 156

                          90
                  ....*....|.
gi 1034590981  81 FFTLARDIMTK 91
Cdd:cd01867   157 FLTLAKDILKK 167

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981    1 MGIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:smart00175  74 VGALLVYDITNRESFENLENWLKELREYASPNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEA 153

                           90
                   ....*....|.
gi 1034590981   81 FFTLARDIMTK 91
Cdd:smart00175 154 FEELAREILKR 164

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAF 81
Cdd:cd01869    77 GIIIVYDVTDQESFNNVKQWLQEIDRYASENVNKLLVGNKCDLTDKKVVDYTEAKEFADELGIPFLETSAKNATNVEEAF 156

                          90
                  ....*....|
gi 1034590981  82 FTLARDIMTK 91
Cdd:cd01869   157 MTMAREIKKR 166

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034590981   5 LVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAF 81
Cdd:cd01861    78 VVYDITNRQSFDNTDKWIDDVRDERGNDVIIVLVGNKTDLSDKRQVSTEEGEKKAKENNAMFIETSAKAGHNVKQLF 154

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 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAF 81
Cdd:cd01866    79 GALLVYDITRRETFNHLTSWLEDARQHSNSNMTIMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKTASNVEEAF 158

                          90
                  ....*....|
gi 1034590981  82 FTLARDIMTK 91
Cdd:cd01866   159 INTAKEIYDK 168

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 1034590981   3 IMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAFF 82
Cdd:cd04112    77 LLLLYDVTNKSSFDNIRAWLTEILEYAQSDVVIMLLGNKADMSGERVVKREDGERLAKEYGVPFMETSAKTGLNVELAFT 156

                  ....*.
gi 1034590981  83 TLARDI 88
Cdd:cd04112   157 AVAKEL 162

Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. p21Ras couples receptor Tyr kinases and G protein receptors to protein kinase cascades

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981    2 GIMLVYDITNEKSFDNIKNWIRNIEE-HASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:smart00173  74 GFLLVYSITDRQSFEEIKKFREQILRvKDRDDVPIVLVGNKCDLESERVVSTEEGKELARQWGCPFLETSAKERVNVDEA 153

                   ....*....
gi 1034590981   81 FFTLARDIM 89
Cdd:smart00173 154 FYDLVREIR 162

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981   5 LVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAFFTL 84
Cdd:cd01860    79 VVYDITSEESFEKAKSWVKELQEHGPPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTEI 158

                  ....
gi 1034590981  85 ARDI 88
Cdd:cd01860   159 ARKL 162

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 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKF-LETSAKSSANVEEA 80
Cdd:cd01864    78 GAIIAYDITRRSSFESVPHWIEEVEKYGASNVVLLLIGNKCDLEEQREVLFEEACTLAEHYGILAvLETSAKESSNVEEA 157

                  ....*...
gi 1034590981  81 FFTLARDI 88
Cdd:cd01864   158 FLLMATEL 165

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 1034590981   2 GIMLVYDITNEKSFDNIKNW---IRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVE 78
Cdd:cd04144    73 GFILVYSITSRSTFERVERFreqIQRVKDESAADVPIMIVGNKCDKVYEREVSTEEGAALARRLGCEFIEASAKTNVNVE 152

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1034590981  79 EAFFTLARDImtklnRKMNDSNSAGAGGPVKITENRSKK 117
Cdd:cd04144   153 RAFYTLVRAL-----RQQRQGGQGPKGGPTKKKEKKKRK 186

Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, with conflicting data reported. Rab21 has been reported to localize in the ER in human intestinal epithelial cells, with partial colocalization with alpha-glucosidase, a late endosomal/lysosomal marker. More recently, Rab21 was shown to colocalize with and affect the morphology of early endosomes. In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate 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 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAF 81
Cdd:cd04123    75 GAILVYDITDADSFQKVKKWIKELKQMRGNNISLVIVGNKIDLERQRVVSKSEAEEYAKSVGAKHFETSAKTGKGIEELF 154

                  ....*...
gi 1034590981  82 FTLARDIM 89
Cdd:cd04123   155 LSLAKRMI 162

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 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMIL-GNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:cd04139    74 GFLLVFSITDMESFTALAEFREQILRVKEDDNVPLLLvGNKCDLEDKRQVSVEEAANLAEQWGVNYVETSAKTRANVDKV 153

                  ....*...
gi 1034590981  81 FFTLARDI 88
Cdd:cd04139   154 FFDLVREI 161

Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. 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 1034590981   4 MLVYDITNEKSFDNIKNWIRNIEEHAS-SDVER---MILGNKCDMNDKRQVSKERGEKLAIDYG-IKFLETSAKSSANVE 78
Cdd:cd01862    77 VLVYDVTNPKSFESLDSWRDEFLIQASpRDPENfpfVVLGNKIDLEEKRQVSTKKAQQWCKSKGnIPYFETSAKEAINVD 156

                          90
                  ....*....|...
gi 1034590981  79 EAFFTLARDIMTK 91
Cdd:cd01862   157 QAFETIARLALEQ 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 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAF 81
Cdd:cd04117    75 GIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEEQKRQVGDEQGNKLAKEYGMDFFETSACTNKNIKESF 154

                  ....
gi 1034590981  82 FTLA 85
Cdd:cd04117   155 TRLT 158

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 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHASSD-VERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:cd04137    75 GYILVYSVTSRKSFEVVKVIYDKILDMLGKEsVPIVLVGNKSDLHMERQVSAEEGKKLAESWGAAFLESSAKENENVEEA 154

                  ....*...
gi 1034590981  81 FFTLARDI 88
Cdd:cd04137   155 FELLIEEI 162

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 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAF 81
Cdd:cd04113    75 GALLVYDITSRESFNALTNWLTDARTLASPDIVIILVGNKKDLEDDREVTFLEASRFAQENGLLFLETSALTGENVEEAF 154

                  ....*..
gi 1034590981  82 FTLARDI 88
Cdd:cd04113   155 LKCARSI 161

Rab GTPase family 40 (Rab40) contains Rab40a, Rab40b and Rab40c; The Rab40 subfamily contains Rab40a, Rab40b, and Rab40c, which are all highly homologous. In rat, Rab40c is localized to the perinuclear recycling compartment (PRC), and is distributed in a tissue-specific manor, with high expression in brain, heart, kidney, and testis, low expression in lung and liver, and no expression in spleen and skeletal muscle. Rab40c is highly expressed in differentiated oligodendrocytes but minimally expressed in oligodendrocyte progenitors, suggesting a role in the vesicular transport of myelin components. Unlike most other Ras-superfamily proteins, Rab40c was shown to have a much lower affinity for GTP, and an affinity for GDP that is lower than for 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. 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 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHASSdVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAF 81
Cdd:cd04121    81 GIILVYDITNRWSFDGIDRWIKEIDEHAPG-VPKILVGNRLHLAFKRQVATEQAQAYAERNGMTFFEVSPLCNFNITESF 159

                          90
                  ....*....|...
gi 1034590981  82 FTLARDIMTKLNR 94
Cdd:cd04121   160 TELARIVLMRHGR 172

Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap subfamily of the Ras family. It can be further divided into the Rap1a and Rap1b isoforms. In humans, Rap1a and Rap1b share 95% sequence homology, but are products of two different genes located on chromosomes 1 and 12, respectively. Rap1a is sometimes called smg p21 or Krev1 in the older literature. Rap1 proteins are believed to perform different cellular functions, depending on the isoform, its subcellular localization, and the effector proteins it binds. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and the microsomal membrane of pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. High expression of Rap1 has been observed in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines; interestingly, in the SCCs, the active GTP-bound form localized to the nucleus, while the inactive GDP-bound form localized to the cytoplasm. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap1a, which is stimulated by T-cell receptor (TCR) activation, is a positive regulator of T cells by directing integrin activation and augmenting lymphocyte responses. In murine hippocampal neurons, Rap1b determines which neurite will become the axon and directs the recruitment of Cdc42, which is required for formation of dendrites and axons. In murine platelets, Rap1b is required for normal homeostasis in vivo and is involved in integrin activation. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981   2 GIMLVYDITNEKSF---DNIKNWIRNIEEhaSSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVE 78
Cdd:cd04175    75 GFVLVYSITAQSTFndlQDLREQILRVKD--TEDVPMILVGNKCDLEDERVVGKEQGQNLARQWGCAFLETSAKAKINVN 152

                          90
                  ....*....|
gi 1034590981  79 EAFFTLARDI 88
Cdd:cd04175   153 EIFYDLVRQI 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 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEEHA-SSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAK---SSANV 77
Cdd:cd04115    78 AVVFVYDVTNMASFHSLPSWIEECEQHSlPNEVPRILVGNKCDLREQIQVPTDLAQRFADAHSMPLFETSAKdpsENDHV 157

                  ....*...
gi 1034590981  78 EEAFFTLA 85
Cdd:cd04115   158 EAIFMTLA 165

Rap-like family consists of Rap1, Rap2 and RSR1; The Rap subfamily consists of the Rap1, Rap2, and RSR1. Rap subfamily proteins perform different cellular functions, depending on the isoform and its subcellular localization. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and microsomal membrane of the pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. Rap1 localizes in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap2 is involved in multiple functions, including activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton and activation of the Wnt/beta-catenin signaling pathway in embryonic Xenopus. A number of effector proteins for Rap2 have been identified, including isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK), and the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. RSR1 is the fungal homolog of Rap1 and Rap2. In budding yeasts, it is involved in selecting a site for bud growth, which directs the establishment of cell polarization. The Rho family GTPase Cdc42 and its GEF, Cdc24, then establish an axis of polarized growth. It is believed that Cdc42 interacts directly with RSR1 in vivo. In filamentous fungi such as Ashbya gossypii, RSR1 is a key regulator of polar growth in the hypha. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981   1 MGIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMIL-GNKCDMNDKRQVSKERGEKLAIDYG-IKFLETSAKSSANVE 78
Cdd:cd04136    74 QGFALVYSITAQQSFNDLQDLREQILRVKDTEDVPMILvGNKCDLEDERVVSKEEGQNLARQWGnCPFLETSAKSKINVD 153

                          90
                  ....*....|
gi 1034590981  79 EAFFTLARDI 88
Cdd:cd04136   154 EIFYDLVRQI 163

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 1034590981   3 IMLVYDITNEKSFDNIKNWIRNIEEHA-SSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAF 81
Cdd:cd04101    80 VCVVYDVTNEVSFNNCSRWINRVRTHShGLHTPGVLVGNKCDLTDRREVDAAQAQALAQANTLKFYETSAKEGVGYEAPF 159

                  ....*
gi 1034590981  82 FTLAR 86
Cdd:cd04101   160 LSLAR 164

rab6; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981   4 MLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAFFT 83
Cdd:PTZ00099   57 IVVYDITNRQSFENTTKWIQDILNERGKDVIIALVGNKTDLGDLRKVTYEEGMQKAQEYNTMFHETSAKAGHNIKVLFKK 136

                          90
                  ....*....|....*..
gi 1034590981  84 LARDIMTKLNRKMNDSN 100
Cdd:PTZ00099  137 IAAKLPNLDNSNSNDAN 153

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 1034590981   3 IMLVYDITNEKSFDNIKN-WIRNIEEHAsSDVERMILGNKCDMND-----------KRQVSKERGEKLAIDYG-IKFLET 69
Cdd:cd00157    75 FLLCFSVDSPSSFENVKTkWYPEIKHYC-PNVPIILVGTKIDLRDdgntlkklekkQKPITPEEGEKLAKEIGaVKYMEC 153

                          90
                  ....*....|....*..
gi 1034590981  70 SAKSSANVEEAFFTLAR 86
Cdd:cd00157   154 SALTQEGLKEVFDEAIR 170

A Ras homolog member I (ARHI); ARHI (A Ras homolog member I) is a member of the Ras family with several unique structural and functional properties. ARHI is expressed in normal human ovarian and breast tissue, but its expression is decreased or eliminated in breast and ovarian cancer. ARHI contains an N-terminal extension of 34 residues (human) that is required to retain its tumor suppressive activity. Unlike most other Ras family members, ARHI is maintained in the constitutively active (GTP-bound) state in resting cells and has modest GTPase activity. ARHI inhibits STAT3 (signal transducers and activators of transcription 3), a latent transcription factor whose abnormal activation plays a critical role in oncogenesis. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981   4 MLVYDITNEKSFDNIKNWIRNIEEHASSDVER---MILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:cd04140    77 ILVYSITSKQSLEELKPIYELICEIKGNNLEKipiMLVGNKCDESPSREVSSSEGAALARTWNCAFMETSAKTNHNVQEL 156

                  ....
gi 1034590981  81 FFTL 84
Cdd:cd04140   157 FQEL 160

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981   2 GIMLVYDITNEKSFDNIKNWIRNIEE-HASSDVERMILGNKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:cd04141    76 GFIICYSVTDRHSFQEASEFKELITRvRLTEDIPLVLVGNKVDLEQQRQVTTEEGRNLAREFNCPFFETSAALRFYIDDA 155

                          90
                  ....*....|....*
gi 1034590981  81 FFTLARDIMTKLNRK 95
Cdd:cd04141   156 FHGLVREIRRKESMP 170

Rho (Ras homology) subfamily of Ras-like small GTPases; Members of this subfamily of Ras-like small GTPases include Cdc42 and Rac, as well as Rho isoforms.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981    3 IMLVYDITNEKSFDNIKN-WIRNIEEHAsSDVERMILGNKCDM----------NDKRQ--VSKERGEKLAIDYG-IKFLE 68
Cdd:smart00174  73 FLICFSVDSPASFENVKEkWYPEVKHFC-PNVPIILVGTKLDLrndkstleelSKKKQepVTYEQGQALAKRIGaVKYLE 151

                           90       100
                   ....*....|....*....|...
gi 1034590981   69 TSAKSSANVEEAFFTLARDIMTK 91
Cdd:smart00174 152 CSALTQEGVREVFEEAIRAALNK 174

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 1034590981   2 GIMLVYDITNEKSFDNIKNWIrnIEEHASSDVERMILGNKCDMNDKRQVS-KERGEKLAIDYGIKFLETSAKSSANVEEA 80
Cdd:cd00882    78 LILLVVDSTDRESEEDAKLLI--LRRLRKEGIPIILVGNKIDLLEEREVEeLLRLEELAKILGVPVFEVSAKTGEGVDEL 155

                  ....*.
gi 1034590981  81 FFTLAR 86
Cdd:cd00882   156 FEKLIE 161

Ras homolog enriched in striatum (Rhes) and activator of G-protein signaling 1 (Dexras1/AGS1); This subfamily includes Rhes (Ras homolog enriched in striatum) and Dexras1/AGS1 (activator of G-protein signaling 1). These proteins are homologous, but exhibit significant differences in tissue distribution and subcellular localization. Rhes is found primarily in the striatum of the brain, but is also expressed in other areas of the brain, such as the cerebral cortex, hippocampus, inferior colliculus, and cerebellum. Rhes expression is controlled by thyroid hormones. In rat PC12 cells, Rhes is farnesylated and localizes to the plasma membrane. Rhes binds and activates PI3K, and plays a role in coupling serpentine membrane receptors with heterotrimeric G-protein signaling. Rhes has recently been shown to be reduced under conditions of dopamine supersensitivity and may play a role in determining dopamine receptor sensitivity. Dexras1/AGS1 is a dexamethasone-induced Ras protein that is expressed primarily in the brain, with low expression levels in other tissues. Dexras1 localizes primarily to the cytoplasm, and is a critical regulator of the circadian master clock to photic and nonphotic input. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034590981   4 MLVYDITNEKSFDNIKNWIRNIEEHASS---------DVERMILGNKCDMNDKRQVSKERGEKL-AIDYGIKFLETSAKS 73
Cdd:cd04143    76 ILVFSLDNRESFEEVCRLREQILETKSClknktkenvKIPMVICGNKADRDFPREVQRDEVEQLvGGDENCAYFEVSAKK 155

                          90       100
                  ....*....|....*....|...
gi 1034590981  74 SANVEEAFFTLArdIMTKLNRKM 96
Cdd:cd04143   156 NSNLDEMFRALF--SLAKLPNEM 176