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 1958670744   1 MNPTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFREN 80
Cdd:cd04132    86 DNPTSLDNVEDKWYPEVNHFCPGTPIVLVGLKTDLRKDKNSVSKLRAQGLEPVTPEQGESVAKSIGAVAYIECSAKLMEN 165

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1958670744  81 VEDVFREATKVALSALKKAQR-QKKQRICLLL 111
Cdd:cd04132   166 VDEVFDAAINVALSKSGRAARkKKKKKKCVIL 197

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 1958670744   1 MNPTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFREN 80
Cdd:cd04132    86 DNPTSLDNVEDKWYPEVNHFCPGTPIVLVGLKTDLRKDKNSVSKLRAQGLEPVTPEQGESVAKSIGAVAYIECSAKLMEN 165

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1958670744  81 VEDVFREATKVALSALKKAQR-QKKQRICLLL 111
Cdd:cd04132   166 VDEVFDAAINVALSKSGRAARkKKKKKKCVIL 197

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 1958670744   2 NPTSYDNVLiKWFPEVTHFCR-GIPMVLIGCKTDLRKDKeqlrklraaqlePITYTQGLSACEQMrGALYLECSAKFREN 80
Cdd:pfam00071  83 SRDSFENVK-KWVEEILRHADeNVPIVLVGNKCDLEDQR------------VVSTEEGEALAKEL-GLPFMETSAKTNEN 148

                          90
                  ....*....|...
gi 1958670744  81 VEDVFREATKVAL 93
Cdd:pfam00071 149 VEEAFEELAREIL 161

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 1958670744   5 SYDNVLIKWFPEVTHFCR-GIPMVLIGCKTDLR--KDKEQLRKLRAaqlepitytqglsaceQMRGALYLECSAKFRENV 81
Cdd:TIGR00231  90 DVEEILEKQTKEIIHHADsGVPIILVGNKIDLKdaDLKTHVASEFA----------------KLNGEPIIPLSAETGKNI 153

                  ....
gi 1958670744  82 EDVF 85
Cdd:TIGR00231 154 DSAF 157

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 1958670744   1 MNPTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFREN 80
Cdd:cd04132    86 DNPTSLDNVEDKWYPEVNHFCPGTPIVLVGLKTDLRKDKNSVSKLRAQGLEPVTPEQGESVAKSIGAVAYIECSAKLMEN 165

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1958670744  81 VEDVFREATKVALSALKKAQR-QKKQRICLLL 111
Cdd:cd04132   166 VDEVFDAAINVALSKSGRAARkKKKKKKCVIL 197

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 1958670744   2 NPTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLrAAQLEPITYTQGLSACEQMRGALYLECSAKFRENV 81
Cdd:cd00157    83 SPSSFENVKTKWYPEIKHYCPNVPIILVGTKIDLRDDGNTLKKL-EKKQKPITPEEGEKLAKEIGAVKYMECSALTQEGL 161

                          90
                  ....*....|
gi 1958670744  82 EDVFREATKV 91
Cdd:cd00157   162 KEVFDEAIRA 171

Ras homolog family, member G (RhoG) of small guanosine triphosphatases (GTPases); RhoG is a GTPase with high sequence similarity to members of the Rac subfamily, including the regions involved in effector recognition and binding. However, RhoG does not bind to known Rac1 and Cdc42 effectors, including proteins containing a Cdc42/Rac interacting binding (CRIB) motif. Instead, RhoG interacts directly with Elmo, an upstream regulator of Rac1, in a GTP-dependent manner and forms a ternary complex with Dock180 to induce activation of Rac1. The RhoG-Elmo-Dock180 pathway is required for activation of Rac1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor. Thus RhoG activates Rac1 through Elmo and Dock180 to control cell morphology. RhoG has also been shown to play a role in caveolar trafficking and has a novel role in signaling the neutrophil respiratory burst stimulated by G protein-coupled receptor (GPCR) agonists. 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 1958670744   2 NPTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFRENV 81
Cdd:cd01875    86 SPSSYENVRHKWHPEVCHHCPNVPILLVGTKKDLRNDADTLKKLKEQGQAPITPQQGGALAKQIHAVKYLECSALNQDGV 165

                          90       100       110
                  ....*....|....*....|....*....|
gi 1958670744  82 EDVFREATKVALSALKKaqrqKKQRICLLL 111
Cdd:cd01875   166 KEVFAEAVRAVLNPTPI----KDTKSCVLL 191

Rho family GTPase subfamily Rnd includes Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8; The Rnd subfamily contains Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8. These novel Rho family proteins have substantial structural differences compared to other Rho members, including N- and C-terminal extensions relative to other Rhos. Rnd3/RhoE is farnesylated at the C-terminal prenylation site, unlike most other Rho proteins that are geranylgeranylated. In addition, Rnd members are unable to hydrolyze GTP and are resistant to GAP activity. They are believed to exist only in the GTP-bound conformation, and are antagonists of RhoA activity. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744   3 PTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFREN-V 81
Cdd:cd04131    85 PETLDSVLKKWKGEVREFCPNTPVLLVGCKSDLRTDLSTLTELSNKRQIPVSHEQGRNLAKQIGAAAYVECSAKTSENsV 164

                          90
                  ....*....|..
gi 1958670744  82 EDVFREATKVAL 93
Cdd:cd04131   165 RDVFEMATLACL 176

Rho-related protein from plants (Rop)-like; The Rop (Rho-related protein from plants) subfamily plays a role in diverse cellular processes, including cytoskeletal organization, pollen and vegetative cell growth, hormone responses, stress responses, and pathogen resistance. Rops are able to regulate several downstream pathways to amplify a specific signal by acting as master switches early in the signaling cascade. They transmit a variety of extracellular and intracellular signals. Rops are involved in establishing cell polarity in root-hair development, root-hair elongation, pollen-tube growth, cell-shape formation, responses to hormones such as abscisic acid (ABA) and auxin, responses to abiotic stresses such as oxygen deprivation, and disease resistance and disease susceptibility. An individual Rop can have a unique function or an overlapping function shared with other Rop proteins; in addition, a given Rop-regulated function can be controlled by one or multiple Rop proteins. For example, Rop1, Rop3, and Rop5 are all involved in pollen-tube growth; Rop2 plays a role in response to low-oxygen environments, cell-morphology, and root-hair development; root-hair development is also regulated by Rop4 and Rop6; Rop6 is also responsible for ABA response, and ABA response is also regulated by Rop10. Plants retain some of the regulatory mechanisms that are shared by other members of the Rho family, but have also developed a number of unique modes for regulating Rops. Unique RhoGEFs have been identified that are exclusively active toward Rop proteins, such as those containing the domain PRONE (plant-specific Rop nucleotide exchanger). Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744   5 SYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQlePITYTQGLSACEQMRGALYLECSAKFRENVEDV 84
Cdd:cd04133    87 SYENVLKKWIPELRHYAPGVPIVLVGTKLDLRDDKQFFADHPGAV--PITTAQGEELRKQIGAAAYIECSSKTQQNVKAV 164

                  ....*....
gi 1958670744  85 FREATKVAL 93
Cdd:cd04133   165 FDAAIKVVL 173

Rnd2/Rho7 GTPases; Rnd2/Rho7 is a member of the novel Rho subfamily Rnd, together with Rnd1/Rho6 and Rnd3/RhoE/Rho8. Rnd2/Rho7 is transiently expressed in radially migrating cells in the brain while they are within the subventricular zone of the hippocampus and cerebral cortex. These migrating cells typically develop into pyramidal neurons. Cells that exogenously expressed Rnd2/Rho7 failed to migrate to upper layers of the brain, suggesting that Rnd2/Rho7 plays a role in the radial migration and morphological changes of developing pyramidal neurons, and that Rnd2/Rho7 degradation is necessary for proper cellular migration. The Rnd2/Rho7 GEF Rapostlin is found primarily in the brain and together with Rnd2/Rho7 induces dendrite branching. Unlike Rnd1/Rho6 and Rnd3/RhoE/Rho8, which are RhoA antagonists, Rnd2/Rho7 binds the GEF Pragmin and significantly stimulates RhoA activity and Rho-A mediated cell contraction. Rnd2/Rho7 is also found to be expressed in spermatocytes and early spermatids, with male-germ-cell Rac GTPase-activating protein (MgcRacGAP), where it localizes to the Golgi-derived pro-acrosomal vesicle. 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 1958670744   3 PTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFREN-V 81
Cdd:cd04173    85 PETLDSVLKKWQGETQEFCPNAKLVLVGCKLDMRTDLSTLRELSKQRLIPVTHEQGSLLARQLGAVAYVECSSRMSENsV 164

                          90       100
                  ....*....|....*....|....*
gi 1958670744  82 EDVFREATKVALSALKKAQRQKKQR 106
Cdd:cd04173   165 RDVFHVTTLASVRREHPSLKRSTSR 189

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744   2 NPTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFRENV 81
Cdd:cd04130    83 NPSSFQNISEKWIPEIRKHNPKAPIILVGTQADLRTDVNVLIQLARYGEKPVSQSRAKALAEKIGACEYIECSALTQKNL 162

                  ....*..
gi 1958670744  82 EDVFREA 88
Cdd:cd04130   163 KEVFDTA 169

Ras homology family 2 (Rho2) of small guanosine triphosphatases (GTPases); Rho2 is a fungal GTPase that plays a role in cell morphogenesis, control of cell wall integrity, control of growth polarity, and maintenance of growth direction. Rho2 activates the protein kinase C homolog Pck2, and Pck2 controls Mok1, the major (1-3) alpha-D-glucan synthase. Together with Rho1 (RhoA), Rho2 regulates the construction of the cell wall. Unlike Rho1, Rho2 is not an essential protein, but its overexpression is lethal. 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 proper intracellular localization via membrane attachment. As with other Rho family GTPases, the GDP/GTP cycling is regulated by GEFs (guanine nucleotide exchange factors), GAPs (GTPase-activating proteins) and GDIs (guanine nucleotide dissociation inhibitors).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744   2 NPTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKeqLRKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFRENV 81
Cdd:cd04129    84 TPDSLENVRTKWIEEVRRYCPNVPVILVGLKKDLRQEA--VAKGNYATDEFVPIQQAKLVARAIGAKKYMECSALTGEGV 161

                          90       100
                  ....*....|....*....|....*....
gi 1958670744  82 EDVFREATKVALSALKKAQRQKKQRICLL 110
Cdd:cd04129   162 DDVFEAATRAALLVRKSGKEEPGANCCII 190

Rho GTPase TC10 (Tc10); TC10 is a Rho family protein that has been shown to induce microspike formation and neurite outgrowth in vitro. Its expression changes dramatically after peripheral nerve injury, suggesting an important role in promoting axonal outgrowth and regeneration. TC10 regulates translocation of insulin-stimulated GLUT4 in adipocytes and has also been shown to bind directly to Golgi COPI coat proteins. GTP-bound TC10 in vitro can bind numerous potential effectors. Depending on its subcellular localization and distinct functional domains, TC10 can differentially regulate two types of filamentous actin in adipocytes. TC10 mRNAs are highly expressed in three types of mouse muscle tissues: leg skeletal muscle, cardiac muscle, and uterus; they were also present in brain, with higher levels in adults than in newborns. TC10 has also been shown to play a role in regulating the expression of cystic fibrosis transmembrane conductance regulator (CFTR) through interactions with CFTR-associated ligand (CAL). The GTP-bound form of TC10 directs the trafficking of CFTR from the juxtanuclear region to the secretory pathway toward the plasma membrane, away from CAL-mediated DFTR degradation in the lysosome. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744   1 MNPTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFREN 80
Cdd:cd04135    82 VNPASFQNVKEEWVPELKEYAPNVPYLLIGTQIDLRDDPKTLARLNDMKEKPITVEQGQKLAKEIGACCYVECSALTQKG 161

                  ....*...
gi 1958670744  81 VEDVFREA 88
Cdd:cd04135   162 LKTVFDEA 169

RhoBTB protein is an atypical member of the Rho family of small GTPases; Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila, and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase domain, a proline rich region, a tandem of two BTB (Broad-Complex, Tramtrack, and Bric a brac) domains, and a C-terminal region of unknown function. RhoBTB proteins may act as docking points for multiple components participating in signal transduction cascades. RhoBTB genes appeared upregulated in some cancer cell lines, suggesting a participation of RhoBTB proteins in the pathogenesis of particular tumors. Note that the Dictyostelium RacA GTPase domain is more closely related to Rac proteins than to RhoBTB proteins, where RacA actually belongs. Thus, the Dictyostelium RacA is not included here. Most Rho proteins contain a lipid modification site at the C-terminus; however, RhoBTB is one of few Rho subfamilies that lack this feature.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744   2 NPTSYDNVLIKWFPEVTHFCRGIPMVLIGCKTDLRK-DKEQLRKLRAAQLEPITYTQGLS-----ACEQMRGALYLECSA 75
Cdd:cd01873    99 SPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYaDLDEVNRARRPLARPIKNADILPpetgrAVAKELGIPYYETSV 178

                          90
                  ....*....|....*..
gi 1958670744  76 KFRENVEDVFREATKVA 92
Cdd:cd01873   179 VTQFGVKDVFDNAIRAA 195

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744    2 NPTSYDNVlIKWFPEV-THFCRGIPMVLIGCKTDLRKDKEqlrklraaqlepITYTQGLSACEQmRGALYLECSAKFREN 80
Cdd:smart00175  84 NRESFENL-ENWLKELrEYASPNVVIMLVGNKSDLEEQRQ------------VSREEAEAFAEE-HGLPFFETSAKTNTN 149

                           90
                   ....*....|...
gi 1958670744   81 VEDVFREATKVAL 93
Cdd:smart00175 150 VEEAFEELAREIL 162

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958670744   24 IPMVLIGCKTDLrkdkEQLRKlraaqlepITYTQGLSACEQMrGALYLECSAKFRENVEDVFRE 87
Cdd:smart00010 108 VPIVLVGNKCDL----ENERV--------VSTEEGKELARQW-GCPFLETSAKERINVDEAFYD 158

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 1958670744  11 IKWFPEVTHFCRGIPMVLIGCKTDLRKDKEQLRKLRAAQLEPITYTQglsaceqmrgalYLECSAKFRENVEDVFREATK 90
Cdd:cd00882    94 AKLLILRRLRKEGIPIILVGNKIDLLEEREVEELLRLEELAKILGVP------------VFEVSAKTGEGVDELFEKLIE 161

Ras-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744  24 IPMVLIGCKTDLRKDKEqlrklraaqlepITYTQGLSACEQMrGALYLECSAKFRENVEDVFREATKVALSALKKAQRQK 103
Cdd:PTZ00369  111 VPMILVGNKCDLDSERQ------------VSTGEGQELAKSF-GIPFLETSAKQRVNVDEAFYELVREIRKYLKEDMPSQ 177

                          90
                  ....*....|..
gi 1958670744 104 KQR----ICLLL 111
Cdd:PTZ00369  178 KQKkkggLCLIL 189

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 1958670744   2 NPTSYdNVLIKWFPEVTHFCR-GIPMVLIGCKTDLRKDKEqlrklraaqlepITYTQGlSACEQMRGALYLECSAKFREN 80
Cdd:cd04113    84 SRESF-NALTNWLTDARTLASpDIVIILVGNKKDLEDDRE------------VTFLEA-SRFAQENGLLFLETSALTGEN 149

                          90
                  ....*....|.
gi 1958670744  81 VEDVFREATKV 91
Cdd:cd04113   150 VEEAFLKCARS 160

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744   5 SYDNVLIKWFPEVTHFCRGIPMV--LIGCKTDlrKDKEQlrklraaqlePITYTQGLSACEQMrGALYLECSAKFRENVE 82
Cdd:PLN03118  100 TFTNLSDVWGKEVELYSTNQDCVkmLVGNKVD--RESER----------DVSREEGMALAKEH-GCLFLECSAKTRENVE 166

                  ....*
gi 1958670744  83 DVFRE 87
Cdd:PLN03118  167 QCFEE 171

GTP-binding nuclear protein Ran; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744   5 SYDNVlIKWFPEVTHFCRGIPMVLIGCKTDLrKDkeqlRKLRAAQlepITYtqglsacEQMRGALYLECSAKFRENVEDV 84
Cdd:PTZ00132   96 TYKNV-PNWHRDIVRVCENIPIVLVGNKVDV-KD----RQVKARQ---ITF-------HRKKNLQYYDISAKSNYNFEKP 159

                  .
gi 1958670744  85 F 85
Cdd:PTZ00132  160 F 160

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 1958670744   5 SYDNVLIKWFPEVTHFCR-GIPMVLIGCKTDLR--KDKEQLRKLRAaqlepitytqglsaceQMRGALYLECSAKFRENV 81
Cdd:TIGR00231  90 DVEEILEKQTKEIIHHADsGVPIILVGNKIDLKdaDLKTHVASEFA----------------KLNGEPIIPLSAETGKNI 153

                  ....
gi 1958670744  82 EDVF 85
Cdd:TIGR00231 154 DSAF 157

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958670744  26 MVLIGCKTDLRKDKEqlrklraaqlepITYTQGLSACEQmRGALYLECSAKFRENVEDVFREATK 90
Cdd:cd04122   110 IFLIGNKADLEAQRD------------VTYEEAKQFADE-NGLLFLECSAKTGENVEDAFLETAK 161

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958670744  24 IPMVLIGCKTDLrKDKEQLRKLRAAQLepitytqglsaCEQMrGALYLECSAKFRENVEDVF 85
Cdd:cd04139   106 VPLLLVGNKCDL-EDKRQVSVEEAANL-----------AEQW-GVNYVETSAKTRANVDKVF 154

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958670744  24 IPMVLIGCKTDLRKDKEqlrklraaqlepITYTQGLSACEQMRGALYLECSAKFRENVEDVFRE 87
Cdd:cd04136   107 VPMILVGNKCDLEDERV------------VSKEEGQNLARQWGNCPFLETSAKSKINVDEIFYD 158

Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, multi-domain proteins that all contain an ArfGAP domain and ankyrin repeats, and in some cases, numerous additional domains. Centaurin gamma contains an additional GTPase domain near its N-terminus. The specific function of this GTPase domain has not been well characterized, but centaurin gamma 2 (CENTG2) may play a role in the development of autism. Centaurin gamma 1 is also called PIKE (phosphatidyl inositol (PI) 3-kinase enhancer) and centaurin gamma 2 is also known as AGAP (ArfGAP protein with a GTPase-like domain, ankyrin repeats and a Pleckstrin homology domain) or GGAP. Three isoforms of PIKE have been identified. PIKE-S (short) and PIKE-L (long) are brain-specific isoforms, with PIKE-S restricted to the nucleus and PIKE-L found in multiple cellular compartments. A third isoform, PIKE-A was identified in human glioblastoma brain cancers and has been found in various tissues. GGAP has been shown to have high GTPase activity due to a direct intramolecular interaction between the N-terminal GTPase domain and the C-terminal ArfGAP domain. In human tissue, AGAP mRNA was detected in skeletal muscle, kidney, placenta, brain, heart, colon, and lung. Reduced expression levels were also observed in the spleen, liver, and small intestine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958670744   2 NPTSYDNVLiKWFPEVTHF--CRGIPMVLIGCKTdlrkdkeqlrKLRAAQLEPITYTQGLSACEQMRGALYLECSAKFRE 79
Cdd:cd04103    77 DEASFQTVY-RLYHQLSSYrnISEIPLILVGTQD----------AISASNPRVIDDARARQLCADMKRCSYYETCATYGL 145

                  ....*....
gi 1958670744  80 NVEDVFREA 88
Cdd:cd04103   146 NVERVFQEA 154

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958670744  24 IPMVLIGCKTDLrkdkEQLRKlraaqlepITYTQGLSACEQMrGALYLECSAKFRENVEDVFRE 87
Cdd:cd01860   107 IVIALAGNKADL----ESKRQ--------VSTEEAQEYADEN-GLLFMETSAKTGENVNELFTE 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 1958670744   8 NVLIKWFPEV-THFCRGIPMVLIGCKTDLRKDKEqlrklraaqlepITYTQGlSACEQMRGALYLECSAKFRENVEDVFR 86
Cdd:cd01866    93 NHLTSWLEDArQHSNSNMTIMLIGNKCDLESRRE------------VSYEEG-EAFAREHGLIFMETSAKTASNVEEAFI 159

                  ....*
gi 1958670744  87 EATKV 91
Cdd:cd01866   160 NTAKE 164