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 90111816  18 TAILRQVacVEDVTNKPYEPTIEDTYQVLLEEPDKAREILILhDTAGVSNYGPieLKKAYVQAADAFVLVYSSADYESFN 97
Cdd:cd00876  13 SALTIRF--VSGEFVEEYDPTIEDSYRKQIVVDGETYTLDIL-DTAGQEEFSA--MRDQYIRNGDGFILVYSITSRESFE 87

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 90111816  98 RVDLLKKWIDRQfgKDKKEVPIVVLANMRD----RPATVDSAFAhsWAAREKVKLFEVTAKDRQ 157
Cdd:cd00876  88 EIKNIREQILRV--KDKEDVPIVLVGNKCDleneRQVSTEEGEA--LAEEWGCPFLETSAKTNI 147

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 90111816  18 TAILRQVacVEDVTNKPYEPTIEDTYQVLLEEPDKAREILILhDTAGVSNYGPieLKKAYVQAADAFVLVYSSADYESFN 97
Cdd:cd00876  13 SALTIRF--VSGEFVEEYDPTIEDSYRKQIVVDGETYTLDIL-DTAGQEEFSA--MRDQYIRNGDGFILVYSITSRESFE 87

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 90111816  98 RVDLLKKWIDRQfgKDKKEVPIVVLANMRD----RPATVDSAFAhsWAAREKVKLFEVTAKDRQ 157
Cdd:cd00876  88 EIKNIREQILRV--KDKEDVPIVLVGNKCDleneRQVSTEEGEA--LAEEWGCPFLETSAKTNI 147

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 90111816    35 YEPTI-EDTYQVLLEEPDKarEILI-LHDTAGVSNYGPieLKKAYVQAADAFVLVYSSADYESFNRVdllKKW---IDRQ 109
Cdd:pfam00071  28 YIPTIgVDFYTKTIEVDGK--TVKLqIWDTAGQERFRA--LRPLYYRGADGFLLVYDITSRDSFENV---KKWveeILRH 100

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 90111816   110 FGKDkkeVPIVVLAN---MRDRPAtVDSAFAHSWAAREKVKLFEVTAKDR 156
Cdd:pfam00071 101 ADEN---VPIVLVGNkcdLEDQRV-VSTEEGEALAKELGLPFMETSAKTN 146

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 90111816    14 KVGKTAILRQVACVEDVTNKpYEPTIEDTYQVLLEEPDKAREILILHDTAGVSNYGPIElkKAYVQAADAFVLVYSSADY 93
Cdd:TIGR00231  11 NVGKSTLLNSLLGNKGSITE-YYPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIR--RLYYPQVERSLRVFDIVIL 87

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 90111816    94 -ESFNrvDLLKKWIDRQFGKDKKEVPIVVLANMRD-RPATVDSAFAHSWAAREKVKLFEVTAKDRQ---SLVDFI 163
Cdd:TIGR00231  88 vLDVE--EILEKQTKEIIHHADSGVPIILVGNKIDlKDADLKTHVASEFAKLNGEPIIPLSAETGKnidSAFKIV 160

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 90111816  18 TAILRQVacVEDVTNKPYEPTIEDTYQVLLEEPDKAREILILhDTAGVSNYGPieLKKAYVQAADAFVLVYSSADYESFN 97
Cdd:cd00876  13 SALTIRF--VSGEFVEEYDPTIEDSYRKQIVVDGETYTLDIL-DTAGQEEFSA--MRDQYIRNGDGFILVYSITSRESFE 87

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 90111816  98 RVDLLKKWIDRQfgKDKKEVPIVVLANMRD----RPATVDSAFAhsWAAREKVKLFEVTAKDRQ 157
Cdd:cd00876  88 EIKNIREQILRV--KDKEDVPIVLVGNKCDleneRQVSTEEGEA--LAEEWGCPFLETSAKTNI 147

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 90111816     35 YEPTIEDTY--QVLLEEPDKAREILilhDTAGVSNYGPieLKKAYVQAADAFVLVYSSADYESFNRVDLLKKWIDRQfgK 112
Cdd:smart00173  29 YDPTIEDSYrkQIEIDGEVCLLDIL---DTAGQEEFSA--MRDQYMRTGEGFLLVYSITDRQSFEEIKKFREQILRV--K 101

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 90111816    113 DKKEVPIVVLANMRDRPA--TVDSAFAHSWAAREKVKLFEVTAKDRQSLVD 161
Cdd:smart00173 102 DRDDVPIVLVGNKCDLESerVVSTEEGKELARQWGCPFLETSAKERVNVDE 152

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 90111816  35 YEPTIEDTY--QVLLEEPDKAREILilhDTAGVSNYgpIELKKAYVQAADAFVLVYSSADYESFNRVDLLKKWIDRQFGK 112
Cdd:cd04144  28 YDPTIEDSYrkQVVVDGQPCMLEVL---DTAGQEEY--TALRDQWIREGEGFILVYSITSRSTFERVERFREQIQRVKDE 102

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 90111816 113 DKKEVPIVVLANMRDRPAT--VDSAFAHSWAAREKVKLFEVTAKDRQSL 159
Cdd:cd04144 103 SAADVPIMIVGNKCDKVYEreVSTEEGAALARRLGCEFIEASAKTNVNV 151

Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active (GTP-bound) Ras interacts with several effector proteins that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 90111816  35 YEPTIEDTY--QVLLEEPDKAREILilhDTAGVSNYGPieLKKAYVQAADAFVLVYSSADYESFNRVDLLKKWIDRQfgK 112
Cdd:cd04138  30 YDPTIEDSYrkQVVIDGETCLLDIL---DTAGQEEYSA--MRDQYMRTGEGFLCVFAINSRKSFEDIHTYREQIKRV--K 102

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 90111816 113 DKKEVPIVVLANMRDRPA-TVDSAFAHSWAAREKVKLFEVTAKDRQSLVD 161
Cdd:cd04138 103 DSDDVPMVLVGNKCDLAArTVSTRQGQDLAKSYGIPYIETSAKTRQGVEE 152

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 90111816  30 VTNKPYEPTI-EDTYQVLLEEPdkaREILILHDTAGVSNYGPIELKKAYVQA---ADAFVLVYSSADYESFNRVDLLkkw 105
Cdd:cd00882  24 EVSDVPGTTRdPDVYVKELDKG---KVKLVLVDTPGLDEFGGLGREELARLLlrgADLILLVVDSTDRESEEDAKLL--- 97

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 90111816 106 IDRQFGKDKKevPIVVLANMRDRPATVDSAFAHS---WAAREKVKLFEVTAKDRQSLVDFI 163
Cdd:cd00882  98 ILRRLRKEGI--PIILVGNKIDLLEEREVEELLRleeLAKILGVPVFEVSAKTGEGVDELF 156

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 90111816  35 YEPTIEDTY--QVLLEEPDKAREILilhDTAGVSNYgpIELKKAYVQAADAFVLVYSSADYESFNRVDLLKKWIDRQfgK 112
Cdd:cd04175  30 YDPTIEDSYrkQVEVDGQQCMLEIL---DTAGTEQF--TAMRDLYMKNGQGFVLVYSITAQSTFNDLQDLREQILRV--K 102

                        90
                ....*....|....*
gi 90111816 113 DKKEVPIVVLANMRD 127
Cdd:cd04175 103 DTEDVPMILVGNKCD 117

Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap subfamily of the Ras family. It consists of Rap2a, Rap2b, and Rap2c. Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton. In human platelets, Rap2 was shown to interact with the cytoskeleton by binding the actin filaments. In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway. The Rap2 interacting protein 9 (RPIP9) is highly expressed in human breast carcinomas and correlates with a poor prognosis, suggesting a role for Rap2 in breast cancer oncogenesis. Rap2b, but not Rap2a, Rap2c, Rap1a, or Rap1b, is expressed in human red blood cells, where it is believed to be involved in vesiculation. A number of additional effector proteins for Rap2 have been identified, including the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. 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 90111816  35 YEPTIEDTYQVLLeEPDKAREILILHDTAGVSNYGpiELKKAYVQAADAFVLVYSSADYESFNRVDLLKKWIDRQfgKDK 114
Cdd:cd04176  30 YDPTIEDFYRKEI-EVDSSPSVLEILDTAGTEQFA--SMRDLYIKNGQGFIVVYSLVNQQTFQDIKPMRDQIVRV--KGY 104

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 90111816 115 KEVPIVVLANMRDRPA--TVDSAFAHSWAAREKVKLFEVTAKDRQ 157
Cdd:cd04176 105 EKVPIILVGNKVDLESerEVSSAEGRALAEEWGCPFMETSAKSKT 149

Ras - dorsal-ventral anterior localization (Ras-dva) family; Ras-dva subfamily. Ras-dva (Ras - dorsal-ventral anterior localization) subfamily consists of a set of proteins characterized only in Xenopus leavis, to date. In Xenopus Ras-dva expression is activated by the transcription factor Otx2 and begins during gastrulation throughout the anterior ectoderm. Ras-dva expression is inhibited in the anterior neural plate by factor Xanf1. Downregulation of Ras-dva results in head development abnormalities through the inhibition of several regulators of the anterior neural plate and folds patterning, including Otx2, BF-1, Xag2, Pax6, Slug, and Sox9. Downregulation of Ras-dva also interferes with the FGF-8a signaling within the anterior ectoderm. 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 90111816  18 TAILRQVacVEDVTNKPYEPTIEDTYQVLLEEPDKAREILILhDTAGvsNYGPIELKKAYVQAADAFVLVYSSADYESFN 97
Cdd:cd04147  13 TALIQRF--LYDTFEPKHRRTVEELHSKEYEVAGVKVTIDIL-DTSG--SYSFPAMRKLSIQNGDAFALVYSVDDPESFE 87

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 90111816  98 RVDLLKKWIDRQfgKDKKEVPIVVLANMRDRPAT--VDSAFAHSWAAREKVKLF-EVTAKDRQSLVD 161
Cdd:cd04147  88 EVKRLREEILEV--KEDKFVPIVVVGNKIDSLAErqVEAADALSTVELDWNNGFvEASAKDNENVTE 152

Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 90111816  57 LILHDTAGVSNYGPIelKKAYVQAADAFVLVYSSADYESFNRVDLLKKWIDRQFGkdkkEVPIVVLANMRD--RPATVDS 134
Cdd:cd04106  53 LMLWDTAGQEEFDAI--TKAYYRGAQACILVFSTTDRESFEAIESWKEKVEAECG----DIPMVLVQTKIDllDQAVITN 126

                        90       100
                ....*....|....*....|.
gi 90111816 135 AFAHSWAAREKVKLFEVTAKD 155
Cdd:cd04106 127 EEAEALAKRLQLPLFRTSVKD 147

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 90111816  35 YEPTIEDTYQVLLeepDKAREILILHDTAGVSNYGPIELKKAYVQAADAFVLVYSSADYESFNRVDLLKKWIDRQFGKDK 114
Cdd:cd04140  30 YIPTIEDTYRQVI---SCSKSICTLQITDTTGSHQFPAMQRLSISKGHAFILVYSITSKQSLEELKPIYELICEIKGNNL 106

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 90111816 115 KEVPIVVLANMRDRPAT--VDSAFAHSWAAREKVKLFEVTAK 154
Cdd:cd04140 107 EKIPIMLVGNKCDESPSreVSSSEGAALARTWNCAFMETSAK 148

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 90111816  13 KKVGKTAILRQVACVEDVtnKPYEPTIEDTY--QVLLEEPDKAREILilhDTAGVSNYGPIelKKAYVQAADAFVLVYSS 90
Cdd:cd04139   9 GGVGKSALTLQFMYDEFV--EDYEPTKADSYrkKVVLDGEEVQLNIL---DTAGQEDYAAI--RDNYFRSGEGFLLVFSI 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 90111816  91 ADYESFNRVDLLKKWIDRQfgKDKKEVPIVVLANMRD----RPATVDSA--FAHSWaareKVKLFEVTAKDRQSL 159
Cdd:cd04139  82 TDMESFTALAEFREQILRV--KEDDNVPLLLVGNKCDledkRQVSVEEAanLAEQW----GVNYVETSAKTRANV 150

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 90111816  17 KTAILRQVACVEDVTNkpYEPTIEDTYQVLLEEPDKAREILILhDTAGVSNYgPiELKKAYVQAADAFVLVYSSADYESF 96
Cdd:cd04143  13 KTAIVSRFLGGRFEEQ--YTPTIEDFHRKLYSIRGEVYQLDIL-DTSGNHPF-P-AMRRLSILTGDVFILVFSLDNRESF 87

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 90111816  97 NRVDLLK------KWIDRQFGKDKKEVPIVVLANMRDR--PATVD-SAFAHSWAAREKVKLFEVTAKDRQSLVDFIH 164
Cdd:cd04143  88 EEVCRLReqiletKSCLKNKTKENVKIPMVICGNKADRdfPREVQrDEVEQLVGGDENCAYFEVSAKKNSNLDEMFR 164

Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 90111816  35 YEPTIEDTYQVL-LEEPDKAREILILhDTAGVSNYgpIELKKAYVQAADAFVLVYSSADYESFnrvDLLKKWID--RQFG 111
Cdd:cd04119  29 YLPTIGIDYGVKkVSVRNKEVRVNFF-DLSGHPEY--LEVRNEFYKDTQGVLLVYDVTDRQSF---EALDSWLKemKQEG 102

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 90111816 112 ---KDKKEVPIVVLANMRDRPA--TVDSAFAHSWAAREKVKLFEVTA 153
Cdd:cd04119 103 gphGNMENIVVVVCANKIDLTKhrAVSEDEGRLWAESKGFKYFETSA 149

Ras-related protein on chromosome 22 (RRP22) family; RRP22 (Ras-related protein on chromosome 22) subfamily consists of proteins that inhibit cell growth and promote caspase-independent cell death. Unlike most Ras proteins, RRP22 is down-regulated in many human tumor cells due to promoter methylation. RRP22 localizes to the nucleolus in a GTP-dependent manner, suggesting a novel function in modulating transport of nucleolar components. 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. Like most Ras family proteins, RRP22 is farnesylated.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 90111816  78 VQAADAFVLVYSSADYESFNRVDLLKKWIDRQFGKDKKEVPIVVLANMRDR 128
Cdd:cd04142  78 LRNSRAFILVYDICSPDSFHYVKLLRQQILETRPAGNKEPPIVVVGNKRDQ 128

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 90111816  35 YEPTIEDTYQVLLEePDKAREILILHDTAGVSNYGPieLKKAYVQAADAFVLVYSSADYESFNRVDllKKWIDrQFGKDK 114
Cdd:cd04130  29 YVPTAFDNFSVVVL-VDGKPVRLQLCDTAGQDEFDK--LRPLCYPDTDVFLLCFSVVNPSSFQNIS--EKWIP-EIRKHN 102

                        90
                ....*....|...
gi 90111816 115 KEVPIVVLANMRD 127
Cdd:cd04130 103 PKAPIILVGTQAD 115

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 90111816    14 KVGKTAILRQVACVEDVTNKpYEPTIEDTYQVLLEEPDKAREILILHDTAGVSNYGPIElkKAYVQAADAFVLVYSSADY 93
Cdd:TIGR00231  11 NVGKSTLLNSLLGNKGSITE-YYPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIR--RLYYPQVERSLRVFDIVIL 87

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 90111816    94 -ESFNrvDLLKKWIDRQFGKDKKEVPIVVLANMRD-RPATVDSAFAHSWAAREKVKLFEVTAKDRQ---SLVDFI 163
Cdd:TIGR00231  88 vLDVE--EILEKQTKEIIHHADSGVPIILVGNKIDlKDADLKTHVASEFAKLNGEPIIPLSAETGKnidSAFKIV 160

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 90111816  31 TNKPYEPTIEDTYQVLLEEPDKAREILILHDTAGVSNYGPIelKKAYVQAADAFVLVYSSADYESFNRVDllkKWIdRQF 110
Cdd:cd04121  31 TESPYGYNMGIDYKTTTILLDGRRVKLQLWDTSGQGRFCTI--FRSYSRGAQGIILVYDITNRWSFDGID---RWI-KEI 104

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 90111816 111 GKDKKEVPIVVLANmRDRPA---TVDSAFAHSWAAREKVKLFEVTA----KDRQSLVDFIHYVGHRHFHP 173
Cdd:cd04121 105 DEHAPGVPKILVGN-RLHLAfkrQVATEQAQAYAERNGMTFFEVSPlcnfNITESFTELARIVLMRHGRP 173