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 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEAS 80
Cdd:cd04176   65 MRDLYIKNGQGFIVVYSLVNQQTFQDIKPMRDQIVRVKGYEKVPIILVGNKVDLESEREVSSAEGRALAEEWGCPFMETS 144

                         90
                 ....*....|....*....
gi 665403353  81 AKDRINVNEVFATIVREMN 99
Cdd:cd04176  145 AKSKTMVNELFAEIVRQMN 163

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 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEAS 80
Cdd:cd04176   65 MRDLYIKNGQGFIVVYSLVNQQTFQDIKPMRDQIVRVKGYEKVPIILVGNKVDLESEREVSSAEGRALAEEWGCPFMETS 144

                         90
                 ....*....|....*....
gi 665403353  81 AKDRINVNEVFATIVREMN 99
Cdd:cd04176  145 AKSKTMVNELFAEIVRQMN 163

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 665403353    1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSqPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEAS 80
Cdd:pfam00071  64 LRPLYYRGADGFLLVYDITSRDSFENVKKWVEEILRHADE-NVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETS 142

                          90
                  ....*....|....*...
gi 665403353   81 AKDRINVNEVFATIVREM 98
Cdd:pfam00071 143 AKTNENVEEAFEELAREI 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 665403353    1 MRDLYIKNGHGFIVMYSLTNHQ-TFQDI-SSMKNVITRVKGSQpAPILLVANKFDLDcQREVSTAEGNALAQLWDCPFIE 78
Cdd:TIGR00231  67 IRRLYYPQVERSLRVFDIVILVlDVEEIlEKQTKEIIHHADSG-VPIILVGNKIDLK-DADLKTHVASEFAKLNGEPIIP 144

                          90
                  ....*....|....*...
gi 665403353   79 ASAKDRINVNEVFATIVR 96
Cdd:TIGR00231 145 LSAETGKNIDSAFKIVEA 162

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 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEAS 80
Cdd:cd04176   65 MRDLYIKNGQGFIVVYSLVNQQTFQDIKPMRDQIVRVKGYEKVPIILVGNKVDLESEREVSSAEGRALAEEWGCPFMETS 144

                         90
                 ....*....|....*....
gi 665403353  81 AKDRINVNEVFATIVREMN 99
Cdd:cd04176  145 AKSKTMVNELFAEIVRQMN 163

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 665403353     1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEAS 80
Cdd:smart00173  64 MRDQYMRTGEGFLLVYSITDRQSFEEIKKFREQILRVKDRDDVPIVLVGNKCDLESERVVSTEEGKELARQWGCPFLETS 143

                           90
                   ....*....|....*....
gi 665403353    81 AKDRINVNEVFATIVREMN 99
Cdd:smart00173 144 AKERVNVDEAFYDLVREIR 162

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 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLW-DCPFIEA 79
Cdd:cd04136   65 MRDLYIKNGQGFALVYSITAQQSFNDLQDLREQILRVKDTEDVPMILVGNKCDLEDERVVSKEEGQNLARQWgNCPFLET 144

                         90       100
                 ....*....|....*....|
gi 665403353  80 SAKDRINVNEVFATIVREMN 99
Cdd:cd04136  145 SAKSKINVDEIFYDLVRQIN 164

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 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEAS 80
Cdd:cd04175   65 MRDLYMKNGQGFVLVYSITAQSTFNDLQDLREQILRVKDTEDVPMILVGNKCDLEDERVVGKEQGQNLARQWGCAFLETS 144

                         90
                 ....*....|....*....
gi 665403353  81 AKDRINVNEVFATIVREMN 99
Cdd:cd04175  145 AKAKINVNEIFYDLVRQIN 163

R-Ras2/TC21, M-Ras/R-Ras3; The M-Ras/R-Ras-like subfamily contains R-Ras2/TC21, M-Ras/R-Ras3, and related members of the Ras family. M-Ras is expressed in lympho-hematopoetic cells. It interacts with some of the known Ras effectors, but appears to also have its own effectors. Expression of mutated M-Ras leads to transformation of several types of cell lines, including hematopoietic cells, mammary epithelial cells, and fibroblasts. Overexpression of M-Ras is observed in carcinomas from breast, uterus, thyroid, stomach, colon, kidney, lung, and rectum. In addition, expression of a constitutively active M-Ras mutant in murine bone marrow induces a malignant mast cell leukemia that is distinct from the monocytic leukemia induced by H-Ras. TC21, along with H-Ras, has been shown to regulate the branching morphogenesis of ureteric bud cell branching in mice. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEAS 80
Cdd:cd04145   66 MREQYMRTGEGFLLVFSVTDRGSFEEVDKFHTQILRVKDRDEFPMILVGNKADLEHQRQVSREEGQELARQLKIPYIETS 145

                         90
                 ....*....|....*.
gi 665403353  81 AKDRINVNEVFATIVR 96
Cdd:cd04145  146 AKDRVNVDKAFHDLVR 161

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 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDcQREVSTAEGNALAQLWDCPFIEAS 80
Cdd:cd04138   65 MRDQYMRTGEGFLCVFAINSRKSFEDIHTYREQIKRVKDSDDVPMVLVGNKCDLA-ARTVSTRQGQDLAKSYGIPYIETS 143

                         90
                 ....*....|....*...
gi 665403353  81 AKDRINVNEVFATIVREM 98
Cdd:cd04138  144 AKTRQGVEEAFYTLVREI 161

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 665403353  10 HGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASAKDRINVNE 89
Cdd:cd04137   74 HGYILVYSVTSRKSFEVVKVIYDKILDMLGKESVPIVLVGNKSDLHMERQVSAEEGKKLAESWGAAFLESSAKENENVEE 153

                         90       100
                 ....*....|....*....|....*
gi 665403353  90 VFATIVREMNLTQENR--QKKNYCC 112
Cdd:cd04137  154 AFELLIEEIEKVENPLppGQKSKCS 178

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 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEAS 80
Cdd:cd04139   64 IRDNYFRSGEGFLLVFSITDMESFTALAEFREQILRVKEDDNVPLLLVGNKCDLEDKRQVSVEEAANLAEQWGVNYVETS 143

                         90
                 ....*....|....*...
gi 665403353  81 AKDRINVNEVFATIVREM 98
Cdd:cd04139  144 AKTRANVDKVFFDLVREI 161

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISS-MKNVitRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEA 79
Cdd:cd00154   65 ITSSYYRGAHGAILVYDVTNRESFENLDKwLNEL--KEYAPPNIPIILVGNKSDLEDERQVSTEEAQQFAKENGLLFFET 142

                         90
                 ....*....|....*..
gi 665403353  80 SAKDRINVNEVFATIVR 96
Cdd:cd00154  143 SAKTGENVDEAFESLAR 159

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 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPA--PILLVANKFDLDCQREVSTAEGNALAQLWDCPFIE 78
Cdd:cd04140   65 MQRLSISKGHAFILVYSITSKQSLEELKPIYELICEIKGNNLEkiPIMLVGNKCDESPSREVSSSEGAALARTWNCAFME 144

                         90
                 ....*....|...
gi 665403353  79 ASAKDRINVNEVF 91
Cdd:cd04140  145 TSAKTNHNVQELF 157

Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like families; RERG (Ras-related and Estrogen- Regulated Growth inhibitor) and Ras-like 11 are members of a novel subfamily of Ras that were identified based on their behavior in breast and prostate tumors, respectively. RERG expression was decreased or lost in a significant fraction of primary human breast tumors that lack estrogen receptor and are correlated with poor clinical prognosis. Elevated RERG expression correlated with favorable patient outcome in a breast tumor subtype that is positive for estrogen receptor expression. In contrast to most Ras proteins, RERG overexpression inhibited the growth of breast tumor cells in vitro and in vivo. RasL11 was found to be ubiquitously expressed in human tissue, but down-regulated in prostate tumors. Both RERG and RasL11 lack the C-terminal CaaX prenylation motif, where a = an aliphatic amino acid and X = any amino acid, and are localized primarily in the cytoplasm. Both are believed to have tumor suppressor activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665403353   5 YIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQ-PAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASA-K 82
Cdd:cd04146   69 SLRWADGFVLVYSITDRSSFDVVSQLLQLIREIKKRDgEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAaE 148

                         90
                 ....*....|....*
gi 665403353  83 DRINVNEVFATIVRE 97
Cdd:cd04146  149 NYLEVQNVFHELCRE 163

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 665403353   5 YIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVkGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASAKDR 84
Cdd:cd01869   71 YYRGAHGIIIVYDVTDQESFNNVKQWLQEIDRY-ASENVNKLLVGNKCDLTDKKVVDYTEAKEFADELGIPFLETSAKNA 149

                         90
                 ....*....|....
gi 665403353  85 INVNEVFATIVREM 98
Cdd:cd01869  150 TNVEEAFMTMAREI 163

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 665403353   4 LYIKNGHGFIVMYSLTNHQTFQDISS-MKNVitRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASAK 82
Cdd:cd01860   69 MYYRGAAAAIVVYDITSEESFEKAKSwVKEL--QEHGPPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAK 146

                         90
                 ....*....|....*.
gi 665403353  83 DRINVNEVFATIVREM 98
Cdd:cd01860  147 TGENVNELFTEIARKL 162

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665403353   5 YIKNGHGFIVMYSLTNHQTFQDISS-MKNVITRVKGSQPApILLVANKFDLDCQREVSTAEGNALAQlwDCP--FIEASA 81
Cdd:cd04111   72 YYRNSVGVLLVFDITNRESFEHVHDwLEEARSHIQPHRPV-FILVGHKCDLESQRQVTREEAEKLAK--DLGmkYIETSA 148

                         90       100       110
                 ....*....|....*....|....*....|.
gi 665403353  82 KDRINVNEVFATIVREMnltqENRQKKNYCC 112
Cdd:cd04111  149 RTGDNVEEAFELLTQEI----YERIKRGELC 175

Rab GTPase family 11 (Rab11)-like includes Rab11a, Rab11b, and Rab25; Rab11a, Rab11b, and Rab25 are closely related, evolutionary conserved Rab proteins that are differentially expressed. Rab11a is ubiquitously synthesized, Rab11b is enriched in brain and heart and Rab25 is only found in epithelia. Rab11/25 proteins seem to regulate recycling pathways from endosomes to the plasma membrane and to the trans-Golgi network. Furthermore, Rab11a is thought to function in the histamine-induced fusion of tubulovesicles containing H+, K+ ATPase with the plasma membrane in gastric parietal cells and in insulin-stimulated insertion of GLUT4 in the plasma membrane of cardiomyocytes. Overexpression of Rab25 has recently been observed in ovarian cancer and breast cancer, and has been correlated with worsened outcomes in both diseases. In addition, Rab25 overexpression has also been observed in prostate cancer, transitional cell carcinoma of the bladder, and invasive breast tumor cells. 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 665403353   5 YIKNGHGFIVMYSLTNHQTFQDISSMKNVItRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASAKDR 84
Cdd:cd01868   72 YYRGAVGALLVYDITKKSTFENVERWLKEL-RDHADSNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIETSALDG 150

                         90
                 ....*....|...
gi 665403353  85 INVNEVFATIVRE 97
Cdd:cd01868  151 TNVEEAFKQLLTE 163

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 665403353   4 LYIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQpAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASAKD 83
Cdd:cd04123   68 IYYRDADGAILVYDITDADSFQKVKKWIKELKQMRGNN-ISLVIVGNKIDLERQRVVSKSEAEEYAKSVGAKHFETSAKT 146

                         90
                 ....*....|....*
gi 665403353  84 RINVNEVFATIVREM 98
Cdd:cd04123  147 GKGIEELFLSLAKRM 161

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665403353   5 YIKNGHGFIVMYSLTNHQTFQDISSM-KNVITRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASAKD 83
Cdd:PLN03118  82 YYRNAQGIILVYDVTRRETFTNLSDVwGKEVELYSTNQDCVKMLVGNKVDRESERDVSREEGMALAKEHGCLFLECSAKT 161

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 665403353  84 RINVNEVF-----------------ATIVREMNLTQ--ENRQKKNYCCCT 114
Cdd:PLN03118 162 RENVEQCFeelalkimevpslleegSTAVKRNILKQkpEHQPPPNGGCCS 211

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 665403353   5 YIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGSQPApILLVANKFDLDCQREVSTAEGNALAQLWDCPF-IEASAKD 83
Cdd:cd01864   72 YYRSANGAIIAYDITRRSSFESVPHWIEEVEKYGASNVV-LLLIGNKCDLEEQREVLFEEACTLAEHYGILAvLETSAKE 150

                         90
                 ....*....|....*
gi 665403353  84 RINVNEVFATIVREM 98
Cdd:cd01864  151 SSNVEEAFLLMATEL 165

Rab GTPase families 18 (Rab18) and 32 (Rab32); Rab38/Rab32 subfamily. Rab32 and Rab38 are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP). Rab38 has been shown to be melanocyte-specific. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVI-TRVKGS--QPAPILLVANKFDLDCQREVSTAEgnALAQL------ 71
Cdd:cd04107   66 MTRVYYKGAVGAIIVFDVTRPSTFEAVLKWKADLdSKVTLPngEPIPALLLANKCDLKKERLAKDPE--QMDQFckengf 143

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 665403353  72 --WdcpfIEASAKDRINVNEVFATIVREM------------------NLTQENRQKKNYCCC 113
Cdd:cd04107  144 igW----FETSAKENINIEEAMRFLVKNIlkndkglqspepdednviDLKQETTTSKSKSCC 201

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 665403353   5 YIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVkGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASAKDR 84
Cdd:cd04112   70 YYRDAHALLLLYDVTNKSSFDNIRAWLTEILEY-AQSDVVIMLLGNKADMSGERVVKREDGERLAKEYGVPFMETSAKTG 148

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 665403353  85 INVNEVFATIVREM---NLTQE-----------NRQKKNYCCC 113
Cdd:cd04112  149 LNVELAFTAVAKELkhrSVEQPdepkfkiqdyvEKQKKSSGCC 191

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 665403353   1 MRDLYIKNGHGFIVMYSLTNHQTFQDISSMKNVI--------TRVKGSQPAPILLVANKFDLDCQREVSTAEGNAL-AQL 71
Cdd:cd04143   64 MRRLSILTGDVFILVFSLDNRESFEEVCRLREQIletksclkNKTKENVKIPMVICGNKADRDFPREVQRDEVEQLvGGD 143

                         90       100       110
                 ....*....|....*....|....*....|..
gi 665403353  72 WDCPFIEASAKDRINVNEVFATIVREMNLTQE 103
Cdd:cd04143  144 ENCAYFEVSAKKNSNLDEMFRALFSLAKLPNE 175

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 665403353   5 YIKNGHGFIVMYSLTNHQTFQDISS-MKNVitRVKGSQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASAKD 83
Cdd:cd01866   73 YYRGAAGALLVYDITRRETFNHLTSwLEDA--RQHSNSNMTIMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKT 150

                         90
                 ....*....|....*
gi 665403353  84 RINVNEVFATIVREM 98
Cdd:cd01866  151 ASNVEEAFINTAKEI 165

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 665403353  12 FIVMYSLTNHQTFQDISSMknVITRVKG-SQPAPILLVANKFDL-----------DCQREVSTAEGNALAQLWDC-PFIE 78
Cdd:cd00157   75 FLLCFSVDSPSSFENVKTK--WYPEIKHyCPNVPIILVGTKIDLrddgntlkkleKKQKPITPEEGEKLAKEIGAvKYME 152

                         90
                 ....*....|....*...
gi 665403353  79 ASAKDRINVNEVFATIVR 96
Cdd:cd00157  153 CSALTQEGLKEVFDEAIR 170

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 665403353  13 IVMYSLTNHQTFQDISSMKN---VITRVKGSQPAPILLVANKFDLDCQREVSTAEgnalAQLW-----DCPFIEASAKDR 84
Cdd:cd01862   77 VLVYDVTNPKSFESLDSWRDeflIQASPRDPENFPFVVLGNKIDLEEKRQVSTKK----AQQWckskgNIPYFETSAKEA 152

                         90
                 ....*....|..
gi 665403353  85 INVNEVFATIVR 96
Cdd:cd01862  153 INVDQAFETIAR 164

rab6; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665403353   5 YIKNGHGFIVMYSLTNHQTFQDISSMKNVITRVKGsQPAPILLVANKFDLDCQREVSTAEGNALAQLWDCPFIEASAKDR 84
Cdd:PTZ00099  49 YIRDSAAAIVVYDITNRQSFENTTKWIQDILNERG-KDVIIALVGNKTDLGDLRKVTYEEGMQKAQEYNTMFHETSAKAG 127

                         90       100
                 ....*....|....*....|....*.
gi 665403353  85 INVNEVFATIVREM-NLTQENRQKKN 109
Cdd:PTZ00099 128 HNIKVLFKKIAAKLpNLDNSNSNDAN 153