Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small GTPases of the ARF, RAB, RAN, RAS, and SAR subfamilies. Others that could not be classified in this way are predicted to be members of the small GTPase superfamily without predictions of the subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334   19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQED-TIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:smart00010  18 LTIQFVQGHFVDEYDPTIEDSYRKQIEIDGEVCLLDILDTAGQEEfSAMRDQYMRTGEGFLLVYSITDRQSFEEIAKFRE 97

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334   98 ILDEIKKPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCREVRRR 167
Cdd:smart00010  98 QILRVKDRDDVPIVLVGNKCDLENERVVSTEEGKELARQWGCPFLETSAKERI-NVDEAFYDLVREIRKS 166

Ras-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334  19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQED-TIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:PTZ00369   21 LTIQFIQNHFIDEYDPTIEDSYRKQCVIDEETCLLDILDTAGQEEySAMRDQYMRTGQGFLCVYSITSRSSFEEIASFRE 100

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462535334  98 ILDEIKKPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSAcTGEGNITEIFYELCREVRR 166
Cdd:PTZ00369  101 QILRVKDKDRVPMILVGNKCDLDSERQVSTGEGQELAKSFGIPFLETSA-KQRVNVDEAFYELVREIRK 168

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334  18 TLVVRFLTKRF-IWEYDPTLEST-YRHQATIDDEVVSMEILDTAGQEdtIQREGHMRWGE------GFVLVYDITDRGSF 89
Cdd:COG1100    18 SLVNRLVGDIFsLEKYLSTNGVTiDKKELKLDGLDVDLVIWDTPGQD--EFRETRQFYARqltgasLYLFVVDGTREETL 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334  90 E-EVLPLKNILDEIKKpknVTLILVGNKADLDHSRQVSTEEG--EKLATELACAFYECSACTGEGnITEIFYELCREVRR 166
Cdd:COG1100    96 QsLYELLESLRRLGKK---SPIILVLNKIDLYDEEEIEDEERlkEALSEDNIVEVVATSAKTGEG-VEELFAALAEILRG 171

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 2462535334  19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQED-TIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:cd00876    15 LTIRFVSGEFVEEYDPTIEDSYRKQIVVDGETYTLDILDTAGQEEfSAMRDQYIRNGDGFILVYSITSRESFEEIKNIRE 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462535334  98 ILDEIKKPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCREV 164
Cdd:cd00876    95 QILRVKDKEDVPIVLVGNKCDLENERQVSTEEGEALAEEWGCPFLETSAKTNI-NIDELFNTLVREI 160

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 2462535334   19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQED-TIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:smart00173  16 LTIQFIQGHFVDDYDPTIEDSYRKQIEIDGEVCLLDILDTAGQEEfSAMRDQYMRTGEGFLLVYSITDRQSFEEIKKFRE 95

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334   98 ILDEIKKPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCREVRRR 167
Cdd:smart00173  96 QILRVKDRDDVPIVLVGNKCDLESERVVSTEEGKELARQWGCPFLETSAKERV-NVDEAFYDLVREIRKK 164

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 2462535334  19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQED-TIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:cd04145    18 LTIQFIQSYFVTDYDPTIEDSYTKQCEIDGQWARLDILDTAGQEEfSAMREQYMRTGEGFLLVFSVTDRGSFEEVDKFHT 97

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462535334  98 ILDEIKKPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSAcTGEGNITEIFYELCREVR 165
Cdd:cd04145    98 QILRVKDRDEFPMILVGNKADLEHQRQVSREEGQELARQLKIPYIETSA-KDRVNVDKAFHDLVRVIR 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 2462535334  19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQED-TIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:cd04175    17 LTVQFVQGIFVEKYDPTIEDSYRKQVEVDGQQCMLEILDTAGTEQfTAMRDLYMKNGQGFVLVYSITAQSTFNDLQDLRE 96

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462535334  98 ILDEIKKPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSAcTGEGNITEIFYELCREVRR 166
Cdd:cd04175    97 QILRVKDTEDVPMILVGNKCDLEDERVVGKEQGQNLARQWGCAFLETSA-KAKINVNEIFYDLVRQINR 164

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 2462535334  19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQED-TIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:cd04138    17 LTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEySAMRDQYMRTGEGFLCVFAINSRKSFEDIHTYRE 96

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462535334  98 ILDEIKKPKNVTLILVGNKADLDhSRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCREVR 165
Cdd:cd04138    97 QIKRVKDSDDVPMVLVGNKCDLA-ARTVSTRQGQDLAKSYGIPYIETSAKTRQ-GVEEAFYTLVREIR 162

RSR1/Bud1p family GTPase; RSR1/Bud1p is a member of the Rap subfamily of the Ras family that is found in fungi. In budding yeasts, RSR1 is involved in selecting a site for bud growth on the cell cortex, which directs the establishment of cell polarization. The Rho family GTPase cdc42 and its GEF, cdc24, then establish an axis of polarized growth by organizing the actin cytoskeleton and secretory apparatus at the bud site. It is believed that cdc42 interacts directly with RSR1 in vivo. In filamentous fungi, polar growth occurs at the tips of hypha and at novel growth sites along the extending hypha. In Ashbya gossypii, RSR1 is a key regulator of hyphal growth, localizing at the tip region and regulating in apical polarization of the actin cytoskeleton. 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 2462535334  19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQED-TIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:cd04177    17 LTVQFVQNVFIESYDPTIEDSYRKQVEIDGRQCDLEILDTAGTEQfTAMRELYIKSGQGFLLVYSVTSEASLNELGELRE 96

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462535334  98 ILDEIKKPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACA-FYECSACTgEGNITEIFYELCREVR 165
Cdd:cd04177    97 QVLRIKDSDNVPMVLVGNKADLEDDRQVSREDGVSLSQQWGNVpFYETSARK-RTNVDEVFIDLVRQII 164

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 2462535334  19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQED-TIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:cd04139    16 LTLQFMYDEFVEDYEPTKADSYRKKVVLDGEEVQLNILDTAGQEDyAAIRDNYFRSGEGFLLVFSITDMESFTALAEFRE 95

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462535334  98 ILDEIKKPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCREVRR 166
Cdd:cd04139    96 QILRVKEDDNVPLLLVGNKCDLEDKRQVSVEEAANLAEQWGVNYVETSAKTRA-NVDKVFFDLVREIRQ 163

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 2462535334  19 LVVRFLTKRFIWEYDPTLESTYR-HQATIDDEVVSMEILDTAGQE--DTIQREgHMRWGEGFVLVYDITDRGSFEEVlpl 95
Cdd:cd00154    16 LLLRFVDNKFSENYKSTIGVDFKsKTIEVDGKKVKLQIWDTAGQErfRSITSS-YYRGAHGAILVYDVTNRESFENL--- 91

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462535334  96 KNILDEIKK--PKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCR 162
Cdd:cd00154    92 DKWLNELKEyaPPNIPIILVGNKSDLEDERQVSTEEAQQFAKENGLLFFETSAKTGE-NVDEAFESLAR 159

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 2462535334  18 TLVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQ-EDTIQREGHMRWGEGFVLVYDITDRGSFE--EVLP 94
Cdd:cd04137    16 SLTVQFVEGHFVESYYPTIENTFSKIITYKGQEYHLEIVDTAGQdEYSILPQKYSIGIHGYILVYSVTSRKSFEvvKVIY 95

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462535334  95 LKnILDEIKKpKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCREVRR 166
Cdd:cd04137    96 DK-ILDMLGK-ESVPIVLVGNKSDLHMERQVSAEEGKKLAESWGAAFLESSAKENE-NVEEAFELLIEEIEK 164

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 2462535334  19 LVVRFlTKRfiwEYDPTLEST-----YRHQATIDDEVVSMEILDTAGQEdtiqRE---GHM--RWGEGFVLVYDITDRGS 88
Cdd:cd01860    17 IVLRF-VKN---EFSENQESTigaafLTQTVNLDDTTVKFEIWDTAGQE----RYrslAPMyyRGAAAAIVVYDITSEES 88

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462535334  89 FEEvlpLKNILDEIKK--PKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCREV 164
Cdd:cd01860    89 FEK---AKSWVKELQEhgPPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAKTGE-NVNELFTEIARKL 162

Rab GTPase families 8, 10, 13 (Rab8, Rab10, Rab13); Rab8/Sec4/Ypt2 are known or suspected to be involved in post-Golgi transport to the plasma membrane. It is likely that these Rabs have functions that are specific to the mammalian lineage and have no orthologs in plants. Rab8 modulates polarized membrane transport through reorganization of actin and microtubules, induces the formation of new surface extensions, and has an important role in directed membrane transport to cell surfaces. The Ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the Ypt/Rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian Rab8. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334  46 IDDEVVSMEILDTAGQE--DTIQrEGHMRWGEGFVLVYDITDRGSFEEVlplKNILDEIKK--PKNVTLILVGNKADLDH 121
Cdd:cd01867    47 LDGKKIKLQIWDTAGQErfRTIT-TSYYRGAMGIILVYDITDEKSFENI---KNWMRNIDEhaSEDVERMLVGNKCDMEE 122

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462535334 122 SRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCREVRRR 167
Cdd:cd01867   123 KRVVSKEEGEALAREYGIKFLETSAKANI-NVEEAFLTLAKDILKK 167

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 2462535334  18 TLVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQEDtiqrEGHMR-----WGEGFVLVYDITDRGSFEev 92
Cdd:cd00157    15 CLLISYTTNKFPTEYVPTVFDNYSANVTVDGKQVNLGLWDTAGQEE----YDRLRplsypQTDVFLLCFSVDSPSSFE-- 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334  93 lplkNILD----EIKKPK-NVTLILVGNKADL-----------DHSRQVSTEEGEKLATEL-ACAFYECSACTGEGnITE 155
Cdd:cd00157    89 ----NVKTkwypEIKHYCpNVPIILVGTKIDLrddgntlkkleKKQKPITPEEGEKLAKEIgAVKYMECSALTQEG-LKE 163

                  ....*..
gi 2462535334 156 IFYELCR 162
Cdd:cd00157   164 VFDEAIR 170

Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways through the Golgi and from endosomes to the Golgi. Rab6A of mammals is implicated in retrograde transport through the Golgi stack, and is also required for a slow, COPI-independent, retrograde transport pathway from the Golgi to the endoplasmic reticulum (ER). This pathway may allow Golgi residents to be recycled through the ER for scrutiny by ER quality-control systems. Yeast Ypt6p, the homolog of the mammalian Rab6 GTPase, is not essential for cell viability. Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER trafficking. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334  19 LVVRFLTKRFIWEYDPTLESTY-RHQATIDDEVVSMEILDTAGQEdtiqR-----EGHMRWGEGFVLVYDITDRGSFEEV 92
Cdd:cd01861    16 IITRFMYDTFDNQYQATIGIDFlSKTMYVDDKTVRLQLWDTAGQE----RfrsliPSYIRDSSVAVVVYDITNRQSFDNT 91

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462535334  93 lplKNILDEIK--KPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSACTGEgNITEIF 157
Cdd:cd01861    92 ---DKWIDDVRdeRGNDVIIVLVGNKTDLSDKRQVSTEEGEKKAKENNAMFIETSAKAGH-NVKQLF 154

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 2462535334  46 IDDEVVSMEILDTAGQE--DTIQrEGHMRWGEGFVLVYDITDRGSFEEVlplKNILDEIKK--PKNVTLILVGNKADLDH 121
Cdd:cd01869    46 LDGKTVKLQIWDTAGQErfRTIT-SSYYRGAHGIIIVYDVTDQESFNNV---KQWLQEIDRyaSENVNKLLVGNKCDLTD 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462535334 122 SRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELCREVRRR 167
Cdd:cd01869   122 KKVVDYTEAKEFADELGIPFLETSAKNAT-NVEEAFMTMAREIKKR 166

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 2462535334  19 LVVRFLTKRFIWEYDPTLESTYRHQATIDDEVVSMEILDTAGQ-EDTIQREGHMRWGEGFVLVYDITDRGSFEEVLPLKN 97
Cdd:cd04147    15 LIQRFLYDTFEPKHRRTVEELHSKEYEVAGVKVTIDILDTSGSySFPAMRKLSIQNGDAFALVYSVDDPESFEEVKRLRE 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334  98 ILDEIKKPKNVTLILVGNKADLDHSRQVSTEEGEKLAT-ELACAFYECSACTGEgNITEIFYELCREV-----------R 165
Cdd:cd04147    95 EILEVKEDKFVPIVVVGNKIDSLAERQVEAADALSTVElDWNNGFVEASAKDNE-NVTEVFKELLQQAnlpswlspalrR 173

                         170
                  ....*....|....
gi 2462535334 166 RRRMVQGKTRRRSS 179
Cdd:cd04147   174 RRESAPSEIQRRPP 187

Rab GTPase family 15 (Rab15); Rab15 colocalizes with the transferrin receptor in early endosome compartments, but not with late endosomal markers. It codistributes with Rab4 and Rab5 on early/sorting endosomes, and with Rab11 on pericentriolar recycling endosomes. It is believed to function as an inhibitory GTPase that regulates distinct steps in early endocytic trafficking. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462535334  19 LVVRFLTKRFIWEYDPTLESTYRHQAT-IDDEVVSMEILDTAGQE--DTIQREgHMRWGEGFVLVYDITDRGSFEEVLPL 95
Cdd:cd04117    16 LLCRFTDNEFHSSHISTIGVDFKMKTIeVDGIKVRIQIWDTAGQEryQTITKQ-YYRRAQGIFLVYDISSERSYQHIMKW 94

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462535334  96 KNILDEIKkPKNVTLILVGNKADLDHSRQVSTEEGEKLATELACAFYECSACTGEgNITEIFYELcREVRRR 167
Cdd:cd04117    95 VSDVDEYA-PEGVQKILIGNKADEEQKRQVGDEQGNKLAKEYGMDFFETSACTNK-NIKESFTRL-TELVLQ 163

Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic transport and is expressed most highly in polarized epithelial cells. However, trypanosomal Rab, TbRAB18, is upregulated in the BSF (Blood Stream Form) stage and localized predominantly to elements of the Golgi complex. In human and mouse cells, Rab18 has been identified in lipid droplets, organelles that store neutral lipids. 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 2462535334  18 TLVVRFLTKRFIWEYDPTLESTYR-HQATIDDEVVSMEILDTAGQED--TIQrEGHMRWGEGFVLVYDITDRGSFEEvlp 94
Cdd:cd01863    15 SLLLRFTDDTFDEDLSSTIGVDFKvKTVTVDGKKVKLAIWDTAGQERfrTLT-SSYYRGAQGVILVYDVTRRDTFDN--- 90

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462535334  95 LKNILDEIKK---PKNVTLILVGNKADLDhSRQVSTEEGEKLATELACAFYECSACTGEGnITEIFYELCREV 164
Cdd:cd01863    91 LDTWLNELDTystNPDAVKMLVGNKIDKE-NREVTREEGQKFARKHNMLFIETSAKTRIG-VQQAFEELVEKI 161