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 1371977054    4 TYRVAVLGARGVGKSAIVRQFLYNEFSEVCVPT---TTRRLylpaVVMNGHVHDLQILD------FppiSAFPvntlqew 74
Cdd:smart00010   2 EYKLVVLGGGGVGKSALTIQFVQGHFVDEYDPTiedSYRKQ----IEIDGEVCLLDILDtagqeeF---SAMR------- 67

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1371977054   75 aDACcrgLRSVHAYILVYDICCFDSFEYVKTIRQQILETRG 115
Cdd:smart00010  68 -DQY---MRTGEGFLLVYSITDRQSFEEIAKFREQILRVKD 104

Ras-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977054   1 MVST-YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRlYLPAVVMNGHVHDLQILDfppisafpVNTLQEWADACC 79
Cdd:PTZ00369    1 MASTeYKLVVVGGGGVGKSALTIQFIQNHFIDEYDPTIEDS-YRKQCVIDEETCLLDILD--------TAGQEEYSAMRD 71

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1371977054  80 RGLRSVHAYILVYDICCFDSFEYVKTIRQQILETR 114
Cdd:PTZ00369   72 QYMRTGQGFLCVYSITSRSSFEEIASFREQILRVK 106

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 1371977054   6 RVAVLGARGVGKSAIVRQFLYNEFSEVCVPtTTRRLYLPAVVMNGHVHDLQILDFPPISAFPvnTLQEwadaccRGLRSV 85
Cdd:cd00876     1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDP-TIEDSYRKQIVVDGETYTLDILDTAGQEEFS--AMRD------QYIRNG 71

                          90       100       110
                  ....*....|....*....|....*....|
gi 1371977054  86 HAYILVYDICCFDSFEYVKTIRQQILETRG 115
Cdd:cd00876    72 DGFILVYSITSRESFEEIKNIREQILRVKD 101

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 1371977054    5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPT---TTRRLylpaVVMNGHVHDLQILD------FppiSAFPvntlqewa 75
Cdd:smart00173   1 YKLVVLGSGGVGKSALTIQFIQGHFVDDYDPTiedSYRKQ----IEIDGEVCLLDILDtagqeeF---SAMR-------- 65

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1371977054   76 DACcrgLRSVHAYILVYDICCFDSFEYVKTIRQQILETRG 115
Cdd:smart00173  66 DQY---MRTGEGFLLVYSITDRQSFEEIKKFREQILRVKD 102

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 1371977054   6 RVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRlYLPAVVMNGHVHDLQILD---------FPPISAFpvntlqewad 76
Cdd:cd04137     3 KIAVLGSRSVGKSSLTVQFVEGHFVESYYPTIENT-FSKIITYKGQEYHLEIVDtagqdeysiLPQKYSI---------- 71

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1371977054  77 accrglrSVHAYILVYDICCFDSFEYVKTIRQQILETRG 115
Cdd:cd04137    72 -------GIHGYILVYSVTSRKSFEVVKVIYDKILDMLG 103

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 1371977054   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPtTTRRLYLPAVVMNGHVHDLQILDFPPISAFPvnTLQEWADAccRGlrs 84
Cdd:cd04140     2 YRVVVFGAGGVGKSSLVLRFVKGTFRESYIP-TIEDTYRQVISCSKSICTLQITDTTGSHQFP--AMQRLSIS--KG--- 73

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1371977054  85 vHAYILVYDICCFDSFEYVKTIRQQILETRG 115
Cdd:cd04140    74 -HAFILVYSITSKQSLEELKPIYELICEIKG 103

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 1371977054   8 AVLGARGVGKSAIVRQFLYNEFSEVC-VPTTTRRLYLPAVVMNGHVHDLQILDFPPISAFPVNTLQEWADACCRGlrsVH 86
Cdd:cd00882     1 VVVGRGGVGKSSLLNALLGGEVGEVSdVPGTTRDPDVYVKELDKGKVKLVLVDTPGLDEFGGLGREELARLLLRG---AD 77

                          90       100
                  ....*....|....*....|....*....
gi 1371977054  87 AYILVYDICCFDSFEYVKTIRQQILETRG 115
Cdd:cd00882    78 LILLVVDSTDRESEEDAKLLILRRLRKEG 106

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 1371977054   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPT-----TTRRlylpaVVMNGHVHDLQILD------FPPI-SAFpvntlq 72
Cdd:cd00154     1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTigvdfKSKT-----IEVDGKKVKLQIWDtagqerFRSItSSY------ 69

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1371977054  73 ewadaccrgLRSVHAYILVYDICCFDSFEYVKTIRQQILE 112
Cdd:cd00154    70 ---------YRGAHGAILVYDVTNRESFENLDKWLNELKE 100

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 1371977054   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPtTTRRLYLPAVVMNGHVHDLQILDFPPISAFpvntlqewadACCRGL-- 82
Cdd:cd04176     2 YKVVVLGSGGVGKSALTVQFVSGTFIEKYDP-TIEDFYRKEIEVDSSPSVLEILDTAGTEQF----------ASMRDLyi 70

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1371977054  83 RSVHAYILVYDICCFDSFEYVKTIRQQILETRG 115
Cdd:cd04176    71 KNGQGFIVVYSLVNQQTFQDIKPMRDQIVRVKG 103

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 1371977054   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPtTTRRLYLPAVVMNGHVHDLQILDFPPISAFpvntlqewadACCRGL-- 82
Cdd:cd04136     2 YKLVVLGSGGVGKSALTVQFVQGIFVDKYDP-TIEDSYRKQIEVDCQQCMLEILDTAGTEQF----------TAMRDLyi 70

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1371977054  83 RSVHAYILVYDICCFDSFEYVKTIRQQILETR 114
Cdd:cd04136    71 KNGQGFALVYSITAQQSFNDLQDLREQILRVK 102

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 1371977054   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRlYLPAVVMNGHVHDLQILDfppisafpVNTLQEWADACCRGLRS 84
Cdd:cd04138     2 YKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDS-YRKQVVIDGETCLLDILD--------TAGQEEYSAMRDQYMRT 72

                          90       100
                  ....*....|....*....|....*..
gi 1371977054  85 VHAYILVYDICCFDSFEYVKTIRQQIL 111
Cdd:cd04138    73 GEGFLCVFAINSRKSFEDIHTYREQIK 99

Ras-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977054   1 MVST-YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRlYLPAVVMNGHVHDLQILDfppisafpVNTLQEWADACC 79
Cdd:PTZ00369    1 MASTeYKLVVVGGGGVGKSALTIQFIQNHFIDEYDPTIEDS-YRKQCVIDEETCLLDILD--------TAGQEEYSAMRD 71

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1371977054  80 RGLRSVHAYILVYDICCFDSFEYVKTIRQQILETR 114
Cdd:PTZ00369   72 QYMRTGQGFLCVYSITSRSSFEEIASFREQILRVK 106

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organization, with tandem GTP-binding domains and two EF hand domains (pfam00036) that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977054   6 RVAVLGARGVGKSAIVRQFLYNEFSEVCVPT---TTRRLYLPAVVMNGHVHDLQILDFppisAFpvntlQEwadaCCRGL 82
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTFDPKYKSTigvDFKTKTVLENDDNGKKIKLNIWDT----AG-----QE----RFRSL 67

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1371977054  83 -----RSVHAYILVYDICCFDSFEY-VKTIRQ 108
Cdd:pfam08477  68 hpfyyRGAAAALLVYDSRTFSNLKYwLRELKK 99

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 1371977054   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRlYLPAVVMNGHVHDLQILDFPPISAFpvntlqewadACCRGL-- 82
Cdd:cd04175     2 YKLVVLGSGGVGKSALTVQFVQGIFVEKYDPTIEDS-YRKQVEVDGQQCMLEILDTAGTEQF----------TAMRDLym 70

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1371977054  83 RSVHAYILVYDICCFDSFEYVKTIRQQILETR 114
Cdd:cd04175    71 KNGQGFVLVYSITAQSTFNDLQDLREQILRVK 102

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 1371977054   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRLYLPAVVMNGHVHDLQILDfppisafpvnTL-QEWADAccrgL- 82
Cdd:cd04123     1 FKVVLLGEGRVGKTSLVLRYVENKFNEKHESTTQASFFQKTVNIGGKRIDLAIWD----------TAgQERYHA----Lg 66

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1371977054  83 ----RSVHAYILVYDICCFDSFEYVKTIRQQILETRG 115
Cdd:cd04123    67 piyyRDADGAILVYDITDADSFQKVKKWIKELKQMRG 103

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977054   4 TYRVAVLGARGVGKSAIVRQFLYNEFSEV-CVPTTTRRlYLPAVVM-NGHVHDLQILDFP 61
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGNKGSITeYYPGTTRN-YVTTVIEeDGKTYKFNLLDTA 59

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977054   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPtTTRRLYLPAVVMNGHVHDLQILDFPPISAFPVNTLQEwadaccrgLRS 84
Cdd:cd04141     3 YKIVMLGAGGVGKSAVTMQFISHSFPDYHDP-TIEDAYKTQARIDNEPALLDILDTAGQAEFTAMRDQY--------MRC 73

                          90       100       110
                  ....*....|....*....|....*....|
gi 1371977054  85 VHAYILVYDICCFDSFEYVKTIRQQILETR 114
Cdd:cd04141    74 GEGFIICYSVTDRHSFQEASEFKELITRVR 103

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 1371977054   4 TYRVAVLGARGVGKSAIVRQFLYNEFSEVCVPtTTRRLYLPAVVM-NGHVHDLQILDfppisafpvnTL-QEWADACC-- 79
Cdd:cd01860     1 QFKLVLLGDSSVGKSSIVLRFVKNEFSENQES-TIGAAFLTQTVNlDDTTVKFEIWD----------TAgQERYRSLApm 69

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1371977054  80 --RGLRsvhAYILVYDICCFDSFE----YVKTIRQQ 109
Cdd:cd01860    70 yyRGAA---AAIVVYDITSEESFEkaksWVKELQEH 102

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 1371977054   5 YRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRLYLPAVVMNGHVHDLQILD------FPPI-SAFpvntlqewada 77
Cdd:cd01869     3 FKLLLIGDSGVGKSCLLLRFADDTYTESYISTIGVDFKIRTIELDGKTVKLQIWDtagqerFRTItSSY----------- 71

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1371977054  78 ccrgLRSVHAYILVYDICCFDSFEYVKTIRQQI 110
Cdd:cd01869    72 ----YRGAHGIIIVYDVTDQESFNNVKQWLQEI 100

Rab GTPase family 4 (Rab4); Rab4 subfamily. Rab4 has been implicated in numerous functions within the cell. It helps regulate endocytosis through the sorting, recycling, and degradation of early endosomes. Mammalian Rab4 is involved in the regulation of many surface proteins including G-protein-coupled receptors, transferrin receptor, integrins, and surfactant protein A. Experimental data implicate Rab4 in regulation of the recycling of internalized receptors back to the plasma membrane. It is also believed to influence receptor-mediated antigen processing in B-lymphocytes, in calcium-dependent exocytosis in platelets, in alpha-amylase secretion in pancreatic cells, and in insulin-induced translocation of Glut4 from internal vesicles to the cell surface. Rab4 is known to share effector proteins with Rab5 and Rab11. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977054   9 VLGARGVGKSAIVRQFLYNEFSEVCVPTTTRRLYLPAVVMNGHVHDLQILDFPPISAFPVNTLQEWADACCRglrsvhay 88
Cdd:cd04113     5 IIGSAGTGKSCLLHQFIENKFKQDSNHTIGVEFGSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGA-------- 76

                          90
                  ....*....|...
gi 1371977054  89 ILVYDICCFDSFE 101
Cdd:cd04113    77 LLVYDITSRESFN 89