arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X4 [Mus musculus]
Protein Classification
Centaurin_gamma and PH-like domain-containing protein( domain architecture ID 10134861)
protein containing domains PRK07764, Centaurin_gamma, and PH-like
List of domain hits
| Name | Accession | Description | Interval | E-value | |||||
| Centaurin_gamma | cd04103 | Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ... |
401-560 | 5.50e-96 | |||||
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, multi-domain proteins that all contain an ArfGAP domain and ankyrin repeats, and in some cases, numerous additional domains. Centaurin gamma contains an additional GTPase domain near its N-terminus. The specific function of this GTPase domain has not been well characterized, but centaurin gamma 2 (CENTG2) may play a role in the development of autism. Centaurin gamma 1 is also called PIKE (phosphatidyl inositol (PI) 3-kinase enhancer) and centaurin gamma 2 is also known as AGAP (ArfGAP protein with a GTPase-like domain, ankyrin repeats and a Pleckstrin homology domain) or GGAP. Three isoforms of PIKE have been identified. PIKE-S (short) and PIKE-L (long) are brain-specific isoforms, with PIKE-S restricted to the nucleus and PIKE-L found in multiple cellular compartments. A third isoform, PIKE-A was identified in human glioblastoma brain cancers and has been found in various tissues. GGAP has been shown to have high GTPase activity due to a direct intramolecular interaction between the N-terminal GTPase domain and the C-terminal ArfGAP domain. In human tissue, AGAP mRNA was detected in skeletal muscle, kidney, placenta, brain, heart, colon, and lung. Reduced expression levels were also observed in the spleen, liver, and small intestine. : Pssm-ID: 133303 Cd Length: 158 Bit Score: 297.48 E-value: 5.50e-96
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| PH-like super family | cl17171 | Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ... |
668-739 | 4.13e-42 | |||||
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins. The actual alignment was detected with superfamily member cd01250: Pssm-ID: 473070 Cd Length: 114 Bit Score: 149.39 E-value: 4.13e-42
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| PHA03247 super family | cl33720 | large tegument protein UL36; Provisional |
52-320 | 6.55e-04 | |||||
large tegument protein UL36; Provisional The actual alignment was detected with superfamily member PHA03247: Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 43.77 E-value: 6.55e-04
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| Name | Accession | Description | Interval | E-value | |||||
| Centaurin_gamma | cd04103 | Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ... |
401-560 | 5.50e-96 | |||||
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, multi-domain proteins that all contain an ArfGAP domain and ankyrin repeats, and in some cases, numerous additional domains. Centaurin gamma contains an additional GTPase domain near its N-terminus. The specific function of this GTPase domain has not been well characterized, but centaurin gamma 2 (CENTG2) may play a role in the development of autism. Centaurin gamma 1 is also called PIKE (phosphatidyl inositol (PI) 3-kinase enhancer) and centaurin gamma 2 is also known as AGAP (ArfGAP protein with a GTPase-like domain, ankyrin repeats and a Pleckstrin homology domain) or GGAP. Three isoforms of PIKE have been identified. PIKE-S (short) and PIKE-L (long) are brain-specific isoforms, with PIKE-S restricted to the nucleus and PIKE-L found in multiple cellular compartments. A third isoform, PIKE-A was identified in human glioblastoma brain cancers and has been found in various tissues. GGAP has been shown to have high GTPase activity due to a direct intramolecular interaction between the N-terminal GTPase domain and the C-terminal ArfGAP domain. In human tissue, AGAP mRNA was detected in skeletal muscle, kidney, placenta, brain, heart, colon, and lung. Reduced expression levels were also observed in the spleen, liver, and small intestine. Pssm-ID: 133303 Cd Length: 158 Bit Score: 297.48 E-value: 5.50e-96
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| PH_AGAP | cd01250 | Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ... |
668-739 | 4.13e-42 | |||||
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain; AGAP (also called centaurin gamma; PIKE/Phosphatidylinositol-3-kinase enhancer) reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. There are 3 isoforms of AGAP (PIKE-A, PIKE-L, and PIKE-S) the longest of which PIKE-L consists of N-terminal proline rich domains (PRDs), followed by a GTPase domain, a split PH domain (PHN and PHC), an ArfGAP domain and two ankyrin repeats. PIKE-S terminates after the PHN domain and PIKE-A is missing the PRD region. Centaurin binds phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 241281 Cd Length: 114 Bit Score: 149.39 E-value: 4.13e-42
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| small_GTPase | smart00010 | Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small ... |
399-566 | 2.77e-14 | |||||
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. Pssm-ID: 197466 [Multi-domain] Cd Length: 166 Bit Score: 71.44 E-value: 2.77e-14
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| Ras | pfam00071 | Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop ... |
405-560 | 1.12e-12 | |||||
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. Pssm-ID: 425451 [Multi-domain] Cd Length: 162 Bit Score: 66.77 E-value: 1.12e-12
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| Gem1 | COG1100 | GTPase SAR1 family domain [General function prediction only]; |
400-558 | 1.74e-08 | |||||
GTPase SAR1 family domain [General function prediction only]; Pssm-ID: 440717 [Multi-domain] Cd Length: 177 Bit Score: 54.99 E-value: 1.74e-08
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| PLN03118 | PLN03118 | Rab family protein; Provisional |
405-561 | 6.27e-05 | |||||
Rab family protein; Provisional Pssm-ID: 215587 [Multi-domain] Cd Length: 211 Bit Score: 45.05 E-value: 6.27e-05
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| PH | smart00233 | Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ... |
671-735 | 1.05e-04 | |||||
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 42.15 E-value: 1.05e-04
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| PHA03247 | PHA03247 | large tegument protein UL36; Provisional |
52-320 | 6.55e-04 | |||||
large tegument protein UL36; Provisional Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 43.77 E-value: 6.55e-04
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| Name | Accession | Description | Interval | E-value | |||||
| Centaurin_gamma | cd04103 | Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ... |
401-560 | 5.50e-96 | |||||
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, multi-domain proteins that all contain an ArfGAP domain and ankyrin repeats, and in some cases, numerous additional domains. Centaurin gamma contains an additional GTPase domain near its N-terminus. The specific function of this GTPase domain has not been well characterized, but centaurin gamma 2 (CENTG2) may play a role in the development of autism. Centaurin gamma 1 is also called PIKE (phosphatidyl inositol (PI) 3-kinase enhancer) and centaurin gamma 2 is also known as AGAP (ArfGAP protein with a GTPase-like domain, ankyrin repeats and a Pleckstrin homology domain) or GGAP. Three isoforms of PIKE have been identified. PIKE-S (short) and PIKE-L (long) are brain-specific isoforms, with PIKE-S restricted to the nucleus and PIKE-L found in multiple cellular compartments. A third isoform, PIKE-A was identified in human glioblastoma brain cancers and has been found in various tissues. GGAP has been shown to have high GTPase activity due to a direct intramolecular interaction between the N-terminal GTPase domain and the C-terminal ArfGAP domain. In human tissue, AGAP mRNA was detected in skeletal muscle, kidney, placenta, brain, heart, colon, and lung. Reduced expression levels were also observed in the spleen, liver, and small intestine. Pssm-ID: 133303 Cd Length: 158 Bit Score: 297.48 E-value: 5.50e-96
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| PH_AGAP | cd01250 | Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ... |
668-739 | 4.13e-42 | |||||
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain; AGAP (also called centaurin gamma; PIKE/Phosphatidylinositol-3-kinase enhancer) reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. There are 3 isoforms of AGAP (PIKE-A, PIKE-L, and PIKE-S) the longest of which PIKE-L consists of N-terminal proline rich domains (PRDs), followed by a GTPase domain, a split PH domain (PHN and PHC), an ArfGAP domain and two ankyrin repeats. PIKE-S terminates after the PHN domain and PIKE-A is missing the PRD region. Centaurin binds phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 241281 Cd Length: 114 Bit Score: 149.39 E-value: 4.13e-42
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| Ras | cd00876 | Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the ... |
402-560 | 1.50e-17 | |||||
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. Pssm-ID: 206642 [Multi-domain] Cd Length: 160 Bit Score: 80.65 E-value: 1.50e-17
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| small_GTPase | smart00010 | Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small ... |
399-566 | 2.77e-14 | |||||
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. Pssm-ID: 197466 [Multi-domain] Cd Length: 166 Bit Score: 71.44 E-value: 2.77e-14
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| RERG_RasL11_like | cd04146 | Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like ... |
403-560 | 6.31e-14 | |||||
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. Pssm-ID: 206713 [Multi-domain] Cd Length: 166 Bit Score: 70.38 E-value: 6.31e-14
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| RAS | smart00173 | Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. ... |
402-556 | 9.17e-14 | |||||
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 Pssm-ID: 214541 [Multi-domain] Cd Length: 164 Bit Score: 69.89 E-value: 9.17e-14
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| Rap_like | cd04136 | Rap-like family consists of Rap1, Rap2 and RSR1; The Rap subfamily consists of the Rap1, Rap2, ... |
400-560 | 2.88e-13 | |||||
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. Pssm-ID: 206708 [Multi-domain] Cd Length: 164 Bit Score: 68.36 E-value: 2.88e-13
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| Rab | cd00154 | Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases ... |
401-558 | 6.93e-13 | |||||
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. Pssm-ID: 206640 [Multi-domain] Cd Length: 159 Bit Score: 67.10 E-value: 6.93e-13
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| Ras_like_GTPase | cd00882 | Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like ... |
404-558 | 7.34e-13 | |||||
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. Pssm-ID: 206648 [Multi-domain] Cd Length: 161 Bit Score: 67.10 E-value: 7.34e-13
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| Ras | pfam00071 | Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop ... |
405-560 | 1.12e-12 | |||||
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. Pssm-ID: 425451 [Multi-domain] Cd Length: 162 Bit Score: 66.77 E-value: 1.12e-12
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| RAB | smart00175 | Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking. |
401-561 | 3.76e-12 | |||||
Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking. Pssm-ID: 197555 [Multi-domain] Cd Length: 164 Bit Score: 65.22 E-value: 3.76e-12
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| M_R_Ras_like | cd04145 | R-Ras2/TC21, M-Ras/R-Ras3; The M-Ras/R-Ras-like subfamily contains R-Ras2/TC21, M-Ras/R-Ras3, ... |
399-560 | 1.07e-11 | |||||
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. Pssm-ID: 133345 [Multi-domain] Cd Length: 164 Bit Score: 63.97 E-value: 1.07e-11
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| Rap2 | cd04176 | Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap ... |
400-560 | 1.69e-11 | |||||
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. Pssm-ID: 133376 [Multi-domain] Cd Length: 163 Bit Score: 63.32 E-value: 1.69e-11
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| Rab7 | cd01862 | Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates ... |
401-566 | 1.71e-11 | |||||
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. Pssm-ID: 206655 [Multi-domain] Cd Length: 172 Bit Score: 63.45 E-value: 1.71e-11
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| Ras2 | cd04144 | Rat sarcoma (Ras) family 2 of small guanosine triphosphatases (GTPases); The Ras2 subfamily, ... |
402-568 | 5.96e-11 | |||||
Rat sarcoma (Ras) family 2 of small guanosine triphosphatases (GTPases); The Ras2 subfamily, found exclusively in fungi, was first identified in Ustilago maydis. In U. maydis, Ras2 is regulated by Sql2, a protein that is homologous to GEFs (guanine nucleotide exchange factors) of the CDC25 family. Ras2 has been shown to induce filamentous growth, but the signaling cascade through which Ras2 and Sql2 regulate cell morphology is not known. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Pssm-ID: 133344 [Multi-domain] Cd Length: 190 Bit Score: 62.56 E-value: 5.96e-11
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| Rab9 | cd04116 | Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate ... |
401-560 | 2.69e-10 | |||||
Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kD (TIP47). Rab9 is a key mediator of vesicular transport from late endosomes to the trans-Golgi network (TGN) by redirecting the MPRs. Rab9 has been identified as a key component for the replication of several viruses, including HIV1, Ebola, Marburg, and measles, making it a potential target for inhibiting a variety of viruses. 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. Pssm-ID: 206697 [Multi-domain] Cd Length: 170 Bit Score: 59.89 E-value: 2.69e-10
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| Ras_dva | cd04147 | Ras - dorsal-ventral anterior localization (Ras-dva) family; Ras-dva subfamily. Ras-dva (Ras - ... |
402-560 | 5.81e-10 | |||||
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. Pssm-ID: 206714 [Multi-domain] Cd Length: 197 Bit Score: 59.85 E-value: 5.81e-10
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| RSR1 | cd04177 | RSR1/Bud1p family GTPase; RSR1/Bud1p is a member of the Rap subfamily of the Ras family that ... |
400-561 | 7.97e-10 | |||||
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. Pssm-ID: 133377 [Multi-domain] Cd Length: 168 Bit Score: 58.65 E-value: 7.97e-10
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| Rab23_like | cd04106 | Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family ... |
405-559 | 1.50e-09 | |||||
Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation. Pssm-ID: 133306 [Multi-domain] Cd Length: 162 Bit Score: 57.84 E-value: 1.50e-09
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| RGK | cd04148 | Rem, Rem2, Rad, Gem/Kir (RGK) subfamily of Ras GTPases; RGK subfamily. The RGK (Rem, Rem2, Rad, ... |
401-566 | 1.62e-09 | |||||
Rem, Rem2, Rad, Gem/Kir (RGK) subfamily of Ras GTPases; RGK subfamily. The RGK (Rem, Rem2, Rad, Gem/Kir) subfamily of Ras GTPases are expressed in a tissue-specific manner and are dynamically regulated by transcriptional and posttranscriptional mechanisms in response to environmental cues. RGK proteins bind to the beta subunit of L-type calcium channels, causing functional down-regulation of these voltage-dependent calcium channels, and either termination of calcium-dependent secretion or modulation of electrical conduction and contractile function. Inhibition of L-type calcium channels by Rem2 may provide a mechanism for modulating calcium-triggered exocytosis in hormone-secreting cells, and has been proposed to influence the secretion of insulin in pancreatic beta cells. RGK proteins also interact with and inhibit the Rho/Rho kinase pathway to modulate remodeling of the cytoskeleton. Two characteristics of RGK proteins cited in the literature are N-terminal and C-terminal extensions beyond the GTPase domain typical of Ras superfamily members. The N-terminal extension is not conserved among family members; the C-terminal extension is reported to be conserved among the family and lack the CaaX prenylation motif typical of membrane-associated Ras proteins. However, a putative CaaX motif has been identified in the alignment of the C-terminal residues of this CD. Pssm-ID: 206715 [Multi-domain] Cd Length: 219 Bit Score: 58.96 E-value: 1.62e-09
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| Rap1 | cd04175 | Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap ... |
400-560 | 5.72e-09 | |||||
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. Pssm-ID: 133375 [Multi-domain] Cd Length: 164 Bit Score: 55.99 E-value: 5.72e-09
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| Gem1 | COG1100 | GTPase SAR1 family domain [General function prediction only]; |
400-558 | 1.74e-08 | |||||
GTPase SAR1 family domain [General function prediction only]; Pssm-ID: 440717 [Multi-domain] Cd Length: 177 Bit Score: 54.99 E-value: 1.74e-08
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| Rhes_like | cd04143 | Ras homolog enriched in striatum (Rhes) and activator of G-protein signaling 1 (Dexras1/AGS1); ... |
402-557 | 5.80e-08 | |||||
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. Pssm-ID: 133343 [Multi-domain] Cd Length: 247 Bit Score: 54.76 E-value: 5.80e-08
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| Rab5_related | cd01860 | Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The ... |
400-560 | 1.64e-07 | |||||
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. Pssm-ID: 206653 [Multi-domain] Cd Length: 163 Bit Score: 51.78 E-value: 1.64e-07
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| Rab21 | cd04123 | Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, ... |
406-561 | 4.30e-07 | |||||
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. Pssm-ID: 133323 [Multi-domain] Cd Length: 162 Bit Score: 50.69 E-value: 4.30e-07
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| RalA_RalB | cd04139 | Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily ... |
412-560 | 9.77e-07 | |||||
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. Pssm-ID: 206710 [Multi-domain] Cd Length: 163 Bit Score: 49.73 E-value: 9.77e-07
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| H_N_K_Ras_like | cd04138 | Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, ... |
400-553 | 1.71e-06 | |||||
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. Pssm-ID: 133338 [Multi-domain] Cd Length: 162 Bit Score: 48.95 E-value: 1.71e-06
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| RJL | cd04119 | Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with ... |
405-554 | 8.44e-06 | |||||
Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Pssm-ID: 133319 [Multi-domain] Cd Length: 168 Bit Score: 46.97 E-value: 8.44e-06
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| ARHI_like | cd04140 | A Ras homolog member I (ARHI); ARHI (A Ras homolog member I) is a member of the Ras family ... |
402-556 | 9.18e-06 | |||||
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. Pssm-ID: 206711 [Multi-domain] Cd Length: 165 Bit Score: 46.74 E-value: 9.18e-06
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| RheB | cd04137 | Ras Homolog Enriched in Brain (RheB) is a small GTPase; Rheb (Ras Homolog Enriched in Brain) ... |
405-560 | 1.34e-05 | |||||
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. Pssm-ID: 206709 [Multi-domain] Cd Length: 180 Bit Score: 46.47 E-value: 1.34e-05
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| Wrch_1 | cd04130 | Wnt-1 responsive Cdc42 homolog (Wrch-1) is a Rho family GTPase similar to Cdc42; Wrch-1 (Wnt-1 ... |
406-553 | 2.32e-05 | |||||
Wnt-1 responsive Cdc42 homolog (Wrch-1) is a Rho family GTPase similar to Cdc42; Wrch-1 (Wnt-1 responsive Cdc42 homolog) is a Rho family GTPase that shares significant sequence and functional similarity with Cdc42. Wrch-1 was first identified in mouse mammary epithelial cells, where its transcription is upregulated in Wnt-1 transformation. Wrch-1 contains N- and C-terminal extensions relative to cdc42, suggesting potential differences in cellular localization and function. The Wrch-1 N-terminal extension contains putative SH3 domain-binding motifs and has been shown to bind the SH3 domain-containing protein Grb2, which increases the level of active Wrch-1 in cells. Unlike Cdc42, which localizes to the cytosol and perinuclear membranes, Wrch-1 localizes extensively with the plasma membrane and endosomes. The membrane association, localization, and biological activity of Wrch-1 indicate an atypical model of regulation distinct from other Rho family GTPases. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation. Pssm-ID: 133330 [Multi-domain] Cd Length: 173 Bit Score: 45.86 E-value: 2.32e-05
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| RRP22 | cd04142 | Ras-related protein on chromosome 22 (RRP22) family; RRP22 (Ras-related protein on chromosome ... |
401-565 | 3.68e-05 | |||||
Ras-related protein on chromosome 22 (RRP22) family; RRP22 (Ras-related protein on chromosome 22) subfamily consists of proteins that inhibit cell growth and promote caspase-independent cell death. Unlike most Ras proteins, RRP22 is down-regulated in many human tumor cells due to promoter methylation. RRP22 localizes to the nucleolus in a GTP-dependent manner, suggesting a novel function in modulating transport of nucleolar components. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Like most Ras family proteins, RRP22 is farnesylated. Pssm-ID: 133342 [Multi-domain] Cd Length: 198 Bit Score: 45.63 E-value: 3.68e-05
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| Rab24 | cd04118 | Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists ... |
401-567 | 5.90e-05 | |||||
Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists primarily in the GTP-bound state, having a low intrinsic GTPase activity; it is not efficiently geranyl-geranylated at the C-terminus; it does not form a detectable complex with Rab GDP-dissociation inhibitors (GDIs); and it has recently been shown to undergo tyrosine phosphorylation when overexpressed in vitro. The specific function of Rab24 still remains unknown. It is found in a transport route between ER-cis-Golgi and late endocytic compartments. It is putatively involved in an autophagic pathway, possibly directing misfolded proteins in the ER to degradative pathways. 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. Pssm-ID: 133318 [Multi-domain] Cd Length: 193 Bit Score: 44.86 E-value: 5.90e-05
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| PLN03118 | PLN03118 | Rab family protein; Provisional |
405-561 | 6.27e-05 | |||||
Rab family protein; Provisional Pssm-ID: 215587 [Multi-domain] Cd Length: 211 Bit Score: 45.05 E-value: 6.27e-05
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| Rab28 | cd04109 | Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown ... |
401-568 | 9.04e-05 | |||||
Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown to be a late embryogenesis-abundant (Lea) protein that is regulated by the plant hormone abcisic acid (ABA). In Arabidopsis, Rab28 is expressed during embryo development and is generally restricted to provascular tissues in mature embryos. Unlike maize Rab28, it is not ABA-inducible. Characterization of the human Rab28 homolog revealed two isoforms, which differ by a 95-base pair insertion, producing an alternative sequence for the 30 amino acids at the C-terminus. The two human isoforms are presumably the result of alternative splicing. Since they differ at the C-terminus but not in the GTP-binding region, they are predicted to be targeted to different cellular locations. 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. Pssm-ID: 206694 [Multi-domain] Cd Length: 213 Bit Score: 44.79 E-value: 9.04e-05
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| PH | smart00233 | Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ... |
671-735 | 1.05e-04 | |||||
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 42.15 E-value: 1.05e-04
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| Rab18 | cd01863 | Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic ... |
401-560 | 1.06e-04 | |||||
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. Pssm-ID: 206656 [Multi-domain] Cd Length: 161 Bit Score: 43.45 E-value: 1.06e-04
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| Roc | pfam08477 | Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial ... |
402-497 | 6.23e-04 | |||||
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. Pssm-ID: 462490 [Multi-domain] Cd Length: 114 Bit Score: 40.18 E-value: 6.23e-04
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| PHA03247 | PHA03247 | large tegument protein UL36; Provisional |
52-320 | 6.55e-04 | |||||
large tegument protein UL36; Provisional Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 43.77 E-value: 6.55e-04
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| RabL2 | cd04124 | Rab GTPase-like family 2 (Rab-like2); RabL2 (Rab-like2) subfamily. RabL2s are novel Rab ... |
401-561 | 7.20e-04 | |||||
Rab GTPase-like family 2 (Rab-like2); RabL2 (Rab-like2) subfamily. RabL2s are novel Rab proteins identified recently which display features that are distinct from other Rabs, and have been termed Rab-like. RabL2 contains RabL2a and RabL2b, two very similar Rab proteins that share > 98% sequence identity in humans. RabL2b maps to the subtelomeric region of chromosome 22q13.3 and RabL2a maps to 2q13, a region that suggests it is also a subtelomeric gene. Both genes are believed to be expressed ubiquitously, suggesting that RabL2s are the first example of duplicated genes in human proximal subtelomeric regions that are both expressed actively. Like other Rab-like proteins, RabL2s lack a prenylation site at the C-terminus. The specific functions of RabL2a and RabL2b remain unknown. 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. Pssm-ID: 133324 [Multi-domain] Cd Length: 161 Bit Score: 41.00 E-value: 7.20e-04
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| Rab6 | cd01861 | Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways ... |
406-559 | 1.69e-03 | |||||
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. Pssm-ID: 206654 [Multi-domain] Cd Length: 161 Bit Score: 39.91 E-value: 1.69e-03
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| PHA03377 | PHA03377 | EBNA-3C; Provisional |
257-326 | 4.65e-03 | |||||
EBNA-3C; Provisional Pssm-ID: 177614 [Multi-domain] Cd Length: 1000 Bit Score: 40.81 E-value: 4.65e-03
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| PHA03247 | PHA03247 | large tegument protein UL36; Provisional |
45-321 | 9.05e-03 | |||||
large tegument protein UL36; Provisional Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 39.92 E-value: 9.05e-03
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