Biology:GPR98
 Generic protein structure example |
ADGRV1, also known as G protein-coupled receptor 98 (GPR98) or Very Large G-protein coupled receptor 1 (VLGR1), is a protein that in humans is encoded by the GPR98 gene.[1] Several alternatively spliced transcripts have been described.[1]
The adhesion GPCR VLGR1 is the largest GPCR known, with a size of 6300 amino acids and consisting of 90 exons.[2] There are 8 splice variants of VlgR1, named VlgR1a-1e and Mass1.1-1.3. The N-terminus consists of 5800 amino acids containing 35 Calx-beta domains, one pentraxin domain, and one epilepsy associated repeat. Mutations of VlgR1 have been shown to result in Usher's syndrome. Knockouts of Vlgr1 in mice have been shown to phenocopy Usher's syndrome and lead to audiogenic seizures.
Function
This gene encodes a member of the adhesion-GPCR family of receptors.[3] The protein binds calcium and is expressed in the central nervous system. It is also known as very large G-protein coupled receptor 1 because it is 6300 residues long. It contains a C-terminal 7-transmembrane receptor domain, whereas the large N-terminal segment (5900 residues) includes 35 calcium binding Calx-beta domains, and 6 EAR domains.
Evolution
The sea urchin genome has a homolog of VLGR1 in it.[4]
Clinical significance
Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures.[1]
References
- ↑ 1.0 1.1 1.2 "Entrez Gene: GPR98 G protein-coupled receptor 98". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84059.
- ↑ Sun, JP; Li, R; Ren, HZ; Xu, AT; Yu, X; Xu, ZG (May 2013). "The very large g protein coupled receptor (vlgr1) in hair cells". J Mol Neurosci 50 (1): 204–14. doi:10.1007/s12031-012-9911-5. PMID 23180093.
- ↑ AdhesionGPCRs: Structure to Function (Advances in Experimental Medicine and Biology). Berlin: Springer. 2011. ISBN 978-1-4419-7912-4.
- ↑ Whittakera, Charles A.; Bergerone, Karl-Frederik; Whittlec, James; Bruce, P. (2006). "Brandhorste, Robert D. Burked, Richard O. Hynes. The echinoderm adhesome". Developmental Biology 300 (1): 252–266. doi:10.1016/j.ydbio.2006.07.044. PMID 16950242.
Further reading
- "The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders.". Trends Biochem. Sci. 27 (9): 441–4. 2002. doi:10.1016/S0968-0004(02)02163-1. PMID 12217514.
- "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.". DNA Res. 5 (3): 169–76. 1998. doi:10.1093/dnares/5.3.169. PMID 9734811.
- "Significant evidence for linkage of febrile seizures to chromosome 5q14-q15.". Hum. Mol. Genet. 9 (1): 87–91. 2000. doi:10.1093/hmg/9.1.87. PMID 10587582.
- "Genetic heterogeneity of Usher syndrome type II: localisation to chromosome 5q.". J. Med. Genet. 37 (4): 256–62. 2000. doi:10.1136/jmg.37.4.256. PMID 10745043.
- "Sequence similarities between a novel putative G protein-coupled receptor and Na+/Ca2+ exchangers define a cation binding domain.". Mol. Endocrinol. 14 (9): 1351–64. 2001. doi:10.1210/me.14.9.1351. PMID 10976914.
- "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. 2001. doi:10.1101/gr.GR1547R. PMID 11230166.
- "A novel gene causing a mendelian audiogenic mouse epilepsy.". Neuron 31 (4): 537–44. 2001. doi:10.1016/S0896-6273(01)00397-X. PMID 11545713.
- "Very large G protein-coupled receptor-1, the largest known cell surface protein, is highly expressed in the developing central nervous system.". J. Biol. Chem. 277 (1): 785–92. 2002. doi:10.1074/jbc.M108929200. PMID 11606593.
- "Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins.". DNA Res. 8 (6): 319–27. 2002. doi:10.1093/dnares/8.6.319. PMID 11853319.
- "A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures.". Ann. Neurol. 52 (5): 654–7. 2002. doi:10.1002/ana.10347. PMID 12402266.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II.". Am. J. Hum. Genet. 74 (2): 357–66. 2004. doi:10.1086/381685. PMID 14740321.
- "The human and mouse repertoire of the adhesion family of G-protein-coupled receptors.". Genomics 84 (1): 23–33. 2005. doi:10.1016/j.ygeno.2003.12.004. PMID 15203201.
- "Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes.". Genomics 84 (1): 205–10. 2005. doi:10.1016/j.ygeno.2004.01.011. PMID 15203218.
- "Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype.". Invest. Ophthalmol. Vis. Sci. 46 (2): 734–43. 2005. doi:10.1167/iovs.04-1136. PMID 15671307.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. 2006. doi:10.1101/gr.4039406. PMID 16344560.
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