Biology:GPR98
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/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=84059.
- ↑ "The very large G protein coupled receptor (Vlgr1) in hair cells". Journal of Molecular Neuroscience 50 (1): 204–214. May 2013. 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.
- ↑ "The echinoderm adhesome". Developmental Biology 300 (1): 252–266. December 2006. 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 in Biochemical Sciences 27 (9): 441–444. September 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 Research 5 (3): 169–176. June 1998. doi:10.1093/dnares/5.3.169. PMID 9734811.
- "Significant evidence for linkage of febrile seizures to chromosome 5q14-q15". Human Molecular Genetics 9 (1): 87–91. January 2000. doi:10.1093/hmg/9.1.87. PMID 10587582.
- "Genetic heterogeneity of Usher syndrome type II: localisation to chromosome 5q". Journal of Medical Genetics 37 (4): 256–262. April 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". Molecular Endocrinology 14 (9): 1351–1364. September 2000. 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 Research 11 (3): 422–435. March 2001. doi:10.1101/gr.GR1547R. PMID 11230166.
- "A novel gene causing a mendelian audiogenic mouse epilepsy". Neuron 31 (4): 537–544. August 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". The Journal of Biological Chemistry 277 (1): 785–792. January 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 Research 8 (6): 319–327. December 2001. doi:10.1093/dnares/8.6.319. PMID 11853319.
- "A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures". Annals of Neurology 52 (5): 654–657. November 2002. doi:10.1002/ana.10347. PMID 12402266.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nature Genetics 36 (1): 40–45. January 2004. doi:10.1038/ng1285. PMID 14702039.
- "Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II". American Journal of Human Genetics 74 (2): 357–366. February 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. July 2004. 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): 205–210. July 2004. 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". Investigative Ophthalmology & Visual Science 46 (2): 734–743. February 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 Research 16 (1): 55–65. January 2006. doi:10.1101/gr.4039406. PMID 16344560.
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