GPR98 explained
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.
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.
Further reading
- Staub E, Pérez-Tur J, Siebert R, Nobile C, Moschonas NK, Deloukas P, Hinzmann B . The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders . Trends in Biochemical Sciences . 27 . 9 . 441–444 . September 2002 . 12217514 . 10.1016/S0968-0004(02)02163-1 .
- Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . 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 . 9734811 . 10.1093/dnares/5.3.169 . free .
- Nakayama J, Hamano K, Iwasaki N, Nakahara S, Horigome Y, Saitoh H, Aoki T, Maki T, Kikuchi M, Migita T, Ohto T, Yokouchi Y, Tanaka R, Hasegawa M, Matsui A, Hamaguchi H, Arinami T . Significant evidence for linkage of febrile seizures to chromosome 5q14-q15 . Human Molecular Genetics . 9 . 1 . 87–91 . January 2000 . 10587582 . 10.1093/hmg/9.1.87 . free .
- Pieke-Dahl S, Möller CG, Kelley PM, Astuto LM, Cremers CW, Gorin MB, Kimberling WJ . Genetic heterogeneity of Usher syndrome type II: localisation to chromosome 5q . Journal of Medical Genetics . 37 . 4 . 256–262 . April 2000 . 10745043 . 1734554 . 10.1136/jmg.37.4.256 .
- Nikkila H, McMillan DR, Nunez BS, Pascoe L, Curnow KM, White PC . 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 . 10976914 . 10.1210/me.14.9.1351 .
- Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . 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 . 11230166 . 311072 . 10.1101/gr.GR1547R .
- Skradski SL, Clark AM, Jiang H, White HS, Fu YH, Ptácek LJ . A novel gene causing a mendelian audiogenic mouse epilepsy . Neuron . 31 . 4 . 537–544 . August 2001 . 11545713 . 10.1016/S0896-6273(01)00397-X . 14468960 . free .
- McMillan DR, Kayes-Wandover KM, Richardson JA, White PC . 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 . 11606593 . 10.1074/jbc.M108929200 . free .
- Nagase T, Kikuno R, Ohara O . 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 . 11853319 . 10.1093/dnares/8.6.319 .
- Nakayama J, Fu YH, Clark AM, Nakahara S, Hamano K, Iwasaki N, Matsui A, Arinami T, Ptácek LJ . A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures . Annals of Neurology . 52 . 5 . 654–657 . November 2002 . 12402266 . 10.1002/ana.10347 . 36357793 .
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nature Genetics . 36 . 1 . 40–45 . January 2004 . 14702039 . 10.1038/ng1285 . free .
- Weston MD, Luijendijk MW, Humphrey KD, Möller C, Kimberling WJ . 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 . 14740321 . 1181933 . 10.1086/381685 .
- Bjarnadóttir TK, Fredriksson R, Höglund PJ, Gloriam DE, Lagerström MC, Schiöth HB . The human and mouse repertoire of the adhesion family of G-protein-coupled receptors . Genomics . 84 . 1 . 23–33 . July 2004 . 15203201 . 10.1016/j.ygeno.2003.12.004 .
- Fu GK, Wang JT, Yang J, Au-Young J, Stuve LL . Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes . Genomics . 84 . 1 . 205–210 . July 2004 . 15203218 . 10.1016/j.ygeno.2004.01.011 .
- Schwartz SB, Aleman TS, Cideciyan AV, Windsor EA, Sumaroka A, Roman AJ, Rane T, Smilko EE, Bennett J, Stone EM, Kimberling WJ, Liu XZ, Jacobson SG . 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 . 15671307 . 10.1167/iovs.04-1136 .
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
External links
Notes and References
- Web site: Entrez Gene: GPR98 G protein-coupled receptor 98.
- Sun JP, Li R, Ren HZ, Xu AT, Yu X, Xu ZG . The very large G protein coupled receptor (Vlgr1) in hair cells . Journal of Molecular Neuroscience . 50 . 1 . 204–214 . May 2013 . 23180093 . 10.1007/s12031-012-9911-5 . 16730555 .
- Book: Stacey M, Yona S . AdhesionGPCRs: Structure to Function (Advances in Experimental Medicine and Biology) . Springer . Berlin . 2011 . 978-1-4419-7912-4 .
- Whittaker CA, Bergeron KF, Whittle J, Brandhorst BP, Burke RD, Hynes RO . The echinoderm adhesome . Developmental Biology . 300 . 1 . 252–266 . December 2006 . 16950242 . 3565218 . 10.1016/j.ydbio.2006.07.044 .