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NameGonadotropin-releasing hormone receptor
Synonyms
  • GnRH receptor
  • GRHR
Gene NameGNRHR
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000405|Gonadotropin-releasing hormone receptor
MANSASPEQNQNHCSAINNSIPLMQGNLPTLTLSGKIRVTVTFFLFLLSATFNASFLLKL
QKWTQKKEKGKKLSRMKLLLKHLTLANLLETLIVMPLDGMWNITVQWYAGELLCKVLSYL
KLFSMYAPAFMMVVISLDRSLAITRPLALKSNSKVGQSMVGLAWILSSVFAGPQLYIFRM
IHLADSSGQTKVFSQCVTHCSFSQWWHQAFYNFFTFSCLFIIPLFIMLICNAKIIFTLTR
VLHQDPHELQLNQSKNNIPRARLKTLKMTVAFATSFTVCWTPYYVLGIWYWFDPEMLNRL
SDPVNHFFFLFAFLNPCFDPLIYGYFSL
Number of residues328
Molecular Weight37730.355
Theoretical pI9.93
GO Classification
Functions
  • gonadotropin-releasing hormone receptor activity
  • peptide binding
Processes
  • G-protein coupled receptor signaling pathway
  • multicellular organismal development
  • cellular response to gonadotropin-releasing hormone
Components
  • membrane
  • plasma membrane
  • integral component of plasma membrane
General FunctionPeptide binding
Specific FunctionReceptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling.
Pfam Domain Function
Transmembrane Regions39-58 78-97 116-137 165-184 213-232 282-300 307-326
GenBank Protein ID183422
UniProtKB IDP30968
UniProtKB Entry NameGNRHR_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0018926|Gonadotropin-releasing hormone receptor (GNRHR)
ATGGCAAACAGTGCCTCTCCTGAACAGAATCAAAATCACTGTTCAGCCATCAACAACAGC
ATCCCACTGATGCAGGGCAACCTCCCCACTCTGACCTTGTCTGGAAAGATCCGAGTGACG
GTTACTTTCTTCCTTTTTCTGCTCTCTGCGACCTTTAATGCTTCTTTCTTGTTGAAACTT
CAGAAGTGGACACAGAAGAAAGAGAAAGGGAAAAAGCTCTCAAGAATGAAGCTGCTCTTA
AAACATCTGACCTTAGCCAACCTGTTGGAGACTCTGATTGTCATGCCACTGGATGGGATG
TGGAACATTACAGTCCAATGGTATGCTGGAGAGTTACTCTGCAAAGTTCTCAGTTATCTA
AAGCTTTTCTCCATGTATGCCCCAGCCTTCATGATGGTGGTGATCAGCCTGGACCGCTCC
CTGGCTATCACGAGGCCCCTAGCTTTGAAAAGCAACAGCAAAGTCGGACAGTCCATGGTT
GGCCTGGCCTGGATCCTCAGTAGTGTCTTTGCAGGACCACAGTTATACATCTTCAGGATG
ATTCATCTAGCAGACAGCTCTGGACAGACAAAAGTTTTCTCTCAATGTGTAACACACTGC
AGTTTTTCACAATGGTGGCATCAAGCATTTTATAACTTTTTCACCTTCAGCTGCCTCTTC
ATCATCCCTCTTTTCATCATGCTGATCTGCAATGCAAAAATCATCTTCACCCTGACACGG
GTCCTTCATCAGGACCCCCACGAACTACAACTGAATCAGTCCAAGAACAATATACCAAGA
GCACGGCTGAAGACTCTAAAAATGACGGTTGCATTTGCCACTTCATTTACTGTCTGCTGG
ACTCCCTACTATGTCCTAGGAATTTGGTATTGGTTTGATCCTGAAATGTTAAACAGGTTG
TCAGACCCAGTAAATCACTTCTTCTTTCTCTTTGCCTTTTTAAACCCATGCTTTGATCCA
CTTATCTATGGATATTTTTCTCTGTGA
GenBank Gene IDL03380
GeneCard IDNot Available
GenAtlas IDGNRHR
HGNC IDHGNC:4421
Chromosome Location4
Locus4q21.2
References
  1. Kakar SS, Musgrove LC, Devor DC, Sellers JC, Neill JD: Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor. Biochem Biophys Res Commun. 1992 Nov 30;189(1):289-95. 1333190
  2. Chi L, Zhou W, Prikhozhan A, Flanagan C, Davidson JS, Golembo M, Illing N, Millar RP, Sealfon SC: Cloning and characterization of the human GnRH receptor. Mol Cell Endocrinol. 1993 Feb;91(1-2):R1-6. 8386108
  3. Kakar SS, Grizzle WE, Neill JD: The nucleotide sequences of human GnRH receptors in breast and ovarian tumors are identical with that found in pituitary. Mol Cell Endocrinol. 1994 Dec;106(1-2):145-9. 7534732
  4. Kakar SS: Molecular structure of the human gonadotropin-releasing hormone receptor gene. Eur J Endocrinol. 1997 Aug;137(2):183-92. 9272108
  5. Grosse R, Schoneberg T, Schultz G, Gudermann T: Inhibition of gonadotropin-releasing hormone receptor signaling by expression of a splice variant of the human receptor. Mol Endocrinol. 1997 Aug;11(9):1305-18. 9259321
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Kottler ML, Bergametti F, Carre MC, Morice S, Decoret E, Lagarde JP, Starzec A, Counis R: Tissue-specific pattern of variant transcripts of the human gonadotropin-releasing hormone receptor gene. Eur J Endocrinol. 1999 Jun;140(6):561-9. 10366411
  8. de Roux N, Young J, Misrahi M, Genet R, Chanson P, Schaison G, Milgrom E: A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N Engl J Med. 1997 Nov 27;337(22):1597-602. 9371856
  9. Layman LC, Cohen DP, Jin M, Xie J, Li Z, Reindollar RH, Bolbolan S, Bick DP, Sherins RR, Duck LW, Musgrove LC, Sellers JC, Neill JD: Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Nat Genet. 1998 Jan;18(1):14-5. 9425890
  10. de Roux N, Young J, Brailly-Tabard S, Misrahi M, Milgrom E, Schaison G: The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred. J Clin Endocrinol Metab. 1999 Feb;84(2):567-72. 10022417
  11. Caron P, Chauvin S, Christin-Maitre S, Bennet A, Lahlou N, Counis R, Bouchard P, Kottler ML: Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration. J Clin Endocrinol Metab. 1999 Mar;84(3):990-6. 10084584
  12. Pralong FP, Gomez F, Castillo E, Cotecchia S, Abuin L, Aubert ML, Portmann L, Gaillard RC: Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor. J Clin Endocrinol Metab. 1999 Oct;84(10):3811-6. 10523035
  13. Pitteloud N, Boepple PA, DeCruz S, Valkenburgh SB, Crowley WF Jr, Hayes FJ: The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor. J Clin Endocrinol Metab. 2001 Jun;86(6):2470-5. 11397842
  14. Soderlund D, Canto P, de la Chesnaye E, Ulloa-Aguirre A, Mendez JP: A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene. Clin Endocrinol (Oxf). 2001 Apr;54(4):493-8. 11318785
  15. Costa EM, Bedecarrats GY, Mendonca BB, Arnhold IJ, Kaiser UB, Latronico AC: Two novel mutations in the gonadotropin-releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction. J Clin Endocrinol Metab. 2001 Jun;86(6):2680-6. 11397871
  16. Maya-Nunez G, Janovick JA, Ulloa-Aguirre A, Soderlund D, Conn PM, Mendez JP: Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E(90)K) GnRH receptor function by a deletion at a distant site. J Clin Endocrinol Metab. 2002 May;87(5):2144-9. 11994356
  17. Karges B, Karges W, Mine M, Ludwig L, Kuhne R, Milgrom E, de Roux N: Mutation Ala(171)Thr stabilizes the gonadotropin-releasing hormone receptor in its inactive conformation, causing familial hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2003 Apr;88(4):1873-9. 12679486
  18. Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N: Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008. 23643382
  19. Marcos S, Sarfati J, Leroy C, Fouveaut C, Parent P, Metz C, Wolczynski S, Gerard M, Bieth E, Kurtz F, Verier-Mine O, Perrin L, Archambeaud F, Cabrol S, Rodien P, Hove H, Prescott T, Lacombe D, Christin-Maitre S, Touraine P, Hieronimus S, Dewailly D, Young J, Pugeat M, Hardelin JP, Dode C: The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients. J Clin Endocrinol Metab. 2014 Oct;99(10):E2138-43. doi: 10.1210/jc.2014-2110. Epub 2014 Jul 31. 25077900