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Identification
HMDB Protein ID HMDBP02806
Secondary Accession Numbers
  • 8312
Name Gonadotropin-releasing hormone receptor
Synonyms
  1. GnRH receptor
  2. GnRH-R
Gene Name GNRHR
Protein Type Unknown
Biological Properties
General Function Involved in G-protein coupled receptor protein signaling pathway
Specific Function Receptor 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
receptor activity
transmembrane receptor activity
protein-hormone receptor activity
gonadotropin-releasing hormone receptor activity
molecular transducer activity
signal transducer activity
g-protein coupled receptor activity
Process
signaling
signaling pathway
cell surface receptor linked signaling pathway
g-protein coupled receptor protein signaling pathway
Cellular Location
  1. Cell membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:4
Locus 4q21.2
SNPs GNRHR
Gene Sequence
>987 bp
ATGGCAAACAGTGCCTCTCCTGAACAGAATCAAAATCACTGTTCAGCCATCAACAACAGC
ATCCCACTGATGCAGGGCAACCTCCCCACTCTGACCTTGTCTGGAAAGATCCGAGTGACG
GTTACTTTCTTCCTTTTTCTGCTCTCTGCGACCTTTAATGCTTCTTTCTTGTTGAAACTT
CAGAAGTGGACACAGAAGAAAGAGAAAGGGAAAAAGCTCTCAAGAATGAAGCTGCTCTTA
AAACATCTGACCTTAGCCAACCTGTTGGAGACTCTGATTGTCATGCCACTGGATGGGATG
TGGAACATTACAGTCCAATGGTATGCTGGAGAGTTACTCTGCAAAGTTCTCAGTTATCTA
AAGCTTTTCTCCATGTATGCCCCAGCCTTCATGATGGTGGTGATCAGCCTGGACCGCTCC
CTGGCTATCACGAGGCCCCTAGCTTTGAAAAGCAACAGCAAAGTCGGACAGTCCATGGTT
GGCCTGGCCTGGATCCTCAGTAGTGTCTTTGCAGGACCACAGTTATACATCTTCAGGATG
ATTCATCTAGCAGACAGCTCTGGACAGACAAAAGTTTTCTCTCAATGTGTAACACACTGC
AGTTTTTCACAATGGTGGCATCAAGCATTTTATAACTTTTTCACCTTCAGCTGCCTCTTC
ATCATCCCTCTTTTCATCATGCTGATCTGCAATGCAAAAATCATCTTCACCCTGACACGG
GTCCTTCATCAGGACCCCCACGAACTACAACTGAATCAGTCCAAGAACAATATACCAAGA
GCACGGCTGAAGACTCTAAAAATGACGGTTGCATTTGCCACTTCATTTACTGTCTGCTGG
ACTCCCTACTATGTCCTAGGAATTTGGTATTGGTTTGATCCTGAAATGTTAAACAGGTTG
TCAGACCCAGTAAATCACTTCTTCTTTCTCTTTGCCTTTTTAAACCCATGCTTTGATCCA
CTTATCTATGGATATTTTTCTCTGTGA
Protein Properties
Number of Residues 328
Molecular Weight 37730.4
Theoretical pI 9.93
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 39-58
  • 78-97
  • 116-137
  • 165-184
  • 213-232
  • 282-300
  • 307-326
Protein Sequence
>Gonadotropin-releasing hormone receptor
MANSASPEQNQNHCSAINNSIPLMQGNLPTLTLSGKIRVTVTFFLFLLSATFNASFLLKL
QKWTQKKEKGKKLSRMKLLLKHLTLANLLETLIVMPLDGMWNITVQWYAGELLCKVLSYL
KLFSMYAPAFMMVVISLDRSLAITRPLALKSNSKVGQSMVGLAWILSSVFAGPQLYIFRM
IHLADSSGQTKVFSQCVTHCSFSQWWHQAFYNFFTFSCLFIIPLFIMLICNAKIIFTLTR
VLHQDPHELQLNQSKNNIPRARLKTLKMTVAFATSFTVCWTPYYVLGIWYWFDPEMLNRL
SDPVNHFFFLFAFLNPCFDPLIYGYFSL
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P30968
UniProtKB/Swiss-Prot Entry Name GNRHR_HUMAN
PDB IDs Not Available
GenBank Gene ID L03380
GeneCard ID GNRHR
GenAtlas ID GNRHR
HGNC ID HGNC:4421
References
General References
  1. 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. [PubMed:15489334 ]
  2. 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. [PubMed:1333190 ]
  3. 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. [PubMed:8386108 ]
  4. 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. [PubMed:7534732 ]
  5. Kakar SS: Molecular structure of the human gonadotropin-releasing hormone receptor gene. Eur J Endocrinol. 1997 Aug;137(2):183-92. [PubMed:9272108 ]
  6. 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. [PubMed:9259321 ]
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:12679486 ]