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Identification
HMDB Protein ID HMDBP02692
Secondary Accession Numbers
  • 8195
Name Follicle-stimulating hormone receptor
Synonyms
  1. FSH-R
  2. Follitropin receptor
Gene Name FSHR
Protein Type Enzyme
Biological Properties
General Function Involved in G-protein coupled receptor protein signaling pathway
Specific Function Receptor for follicle-stimulating hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase
Pathways
  • Intracellular Signalling Through FSH Receptor and Follicle Stimulating Hormone
  • Vasopressin Regulation of Water Homeostasis
Reactions Not Available
GO Classification
Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
binding
follicle-stimulating hormone receptor activity
receptor activity
transmembrane receptor activity
protein-hormone receptor activity
protein binding
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:2
Locus 2p21-p16
SNPs FSHR
Gene Sequence
>2088 bp
ATGGCCCTGCTCCTGGTCTCTTTGCTGGCATTCCTGAGCTTGGGCTCAGGATGTCATCAT
CGGATCTGTCACTGCTCTAACAGGGTTTTTCTCTGCCAAGAGAGCAAGGTGACAGAGATT
CCTTCTGACCTCCCGAGGAATGCCATTGAACTGAGGTTTGTCCTCACCAAGCTTCGAGTC
ATCCAAAAAGGTGCATTTTCAGGATTTGGGGACCTGGAGAAAATAGAGATCTCTCAGAAT
GATGTCTTGGAGGTGATAGAGGCAGATGTGTTCTCCAACCTTCCCAAATTACATGAAATT
AGAATTGAAAAGGCCAACAACCTGCTCTACATCACCCCTGAGGCCTTCCAGAACCTTCCC
AACCTTCAATATCTGTTAATATCCAACACAGGTATTAAGCACCTTCCAGATGTTCACAAG
ATTCATTCTCTCCAAAAGGTTTTACTTGACATTCAAGATAACATAAACATCCACACAATT
GAAAGAAATTCTTTCGTGGGGCTGAGCTTTGAAAGTGTGATTCTATGGCTGAATAAGAAT
GGGATTCAAGAAATACACAACTGTGCATTCAATGGAACCCAACTAGATGCAGTGAATCTA
AGCGATAATAATAATTTAGAAGAATTGCCTAATGATGTTTTCCACGGAGCCTCTGGACCA
GTCATTCTAGATATTTCAAGAACAAGGATCCATTCCCTGCCTAGCTATGGCTTAGAAAAT
CTTAAGAAGCTGAGGGCCAGGTCGACTTACAACTTAAAAAAGCTGCCTACTCTGGAAAAG
CTTGTCGCCCTCATGGAAGCCAGCCTCACCTATCCCAGCCATTGCTGTGCCTTTGCAAAC
TGGAGACGGCAAATCTCTGAGCTTCATCCAATTTGCAACAAATCTATTTTAAGGCAAGAA
GTTGATTATATGACTCAGGCTAGGGGTCAGAGATCCTCTCTGGCAGAAGACAATGAGTCC
AGCTACAGCAGAGGATTTGACATGACGTACACTGAGTTTGACTATGACTTATGCAATGAA
GTGGTTGACGTGACCTGCTCCCCTAAGCCAGATGCATTCAACCCATGTGAAGATATCATG
GGGTACAACATCCTCAGAGTCCTGATATGGTTTATCAGCATCCTGGCCATCACTGGGAAC
ATCATAGTGCTAGTGATCCTAACTACCAGCCAATATAAACTCACAGTCCCCAGGTTCCTT
ATGTGCAACCTGGCCTTTGCTGATCTCTGCATTGGAATCTACCTGCTGCTCATTGCATCA
GTTGATATCCATACCAAGAGCCAATATCACAACTATGCCATTGACTGGCAAACTGGGGCA
GGCTGTGATGCTGCTGGCTTTTTCACTGTCTTTGCCAGTGAGCTGTCAGTCTACACTCTG
ACAGCTATCACCTTGGAAAGATGGCATACCATCACGCATGCCATGCAGCTGGACTGCAAG
GTGCAGCTCCGCCATGCTGCCAGTGTCATGGTGATGGGCTGGATTTTTGCTTTTGCAGCT
GCCCTCTTTCCCATCTTTGGCATCAGCAGCTACATGAAGGTGAGCATCTGCCTGCCCATG
GATATTGACAGCCCTTTGTCACAGCTGTATGTCATGTCCCTCCTTGTGCTCAATGTCCTG
GCCTTTGTGGTCATCTGTGGCTGCTATATCCACATCTACCTCACAGTGCGGAACCCCAAC
ATCGTGTCCTCCTCTAGTGACACCAGGATCGCCAAGCGCATGGCCATGCTCATCTTCACT
GACTTCCTCTGCATGGCACCCATTTCTTTCTTTGCCATTTCTGCCTCCCTCAAGGTGCCC
CTCATCACTGTGTCCAAAGCAAAGATTCTGCTGGTTCTGTTTCACCCCATCAACTCCTGT
GCCAACCCCTTCCTCTATGCCATCTTTACCAAAAACTTTCGCAGAGATTTCTTCATTCTG
CTGAGCAAGTGTGGCTGCTATGAAATGCAAGCCCAAATTTATAGGACAGAAACTTCATCC
ACTGTCCACAACACCCATCCAAGGAATGGCCACTGCTCTTCAGCTCCCAGAGTCACCAGT
GGTTCCACTTACATACTTGTCCCTCTAAGTCATTTAGCCCAAAACTAA
Protein Properties
Number of Residues 695
Molecular Weight 78294.1
Theoretical pI 7.19
Pfam Domain Function
Signals
  • 1-17
Transmembrane Regions
  • 367-387
  • 399-421
  • 444-465
  • 486-508
  • 529-550
  • 574-597
  • 609-630
Protein Sequence
>Follicle-stimulating hormone receptor
MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNAIELRFVLTKLRV
IQKGAFSGFGDLEKIEISQNDVLEVIEADVFSNLPKLHEIRIEKANNLLYINPEAFQNLP
NLQYLLISNTGIKHLPDVHKIHSLQKVLLDIQDNINIHTIERNSFVGLSFESVILWLNKN
GIQEIHNCAFNGTQLDELNLSDNNNLEELPNDVFHGASGPVILDISRTRIHSLPSYGLEN
LKKLRARSTYNLKKLPTLEKLVALMEASLTYPSHCCAFANWRRQISELHPICNKSILRQE
VDYMTQTRGQRSSLAEDNESSYSRGFDMTYTEFDYDLCNEVVDVTCSPKPDAFNPCEDIM
GYNILRVLIWFISILAITGNIIVLVILTTSQYKLTVPRFLMCNLAFADLCIGIYLLLIAS
VDIHTKSQYHNYAIDWQTGAGCDAAGFFTVFASELSVYTLTAITLERWHTITHAMQLDCK
VQLRHAASVMVMGWIFAFAAALFPIFGISSYMKVSICLPMDIDSPLSQLYVMSLLVLNVL
AFVVICGCYIHIYLTVRNPNIVSSSSDTRIAKRMAMLIFTDFLCMAPISFFAISASLKVP
LITVSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLSKCGCYEMQAQIYRTETSS
TVHNTHPRNGHCSSAPRVTNGSTYILVPLSHLAQN
GenBank ID Protein 182771
UniProtKB/Swiss-Prot ID P23945
UniProtKB/Swiss-Prot Entry Name FSHR_HUMAN
PDB IDs
GenBank Gene ID M65085
GeneCard ID FSHR
GenAtlas ID FSHR
HGNC ID HGNC:3969
References
General References
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  4. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed:10391209 ]
  5. Jiang X, Dreano M, Buckler DR, Cheng S, Ythier A, Wu H, Hendrickson WA, el Tayar N: Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions. Structure. 1995 Dec 15;3(12):1341-53. [PubMed:8747461 ]
  6. Minegishi T, Nakamura K, Takakura Y, Ibuki Y, Igarashi M, Minegish T [corrected to Minegishi T]: Cloning and sequencing of human FSH receptor cDNA. Biochem Biophys Res Commun. 1991 Mar 29;175(3):1125-30. [PubMed:1709010 ]
  7. Tilly JL, Aihara T, Nishimori K, Jia XC, Billig H, Kowalski KI, Perlas EA, Hsueh AJ: Expression of recombinant human follicle-stimulating hormone receptor: species-specific ligand binding, signal transduction, and identification of multiple ovarian messenger ribonucleic acid transcripts. Endocrinology. 1992 Aug;131(2):799-806. [PubMed:1322283 ]
  8. Kelton CA, Cheng SV, Nugent NP, Schweickhardt RL, Rosenthal JL, Overton SA, Wands GD, Kuzeja JB, Luchette CA, Chappel SC: The cloning of the human follicle stimulating hormone receptor and its expression in COS-7, CHO, and Y-1 cells. Mol Cell Endocrinol. 1992 Nov;89(1-2):141-51. [PubMed:1301382 ]
  9. Gromoll J, Gudermann T, Nieschlag E: Molecular cloning of a truncated isoform of the human follicle stimulating hormone receptor. Biochem Biophys Res Commun. 1992 Nov 16;188(3):1077-83. [PubMed:1359889 ]
  10. Gromoll J, Dankbar B, Gudermann T: Characterization of the 5' flanking region of the human follicle-stimulating hormone receptor gene. Mol Cell Endocrinol. 1994 Jun;102(1-2):93-102. [PubMed:7926278 ]
  11. Gromoll J, Ried T, Holtgreve-Grez H, Nieschlag E, Gudermann T: Localization of the human FSH receptor to chromosome 2 p21 using a genomic probe comprising exon 10. J Mol Endocrinol. 1994 Jun;12(3):265-71. [PubMed:7916967 ]
  12. Fan QR, Hendrickson WA: Structure of human follicle-stimulating hormone in complex with its receptor. Nature. 2005 Jan 20;433(7023):269-77. [PubMed:15662415 ]
  13. Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR, Nieschlag E, Huhtaniemi I, de la Chapelle A: Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995 Sep 22;82(6):959-68. [PubMed:7553856 ]
  14. Kotlar TJ, Young RH, Albanese C, Crowley WF Jr, Scully RE, Jameson JL: A mutation in the follicle-stimulating hormone receptor occurs frequently in human ovarian sex cord tumors. J Clin Endocrinol Metab. 1997 Apr;82(4):1020-6. [PubMed:9100567 ]
  15. Gromoll J, Simoni M, Nieschlag E: An activating mutation of the follicle-stimulating hormone receptor autonomously sustains spermatogenesis in a hypophysectomized man. J Clin Endocrinol Metab. 1996 Apr;81(4):1367-70. [PubMed:8636335 ]
  16. Jiang M, Aittomaki K, Nilsson C, Pakarinen P, Iitia A, Torresani T, Simonsen H, Goh V, Pettersson K, de la Chapelle A, Huhtaniemi I: The frequency of an inactivating point mutation (566C-->T) of the human follicle-stimulating hormone receptor gene in four populations using allele-specific hybridization and time-resolved fluorometry. J Clin Endocrinol Metab. 1998 Dec;83(12):4338-43. [PubMed:9851774 ]
  17. Beau I, Touraine P, Meduri G, Gougeon A, Desroches A, Matuchansky C, Milgrom E, Kuttenn F, Misrahi M: A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor. J Clin Invest. 1998 Oct 1;102(7):1352-9. [PubMed:9769327 ]
  18. Touraine P, Beau I, Gougeon A, Meduri G, Desroches A, Pichard C, Detoeuf M, Paniel B, Prieur M, Zorn JR, Milgrom E, Kuttenn F, Misrahi M: New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol Endocrinol. 1999 Nov;13(11):1844-54. [PubMed:10551778 ]
  19. Asatiani K, Gromoll J, Eckardstein SV, Zitzmann M, Nieschlag E, Simoni M: Distribution and function of FSH receptor genetic variants in normal men. Andrologia. 2002 Jun;34(3):172-6. [PubMed:12059813 ]
  20. Doherty E, Pakarinen P, Tiitinen A, Kiilavuori A, Huhtaniemi I, Forrest S, Aittomaki K: A Novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure. J Clin Endocrinol Metab. 2002 Mar;87(3):1151-5. [PubMed:11889179 ]
  21. Allen LA, Achermann JC, Pakarinen P, Kotlar TJ, Huhtaniemi IT, Jameson JL, Cheetham TD, Ball SG: A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics. Hum Reprod. 2003 Feb;18(2):251-6. [PubMed:12571157 ]
  22. Meduri G, Touraine P, Beau I, Lahuna O, Desroches A, Vacher-Lavenu MC, Kuttenn F, Misrahi M: Delayed puberty and primary amenorrhea associated with a novel mutation of the human follicle-stimulating hormone receptor: clinical, histological, and molecular studies. J Clin Endocrinol Metab. 2003 Aug;88(8):3491-8. [PubMed:12915623 ]
  23. Vasseur C, Rodien P, Beau I, Desroches A, Gerard C, de Poncheville L, Chaplot S, Savagner F, Croue A, Mathieu E, Lahlou N, Descamps P, Misrahi M: A chorionic gonadotropin-sensitive mutation in the follicle-stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome. N Engl J Med. 2003 Aug 21;349(8):753-9. [PubMed:12930927 ]
  24. Smits G, Olatunbosun O, Delbaere A, Pierson R, Vassart G, Costagliola S: Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor. N Engl J Med. 2003 Aug 21;349(8):760-6. [PubMed:12930928 ]
  25. Montanelli L, Delbaere A, Di Carlo C, Nappi C, Smits G, Vassart G, Costagliola S: A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome. J Clin Endocrinol Metab. 2004 Apr;89(4):1255-8. [PubMed:15080154 ]
  26. De Leener A, Montanelli L, Van Durme J, Chae H, Smits G, Vassart G, Costagliola S: Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology. J Clin Endocrinol Metab. 2006 Feb;91(2):555-62. Epub 2005 Nov 8. [PubMed:16278261 ]
  27. De Leener A, Caltabiano G, Erkan S, Idil M, Vassart G, Pardo L, Costagliola S: Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome. Hum Mutat. 2008 Jan;29(1):91-8. [PubMed:17721928 ]