Follicle-stimulating hormone receptor

Details

Name
Follicle-stimulating hormone receptor
Synonyms
  • Follitropin receptor
  • FSH-R
  • LGR1
Gene Name
FSHR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037007|Follicle-stimulating hormone receptor
MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNAIELRFVLTKLRV
IQKGAFSGFGDLEKIEISQNDVLEVIEADVFSNLPKLHEIRIEKANNLLYINPEAFQNLP
NLQYLLISNTGIKHLPDVHKIHSLQKVLLDIQDNINIHTIERNSFVGLSFESVILWLNKN
GIQEIHNCAFNGTQLDELNLSDNNNLEELPNDVFHGASGPVILDISRTRIHSLPSYGLEN
LKKLRARSTYNLKKLPTLEKLVALMEASLTYPSHCCAFANWRRQISELHPICNKSILRQE
VDYMTQARGQRSSLAEDNESSYSRGFDMTYTEFDYDLCNEVVDVTCSPKPDAFNPCEDIM
GYNILRVLIWFISILAITGNIIVLVILTTSQYKLTVPRFLMCNLAFADLCIGIYLLLIAS
VDIHTKSQYHNYAIDWQTGAGCDAAGFFTVFASELSVYTLTAITLERWHTITHAMQLDCK
VQLRHAASVMVMGWIFAFAAALFPIFGISSYMKVSICLPMDIDSPLSQLYVMSLLVLNVL
AFVVICGCYIHIYLTVRNPNIVSSSSDTRIAKRMAMLIFTDFLCMAPISFFAISASLKVP
LITVSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLSKCGCYEMQAQIYRTETSS
TVHNTHPRNGHCSSAPRVTNGSTYILVPLSHLAQN
Number of residues
695
Molecular Weight
78264.07
Theoretical pI
7.19
GO Classification
Functions
follicle-stimulating hormone receptor activity / G-protein coupled peptide receptor activity
Processes
activation of adenylate cyclase activity / adenylate cyclase-activating G-protein coupled receptor signaling pathway / female gamete generation / female gonad development / follicle-stimulating hormone signaling pathway / G-protein coupled receptor signaling pathway / gonad development / hormone-mediated signaling pathway / male gonad development / positive regulation of ERK1 and ERK2 cascade / positive regulation of phosphatidylinositol 3-kinase signaling / primary ovarian follicle growth / regulation of osteoclast differentiation / regulation of protein kinase A signaling / spermatogenesis / uterus development
Components
integral component of membrane / integral component of plasma membrane / plasma membrane
General Function
G-protein coupled peptide receptor activity
Specific Function
Receptor for follicle-stimulating hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Induces cAMP production through the activation of PI3K-AKT and SRC-ERK1/2 signaling pathways.
Pfam Domain Function
Transmembrane Regions
367-387 399-421 444-465 486-508 529-550 574-597 609-630
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0018946|Follicle-stimulating hormone receptor (FSHR)
ATGGCCCTGCTCCTGGTCTCTTTGCTGGCATTCCTGAGCTTGGGCTCAGGATGTCATCAT
CGGATCTGTCACTGCTCTAACAGGGTTTTTCTCTGCCAAGAGAGCAAGGTGACAGAGATT
CCTTCTGACCTCCCGAGGAATGCCATTGAACTGAGGTTTGTCCTCACCAAGCTTCGAGTC
ATCCAAAAAGGTGCATTTTCAGGATTTGGGGACCTGGAGAAAATAGAGATCTCTCAGAAT
GATGTCTTGGAGGTGATAGAGGCAGATGTGTTCTCCAACCTTCCCAAATTACATGAAATT
AGAATTGAAAAGGCCAACAACCTGCTCTACATCAACCCTGAGGCCTTCCAGAACCTTCCC
AACCTTCAATATCTGTTAATATCCAACACAGGTATTAAGCACCTTCCAGATGTTCACAAG
ATTCATTCTCTCCAAAAAGTTTTACTTGACATTCAAGATAACATAAACATCCACACAATT
GAAAGAAATTCTTTCGTGGGGCTGAGCTTTGAAAGTGTGATTCTATGGCTGAATAAGAAT
GGGATTCAAGAAATACACAACTGTGCATTCAATGGAACCCAACTAGATGAGCTGAATCTA
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
Chromosome Location
2
Locus
2p21-p16
External Identifiers
ResourceLink
UniProtKB IDP23945
UniProtKB Entry NameFSHR_HUMAN
GenBank Protein ID182771
GenBank Gene IDM65085
GenAtlas IDFSHR
HGNC IDHGNC:3969
General References
  1. 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]
  2. 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]
  3. 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]
  4. 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. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  5. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621]
  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. [PubMed:15489334]
  7. 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]
  8. 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]
  9. 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]
  10. Song GJ, Park YS, Lee YS, Lee CC, Kang IS: Alternatively spliced variants of the follicle-stimulating hormone receptor gene in the testis of infertile men. Fertil Steril. 2002 Mar;77(3):499-504. [PubMed:11872202]
  11. 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]
  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. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
  24. 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]
  25. 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]
  26. 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]
  27. 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]
  28. 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]
  29. Uchida S, Uchida H, Maruyama T, Kajitani T, Oda H, Miyazaki K, Kagami M, Yoshimura Y: Molecular analysis of a mutated FSH receptor detected in a patient with spontaneous ovarian hyperstimulation syndrome. PLoS One. 2013 Sep 13;8(9):e75478. doi: 10.1371/journal.pone.0075478. eCollection 2013. [PubMed:24058690]
  30. Desai SS, Achrekar SK, Sahasrabuddhe KA, Meharji PK, Desai SK, Mangoli VS, Mahale SD: Functional characterization of two naturally occurring mutations (Val514Ala and Ala575Val) in follicle-stimulating hormone receptor. J Clin Endocrinol Metab. 2015 Apr;100(4):E638-45. doi: 10.1210/jc.2014-3662. Epub 2015 Jan 12. [PubMed:25581598]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00032MenotropinsapprovedyesbinderDetails
DB00066FollitropinapprovedyesagonistDetails
DB00094Urofollitropinapproved, vet_approvedyesagonistDetails
DB00097Choriogonadotropin alfaapprovedyesbinderDetails
DB04786SuramininvestigationalyesantagonistDetails
DB09066Corifollitropin alfaapproved, investigationalyesagonistDetails