FSHR_HUMAN
ID FSHR_HUMAN Reviewed; 695 AA.
AC P23945; A0A0A0MSC5; A8K947; G5CBS7; G5E967; J3KQ00; Q05AH0; Q16225; Q4QRJ3;
AC Q4ZFZ2; Q53RW2;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Follicle-stimulating hormone receptor;
DE Short=FSH-R;
DE AltName: Full=Follitropin receptor;
DE Flags: Precursor;
GN Name=FSHR; Synonyms=LGR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND VARIANT SER-680.
RC TISSUE=Ovary;
RX PubMed=1709010; DOI=10.1016/0006-291x(91)91682-3;
RA Minegish T., Nakamura K., Takakura Y., Ibuki Y., Igarashi M.;
RT "Cloning and sequencing of human FSH receptor cDNA.";
RL Biochem. Biophys. Res. Commun. 175:1125-1130(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND VARIANT THR-307.
RX PubMed=1322283; DOI=10.1210/endo.131.2.1322283;
RA Tilly J.L., Aihara T., Nishimori K., Jia X.-C., Billig H., Kowalski K.I.,
RA Perlas E.A., Hsueh A.J.;
RT "Expression of recombinant human follicle-stimulating hormone receptor:
RT species-specific ligand binding, signal transduction, and identification of
RT multiple ovarian messenger ribonucleic acid transcripts.";
RL Endocrinology 131:799-806(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND VARIANT THR-307.
RC TISSUE=Testis;
RX PubMed=1301382; DOI=10.1016/0303-7207(92)90220-z;
RA Kelton C.A., Cheng S.V., Nugent N.P., Schweickhardt R.L., Rosenthal J.L.,
RA Overton S.A., Wands G.D., Kuzeja J.B., Luchette C.A., Chappel S.C.;
RT "The cloning of the human follicle stimulating hormone receptor and its
RT expression in COS-7, CHO, and Y-1 cells.";
RL Mol. Cell. Endocrinol. 89:141-151(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RC TISSUE=Adipose tissue;
RA Liu X., Huang H., Sheng J.;
RT "FSHR expression in adipose tissue.";
RL Submitted (MAY-2011) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), AND VARIANT THR-307.
RC TISSUE=Testis;
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), AND VARIANT THR-307.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-680.
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-680.
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND 3), AND VARIANTS
RP THR-307 AND SER-680.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-342 (ISOFORM SHORT), AND VARIANT THR-307.
RC TISSUE=Testis;
RX PubMed=1359889; DOI=10.1016/0006-291x(92)91341-m;
RA Gromoll J., Gudermann T., Nieschlag E.;
RT "Molecular cloning of a truncated isoform of the human follicle stimulating
RT hormone receptor.";
RL Biochem. Biophys. Res. Commun. 188:1077-1083(1992).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-51.
RX PubMed=7926278; DOI=10.1016/0303-7207(94)90102-3;
RA Gromoll J., Dankbar B., Gudermann T.;
RT "Characterization of the 5' flanking region of the human follicle-
RT stimulating hormone receptor gene.";
RL Mol. Cell. Endocrinol. 102:93-102(1994).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 286-695, AND VARIANTS THR-307 AND
RP SER-680.
RX PubMed=7916967; DOI=10.1677/jme.0.0120265;
RA Gromoll J., Ried T., Holtgreve-Grez H., Nieschlag E., Gudermann T.;
RT "Localization of the human FSH receptor to chromosome 2p21 using a genomic
RT probe comprising exon 10.";
RL J. Mol. Endocrinol. 12:265-271(1994).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, SULFATION AT TYR-335, AND MUTAGENESIS OF
RP TYR-330 AND TYR-335.
RX PubMed=11847099; DOI=10.1093/emboj/21.4.504;
RA Costagliola S., Panneels V., Bonomi M., Koch J., Many M.C., Smits G.,
RA Vassart G.;
RT "Tyrosine sulfation is required for agonist recognition by glycoprotein
RT hormone receptors.";
RL EMBO J. 21:504-513(2002).
RN [14]
RP ALTERNATIVE SPLICING (ISOFORM 4).
RX PubMed=11872202; DOI=10.1016/s0015-0282(01)03221-6;
RA Song G.J., Park Y.S., Lee Y.S., Lee C.C., Kang I.S.;
RT "Alternatively spliced variants of the follicle-stimulating hormone
RT receptor gene in the testis of infertile men.";
RL Fertil. Steril. 77:499-504(2002).
RN [15]
RP INTERACTION WITH APPL2.
RX PubMed=17030088; DOI=10.1016/j.mce.2006.08.014;
RA Nechamen C.A., Thomas R.M., Dias J.A.;
RT "APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling
RT complex.";
RL Mol. Cell. Endocrinol. 260:93-99(2007).
RN [16]
RP 3D-STRUCTURE MODELING OF 49-228.
RX PubMed=8747461; DOI=10.1016/s0969-2126(01)00272-6;
RA Jiang X., Dreano M., Buckler D.R., Cheng S., Ythier A., Wu H.,
RA Hendrickson W.A., el Tayar N.;
RT "Structural predictions for the ligand-binding region of glycoprotein
RT hormone receptors and the nature of hormone-receptor interactions.";
RL Structure 3:1341-1353(1995).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.92 ANGSTROMS) OF 17-268 IN COMPLEX WITH FSHA AND
RP FSHB, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-191.
RX PubMed=15662415; DOI=10.1038/nature03206;
RA Fan Q.R., Hendrickson W.A.;
RT "Structure of human follicle-stimulating hormone in complex with its
RT receptor.";
RL Nature 433:269-277(2005).
RN [18] {ECO:0007744|PDB:4MQW}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 16-366 OF HOMOTRIMER IN COMPLEX
RP WITH CGA AND FSHB, FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION AT
RP ASN-191, AND DISULFIDE BONDS.
RX PubMed=24692546; DOI=10.1074/jbc.m114.549592;
RA Jiang X., Fischer D., Chen X., McKenna S.D., Liu H., Sriraman V., Yu H.N.,
RA Goutopoulos A., Arkinstall S., He X.;
RT "Evidence for follicle-stimulating hormone receptor as a functional
RT trimer.";
RL J. Biol. Chem. 289:14273-14282(2014).
RN [19]
RP VARIANT ODG1 VAL-189.
RX PubMed=7553856; DOI=10.1016/0092-8674(95)90275-9;
RA Aittomaeki K., Lucena J.L.D., Pakarinen P., Sistonen P., Tapanainen J.,
RA Gromoll J., Kaskikari R., Sankila E.-M., Lehvaslaiho H., Engel A.R.,
RA Nieschlag E., Huhtaniemi I., de la Chapelle A.;
RT "Mutation in the follicle-stimulating hormone receptor gene causes
RT hereditary hypergonadotropic ovarian failure.";
RL Cell 82:959-968(1995).
RN [20]
RP VARIANT OVARIAN SEX CORD TUMOR SER-591.
RX PubMed=9100567; DOI=10.1210/jcem.82.4.3870;
RA Kotlar T.J., Young R.H., Albanese C., Crowley W.F. Jr., Scully R.E.,
RA Jameson J.L.;
RT "A mutation in the follicle-stimulating hormone receptor occurs frequently
RT in human ovarian sex cord tumors.";
RL J. Clin. Endocrinol. Metab. 82:1020-1026(1997).
RN [21]
RP VARIANT FSHR ACTIVATION GLY-567, AND CHARACTERIZATION OF VARIANT FSHR
RP ACTIVATION GLY-567.
RX PubMed=8636335; DOI=10.1210/jcem.81.4.8636335;
RA Gromoll J., Simoni M., Nieschlag E.;
RT "An activating mutation of the follicle-stimulating hormone receptor
RT autonomously sustains spermatogenesis in a hypophysectomized man.";
RL J. Clin. Endocrinol. Metab. 81:1367-1370(1996).
RN [22]
RP VARIANT ODG1 VAL-189.
RX PubMed=9851774; DOI=10.1210/jcem.83.12.5306;
RA Jiang M., Aittomaeki K., Nilsson C., Pakarinen P., Iitia A., Torresani T.,
RA Simonsen H., Goh V., Pettersson K., de la Chapelle A., Huhtaniemi I.;
RT "The frequency of an inactivating point mutation (566C-->T) of the human
RT follicle-stimulating hormone receptor gene in four populations using
RT allele-specific hybridization and time-resolved fluorometry.";
RL J. Clin. Endocrinol. Metab. 83:4338-4343(1998).
RN [23]
RP VARIANTS ODG1 THR-160 AND CYS-573.
RX PubMed=9769327; DOI=10.1172/jci3795;
RA Beau I., Touraine P., Meduri G., Gougeon A., Desroches A., Matuchansky C.,
RA Milgrom E., Kuttenn F., Misrahi M.;
RT "A novel phenotype related to partial loss of function mutations of the
RT follicle stimulating hormone receptor.";
RL J. Clin. Invest. 102:1352-1359(1998).
RN [24]
RP VARIANTS ODG1 VAL-224 AND VAL-601, AND CHARACTERIZATION OF VARIANTS ODG1
RP VAL-224; CYS-573 AND VAL-601.
RX PubMed=10551778; DOI=10.1210/mend.13.11.0370;
RA Touraine P., Beau I., Gougeon A., Meduri G., Desroches A., Pichard C.,
RA Detoeuf M., Paniel B., Prieur M., Zorn J.-R., Milgrom E., Kuttenn F.,
RA Misrahi M.;
RT "New natural inactivating mutations of the follicle-stimulating hormone
RT receptor: correlations between receptor function and phenotype.";
RL Mol. Endocrinol. 13:1844-1854(1999).
RN [25]
RP VARIANTS THR-307; ARG-524 AND SER-680.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [26]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [27]
RP VARIANTS THR-307 AND SER-680.
RX PubMed=12059813; DOI=10.1046/j.1439-0272.2002.00493.x;
RA Asatiani K., Gromoll J., Eckardstein S.V., Zitzmann M., Nieschlag E.,
RA Simoni M.;
RT "Distribution and function of FSH receptor genetic variants in normal
RT men.";
RL Andrologia 34:172-176(2002).
RN [28]
RP VARIANT ODG1 THR-419, AND CHARACTERIZATION OF VARIANT ODG1 THR-419.
RX PubMed=11889179; DOI=10.1210/jcem.87.3.8319;
RA Doherty E., Pakarinen P., Tiitinen A., Kiilavuori A., Huhtaniemi I.,
RA Forrest S., Aittomaeki K.;
RT "A novel mutation in the FSH receptor inhibiting signal transduction and
RT causing primary ovarian failure.";
RL J. Clin. Endocrinol. Metab. 87:1151-1155(2002).
RN [29]
RP VARIANT ODG1 ARG-348.
RX PubMed=12571157; DOI=10.1093/humrep/deg046;
RA Allen L.A., Achermann J.C., Pakarinen P., Kotlar T.J., Huhtaniemi I.T.,
RA Jameson J.L., Cheetham T.D., Ball S.G.;
RT "A novel loss of function mutation in exon 10 of the FSH receptor gene
RT causing hypergonadotrophic hypogonadism: clinical and molecular
RT characteristics.";
RL Hum. Reprod. 18:251-256(2003).
RN [30]
RP VARIANT ODG1 THR-519, AND CHARACTERIZATION OF VARIANT ODG1 THR-519.
RX PubMed=12915623; DOI=10.1210/jc.2003-030217;
RA Meduri G., Touraine P., Beau I., Lahuna O., Desroches A.,
RA Vacher-Lavenu M.C., Kuttenn F., Misrahi M.;
RT "Delayed puberty and primary amenorrhea associated with a novel mutation of
RT the human follicle-stimulating hormone receptor: clinical, histological,
RT and molecular studies.";
RL J. Clin. Endocrinol. Metab. 88:3491-3498(2003).
RN [31]
RP VARIANT OHSS ILE-449.
RX PubMed=12930927; DOI=10.1056/nejmoa030065;
RA Vasseur C., Rodien P., Beau I., Desroches A., Gerard C., de Poncheville L.,
RA Chaplot S., Savagner F., Croue A., Mathieu E., Lahlou N., Descamps P.,
RA Misrahi M.;
RT "A chorionic gonadotropin-sensitive mutation in the follicle-stimulating
RT hormone receptor as a cause of familial gestational spontaneous ovarian
RT hyperstimulation syndrome.";
RL N. Engl. J. Med. 349:753-759(2003).
RN [32]
RP VARIANT OHSS ASN-567.
RX PubMed=12930928; DOI=10.1056/nejmoa030064;
RA Smits G., Olatunbosun O., Delbaere A., Pierson R., Vassart G.,
RA Costagliola S.;
RT "Ovarian hyperstimulation syndrome due to a mutation in the follicle-
RT stimulating hormone receptor.";
RL N. Engl. J. Med. 349:760-766(2003).
RN [33]
RP VARIANT OHSS ALA-449, AND CHARACTERIZATION OF VARIANT OHSS ALA-449.
RX PubMed=15080154; DOI=10.1210/jc.2003-031910;
RA Montanelli L., Delbaere A., Di Carlo C., Nappi C., Smits G., Vassart G.,
RA Costagliola S.;
RT "A mutation in the follicle-stimulating hormone receptor as a cause of
RT familial spontaneous ovarian hyperstimulation syndrome.";
RL J. Clin. Endocrinol. Metab. 89:1255-1258(2004).
RN [34]
RP VARIANT OHSS THR-545, AND CHARACTERIZATION OF VARIANT OHSS THR-545.
RX PubMed=16278261; DOI=10.1210/jc.2005-1580;
RA De Leener A., Montanelli L., Van Durme J., Chae H., Smits G., Vassart G.,
RA Costagliola S.;
RT "Presence and absence of follicle-stimulating hormone receptor mutations
RT provide some insights into spontaneous ovarian hyperstimulation syndrome
RT physiopathology.";
RL J. Clin. Endocrinol. Metab. 91:555-562(2006).
RN [35]
RP VARIANT OHSS TYR-128, AND CHARACTERIZATION OF VARIANT OHSS TYR-128.
RX PubMed=17721928; DOI=10.1002/humu.20604;
RA De Leener A., Caltabiano G., Erkan S., Idil M., Vassart G., Pardo L.,
RA Costagliola S.;
RT "Identification of the first germline mutation in the extracellular domain
RT of the follitropin receptor responsible for spontaneous ovarian
RT hyperstimulation syndrome.";
RL Hum. Mutat. 29:91-98(2008).
RN [36]
RP VARIANT OHSS ILE-512, CHARACTERIZATION OF VARIANT OHSS ILE-512, AND
RP FUNCTION.
RX PubMed=24058690; DOI=10.1371/journal.pone.0075478;
RA Uchida S., Uchida H., Maruyama T., Kajitani T., Oda H., Miyazaki K.,
RA Kagami M., Yoshimura Y.;
RT "Molecular analysis of a mutated FSH receptor detected in a patient with
RT spontaneous ovarian hyperstimulation syndrome.";
RL PLoS ONE 8:E75478-E75478(2013).
RN [37]
RP VARIANTS OHSS ALA-514 AND VAL-575, AND CHARACTERIZATION OF VARIANTS OHSS
RP ALA-514 AND VAL-575.
RX PubMed=25581598; DOI=10.1210/jc.2014-3662;
RA Desai S.S., Achrekar S.K., Sahasrabuddhe K.A., Meharji P.K., Desai S.K.,
RA Mangoli V.S., Mahale S.D.;
RT "Functional characterization of two naturally occurring mutations
RT (Val514Ala and Ala575Val) in follicle-stimulating hormone receptor.";
RL J. Clin. Endocrinol. Metab. 100:E638-E645(2015).
CC -!- FUNCTION: G protein-coupled receptor for follitropin, the follicle-
CC stimulating hormone (PubMed:11847099, PubMed:24058690,
CC PubMed:24692546). Through cAMP production activates the downstream
CC PI3K-AKT and ERK1/ERK2 signaling pathways (PubMed:24058690).
CC {ECO:0000269|PubMed:11847099, ECO:0000269|PubMed:24058690,
CC ECO:0000269|PubMed:24692546}.
CC -!- SUBUNIT: Homotrimer. Functions as a homotrimer binding the FSH hormone
CC heterodimer composed of CGA and FSHB (PubMed:24692546). Interacts with
CC ARRB2 (By similarity). Interacts with APPL2; interaction is independent
CC of follicle stimulating hormone stimulation (PubMed:17030088).
CC {ECO:0000250|UniProtKB:P20395, ECO:0000269|PubMed:17030088,
CC ECO:0000269|PubMed:24692546}.
CC -!- INTERACTION:
CC P23945; P27348: YWHAQ; NbExp=4; IntAct=EBI-848239, EBI-359854;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11847099,
CC ECO:0000269|PubMed:24692546}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=Long; Synonyms=R1;
CC IsoId=P23945-1; Sequence=Displayed;
CC Name=Short; Synonyms=E9Del;
CC IsoId=P23945-2; Sequence=VSP_001953;
CC Name=3; Synonyms=E6Del;
CC IsoId=P23945-3; Sequence=VSP_043181;
CC Name=4; Synonyms=E8'Inc;
CC IsoId=P23945-4; Sequence=VSP_053411;
CC -!- TISSUE SPECIFICITY: Sertoli cells and ovarian granulosa cells.
CC -!- PTM: Sulfated. {ECO:0000269|PubMed:11847099}.
CC -!- PTM: N-glycosylated; indirectly required for FSH-binding, possibly via
CC a conformational change that allows high affinity binding of hormone.
CC {ECO:0000250|UniProtKB:P20395}.
CC -!- DISEASE: Ovarian dysgenesis 1 (ODG1) [MIM:233300]: An autosomal
CC recessive disease characterized by primary amenorrhea, variable
CC development of secondary sex characteristics, poorly developed streak
CC ovaries, and high serum levels of follicle-stimulating hormone (FSH)
CC and luteinizing hormone (LH). {ECO:0000269|PubMed:10551778,
CC ECO:0000269|PubMed:11889179, ECO:0000269|PubMed:12571157,
CC ECO:0000269|PubMed:12915623, ECO:0000269|PubMed:7553856,
CC ECO:0000269|PubMed:9769327, ECO:0000269|PubMed:9851774}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Ovarian hyperstimulation syndrome (OHSS) [MIM:608115]:
CC Disorder which occurs either spontaneously or most often as an
CC iatrogenic complication of ovarian stimulation treatments for in vitro
CC fertilization. The clinical manifestations vary from abdominal
CC distention and discomfort to potentially life-threatening, massive
CC ovarian enlargement and capillary leak with fluid sequestration.
CC Pathologic features of this syndrome include the presence of multiple
CC serous and hemorrhagic follicular cysts lined by luteinized cells, a
CC condition called hyperreactio luteinalis. {ECO:0000269|PubMed:12930927,
CC ECO:0000269|PubMed:12930928, ECO:0000269|PubMed:15080154,
CC ECO:0000269|PubMed:16278261, ECO:0000269|PubMed:17721928,
CC ECO:0000269|PubMed:24058690, ECO:0000269|PubMed:25581598}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC FSH/LSH/TSH subfamily. {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=Sequence-structure-function-analysis of glycoprotein
CC hormone receptors;
CC URL="http://www.ssfa-gphr.de/";
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DR EMBL; M65085; AAA52477.1; -; mRNA.
DR EMBL; M95489; AAA52478.1; -; mRNA.
DR EMBL; S59900; AAB26480.1; -; mRNA.
DR EMBL; JN003607; AEI86722.1; -; mRNA.
DR EMBL; AY429104; AAR07899.1; -; mRNA.
DR EMBL; AK292562; BAF85251.1; -; mRNA.
DR EMBL; AC007189; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079394; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092533; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAX00188.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00189.1; -; Genomic_DNA.
DR EMBL; BC096831; AAH96831.1; -; mRNA.
DR EMBL; BC118548; AAI18549.1; -; mRNA.
DR EMBL; BC125270; AAI25271.1; -; mRNA.
DR EMBL; X68044; CAA48179.1; -; mRNA.
DR EMBL; S73199; AAB32071.1; -; Genomic_DNA.
DR EMBL; S73526; AAB32225.1; -; Genomic_DNA.
DR CCDS; CCDS1843.1; -. [P23945-1]
DR CCDS; CCDS1844.2; -. [P23945-3]
DR PIR; I57661; QRHUFT.
DR RefSeq; NP_000136.2; NM_000145.3.
DR RefSeq; NP_852111.2; NM_181446.2.
DR PDB; 1XWD; X-ray; 2.92 A; C/F=17-268.
DR PDB; 4AY9; X-ray; 2.50 A; X/Y/Z=17-366.
DR PDB; 4MQW; X-ray; 2.90 A; X/Y/Z=16-366.
DR PDBsum; 1XWD; -.
DR PDBsum; 4AY9; -.
DR PDBsum; 4MQW; -.
DR AlphaFoldDB; P23945; -.
DR SMR; P23945; -.
DR BioGRID; 108770; 36.
DR DIP; DIP-35605N; -.
DR IntAct; P23945; 21.
DR MINT; P23945; -.
DR STRING; 9606.ENSP00000384708; -.
DR BindingDB; P23945; -.
DR ChEMBL; CHEMBL2024; -.
DR DrugBank; DB00097; Choriogonadotropin alfa.
DR DrugBank; DB09066; Corifollitropin alfa.
DR DrugBank; DB00066; Follitropin.
DR DrugBank; DB00032; Menotropins.
DR DrugBank; DB04786; Suramin.
DR DrugBank; DB00094; Urofollitropin.
DR DrugCentral; P23945; -.
DR GuidetoPHARMACOLOGY; 253; -.
DR TCDB; 9.A.14.1.5; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P23945; 4 sites.
DR iPTMnet; P23945; -.
DR PhosphoSitePlus; P23945; -.
DR BioMuta; FSHR; -.
DR DMDM; 311033420; -.
DR MassIVE; P23945; -.
DR PaxDb; P23945; -.
DR PeptideAtlas; P23945; -.
DR PRIDE; P23945; -.
DR Antibodypedia; 15300; 706 antibodies from 36 providers.
DR DNASU; 2492; -.
DR Ensembl; ENST00000304421.8; ENSP00000306780.4; ENSG00000170820.12.
DR GeneID; 2492; -.
DR KEGG; hsa:2492; -.
DR UCSC; uc002rww.4; human.
DR UCSC; uc010fbn.4; human. [P23945-1]
DR CTD; 2492; -.
DR DisGeNET; 2492; -.
DR GeneCards; FSHR; -.
DR HGNC; HGNC:3969; FSHR.
DR HPA; ENSG00000170820; Tissue enhanced (ovary, testis).
DR MalaCards; FSHR; -.
DR MIM; 136435; gene.
DR MIM; 233300; phenotype.
DR MIM; 608115; phenotype.
DR neXtProt; NX_P23945; -.
DR Orphanet; 243; 46,XX gonadal dysgenesis.
DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR Orphanet; 64739; Ovarian hyperstimulation syndrome.
DR PharmGKB; PA28386; -.
DR VEuPathDB; HostDB:ENSG00000170820; -.
DR eggNOG; KOG2087; Eukaryota.
DR HOGENOM; CLU_006130_1_1_1; -.
DR InParanoid; P23945; -.
DR OrthoDB; 257031at2759; -.
DR PhylomeDB; P23945; -.
DR TreeFam; TF316814; -.
DR PathwayCommons; P23945; -.
DR Reactome; R-HSA-375281; Hormone ligand-binding receptors.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P23945; -.
DR SIGNOR; P23945; -.
DR BioGRID-ORCS; 2492; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; FSHR; human.
DR EvolutionaryTrace; P23945; -.
DR GeneWiki; Follicle-stimulating_hormone_receptor; -.
DR GenomeRNAi; 2492; -.
DR Pharos; P23945; Tclin.
DR PRO; PR:P23945; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P23945; protein.
DR Bgee; ENSG00000170820; Expressed in lower esophagus mucosa and 70 other tissues.
DR ExpressionAtlas; P23945; baseline and differential.
DR Genevisible; P23945; HS.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:UniProtKB.
DR GO; GO:0004963; F:follicle-stimulating hormone receptor activity; IDA:UniProtKB.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IMP:UniProtKB.
DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc.
DR GO; GO:0008585; P:female gonad development; TAS:ProtInc.
DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0008406; P:gonad development; TAS:ProtInc.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0008584; P:male gonad development; IEP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
DR GO; GO:0010738; P:regulation of protein kinase A signaling; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; TAS:ProtInc.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR002272; FSH_rcpt.
DR InterPro; IPR024635; GnHR_TM.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR002131; Gphrmn_rcpt_fam.
DR InterPro; IPR026906; LRR_5.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR PANTHER; PTHR24372:SF5; PTHR24372:SF5; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF12369; GnHR_trans; 1.
DR Pfam; PF13306; LRR_5; 2.
DR Pfam; PF01462; LRRNT; 1.
DR PRINTS; PR01143; FSHRECEPTOR.
DR PRINTS; PR00373; GLYCHORMONER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM00013; LRRNT; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disease variant;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Leucine-rich repeat; Membrane; Receptor; Reference proteome; Repeat;
KW Signal; Sulfation; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..695
FT /note="Follicle-stimulating hormone receptor"
FT /id="PRO_0000012771"
FT TOPO_DOM 18..366
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 367..387
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 388..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 399..421
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 422..443
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 444..465
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 466..485
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 486..508
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 509..528
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 529..550
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 551..573
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 574..597
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 598..608
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 609..630
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 631..695
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 18..46
FT /note="LRRNT"
FT REPEAT 49..72
FT /note="LRR 1"
FT REPEAT 73..97
FT /note="LRR 2"
FT REPEAT 98..118
FT /note="LRR 3"
FT REPEAT 119..143
FT /note="LRR 4"
FT REPEAT 144..169
FT /note="LRR 5"
FT REPEAT 170..192
FT /note="LRR 6"
FT REPEAT 193..216
FT /note="LRR 7"
FT REPEAT 217..240
FT /note="LRR 8"
FT REPEAT 241..259
FT /note="LRR 9"
FT MOD_RES 335
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000305|PubMed:11847099"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15662415,
FT ECO:0000269|PubMed:24692546, ECO:0007744|PDB:4MQW"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 18..25
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:15662415, ECO:0000269|PubMed:24692546,
FT ECO:0007744|PDB:4MQW"
FT DISULFID 23..32
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:15662415, ECO:0000269|PubMed:24692546,
FT ECO:0007744|PDB:4MQW"
FT DISULFID 275..346
FT /evidence="ECO:0000269|PubMed:24692546,
FT ECO:0007744|PDB:4MQW"
FT DISULFID 276..356
FT /evidence="ECO:0000269|PubMed:24692546,
FT ECO:0007744|PDB:4MQW"
FT DISULFID 276..292
FT /evidence="ECO:0000269|PubMed:24692546,
FT ECO:0007744|PDB:4MQW"
FT DISULFID 292..338
FT /evidence="ECO:0000269|PubMed:24692546,
FT ECO:0007744|PDB:4MQW"
FT DISULFID 442..517
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 149..174
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043181"
FT VAR_SEQ 223
FT /note="L -> LNRRTRTPTEPNVLLAKYPSGQGVLEEPESLSSSI (in isoform
FT 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_053411"
FT VAR_SEQ 224..285
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:1359889"
FT /id="VSP_001953"
FT VARIANT 128
FT /note="S -> Y (in OHSS; displays increase in affinity and
FT sensitivity toward hCG and does not show any constitutive
FT activity nor promiscuous activation by TSH;
FT dbSNP:rs121909665)"
FT /evidence="ECO:0000269|PubMed:17721928"
FT /id="VAR_039279"
FT VARIANT 160
FT /note="I -> T (in ODG1; impairs cell surface expression)"
FT /evidence="ECO:0000269|PubMed:9769327"
FT /id="VAR_018045"
FT VARIANT 189
FT /note="A -> V (in ODG1; very frequent in the Finnish
FT population)"
FT /evidence="ECO:0000269|PubMed:7553856,
FT ECO:0000269|PubMed:9851774"
FT /id="VAR_018046"
FT VARIANT 224
FT /note="D -> V (in ODG1; FSH binding is barely detectable;
FT impaired targeting to the cell membrane; adenylate cyclase
FT stimulation by FSH is 4 +-2% residual activity)"
FT /evidence="ECO:0000269|PubMed:10551778"
FT /id="VAR_039280"
FT VARIANT 307
FT /note="A -> T (in dbSNP:rs6165)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:12059813, ECO:0000269|PubMed:1301382,
FT ECO:0000269|PubMed:1322283, ECO:0000269|PubMed:1359889,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7916967, ECO:0000269|Ref.5"
FT /id="VAR_013903"
FT VARIANT 348
FT /note="P -> R (in ODG1)"
FT /evidence="ECO:0000269|PubMed:12571157"
FT /id="VAR_039281"
FT VARIANT 419
FT /note="A -> T (in ODG1)"
FT /evidence="ECO:0000269|PubMed:11889179"
FT /id="VAR_018047"
FT VARIANT 449
FT /note="T -> A (in OHSS; increase of receptor sensitivity to
FT both hCG and TSH together with an increase in basal
FT activity)"
FT /evidence="ECO:0000269|PubMed:15080154"
FT /id="VAR_039282"
FT VARIANT 449
FT /note="T -> I (in OHSS; dbSNP:rs28928870)"
FT /evidence="ECO:0000269|PubMed:12930927"
FT /id="VAR_017244"
FT VARIANT 512
FT /note="M -> I (in OHSS; inhibits activation of PI3K/AKT
FT signaling pathway; reduces cAMP production; no effect on
FT ERK1/2 signaling pathway activation)"
FT /evidence="ECO:0000269|PubMed:24058690"
FT /id="VAR_074535"
FT VARIANT 514
FT /note="V -> A (in OHSS; increases cell surface expression;
FT no effect on hormone binding; increases signaling
FT activity)"
FT /evidence="ECO:0000269|PubMed:25581598"
FT /id="VAR_074536"
FT VARIANT 519
FT /note="P -> T (in ODG1; totally impairs adenylate cyclase
FT stimulation in vitro; alters the cell surface targeting of
FT the receptor which remains trapped intracellularly)"
FT /evidence="ECO:0000269|PubMed:12915623"
FT /id="VAR_039283"
FT VARIANT 524
FT /note="S -> R (in dbSNP:rs6167)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_013904"
FT VARIANT 545
FT /note="I -> T (in OHSS; displays promiscuous activation by
FT both hCG and TSH together with detectable constitutive
FT activity)"
FT /evidence="ECO:0000269|PubMed:16278261"
FT /id="VAR_039284"
FT VARIANT 567
FT /note="D -> G (activating mutation resulting in 1.5-fold
FT increase in basal cAMP production compared to the wild-type
FT receptor)"
FT /evidence="ECO:0000269|PubMed:8636335"
FT /id="VAR_039285"
FT VARIANT 567
FT /note="D -> N (in OHSS; dbSNP:rs28928871)"
FT /evidence="ECO:0000269|PubMed:12930928"
FT /id="VAR_017245"
FT VARIANT 573
FT /note="R -> C (in ODG1; alters signal transduction of the
FT receptor; adenylate cyclase stimulation by FSH is 24 +-4%
FT residual activity)"
FT /evidence="ECO:0000269|PubMed:10551778,
FT ECO:0000269|PubMed:9769327"
FT /id="VAR_018048"
FT VARIANT 575
FT /note="A -> V (in OHSS; decreases cell surface expression;
FT no effect on hormone binding; increases levels of
FT internalized hormone receptor complex; cAMP levels are
FT similar to basal levels even at high doses of FSH
FT stimulation indicating reduced signaling)"
FT /evidence="ECO:0000269|PubMed:25581598"
FT /id="VAR_074537"
FT VARIANT 591
FT /note="F -> S (in ovarian sex cord tumor; loss of
FT function)"
FT /evidence="ECO:0000269|PubMed:9100567"
FT /id="VAR_018049"
FT VARIANT 601
FT /note="L -> V (in ODG1; binds FSH with a similar affinity
FT than the wild-type receptor; adenylate cyclase stimulation
FT by FSH is 12 +-3% residual activity)"
FT /evidence="ECO:0000269|PubMed:10551778"
FT /id="VAR_039286"
FT VARIANT 680
FT /note="N -> S (associated with longer menstrual cycles;
FT dbSNP:rs6166)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:12059813, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15815621, ECO:0000269|PubMed:1709010,
FT ECO:0000269|PubMed:7916967, ECO:0000269|Ref.8"
FT /id="VAR_013905"
FT MUTAGEN 330
FT /note="Y->F: No change in intracellular cAMP accumulation."
FT /evidence="ECO:0000269|PubMed:11847099"
FT MUTAGEN 335
FT /note="Y->F: Reduces intracellular cAMP accumulation."
FT /evidence="ECO:0000269|PubMed:11847099"
FT CONFLICT 13
FT /note="S -> R (in Ref. 10; CAA48179)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="N -> T (in Ref. 1; AAA52477)"
FT /evidence="ECO:0000305"
FT CONFLICT 197..198
FT /note="EL -> AV (in Ref. 1; AAA52477)"
FT /evidence="ECO:0000305"
FT CONFLICT 295
FT /note="S -> P (in Ref. 10; CAA48179)"
FT /evidence="ECO:0000305"
FT STRAND 21..26
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 49..55
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:4AY9"
FT TURN 63..68
FT /evidence="ECO:0007829|PDB:1XWD"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:4AY9"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:4MQW"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:1XWD"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:4AY9"
FT TURN 187..192
FT /evidence="ECO:0007829|PDB:4MQW"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:4AY9"
FT TURN 211..216
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:4AY9"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:4AY9"
FT HELIX 272..280
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:4AY9"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:4MQW"
SQ SEQUENCE 695 AA; 78265 MW; 766BC421014CD5A4 CRC64;
MALLLVSLLA FLSLGSGCHH RICHCSNRVF LCQESKVTEI PSDLPRNAIE LRFVLTKLRV
IQKGAFSGFG DLEKIEISQN DVLEVIEADV FSNLPKLHEI RIEKANNLLY INPEAFQNLP
NLQYLLISNT GIKHLPDVHK IHSLQKVLLD IQDNINIHTI ERNSFVGLSF ESVILWLNKN
GIQEIHNCAF NGTQLDELNL SDNNNLEELP NDVFHGASGP VILDISRTRI HSLPSYGLEN
LKKLRARSTY NLKKLPTLEK LVALMEASLT YPSHCCAFAN WRRQISELHP ICNKSILRQE
VDYMTQARGQ RSSLAEDNES SYSRGFDMTY TEFDYDLCNE VVDVTCSPKP DAFNPCEDIM
GYNILRVLIW FISILAITGN IIVLVILTTS QYKLTVPRFL MCNLAFADLC IGIYLLLIAS
VDIHTKSQYH NYAIDWQTGA GCDAAGFFTV FASELSVYTL TAITLERWHT ITHAMQLDCK
VQLRHAASVM VMGWIFAFAA ALFPIFGISS YMKVSICLPM DIDSPLSQLY VMSLLVLNVL
AFVVICGCYI HIYLTVRNPN IVSSSSDTRI AKRMAMLIFT DFLCMAPISF FAISASLKVP
LITVSKAKIL LVLFHPINSC ANPFLYAIFT KNFRRDFFIL LSKCGCYEMQ AQIYRTETSS
TVHNTHPRNG HCSSAPRVTN GSTYILVPLS HLAQN
