ID FSHR_HUMAN STANDARD; PRT; 695 AA. AC P23945; Q16225; DT 01-MAR-1992 (Rel. 21, Created) DT 01-JUN-1994 (Rel. 29, Last sequence update) DT 24-JAN-2006 (Rel. 49, Last annotation update) DE Follicle-stimulating hormone receptor precursor (FSH-R) (Follitropin DE receptor). GN Name=FSHR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ALA-307 AND SER-680. RC TISSUE=Ovary; RX MEDLINE=91222171; PubMed=1709010; 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. RC TISSUE=Testis; RX MEDLINE=93246012; PubMed=1301382; DOI=10.1016/0303-7207(92)90220-Z; RA Kelton C.A., Cheng S.V., Nugent N.P., Schweickhardt R.L., RA Rosenthal J.L., Overton S.A., Wands G.D., Kuzeja J.B., Luchette C.A., RA Chappel S.C.; RT "The cloning of the human follicle stimulating hormone receptor and RT its expression in COS-7, CHO, and Y-1 cells."; RL Mol. Cell. Endocrinol. 89:141-151(1992). RN [3] RP NUCLEOTIDE SEQUENCE. RX PubMed=1322283; DOI=10.1210/en.131.2.799; RA Tilly J.L., Aihara T., Nishimori K., Jia X.-C., Billig H., RA Kowalski K.I., Perlas E.A., Hsueh A.J.; RT "Expression of recombinant human follicle-stimulating hormone RT receptor: species-specific ligand binding, signal transduction, and RT identification of multiple ovarian messenger ribonucleic acid RT transcripts."; RL Endocrinology 131:799-806(1992). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RA Kopatz S.A., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction RT sequenced by the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE OF 1-342. RC TISSUE=Testis; RX MEDLINE=93075197; PubMed=1359889; RA Gromoll J., Gudermann T., Nieschlag E.; RT "Molecular cloning of a truncated isoform of the human follicle RT stimulating hormone receptor."; RL Biochem. Biophys. Res. Commun. 188:1077-1083(1992). RN [6] RP NUCLEOTIDE SEQUENCE OF 1-51. RX MEDLINE=95011044; 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 [7] RP NUCLEOTIDE SEQUENCE OF 286-695, AND VARIANT SER-680. RX MEDLINE=95000244; PubMed=7916967; RA Gromoll J., Ried T., Holtgreve-Grez H., Nieschlag E., Gudermann T.; RT "Localization of the human FSH receptor to chromosome 2p21 using a RT genomic probe comprising exon 10."; RL J. Mol. Endocrinol. 12:265-271(1994). RN [8] RP 3D-STRUCTURE MODELING OF 49-228. RX MEDLINE=96363672; 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 [9] 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., RA Tapanainen J., Gromoll J., Kaskikari R., Sankila E.-M., RA Lehvaslaiho H., Engel A.R., Nieschlag E., Huhtaniemi I., RA 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 [10] RP VARIANT OVARIAN SEX CORD TUMOR SER-591. RX PubMed=9100567; DOI=10.1210/jc.82.4.1020; 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 RT frequently in human ovarian sex cord tumors."; RL J. Clin. Endocrinol. Metab. 82:1020-1026(1997). RN [11] RP VARIANT ODG1 VAL-189. RX PubMed=9851774; DOI=10.1210/jc.83.12.4338; RA Jiang M., Aittomaeki K., Nilsson C., Pakarinen P., Iitia A., RA Torresani T., Simonsen H., Goh V., Pettersson K., de la Chapelle A., RA Huhtaniemi I.; RT "The frequency of an inactivating point mutation (566C-->T) of the RT human follicle-stimulating hormone receptor gene in four populations RT using allele-specific hybridization and time-resolved fluorometry."; RL J. Clin. Endocrinol. Metab. 83:4338-4343(1998). RN [12] RP VARIANTS ODG1 THR-160 AND CYS-573. RX MEDLINE=98443225; PubMed=9769327; RA Beau I., Touraine P., Meduri G., Gougeon A., Desroches A., RA Matuchansky C., Milgrom E., Kuttenn F., Misrahi M.; RT "A novel phenotype related to partial loss of function mutations of RT the follicle stimulating hormone receptor."; RL J. Clin. Invest. 102:1352-1359(1998). RN [13] RP VARIANTS ALA-307; ARG-524 AND SER-680. RX MEDLINE=99318093; 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 RT of human genes."; RL Nat. Genet. 22:231-238(1999). RN [14] RP ERRATUM. 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 [15] RP VARIANTS ALA-307 AND SER-680. RX MEDLINE=22054685; PubMed=12059813; RX 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 [16] RP VARIANT ODG1 THR-418. RX PubMed=11889179; DOI=10.1210/jc.87.3.1151; 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 RT and causing primary ovarian failure."; RL J. Clin. Endocrinol. Metab. 87:1151-1155(2002). RN [17] RP VARIANT OHSS ILE-449. RX MEDLINE=22812036; PubMed=12930927; DOI=10.1056/NEJMoa030065; RA Vasseur C., Rodien P., Beau I., Desroches A., Gerard C., RA de Poncheville L., Chaplot S., Savagner F., Croue A., Mathieu E., RA Lahlou N., Descamps P., Misrahi M.; RT "A chorionic gonadotropin-sensitive mutation in the follicle- RT stimulating hormone receptor as a cause of familial gestational RT spontaneous ovarian hyperstimulation syndrome."; RL N. Engl. J. Med. 349:753-759(2003). RN [18] RP VARIANT OHSS ASN-567. RX MEDLINE=22812037; 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). CC -!- FUNCTION: Receptor for follicle-stimulating hormone. The activity CC of this receptor is mediated by G proteins which activate CC adenylate cyclase. CC -!- SUBCELLULAR LOCATION: Membrane; multi-pass membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=P23945-1; Sequence=Displayed; CC Name=Short; CC IsoId=P23945-2; Sequence=VSP_001953, VSP_001954; CC -!- TISSUE SPECIFICITY: Sertoli cells and ovarian granulosa cells. CC -!- PTM: N-glycosylated; indirectly required for FSH-binding, possibly CC via a conformational change that allows high affinity binding of CC hormone (By similarity). CC -!- DISEASE: Defects in FSHR are a cause of ovarian dysgenesis 1 CC (ODG1) [MIM:233300]; also known as premature ovarian failure or CC gonadal dysgenesis XX type or XX gonadal dysgenesis (XXGD) or CC hereditary hypergonadotropic ovarian failure or hypergonadotropic CC ovarian dysgenesis with normal karyotype. ODG1 is an autosomal CC recessive disease characterized by primary amenorrhea, variable CC development of secondary sex characteristics, and high serum CC levels of follicle-stimulating hormone (FSH) and luteinizing CC hormone (LH). CC -!- DISEASE: Defects in FSHR are a cause of ovarian hyperstimulation CC syndrome (OHSS) [MIM:608115]. OHSS is a disorder which occurs CC either spontaneously or most often as an iatrogenic complication CC of ovarian stimulation treatments for in vitro fertilization. The CC clinical manifestations vary from abdominal distention and CC discomfort to potentially life-threatening, massive ovarian CC enlargement and capillary leak with fluid sequestration. CC Pathologic features of this syndrome include the presence of CC multiple serous and hemorrhagic follicular cysts lined by CC luteinized cells, a condition called hyperreactio luteinalis. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC FSH/LSH/TSH subfamily. CC -!- SIMILARITY: Contains 5 LRR (leucine-rich) repeats. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M65085; AAA52477.1; -; mRNA. DR EMBL; S59900; AAB26480.1; -; mRNA. DR EMBL; M95489; AAA52478.1; -; mRNA. DR EMBL; AY429104; AAR07899.1; -; mRNA. DR EMBL; X68044; CAA48179.1; -; mRNA. DR EMBL; S73199; AAB32071.1; -; Genomic_DNA. DR EMBL; S73526; AAB32225.1; -; Genomic_DNA. DR PIR; I57661; QRHUFT. DR PDB; 1XUN; Model; @=49-228. DR PDB; 1XWD; X-ray; C/F=17-268. DR Ensembl; ENSG00000170820; Homo sapiens. DR HGNC; HGNC:3969; FSHR. DR MIM; 136435; -. DR MIM; 233300; -. DR MIM; 608115; -. DR GO; GO:0016021; C:integral to membrane; TAS. DR GO; GO:0005886; C:plasma membrane; TAS. DR GO; GO:0004963; F:follicle stimulating hormone receptor activity; TAS. DR GO; GO:0007292; P:female gamete generation; TAS. DR GO; GO:0008585; P:female gonad development; TAS. DR GO; GO:0007186; P:G-protein coupled receptor protein signalin...; TAS. DR GO; GO:0007283; P:spermatogenesis; TAS. DR InterPro; IPR002272; FSH_receptor. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR002131; Gphrmn_receptor. DR InterPro; IPR001611; LRR. DR InterPro; IPR000372; LRR_Nterm. DR PANTHER; PTHR11319:SF8; FSH_receptor; 1. DR Pfam; PF00001; 7tm_1; 1. DR Pfam; PF00560; LRR_1; 3. 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. KW 3D-structure; Alternative splicing; Disease mutation; KW G-protein coupled receptor; Glycoprotein; Leucine-rich repeat; KW Membrane; Phosphorylation; Polymorphism; Receptor; Repeat; Signal; KW Transducer; Transmembrane. FT SIGNAL 1 17 Potential. FT CHAIN 18 695 Follicle-stimulating hormone receptor. FT /FTId=PRO_0000012771. FT TOPO_DOM 18 366 Extracellular (Potential). FT TRANSMEM 367 387 1 (Potential). FT TOPO_DOM 388 398 Cytoplasmic (Potential). FT TRANSMEM 399 421 2 (Potential). FT TOPO_DOM 422 443 Extracellular (Potential). FT TRANSMEM 444 465 3 (Potential). FT TOPO_DOM 466 485 Cytoplasmic (Potential). FT TRANSMEM 486 508 4 (Potential). FT TOPO_DOM 509 528 Extracellular (Potential). FT TRANSMEM 529 550 5 (Potential). FT TOPO_DOM 551 573 Cytoplasmic (Potential). FT TRANSMEM 574 597 6 (Potential). FT TOPO_DOM 598 608 Extracellular (Potential). FT TRANSMEM 609 630 7 (Potential). FT TOPO_DOM 631 695 Cytoplasmic (Potential). FT REPEAT 69 93 LRR 1. FT REPEAT 119 143 LRR 2. FT REPEAT 170 192 LRR 3. FT REPEAT 193 216 LRR 4. FT REPEAT 218 240 LRR 5. FT CARBOHYD 191 191 N-linked (GlcNAc...) (By similarity). FT CARBOHYD 199 199 N-linked (GlcNAc...) (Potential). FT CARBOHYD 293 293 N-linked (GlcNAc...) (By similarity). FT CARBOHYD 318 318 N-linked (GlcNAc...) (Potential). FT DISULFID 442 517 By similarity. FT VARSPLIC 224 285 Missing (in isoform Short). FT /FTId=VSP_001953. FT VARSPLIC 342 695 Missing (in isoform Short). FT /FTId=VSP_001954. FT VARIANT 160 160 I -> T (in ODG1; impairs cell surface FT expression). FT /FTId=VAR_018045. FT VARIANT 189 189 A -> V (in ODG1; very frequent in the FT Finnish population). FT /FTId=VAR_018046. FT VARIANT 307 307 T -> A (in dbSNP:6165). FT /FTId=VAR_013903. FT VARIANT 418 418 I -> T (in ODG1). FT /FTId=VAR_018047. FT VARIANT 449 449 T -> I (in OHSS). FT /FTId=VAR_017244. FT VARIANT 524 524 S -> R (in dbSNP:6167). FT /FTId=VAR_013904. FT VARIANT 567 567 D -> N (in OHSS). FT /FTId=VAR_017245. FT VARIANT 573 573 R -> C (in ODG1; alters signal FT transduction of the receptor). FT /FTId=VAR_018048. FT VARIANT 591 591 F -> S (in ovarian sex cord tumor; loss FT of function). FT /FTId=VAR_018049. FT VARIANT 680 680 N -> S (in dbSNP:6166). FT /FTId=VAR_013905. FT CONFLICT 13 13 S -> R (in Ref. 5). FT CONFLICT 112 112 N -> T (in Ref. 1). FT CONFLICT 197 198 EL -> AV (in Ref. 1). FT CONFLICT 295 295 S -> P (in Ref. 5). FT STRAND 50 52 FT TURN 54 55 FT TURN 59 67 FT STRAND 74 76 FT TURN 78 79 FT TURN 91 93 FT STRAND 99 101 FT TURN 108 110 FT HELIX 113 116 FT TURN 117 117 FT STRAND 124 126 FT HELIX 135 139 FT STRAND 148 150 FT TURN 152 153 FT TURN 155 159 FT HELIX 163 165 FT TURN 166 166 FT STRAND 174 176 FT TURN 178 179 FT TURN 185 191 FT STRAND 197 199 FT TURN 204 208 FT HELIX 212 214 FT TURN 215 216 FT STRAND 222 224 FT TURN 226 227 SQ SEQUENCE 695 AA; 78295 MW; 723B8E71F76D2CD5 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 VDYMTQTRGQ 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 //