Reviewed, UniProtKB/Swiss-Prot P23945 (FSHR_HUMAN)

Names and origin

Protein names

Recommended name:
    Follicle-stimulating hormone receptor
      Short name=FSH-R
Alternative name(s):
    Follitropin receptor

Gene names

Name:	FSHR
Synonyms:	LGR1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	695 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for follicle-stimulating hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Sertoli cells and ovarian granulosa cells.
Post-translational modification	N-glycosylated; indirectly required for FSH-binding, possibly via a conformational change that allows high affinity binding of hormone By similarity.
Involvement in disease	Defects in FSHR are a cause of ovarian dysgenesis 1 (ODG1) [MIM:233300]; also known as premature ovarian failure or gonadal dysgenesis XX type or XX gonadal dysgenesis (XXGD) or hereditary hypergonadotropic ovarian failure or hypergonadotropic ovarian dysgenesis with normal karyotype. ODG1 is an autosomal recessive disease characterized by primary amenorrhea, variable development of secondary sex characteristics, and high serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Ref.13 Ref.16 Ref.17 Ref.18 Ref.22 Ref.23 Ref.24 Defects in FSHR are a cause of ovarian hyperstimulation syndrome (OHSS) [MIM:608115]. OHSS is a disorder which occurs either spontaneously or most often as an iatrogenic complication of ovarian stimulation treatments for in vitro fertilization. The clinical manifestations vary from abdominal distention and discomfort to potentially life-threatening, massive ovarian enlargement and capillary leak with fluid sequestration. Pathologic features of this syndrome include the presence of multiple serous and hemorrhagic follicular cysts lined by luteinized cells, a condition called hyperreactio luteinalis. Ref.25 Ref.26 Ref.27 Ref.28 Ref.29
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily. Contains 10 LRR (leucine-rich) repeats.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Leucine-rich repeat Repeat Signal Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Traceable author statement. Source: ProtInc female gamete generation Traceable author statement. Source: ProtInc female gonad development Ref.13 Traceable author statement. Source: ProtInc spermatogenesis Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Traceable author statement. Source: ProtInc plasma membrane Traceable author statement. Source: ProtInc
Molecular function	follicle-stimulating hormone receptor activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
YWHAQ	P27348	3	EBI-848239,EBI-359854

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P23945-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P23945-2)

The sequence of this isoform differs from the canonical sequence as follows:
     224-285: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Potential

Chain

18 – 695

678

Follicle-stimulating hormone receptor

PRO_0000012771

Regions

Topological domain

18 – 366

349

Extracellular Potential

Transmembrane

367 – 387

21

1 Potential

Topological domain

388 – 398

11

Cytoplasmic Potential

Transmembrane

399 – 421

23

2 Potential

Topological domain

422 – 443

22

Extracellular Potential

Transmembrane

444 – 465

22

3 Potential

Topological domain

466 – 485

20

Cytoplasmic Potential

Transmembrane

486 – 508

23

4 Potential

Topological domain

509 – 528

20

Extracellular Potential

Transmembrane

529 – 550

22

5 Potential

Topological domain

551 – 573

23

Cytoplasmic Potential

Transmembrane

574 – 597

24

6 Potential

Topological domain

598 – 608

11

Extracellular Potential

Transmembrane

609 – 630

22

7 Potential

Topological domain

631 – 695

65

Cytoplasmic Potential

Repeat

18 – 48

31

LRR 1

Repeat

49 – 72

24

LRR 2

Repeat

73 – 97

25

LRR 3

Repeat

98 – 118

21

LRR 4

Repeat

119 – 143

25

LRR 5

Repeat

144 – 169

26

LRR 6

Repeat

170 – 192

23

LRR 7

Repeat

193 – 216

24

LRR 8

Repeat

217 – 240

24

LRR 9

Repeat

241 – 259

19

LRR 10

Amino acid modifications

Glycosylation

191

1

N-linked (GlcNAc...) Ref.12

Glycosylation

199

1

N-linked (GlcNAc...) Potential

Glycosylation

293

1

N-linked (GlcNAc...) By similarity

Glycosylation

318

1

N-linked (GlcNAc...) Potential

Disulfide bond

18 ↔ 25

Ref.12

Disulfide bond

23 ↔ 32

Ref.12

Disulfide bond

442 ↔ 517

By similarity

Natural variations

Alternative sequence

224 – 285

62

Missing in isoform Short.

VSP_001953

Natural variant

128

1

S → Y in OHSS; displays increase in affinity and sensitivity toward hCG and does not show any constitutive activity nor promiscuous activation by TSH. Ref.29

VAR_039279

Natural variant

160

1

I → T in ODG1; impairs cell surface expression. Ref.17

VAR_018045

Natural variant

189

1

A → V in ODG1; very frequent in the Finnish population. Ref.13 Ref.16

VAR_018046

Natural variant

224

1

D → V in ODG1; FSH binding is barely detectable; impaired targeting to the cell membrane; adenylate cyclase stimulation by FSH is 4 +-2% residual activity. Ref.18

VAR_039280

Natural variant

307

1

T → A: dbSNP rs6165. Ref.1 Ref.19 Ref.21

VAR_013903

Natural variant

348

1

P → R in ODG1. Ref.23

VAR_039281

Natural variant

419

1

A → T in ODG1. Ref.22

VAR_018047

Natural variant

449

1

T → A in OHSS; increase of receptor sensitivity to both hCG and TSH together with an increase in basal activity. Ref.25 Ref.27

VAR_039282

Natural variant

449

1

T → I in OHSS. dbSNP rs28928870. Ref.25 Ref.27

VAR_017244

Natural variant

519

1

P → T in ODG1; totally impairs adenylate cyclase stimulation in vitro; alters the cell surface targeting of the receptor which remains trapped intracellularly. Ref.24

VAR_039283

Natural variant

524

1

S → R: dbSNP rs6167. Ref.19

VAR_013904

Natural variant

545

1

I → T in OHSS; displays promiscuous activation by both hCG and TSH together with detectable constitutive activity. Ref.28

VAR_039284

Natural variant

567

1

D → G in FSHR activation; 1.5-fold increase in basal cAMP production compared to the wild-type receptor indicating that this mutation leads to ligand-independent constitutive activation.

VAR_039285

Natural variant

567

1

D → N in OHSS. dbSNP rs28928871. Ref.26

VAR_017245

Natural variant

573

1

R → C in ODG1; alters signal transduction of the receptor; adenylate cyclase stimulation by FSH is 24 +-4% residual activity. Ref.17 Ref.18

VAR_018048

Natural variant

591

1

F → S in ovarian sex cord tumor; loss of function. Ref.14

VAR_018049

Natural variant

601

1

L → V in ODG1; binds FSH with a similar affinity than the wild-type receptor; adenylate cyclase stimulation by FSH is 12 +-3% residual activity. Ref.18

VAR_039286

Natural variant

680

1

N → S Associated with longer menstrual cycles. dbSNP rs6166. Ref.1 Ref.19 Ref.21 Ref.10

VAR_013905

Experimental info

Sequence conflict

13

1

S → R in CAA48179. Ref.8

Sequence conflict

112

1

N → T in AAA52477. Ref.1

Sequence conflict

197 – 198

2

EL → AV in AAA52477. Ref.1

Sequence conflict

295

1

S → P in CAA48179. Ref.8

Secondary structure

1

.

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695

Helix Strand Turn

Details...

Beta strand

21 – 25

5

Beta strand

27 – 34

8

Beta strand

49 – 55

7

Turn

63 – 68

6

Beta strand

74 – 79

6

Beta strand

88 – 93

6

Beta strand

99 – 103

5

Beta strand

115 – 117

3

Beta strand

124 – 129

6

Beta strand

143 – 145

3

Beta strand

147 – 153

7

Beta strand

168 – 171

4

Beta strand

173 – 176

4

Turn

187 – 192

6

Beta strand

195 – 199

5

Turn

211 – 216

6

Beta strand

221 – 224

4

Beta strand

235 – 237

3

Beta strand

243 – 253

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified June 1, 1994. Version 2. Checksum: 723B8E71F76D2CD5	FASTA	695	78,295
	10 20 30 40 50 60 MALLLVSLLA FLSLGSGCHH RICHCSNRVF LCQESKVTEI PSDLPRNAIE LRFVLTKLRV 70 80 90 100 110 120 IQKGAFSGFG DLEKIEISQN DVLEVIEADV FSNLPKLHEI RIEKANNLLY INPEAFQNLP 130 140 150 160 170 180 NLQYLLISNT GIKHLPDVHK IHSLQKVLLD IQDNINIHTI ERNSFVGLSF ESVILWLNKN 190 200 210 220 230 240 GIQEIHNCAF NGTQLDELNL SDNNNLEELP NDVFHGASGP VILDISRTRI HSLPSYGLEN 250 260 270 280 290 300 LKKLRARSTY NLKKLPTLEK LVALMEASLT YPSHCCAFAN WRRQISELHP ICNKSILRQE 310 320 330 340 350 360 VDYMTQTRGQ RSSLAEDNES SYSRGFDMTY TEFDYDLCNE VVDVTCSPKP DAFNPCEDIM 370 380 390 400 410 420 GYNILRVLIW FISILAITGN IIVLVILTTS QYKLTVPRFL MCNLAFADLC IGIYLLLIAS 430 440 450 460 470 480 VDIHTKSQYH NYAIDWQTGA GCDAAGFFTV FASELSVYTL TAITLERWHT ITHAMQLDCK 490 500 510 520 530 540 VQLRHAASVM VMGWIFAFAA ALFPIFGISS YMKVSICLPM DIDSPLSQLY VMSLLVLNVL 550 560 570 580 590 600 AFVVICGCYI HIYLTVRNPN IVSSSSDTRI AKRMAMLIFT DFLCMAPISF FAISASLKVP 610 620 630 640 650 660 LITVSKAKIL LVLFHPINSC ANPFLYAIFT KNFRRDFFIL LSKCGCYEMQ AQIYRTETSS 670 680 690 TVHNTHPRNG HCSSAPRVTN GSTYILVPLS HLAQN
	Isoform Short. Checksum: AAE5AC8E8F245430	FASTA	633	71,109
	10 20 30 40 50 60 MALLLVSLLA FLSLGSGCHH RICHCSNRVF LCQESKVTEI PSDLPRNAIE LRFVLTKLRV 70 80 90 100 110 120 IQKGAFSGFG DLEKIEISQN DVLEVIEADV FSNLPKLHEI RIEKANNLLY INPEAFQNLP 130 140 150 160 170 180 NLQYLLISNT GIKHLPDVHK IHSLQKVLLD IQDNINIHTI ERNSFVGLSF ESVILWLNKN 190 200 210 220 230 240 GIQEIHNCAF NGTQLDELNL SDNNNLEELP NDVFHGASGP VILSELHPIC NKSILRQEVD 250 260 270 280 290 300 YMTQTRGQRS SLAEDNESSY SRGFDMTYTE FDYDLCNEVV DVTCSPKPDA FNPCEDIMGY 310 320 330 340 350 360 NILRVLIWFI SILAITGNII VLVILTTSQY KLTVPRFLMC NLAFADLCIG IYLLLIASVD 370 380 390 400 410 420 IHTKSQYHNY AIDWQTGAGC DAAGFFTVFA SELSVYTLTA ITLERWHTIT HAMQLDCKVQ 430 440 450 460 470 480 LRHAASVMVM GWIFAFAAAL FPIFGISSYM KVSICLPMDI DSPLSQLYVM SLLVLNVLAF 490 500 510 520 530 540 VVICGCYIHI YLTVRNPNIV SSSSDTRIAK RMAMLIFTDF LCMAPISFFA ISASLKVPLI 550 560 570 580 590 600 TVSKAKILLV LFHPINSCAN PFLYAIFTKN FRRDFFILLS KCGCYEMQAQ IYRTETSSTV 610 620 630 HNTHPRNGHC SSAPRVTNGS TYILVPLSHL AQN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of human FSH receptor cDNA." Minegish T., Nakamura K., Takakura Y., Ibuki Y., Igarashi M. Biochem. Biophys. Res. Commun. 175:1125-1130(1991) [PubMed: 1709010] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-307 AND SER-680. Tissue: Ovary.
[2]	"Expression of recombinant human follicle-stimulating hormone receptor: species-specific ligand binding, signal transduction, and identification of multiple ovarian messenger ribonucleic acid transcripts." Tilly J.L., Aihara T., Nishimori K., Jia X.-C., Billig H., Kowalski K.I., Perlas E.A., Hsueh A.J. Endocrinology 131:799-806(1992) [PubMed: 1322283] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The cloning of the human follicle stimulating hormone receptor and its expression in COS-7, CHO, and Y-1 cells." Kelton C.A., Cheng S.V., Nugent N.P., Schweickhardt R.L., Rosenthal J.L., Overton S.A., Wands G.D., Kuzeja J.B., Luchette C.A., Chappel S.C. Mol. Cell. Endocrinol. 89:141-151(1992) [PubMed: 1301382] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[4]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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 T.-O., 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Testis.
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., 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 E.A., 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 S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS ALA-307 AND SER-680.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"Molecular cloning of a truncated isoform of the human follicle stimulating hormone receptor." Gromoll J., Gudermann T., Nieschlag E. Biochem. Biophys. Res. Commun. 188:1077-1083(1992) [PubMed: 1359889] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-342 (ISOFORM SHORT). Tissue: Testis.
[9]	"Characterization of the 5' flanking region of the human follicle-stimulating hormone receptor gene." Gromoll J., Dankbar B., Gudermann T. Mol. Cell. Endocrinol. 102:93-102(1994) [PubMed: 7926278] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-51.
[10]	"Localization of the human FSH receptor to chromosome 2p21 using a genomic probe comprising exon 10." Gromoll J., Ried T., Holtgreve-Grez H., Nieschlag E., Gudermann T. J. Mol. Endocrinol. 12:265-271(1994) [PubMed: 7916967] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 286-695, VARIANT SER-680.
[11]	"Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions." Jiang X., Dreano M., Buckler D.R., Cheng S., Ythier A., Wu H., Hendrickson W.A., el Tayar N. Structure 3:1341-1353(1995) [PubMed: 8747461] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 49-228.
[12]	"Structure of human follicle-stimulating hormone in complex with its receptor." Fan Q.R., Hendrickson W.A. Nature 433:269-277(2005) [PubMed: 15662415] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.92 ANGSTROMS) OF 17-268 IN COMPLEX WITH FSHA AND FSHB, DISULFIDE BONDS, GLYCOSYLATION AT ASN-191.
[13]	"Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure." Aittomaeki K., Lucena J.L.D., Pakarinen P., Sistonen P., Tapanainen J., Gromoll J., Kaskikari R., Sankila E.-M., Lehvaslaiho H., Engel A.R., Nieschlag E., Huhtaniemi I., de la Chapelle A. Cell 82:959-968(1995) [PubMed: 7553856] [Abstract] Cited for: VARIANT ODG1 VAL-189.
[14]	"A mutation in the follicle-stimulating hormone receptor occurs frequently in human ovarian sex cord tumors." Kotlar T.J., Young R.H., Albanese C., Crowley W.F. Jr., Scully R.E., Jameson J.L. J. Clin. Endocrinol. Metab. 82:1020-1026(1997) [PubMed: 9100567] [Abstract] Cited for: VARIANT OVARIAN SEX CORD TUMOR SER-591.
[15]	"An activating mutation of the follicle-stimulating hormone receptor autonomously sustains spermatogenesis in a hypophysectomized man." Gromoll J., Simoni M., Nieschlag E. J. Clin. Endocrinol. Metab. 81:1367-1370(1996) [PubMed: 8636335] [Abstract] Cited for: VARIANT FSHR ACTIVATION GLY-567, CHARACTERIZATION OF VARIANT FSHR ACTIVATION GLY-567.
[16]	"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." Jiang M., Aittomaeki K., Nilsson C., Pakarinen P., Iitia A., Torresani T., Simonsen H., Goh V., Pettersson K., de la Chapelle A., Huhtaniemi I. J. Clin. Endocrinol. Metab. 83:4338-4343(1998) [PubMed: 9851774] [Abstract] Cited for: VARIANT ODG1 VAL-189.
[17]	"A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor." Beau I., Touraine P., Meduri G., Gougeon A., Desroches A., Matuchansky C., Milgrom E., Kuttenn F., Misrahi M. J. Clin. Invest. 102:1352-1359(1998) [PubMed: 9769327] [Abstract] Cited for: VARIANTS ODG1 THR-160 AND CYS-573.
[18]	"New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype." Touraine P., Beau I., Gougeon A., Meduri G., Desroches A., Pichard C., Detoeuf M., Paniel B., Prieur M., Zorn J.-R., Milgrom E., Kuttenn F., Misrahi M. Mol. Endocrinol. 13:1844-1854(1999) [PubMed: 10551778] [Abstract] Cited for: VARIANTS ODG1 VAL-224 AND VAL-601, CHARACTERIZATION OF VARIANTS ODG1 VAL-224; CYS-573 AND VAL-601.
[19]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANTS ALA-307; ARG-524 AND SER-680.
[20]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
[21]	"Distribution and function of FSH receptor genetic variants in normal men." Asatiani K., Gromoll J., Eckardstein S.V., Zitzmann M., Nieschlag E., Simoni M. Andrologia 34:172-176(2002) [PubMed: 12059813] [Abstract] Cited for: VARIANTS ALA-307 AND SER-680.
[22]	"A novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure." Doherty E., Pakarinen P., Tiitinen A., Kiilavuori A., Huhtaniemi I., Forrest S., Aittomaeki K. J. Clin. Endocrinol. Metab. 87:1151-1155(2002) [PubMed: 11889179] [Abstract] Cited for: VARIANT ODG1 THR-419, CHARACTERIZATION OF VARIANT ODG1 THR-419.
[23]	"A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics." Allen L.A., Achermann J.C., Pakarinen P., Kotlar T.J., Huhtaniemi I.T., Jameson J.L., Cheetham T.D., Ball S.G. Hum. Reprod. 18:251-256(2003) [PubMed: 12571157] [Abstract] Cited for: VARIANT ODG1 ARG-348.
[24]	"Delayed puberty and primary amenorrhea associated with a novel mutation of the human follicle-stimulating hormone receptor: clinical, histological, and molecular studies." Meduri G., Touraine P., Beau I., Lahuna O., Desroches A., Vacher-Lavenu M.C., Kuttenn F., Misrahi M. J. Clin. Endocrinol. Metab. 88:3491-3498(2003) [PubMed: 12915623] [Abstract] Cited for: VARIANT ODG1 THR-519, CHARACTERIZATION OF VARIANT ODG1 THR-519.
[25]	"A chorionic gonadotropin-sensitive mutation in the follicle-stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome." 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. N. Engl. J. Med. 349:753-759(2003) [PubMed: 12930927] [Abstract] Cited for: VARIANT OHSS ILE-449.
[26]	"Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor." Smits G., Olatunbosun O., Delbaere A., Pierson R., Vassart G., Costagliola S. N. Engl. J. Med. 349:760-766(2003) [PubMed: 12930928] [Abstract] Cited for: VARIANT OHSS ASN-567.
[27]	"A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome." Montanelli L., Delbaere A., Di Carlo C., Nappi C., Smits G., Vassart G., Costagliola S. J. Clin. Endocrinol. Metab. 89:1255-1258(2004) [PubMed: 15080154] [Abstract] Cited for: VARIANT OHSS ALA-449, CHARACTERIZATION OF VARIANT OHSS ALA-449.
[28]	"Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology." De Leener A., Montanelli L., Van Durme J., Chae H., Smits G., Vassart G., Costagliola S. J. Clin. Endocrinol. Metab. 91:555-562(2006) [PubMed: 16278261] [Abstract] Cited for: VARIANT OHSS THR-545, CHARACTERIZATION OF VARIANT OHSS THR-545.
[29]	"Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome." De Leener A., Caltabiano G., Erkan S., Idil M., Vassart G., Pardo L., Costagliola S. Hum. Mutat. 29:91-98(2008) [PubMed: 17721928] [Abstract] Cited for: VARIANT OHSS TYR-128, CHARACTERIZATION OF VARIANT OHSS TYR-128.
+	Additional computationally mapped references.

Web resources

GRIS

Glycoprotein-hormone Receptors Information System

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBLGenBankDDBJ

M65085 mRNA. Translation: AAA52477.1.
M95489 mRNA. Translation: AAA52478.1.
S59900 mRNA. Translation: AAB26480.1.
AY429104 mRNA. Translation: AAR07899.1.
AK292562 mRNA. Translation: BAF85251.1.
AC007189 Genomic DNA. No translation available.
AC079394 Genomic DNA. Translation: AAX93229.1.
AC092533 Genomic DNA. Translation: AAX88895.1.
BC096831 mRNA. Translation: AAH96831.1.
BC118548 mRNA. Translation: AAI18549.1.
X68044 mRNA. Translation: CAA48179.1.
S73199 Genomic DNA. Translation: AAB32071.1.
S73526 Genomic DNA. Translation: AAB32225.1.

IPI

IPI00303575.
IPI00328365.

PIR

QRHUFT. I57661.

RefSeq

NP_000136.2.
NP_852111.1.

UniGene

Hs.1428

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XUN	model	-	A	49-228	[»]
1XWD	X-ray	2.92	C/F	17-268	[»]

SMR

Q53RW2. Positions 52-125.

ModBase

Search...

Protein-protein interaction databases

IntAct

P23945. 2 interactions.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P23945.

Proteomic databases

PRIDE

P23945.

Genome annotation databases

Ensembl

ENSG00000170820. Homo sapiens. [Contig view]

GeneID

2492.

KEGG

hsa:2492.

Organism-specific databases

GeneCards

GC02M049101.

H-InvDB

HIX0029905.

HGNC

HGNC:3969. FSHR.

MIM

136435. gene.
233300. phenotype.
608115. phenotype.

Orphanet

243. Gonadal dysgenesis, XX type.
64739. Ovarian hyperstimulation syndrome.
619. Premature ovarian failure.

PharmGKB

PA28386.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P23945.

HOVERGEN

P23945.

Enzyme and pathway databases

Reactome

REACT_14797. Signaling by GPCR.

Gene expression databases

ArrayExpress

P23945.

Bgee

P23945.

CleanEx

HS_FSHR.

GermOnline

ENSG00000170820. Homo sapiens.

Family and domain databases

InterPro

IPR000276. 7TM_GPCR_Rhodpsn.
IPR002272. FSH_rcpt.
IPR017452. GPCR_Rhodpsn_supfam.
IPR002131. Gphrmn_rcpt.
IPR001611. Leu-rich_rpt.
IPR000372. Leu-rich_rpt_Cys-rich-reg_N.
[Graphical view]

PANTHER

PTHR23154:SF31. FSH_rcpt. 1 hit.

Pfam

PF00001. 7tm_1. 1 hit.
PF00560. LRR_1. 1 hit.
PF01462. LRRNT. 1 hit.
[Graphical view]

PRINTS

PR01143. FSHRECEPTOR.
PR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.

SMART

SM00013. LRRNT. 1 hit.
[Graphical view]

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00097. Choriogonadotropin alfa.
DB00066. Follitropin beta.
DB00032. Menotropins.
DB00094. Urofollitropin.

NextBio

9843.

SOURCE

Search...

Entry information

Entry name

FSHR_HUMAN

Accession

Primary (citable) accession number: P23945
Secondary accession number(s): A8K947 , Q16225, Q4QRJ3, Q4ZFZ2, Q53RW2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	June 1, 1994
Last modified:	July 7, 2009
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)