FSHR_RAT
ID FSHR_RAT Reviewed; 692 AA.
AC P20395; Q64183;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Follicle-stimulating hormone receptor;
DE Short=FSH-R;
DE AltName: Full=Follitropin receptor;
DE Flags: Precursor;
GN Name=Fshr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Sertoli cell;
RX PubMed=2126341; DOI=10.1210/mend-4-4-525;
RA Sprengel R., Braun T., Nikolics K., Segaloff D.L., Seeburg P.H.;
RT "The testicular receptor for follicle stimulating hormone: structure and
RT functional expression of cloned cDNA.";
RL Mol. Endocrinol. 4:525-530(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1738373; DOI=10.1210/mend.6.1.1738373;
RA Heckert L.L., Daley I.J., Griswold M.D.;
RT "Structural organization of the follicle-stimulating hormone receptor
RT gene.";
RL Mol. Endocrinol. 6:70-80(1992).
RN [3]
RP GLYCOSYLATION AT ASN-191 AND ASN-293, AND MUTAGENESIS OF ASN-191; ASN-199
RP AND ASN-293.
RX PubMed=7776966; DOI=10.1210/mend.9.2.7776966;
RA Davis D., Liu X., Segaloff D.L.;
RT "Identification of the sites of N-linked glycosylation on the follicle-
RT stimulating hormone (FSH) receptor and assessment of their role in FSH
RT receptor function.";
RL Mol. Endocrinol. 9:159-170(1995).
RN [4]
RP INTERACTION WITH ARRB2, AND MUTAGENESIS OF THR-387; SER-389; THR-394;
RP ASP-407 AND TYR-548.
RX PubMed=12850288; DOI=10.1016/s0303-7207(03)00088-1;
RA Krishnamurthy H., Galet C., Ascoli M.;
RT "The association of arrestin-3 with the follitropin receptor depends on
RT receptor activation and phosphorylation.";
RL Mol. Cell. Endocrinol. 204:127-140(2003).
CC -!- FUNCTION: G protein-coupled receptor for follitropin, the follicle-
CC stimulating hormone. Through cAMP production activates the downstream
CC PI3K-AKT and ERK1/ERK2 signaling pathways.
CC {ECO:0000250|UniProtKB:P23945}.
CC -!- SUBUNIT: Homotrimer. Functions as a homotrimer binding the FSH hormone
CC heterodimer composed of CGA and FSHB (By similarity). Interacts with
CC ARRB2 (PubMed:12850288). Interacts with APPL2; interaction is
CC independent of follicle stimulating hormone stimulation (By
CC similarity). {ECO:0000250|UniProtKB:P23945,
CC ECO:0000269|PubMed:12850288}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P23945};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P23945}.
CC -!- TISSUE SPECIFICITY: Sertoli cells and ovarian granulosa cells.
CC -!- PTM: N-glycosylated; indirectly required for FSH-binding, possibly via
CC a conformational change that allows high affinity binding of hormone.
CC {ECO:0000269|PubMed:7776966}.
CC -!- PTM: Sulfated. {ECO:0000250|UniProtKB:P23945}.
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; L02842; AAA41175.1; -; mRNA.
DR EMBL; S81198; AAB21415.2; -; Genomic_DNA.
DR EMBL; S81117; AAB21415.2; JOINED; Genomic_DNA.
DR EMBL; S81119; AAB21415.2; JOINED; Genomic_DNA.
DR EMBL; S81171; AAB21415.2; JOINED; Genomic_DNA.
DR EMBL; S81121; AAB21415.2; JOINED; Genomic_DNA.
DR EMBL; S81174; AAB21415.2; JOINED; Genomic_DNA.
DR EMBL; S81183; AAB21415.2; JOINED; Genomic_DNA.
DR EMBL; S81194; AAB21415.2; JOINED; Genomic_DNA.
DR EMBL; S81185; AAB21415.2; JOINED; Genomic_DNA.
DR EMBL; S81178; AAB21415.2; JOINED; Genomic_DNA.
DR PIR; A34548; A34548.
DR RefSeq; NP_954707.1; NM_199237.1.
DR AlphaFoldDB; P20395; -.
DR SMR; P20395; -.
DR STRING; 10116.ENSRNOP00000022802; -.
DR BindingDB; P20395; -.
DR ChEMBL; CHEMBL4288; -.
DR GlyGen; P20395; 3 sites.
DR iPTMnet; P20395; -.
DR PhosphoSitePlus; P20395; -.
DR PaxDb; P20395; -.
DR Ensembl; ENSRNOT00000022802; ENSRNOP00000022802; ENSRNOG00000016783.
DR GeneID; 25449; -.
DR KEGG; rno:25449; -.
DR UCSC; RGD:2632; rat.
DR CTD; 2492; -.
DR RGD; 2632; Fshr.
DR eggNOG; KOG2087; Eukaryota.
DR GeneTree; ENSGT00940000158952; -.
DR HOGENOM; CLU_006130_1_1_1; -.
DR InParanoid; P20395; -.
DR OMA; GAETQKM; -.
DR OrthoDB; 257031at2759; -.
DR PhylomeDB; P20395; -.
DR TreeFam; TF316814; -.
DR Reactome; R-RNO-375281; Hormone ligand-binding receptors.
DR PRO; PR:P20395; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000016783; Expressed in ovary and 1 other tissue.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISS:UniProtKB.
DR GO; GO:0004963; F:follicle-stimulating hormone receptor activity; IDA:RGD.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:RGD.
DR GO; GO:0017046; F:peptide hormone binding; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0071711; P:basement membrane organization; ISO:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; ISS:UniProtKB.
DR GO; GO:0009992; P:cellular water homeostasis; ISO:RGD.
DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; IDA:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0008584; P:male gonad development; ISO:RGD.
DR GO; GO:0045779; P:negative regulation of bone resorption; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; ISO:RGD.
DR GO; GO:0001541; P:ovarian follicle development; ISO:RGD.
DR GO; GO:0022602; P:ovulation cycle process; ISO:RGD.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0001545; P:primary ovarian follicle growth; ISO:RGD.
DR GO; GO:0060408; P:regulation of acetylcholine metabolic process; ISO:RGD.
DR GO; GO:0033044; P:regulation of chromosome organization; ISO:RGD.
DR GO; GO:0032350; P:regulation of hormone metabolic process; ISO:RGD.
DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; ISO:RGD.
DR GO; GO:0043408; P:regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; ISO:RGD.
DR GO; GO:0010640; P:regulation of platelet-derived growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0010738; P:regulation of protein kinase A signaling; ISS:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; ISO:RGD.
DR GO; GO:0060009; P:Sertoli cell development; ISO:RGD.
DR GO; GO:0060011; P:Sertoli cell proliferation; ISO:RGD.
DR GO; GO:0035092; P:sperm DNA condensation; ISO:RGD.
DR GO; GO:0007286; P:spermatid development; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR GO; GO:0035093; P:spermatogenesis, exchange of chromosomal proteins; ISO:RGD.
DR GO; GO:0045056; P:transcytosis; IDA:RGD.
DR GO; GO:0060065; P:uterus development; ISO:RGD.
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; IPR001611; Leu-rich_rpt.
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.
DR PROSITE; PS51450; LRR; 3.
PE 1: Evidence at protein level;
KW Cell membrane; 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..692
FT /note="Follicle-stimulating hormone receptor"
FT /id="PRO_0000012775"
FT TOPO_DOM 18..365
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 366..386
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 387..397
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 398..420
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 421..442
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..464
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 465..484
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 485..507
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 508..527
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 528..549
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..572
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 573..596
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 597..607
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 608..629
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 630..692
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 334
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7776966"
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:0000269|PubMed:7776966"
FT DISULFID 18..25
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 23..32
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 275..345
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT DISULFID 276..355
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT DISULFID 276..292
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT DISULFID 292..337
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT DISULFID 441..516
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT MUTAGEN 191
FT /note="N->Q: Reduces N-glycosylation level."
FT /evidence="ECO:0000269|PubMed:7776966"
FT MUTAGEN 199
FT /note="N->Q: Does not affect N-glycosylation level."
FT /evidence="ECO:0000269|PubMed:7776966"
FT MUTAGEN 293
FT /note="N->Q: Reduces N-glycosylation level."
FT /evidence="ECO:0000269|PubMed:7776966"
FT MUTAGEN 387
FT /note="T->I: Reduces interaction with ARRB2; when
FT associated with I-389 and N-394."
FT /evidence="ECO:0000269|PubMed:12850288"
FT MUTAGEN 389
FT /note="S->I: Reduces interaction with ARRB2; when
FT associated with I-387 and N-394."
FT /evidence="ECO:0000269|PubMed:12850288"
FT MUTAGEN 394
FT /note="T->N: Reduces interaction with ARRB2; when
FT associated with I-387 and I-389."
FT /evidence="ECO:0000269|PubMed:12850288"
FT MUTAGEN 407
FT /note="D->N: Reduces interaction with ARRB2."
FT /evidence="ECO:0000269|PubMed:12850288"
FT MUTAGEN 548
FT /note="Y->F: Reduces interaction with ARRB2."
FT /evidence="ECO:0000269|PubMed:12850288"
FT CONFLICT 172..175
FT /note="Missing (in Ref. 2; AAB21415)"
FT /evidence="ECO:0000305"
FT CONFLICT 252
FT /note="L -> W (in Ref. 2; AAB21415)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 692 AA; 77681 MW; 267EA78C7CFD8EC6 CRC64;
MALLLVSLLA FLGTGSGCHH WLCHCSNRVF LCQDSKVTEI PTDLPRNAIE LRFVLTKLRV
IPKGSFAGFG DLEKIEISQN DVLEVIEADV FSNLPKLHEI RIEKANNLLY INPEAFQNLP
SLRYLLISNT GIKHLPAVHK IQSLQKVLLD IQDNINIHIV ARNSFMGLSF ESVILWLSKN
GIEEIHNCAF NGTQLDELNL SDNNNLEELP NDVFQGASGP VILDISRTKV HSLPNHGLEN
LKKLRARSTY RLKKLPNLDK FVTLMEASLT YPSHCCAFAN LKRQISELHP ICNKSILRQD
IDDMTQIGDQ RVSLIDDEPS YGKGSDMMYN EFDYDLCNEV VDVTCSPKPD AFNPCEDIMG
YNILRVLIWF ISILAITGNT TVLVVLTTSQ YKLTVPRFLM CNLAFADLCI GIYLLLIASV
DIHTKSQYHN YAIDWQTGAG CDAAGFFTVF ASELSVYTLT AITLERWHTI THAMQLECKV
QLRHAASVMV LGWTFAFAAA LFPIFGISSY MKVSICLPMD IDSPLSQLYV MALLVLNVLA
FVVICGCYTH IYLTVRNPTI VSSSSDTKIA KRMATLIFTD FLCMAPISFF AISASLKVPL
ITVSKAKILL VLFYPINSCA NPFLYAIFTK NFRRDFFILL SKFGCYEMQA QIYRTETSSA
THNFHARKSH CSSAPRVTNS YVLVPLNHSS QN
