FSHR_SHEEP
ID FSHR_SHEEP Reviewed; 695 AA.
AC P35379; Q28573; Q28574; Q9TSI9;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 25-MAY-2022, entry version 136.
DE RecName: Full=Follicle-stimulating hormone receptor;
DE Short=FSH-R;
DE AltName: Full=Follitropin receptor;
DE Flags: Precursor;
GN Name=FSHR;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FSH-R1).
RC TISSUE=Testis;
RX PubMed=8394255; DOI=10.1016/0303-7207(93)90127-6;
RA Yarney T.A., Sairam M.R., Khan H., Ravindranath N., Payne S., Seidah N.G.;
RT "Molecular cloning and expression of the ovine testicular follicle
RT stimulating hormone receptor.";
RL Mol. Cell. Endocrinol. 93:219-226(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS FSH-R4 AND FSH-R3).
RC STRAIN=Dorset-Leicester-Suffolk 1; TISSUE=Testis;
RX PubMed=8439338; DOI=10.1006/bbrc.1993.1132;
RA Khan H., Yarney T.A., Sairam M.R.;
RT "Cloning of alternately spliced mRNA transcripts coding for variants of
RT ovine testicular follitropin receptor lacking the G protein coupling
RT domains.";
RL Biochem. Biophys. Res. Commun. 190:888-894(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FSH-R2), SUBCELLULAR LOCATION (ISOFORMS
RP FSH-R1 AND FSH-R2), AND FUNCTION (ISOFORMS FSH-R1 AND FSH-R2).
RC STRAIN=Dorset-Leicester-Suffolk 1; TISSUE=Testis;
RX PubMed=9364440;
RX DOI=10.1002/(sici)1098-2795(199712)48:4<458::aid-mrd6>3.0.co;2-p;
RA Yarney T.A., Jiang L., Khan H., MacDonald E.A., Laird D.W., Sairam M.R.;
RT "Molecular cloning, structure, and expression of a testicular follitropin
RT receptor with selective alteration in the carboxy terminus that affects
RT signaling function.";
RL Mol. Reprod. Dev. 48:458-470(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE (ISOFORM FSH-R3), SUBCELLULAR LOCATION (ISOFORM
RP FSH-R3), AND FUNCTION (ISOFORM FSH-R3).
RC STRAIN=Dorset-Leicester-Suffolk 1; TISSUE=Ovary;
RX PubMed=10527886; DOI=10.1006/mcbr.1999.0139;
RA Babu P.S., Jiang L., Sairam A.M., Touyz R.M., Sairam M.R.;
RT "Structural features and expression of an alternatively spliced growth
RT factor type I receptor for follitropin signaling in the developing ovary.";
RL Mol. Cell Biol. Res. Commun. 2:21-27(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-51.
RX PubMed=9364442;
RX DOI=10.1002/(sici)1098-2795(199712)48:4<480::aid-mrd8>3.0.co;2-m;
RA Sairam M.R., Subbarayan V.S.R.;
RT "Characterization of the 5' flanking region and potential control elements
RT of the ovine follitropin receptor gene.";
RL Mol. Reprod. Dev. 48:480-487(1997).
CC -!- FUNCTION: G protein-coupled receptor for follitropin, the follicle-
CC stimulating hormone. The activity of isoform FSH-R1 is mediated by G
CC proteins which activate adenylate cyclase (PubMed:10527886,
CC PubMed:9364440). Isoform FSH-R2 and isoform FSH-R3 also bind FSH, but
CC this does not result in activation of adenylate cyclase
CC (PubMed:10527886, PubMed:9364440). Isoform FSH-R3 may be involved in
CC calcium signaling (PubMed:10527886). Through cAMP production activates
CC the downstream PI3K-AKT and ERK1/ERK2 signaling pathways (By
CC similarity). {ECO:0000250|UniProtKB:P23945,
CC ECO:0000269|PubMed:10527886, ECO:0000269|PubMed:9364440}.
CC -!- SUBUNIT: Homotrimer. Functions as a homotrimer binding the FSH hormone
CC heterodimer composed of CGA and FSHB (By similarity). Interacts with
CC ARRB2 (By similarity). Interacts with APPL2; interaction is independent
CC of follicle stimulating hormone stimulation (By similarity).
CC {ECO:0000250|UniProtKB:P20395, ECO:0000250|UniProtKB:P23945}.
CC -!- SUBCELLULAR LOCATION: [Isoform FSH-R1]: Cell membrane; Multi-pass
CC membrane protein {ECO:0000269|PubMed:9364440}.
CC -!- SUBCELLULAR LOCATION: [Isoform FSH-R2]: Cell membrane; Multi-pass
CC membrane protein {ECO:0000269|PubMed:9364440}.
CC -!- SUBCELLULAR LOCATION: [Isoform FSH-R3]: Cell membrane
CC {ECO:0000305|PubMed:10527886}; Single-pass membrane protein
CC {ECO:0000305|PubMed:10527886}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=FSH-R1;
CC IsoId=P35379-1; Sequence=Displayed;
CC Name=FSH-R2;
CC IsoId=P35379-2; Sequence=VSP_001959, VSP_001960;
CC Name=FSH-R3;
CC IsoId=P35379-3; Sequence=VSP_001957, VSP_001958;
CC Name=FSH-R4;
CC IsoId=P35379-4; Sequence=VSP_001955, VSP_001956;
CC -!- TISSUE SPECIFICITY: Isoform FSH-R3 is expressed in ovary and testis,
CC but not in kidney (at protein level). {ECO:0000269|PubMed:9364440}.
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 -!- 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}.
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DR EMBL; L07302; AAA31525.1; -; mRNA.
DR EMBL; L12766; AAA31523.1; -; mRNA.
DR EMBL; L12767; AAA31524.1; -; mRNA.
DR EMBL; L36115; AAK70667.1; -; mRNA.
DR EMBL; AJ131735; CAA10495.1; -; Genomic_DNA.
DR EMBL; AF090438; AAC61749.1; -; Genomic_DNA.
DR PIR; JC1493; JC1493.
DR RefSeq; NP_001009289.1; NM_001009289.1. [P35379-1]
DR AlphaFoldDB; P35379; -.
DR SMR; P35379; -.
DR STRING; 9940.ENSOARP00000004647; -.
DR GeneID; 443299; -.
DR KEGG; oas:443299; -.
DR CTD; 2492; -.
DR eggNOG; KOG2087; Eukaryota.
DR OrthoDB; 257031at2759; -.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISS:UniProtKB.
DR GO; GO:0004963; F:follicle-stimulating hormone receptor activity; IMP:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IMP:UniProtKB.
DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045762; P:positive regulation of adenylate cyclase activity; IMP:UniProtKB.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0010738; P:regulation of protein kinase A signaling; ISS:UniProtKB.
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 Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Leucine-rich repeat; Membrane;
KW Receptor; Reference proteome; Repeat; Signal; Sulfation; Transducer;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..695
FT /note="Follicle-stimulating hormone receptor"
FT /id="PRO_0000012776"
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 48..70
FT /note="LRR 1"
FT REPEAT 71..93
FT /note="LRR 2"
FT REPEAT 96..118
FT /note="LRR 3"
FT REPEAT 121..142
FT /note="LRR 4"
FT REPEAT 143..167
FT /note="LRR 5"
FT REPEAT 171..192
FT /note="LRR 6"
FT REPEAT 194..216
FT /note="LRR 7"
FT REPEAT 219..239
FT /note="LRR 8"
FT REPEAT 240..262
FT /note="LRR 9"
FT MOD_RES 335
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
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 DISULFID 18..25
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 23..32
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 275..346
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT DISULFID 276..356
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT DISULFID 276..292
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT DISULFID 292..338
FT /evidence="ECO:0000250|UniProtKB:P23945"
FT DISULFID 442..517
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 126..133
FT /note="LISNTGIK -> FKRWRNRI (in isoform FSH-R4)"
FT /evidence="ECO:0000303|PubMed:8439338"
FT /id="VSP_001955"
FT VAR_SEQ 135..695
FT /note="Missing (in isoform FSH-R4)"
FT /evidence="ECO:0000303|PubMed:8439338"
FT /id="VSP_001956"
FT VAR_SEQ 224..259
FT /note="DISRTRIRSLPSYGLENLKKLRAKSTYHLKKLPSLE -> SPLLHCWAHLQS
FT FFFVVCGQREHISEFGLKSKQHPN (in isoform FSH-R3)"
FT /evidence="ECO:0000303|PubMed:8439338"
FT /id="VSP_001957"
FT VAR_SEQ 260..695
FT /note="Missing (in isoform FSH-R3)"
FT /evidence="ECO:0000303|PubMed:8439338"
FT /id="VSP_001958"
FT VAR_SEQ 643..670
FT /note="KFGCYEVQAQTYRSETSFTAHNFHPRNG -> LHCCTVGLICNHFSSLFVAR
FT GNIFLNLD (in isoform FSH-R2)"
FT /evidence="ECO:0000303|PubMed:9364440"
FT /id="VSP_001959"
FT VAR_SEQ 671..695
FT /note="Missing (in isoform FSH-R2)"
FT /evidence="ECO:0000303|PubMed:9364440"
FT /id="VSP_001960"
SQ SEQUENCE 695 AA; 78238 MW; FBF75D89D88C0D4B CRC64;
MALFLVALLA FLSLGSGCHH RLCHCSNGVF LCQDSKVTEM PSDLPRDAVE LRFVLTKLRV
IPEGAFSGFG DLEKIEISQN DVLEVIEANV FSNLPKLHEI RIEKANNLLY IDPDAFQNLP
NLRYLLISNT GIKHLPAVHK IQSLQKVLLD IQDNINIHTV ERNSFMGLSF ESMIVWLSKN
GIQEIHNCAF NGTQLDELNL SDNSNLEELP NDVFQGASGP VILDISRTRI RSLPSYGLEN
LKKLRAKSTY HLKKLPSLEK FVTLVEASLT YPSHCCAFAN WRRQTSDLHP ICNKSILRQE
VDDMTQARGQ RISLAEDDEP SYAKGFDMMY SEFDYDLCSE VVDVTCSPEP DAFNPCEDIM
GYDILRVLIW FISILAITGN ILVLVILITS QYKLTVPRFL MCNLAFADLC IGIYLLLIAS
VDVHTKSQYH NYAIDWQTGA GCDAAGFFTV FASELSVYTL TAITLERWHT ITHAMQLECK
VHVRHAASIM LVGWVFAFAV ALFPIFGISS YMKVSICLPM DIDSPLSQLY VMSLLVLNVL
AFVVICGCYT HIYLTVRNPN ITSSSSDTKI AKRMAMLIFT DFLCMAPISF FAISASLKVP
LITVSKSKIL LVLFYPINSC ANPFLYAIFT RNFRRDFFIL LSKFGCYEVQ AQTYRSETSF
TAHNFHPRNG HCPPAPRVTN GSNYTLIPLR HLAKN
