ID TSHR_SHEEP Reviewed; 764 AA.
AC P56495;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 1.
DT 24-JAN-2024, entry version 136.
DE RecName: Full=Thyrotropin receptor;
DE AltName: Full=Thyroid-stimulating hormone receptor;
DE Short=TSH-R;
DE Flags: Precursor;
GN Name=TSHR;
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].
RC TISSUE=Pituitary;
RX PubMed=9299474; DOI=10.1006/bbrc.1997.7268;
RA Bockmann J., Winter C., Wittkowski W., Kreutz M.R., Boeckers T.M.;
RT "Cloning and expression of a brain-derived TSH receptor.";
RL Biochem. Biophys. Res. Commun. 238:173-178(1997).
CC -!- FUNCTION: Receptor for the thyroid-stimulating hormone (TSH) or
CC thyrotropin. Also acts as a receptor for the heterodimeric glycoprotein
CC hormone (GPHA2:GPHB5) or thyrostimulin. The activity of this receptor
CC is mediated by G proteins which activate adenylate cyclase. Plays a
CC central role in controlling thyroid cell metabolism.
CC {ECO:0000250|UniProtKB:P16473, ECO:0000250|UniProtKB:P21463}.
CC -!- SUBUNIT: Interacts with heterodimer GPHA2:GPHB5; this interaction
CC stimulates cAMP production. Interacts (via the PDZ-binding motif) with
CC SCRIB; regulates TSHR trafficking and function.
CC {ECO:0000250|UniProtKB:P16473}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P16473};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P16473}. Basolateral
CC cell membrane {ECO:0000250|UniProtKB:P16473}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P16473}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P16473}.
CC -!- PTM: Sulfated. Sulfation on Tyr-385 plays a role in thyrotropin
CC receptor binding and activation. {ECO:0000250|UniProtKB:P16473}.
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; Y13434; CAA73846.1; -; mRNA.
DR PIR; JC5643; JC5643.
DR RefSeq; NP_001009410.1; NM_001009410.1.
DR AlphaFoldDB; P56495; -.
DR SMR; P56495; -.
DR STRING; 9940.ENSOARP00000003068; -.
DR GlyCosmos; P56495; 5 sites, No reported glycans.
DR PaxDb; 9940-ENSOARP00000003068; -.
DR Ensembl; ENSOART00000003128.1; ENSOARP00000003068.1; ENSOARG00000002882.1.
DR Ensembl; ENSOART00020016800; ENSOARP00020013876; ENSOARG00020010887.
DR GeneID; 443428; -.
DR KEGG; oas:443428; -.
DR CTD; 7253; -.
DR eggNOG; KOG2087; Eukaryota.
DR HOGENOM; CLU_006130_1_1_1; -.
DR OMA; TRDMRQS; -.
DR OrthoDB; 1202285at2759; -.
DR Proteomes; UP000002356; Chromosome 7.
DR Bgee; ENSOARG00000002882; Expressed in thyroid gland and 2 other cell types or tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISS:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; ISS:UniProtKB.
DR GO; GO:0004996; F:thyroid-stimulating hormone receptor activity; ISS:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:1904588; P:cellular response to glycoprotein; ISS:UniProtKB.
DR GO; GO:1905229; P:cellular response to thyrotropin-releasing hormone; ISS:UniProtKB.
DR GO; GO:0090103; P:cochlea morphogenesis; IEA:Ensembl.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IEA:Ensembl.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IEA:Ensembl.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0040012; P:regulation of locomotion; IEA:Ensembl.
DR GO; GO:0038194; P:thyroid-stimulating hormone signaling pathway; ISS:UniProtKB.
DR CDD; cd15964; 7tmA_TSH-R; 1.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
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; IPR002274; TSH_rcpt.
DR PANTHER; PTHR24372; GLYCOPROTEIN HORMONE RECEPTOR; 1.
DR PANTHER; PTHR24372:SF0; THYROTROPIN RECEPTOR; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF13306; LRR_5; 2.
DR PRINTS; PR00373; GLYCHORMONER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01145; TSHRECEPTOR.
DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR SUPFAM; SSF52058; L domain-like; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript 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..21
FT /evidence="ECO:0000255"
FT CHAIN 22..764
FT /note="Thyrotropin receptor"
FT /id="PRO_0000012789"
FT TOPO_DOM 22..413
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..441
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 442..450
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..473
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 474..494
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..517
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 518..537
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 538..560
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 561..580
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 581..602
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 603..625
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 626..649
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 650..660
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 661..682
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 683..764
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 51..74
FT /note="LRR 1"
FT REPEAT 125..150
FT /note="LRR 2"
FT REPEAT 152..174
FT /note="LRR 3"
FT REPEAT 176..199
FT /note="LRR 4"
FT REPEAT 201..223
FT /note="LRR 5"
FT REPEAT 225..248
FT /note="LRR 6"
FT MOTIF 762..764
FT /note="PDZ-binding"
FT MOD_RES 385
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P16473"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..41
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 494..569
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 764 AA; 86674 MW; 32423497056FB896 CRC64;
MRPTPLLRLA LLLVLPSSLW GERCPSPPCE CRQEDDFRVT CKDIQRIPSL PPSTQTLKFI
ETHLKTIPSR AFSNLPNISR IYLSIDATLQ QLESHSFYNL SKVTHIEIRN TRSLTYIDSG
ALKELPLLKF LGIFNTGLRV FPDLTKIYST DVFFILEITD NPYMTSVPAN AFQGLSNETL
TLKLYNNGFT SIQGHAFNGT KLDAVYLNKN KYLTVIDQDA FAGVYSGPTL LDISYTSVTA
LPSKGLEHLK ELIARNTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK NIRGILQSLM
CNESSIWGLR QRKSASALNG PFYQEYEEDL GDGSAGYKEN SKFQDTHSNS HYYVFFEDQE
DEIIGFGQEL KNPQEETLQA FDNHYDYTVC GGSEEMVCTP KSDEFNPCED IMGYKFLRIV
VWFVSLLALL GNVFVLVILL TSHYKLTVPR FLMCNLAFAD FCMGLYLLLI ASVDLYTQSE
YYNHAIDWQT GPGCNTAGFF TVFASELSVY TLTVITLERW YAITFAMHLD RKIRLWHAYV
IMLGGWVCCF LLALLPLVGI SSYAKVSICL PMDTETPLAL AYIILVLLLN IIAFIIVCAC
YVKIYITVRN PHYNPGDKDT RIAKRMAVLI FTDFMCMAPI SFYALSALMN KPLITVTNSK
ILLVLFYPLN SCANPFLYAI FTKAFQRDVF MLLSKFGICK RQAQAYRGQR VSSKNSTGIR
VQKVPPDVRQ SLPNVQDDYE LLGNSHLTPK QQDQTSKEYK QTVL
//
