TSHR_RAT
ID TSHR_RAT Reviewed; 764 AA.
AC P21463;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Thyrotropin receptor;
DE AltName: Full=Thyroid-stimulating hormone receptor;
DE Short=TSH-R;
DE Flags: Precursor;
GN Name=Tshr;
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], AND FUNCTION.
RX PubMed=1696008; DOI=10.1073/pnas.87.15.5677;
RA Akamizu T., Ikuyama S., Saji M., Kosugi S., Kozak C., McBride O.W.,
RA Kohn L.D.;
RT "Cloning, chromosomal assignment, and regulation of the rat thyrotropin
RT receptor: expression of the gene is regulated by thyrotropin, agents that
RT increase cAMP levels, and thyroid autoantibodies.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5677-5681(1990).
RN [2]
RP MUTAGENESIS OF ALA-623.
RX PubMed=1332945; DOI=10.1016/s0021-9258(18)35740-5;
RA Kosugi S., Okajima F., Ban T., Hidaka A., Shenker A., Kohn L.D.;
RT "Mutation of alanine 623 in the third cytoplasmic loop of the rat
RT thyrotropin (TSH) receptor results in a loss in the phosphoinositide but
RT not cAMP signal induced by TSH and receptor autoantibodies.";
RL J. Biol. Chem. 267:24153-24156(1992).
RN [3]
RP FUNCTION.
RX PubMed=12045258; DOI=10.1172/jci14340;
RA Nakabayashi K., Matsumi H., Bhalla A., Bae J., Mosselman S., Hsu S.Y.,
RA Hsueh A.J.W.;
RT "Thyrostimulin, a heterodimer of two new human glycoprotein hormone
RT subunits, activates the thyroid-stimulating hormone receptor.";
RL J. Clin. Invest. 109:1445-1452(2002).
CC -!- FUNCTION: Receptor for the thyroid-stimulating hormone (TSH) or
CC thyrotropin (PubMed:1696008). Also acts as a receptor for the
CC heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin
CC (PubMed:12045258). The activity of this receptor is mediated by G
CC proteins which activate adenylate cyclase (By similarity). Plays a
CC central role in controlling thyroid cell metabolism (PubMed:12045258).
CC {ECO:0000250|UniProtKB:P16473, ECO:0000269|PubMed:12045258,
CC ECO:0000269|PubMed:1696008}.
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; M34842; AAA42302.1; -; mRNA.
DR PIR; A35956; A35956.
DR RefSeq; NP_037020.1; NM_012888.1.
DR AlphaFoldDB; P21463; -.
DR SMR; P21463; -.
DR IntAct; P21463; 1.
DR STRING; 10116.ENSRNOP00000005671; -.
DR GlyGen; P21463; 5 sites.
DR iPTMnet; P21463; -.
DR PhosphoSitePlus; P21463; -.
DR PaxDb; P21463; -.
DR PRIDE; P21463; -.
DR GeneID; 25360; -.
DR KEGG; rno:25360; -.
DR UCSC; RGD:3911; rat.
DR CTD; 7253; -.
DR RGD; 3911; Tshr.
DR eggNOG; KOG2087; Eukaryota.
DR InParanoid; P21463; -.
DR OrthoDB; 257031at2759; -.
DR PhylomeDB; P21463; -.
DR Reactome; R-RNO-375281; Hormone ligand-binding receptors.
DR PRO; PR:P21463; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
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; IMP: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; ISS:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
DR GO; GO:0030183; P:B cell differentiation; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; ISO:RGD.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0060119; P:inner ear receptor cell development; ISO:RGD.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0040012; P:regulation of locomotion; ISO:RGD.
DR GO; GO:0038194; P:thyroid-stimulating hormone signaling pathway; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 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:SF0; PTHR24372:SF0; 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 PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
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..21
FT CHAIN 22..764
FT /note="Thyrotropin receptor"
FT /id="PRO_0000012788"
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 100..124
FT /note="LRR 1"
FT REPEAT 125..150
FT /note="LRR 2"
FT REPEAT 151..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 REPEAT 264..288
FT /note="LRR 7"
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"
FT MUTAGEN 623
FT /note="A->E,K: Loss of TSH-increased inositol phosphate,
FT but not cAMP formation."
FT /evidence="ECO:0000269|PubMed:1332945"
SQ SEQUENCE 764 AA; 86475 MW; 79FC45CC9D26167B CRC64;
MRPGSLLQLT LLLALPRSLW GRGCTSPPCE CHQEDDFRVT CKELHQIPSL PPSTQTLKLI
ETHLKTIPSL AFSSLPNISR IYLSIDATLQ RLEPHSFYNL SKMTHIEIRN TRSLTYIDPD
ALTELPLLKF LGIFNTGLRI FPDLTKIYST DVFFILEITD NPYMTSVPEN AFQGLCNETL
TLKLYNNGFT SIQGHAFNGT KLDAVYLNKN KYLTAIDKDA FGGVYSGPTL LDVSSTSVTA
LPSKGLEHLK ELIAKNTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM
CNESSIRNLR QRKSVNVMRG PVYQEYEEGL GDNHVGYKQN SKFQEGPSNS HYYVFFEEQE
DEIIGFGQEL KNPQEETLQA FDSHYDYTVC GDNEDMVCTP KSDEFNPCED IMGYKFLRIV
VWFVSPMALL GNVFVLFVLL TSHYKLTVPR FLMCNLAFAD FCMGVYLLLI ASVDLYTHTE
YYNHAIDWQT GPGCNTAGFF TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHAYT
IMAGGWVSCF LLALLPMVGI SSYAKVSICL PMDTDTPLAL AYIALVLLLN VVAFVIVCSC
YVKIYITVRN PQYNPRDKDT KIAKRMAVLI FTDFMCMAPI SFYALSALMN KPLITVTNSG
VLLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGLCK HQAQAYQAQR VCPNNNTGIQ
IQKIPQDTRQ SLPNVQDTYE PLGSSHLTPK LQGRISEEYT QTAL
