ID A0A0A0MTJ0_HUMAN Unreviewed; 764 AA.
AC A0A0A0MTJ0;
DT 07-JAN-2015, integrated into UniProtKB/TrEMBL.
DT 07-JAN-2015, sequence version 1.
DT 27-MAR-2024, entry version 66.
DE RecName: Full=Thyrotropin receptor {ECO:0000256|ARBA:ARBA00017324, ECO:0000256|RuleBase:RU361222};
GN Name=TSHR {ECO:0000256|RuleBase:RU361222,
GN ECO:0000313|Ensembl:ENSP00000441235.2};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000313|Ensembl:ENSP00000441235.2, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0000313|Ensembl:ENSP00000441235.2, ECO:0000313|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [2] {ECO:0007829|PDB:7T9I, ECO:0007829|PDB:7T9N}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.40 ANGSTROMS) OF 21-764, AND DISULFIDE
RP BONDS.
RX PubMed=35940205; DOI=10.1038/s41586-022-05159-1;
RA Faust B., Billesbolle C.B., Suomivuori C.M., Singh I., Zhang K., Hoppe N.,
RA Pinto A.F.M., Diedrich J.K., Muftuoglu Y., Szkudlinski M.W.,
RA Saghatelian A., Dror R.O., Cheng Y., Manglik A.;
RT "Autoantibody mimicry of hormone action at the thyrotropin receptor.";
RL Nature 609:846-853(2022).
RN [3] {ECO:0000313|Ensembl:ENSP00000441235.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|RuleBase:RU361222}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000256|ARBA:ARBA00004554}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004554}. Cell membrane
CC {ECO:0000256|ARBA:ARBA00004651, ECO:0000256|RuleBase:RU361222}; Multi-
CC pass membrane protein {ECO:0000256|ARBA:ARBA00004651,
CC ECO:0000256|RuleBase:RU361222}. Lateral cell membrane
CC {ECO:0000256|ARBA:ARBA00034693}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00034693}. Membrane
CC {ECO:0000256|ARBA:ARBA00004141}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004141}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC FSH/LSH/TSH subfamily. {ECO:0000256|RuleBase:RU361222}.
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DR EMBL; AC007262; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010582; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136040; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_000360.2; NM_000369.2.
DR RefSeq; XP_005268094.1; XM_005268037.4.
DR PDB; 7T9I; EM; 2.90 A; R=22-764.
DR PDB; 7T9N; EM; 2.90 A; R=22-764.
DR PDB; 7UTZ; EM; 2.40 A; R=21-764.
DR EMDB; EMD-25758; -.
DR EMDB; EMD-25763; -.
DR EMDB; EMD-26795; -.
DR Antibodypedia; 4379; 1253 antibodies from 38 providers.
DR DNASU; 7253; -.
DR Ensembl; ENST00000298171.7; ENSP00000298171.2; ENSG00000165409.18.
DR Ensembl; ENST00000541158.6; ENSP00000441235.2; ENSG00000165409.18.
DR GeneID; 7253; -.
DR KEGG; hsa:7253; -.
DR MANE-Select; ENST00000298171.7; ENSP00000298171.2; NM_000369.5; NP_000360.2.
DR UCSC; uc001xvd.1; human.
DR CTD; 7253; -.
DR HGNC; HGNC:12373; TSHR.
DR VEuPathDB; HostDB:ENSG00000165409; -.
DR GeneTree; ENSGT00940000156510; -.
DR HOGENOM; CLU_006130_1_1_1; -.
DR OMA; TRDMRQS; -.
DR OrthoDB; 1202285at2759; -.
DR BioGRID-ORCS; 7253; 11 hits in 1154 CRISPR screens.
DR ChiTaRS; TSHR; human.
DR GenomeRNAi; 7253; -.
DR Proteomes; UP000005640; Chromosome 14.
DR Bgee; ENSG00000165409; Expressed in left lobe of thyroid gland and 109 other cell types or tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016328; C:lateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004996; F:thyroid-stimulating hormone receptor activity; IEA:Ensembl.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
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 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 1: Evidence at protein level;
KW 3D-structure {ECO:0007829|PDB:7T9I, ECO:0007829|PDB:7T9N};
KW Cell membrane {ECO:0000256|ARBA:ARBA00022475,
KW ECO:0000256|RuleBase:RU361222};
KW G-protein coupled receptor {ECO:0000256|RuleBase:RU361222};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU361222};
KW Proteomics identification {ECO:0007829|PeptideAtlas:A0A0A0MTJ0,
KW ECO:0007829|ProteomicsDB:A0A0A0MTJ0};
KW Receptor {ECO:0000256|ARBA:ARBA00023170, ECO:0000256|RuleBase:RU361222};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Signal {ECO:0000256|RuleBase:RU361222};
KW Transducer {ECO:0000256|ARBA:ARBA00023224, ECO:0000256|RuleBase:RU361222};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW ECO:0000256|RuleBase:RU361222};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|RuleBase:RU361222}.
FT SIGNAL 1..21
FT /evidence="ECO:0000256|RuleBase:RU361222"
FT CHAIN 22..764
FT /note="Thyrotropin receptor"
FT /evidence="ECO:0000256|RuleBase:RU361222"
FT /id="PRO_5013980011"
FT TRANSMEM 419..440
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361222"
FT TRANSMEM 452..477
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361222"
FT TRANSMEM 497..517
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361222"
FT TRANSMEM 538..560
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361222"
FT TRANSMEM 580..606
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361222"
FT TRANSMEM 627..649
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361222"
FT TRANSMEM 661..681
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU361222"
FT DOMAIN 431..678
FT /note="G-protein coupled receptors family 1 profile"
FT /evidence="ECO:0000259|PROSITE:PS50262"
FT DISULFID 24..31
FT /evidence="ECO:0007829|PDB:7T9I, ECO:0007829|PDB:7UTZ"
FT DISULFID 29..41
FT /evidence="ECO:0007829|PDB:7T9I, ECO:0007829|PDB:7UTZ"
FT DISULFID 283..398
FT /evidence="ECO:0007829|PDB:7T9I, ECO:0007829|PDB:7T9N"
FT DISULFID 284..408
FT /evidence="ECO:0007829|PDB:7T9N, ECO:0007829|PDB:7UTZ"
FT DISULFID 301..390
FT /evidence="ECO:0007829|PDB:7T9I, ECO:0007829|PDB:7UTZ"
FT DISULFID 494..569
FT /evidence="ECO:0007829|PDB:7T9I, ECO:0007829|PDB:7T9N"
SQ SEQUENCE 764 AA; 86844 MW; 27EE9CEBFD650D45 CRC64;
MRPADLLQLV LLLDLPRDLG GMGCSSPPCE CHQEEDFRVT CKDIQRIPSL PPSTQTLKLI
ETHLRTIPSH AFSNLPNISR IYVSIDVTLQ QLESHSFYNL SKVTHIEIRN TRNLTYIDPD
ALKELPLLKF LGIFNTGLKM FPDLTKVYST DIFFILEITD NPYMTSIPVN AFQGLCNETL
TLKLYNNGFT SVQGYAFNGT KLDAVYLNKN KYLTVIDKDA FGGVYSGPSL LDVSQTSVTA
LPSKGLEHLK ELIARNTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM
CNESSMQSLR QRKSVNALNS PLHQEYEENL GDSIVGYKEK SKFQDTHNNA HYYVFFEEQE
DEIIGFGQEL KNPQEETLQA FDSHYDYTIC GDSEDMVCTP KSDEFNPCED IMGYKFLRIV
VWFVSLLALL GNVFVLLILL TSHYKLNVPR FLMCNLAFAD FCMGMYLLLI ASVDLYTHSE
YYNHAIDWQT GPGCNTAGFF TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHACA
IMVGGWVCCF LLALLPLVGI SSYAKVSICL PMDTETPLAL AYIVFVLTLN IVAFVIVCCC
YVKIYITVRN PQYNPGDKDT KIAKRMAVLI FTDFICMAPI SFYALSAILN KPLITVSNSK
ILLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGICK RQAQAYRGQR VPPKNSTDIQ
VQKVTHEMRQ GLHNMEDVYE LIENSHLTPK KQGQISEEYM QTVL
//
