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UniProtKB - P16473 (TSHR_HUMAN)

Protein

Thyrotropin receptor

Gene

TSHR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin (PubMed:12045258). The activity of this receptor is mediated by G proteins which activate adenylate cyclase (PubMed:11847099). Plays a central role in controlling thyroid cell metabolism (By similarity).By similarity2 Publications

GO - Molecular functioni

  • G protein-coupled peptide receptor activity Source: GO_Central
  • protein-containing complex binding Source: UniProtKB
  • signaling receptor activity Source: UniProtKB
  • thyroid-stimulating hormone receptor activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-375281 Hormone ligand-binding receptors
R-HSA-418555 G alpha (s) signalling events
SignaLinkiP16473
SIGNORiP16473

Names & Taxonomyi

Protein namesi
Recommended name:
Thyrotropin receptor
Alternative name(s):
Thyroid-stimulating hormone receptor
Short name:
TSH-R
Gene namesi
Name:TSHR
Synonyms:LGR3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000165409.15
HGNCiHGNC:12373 TSHR
MIMi603372 gene+phenotype
neXtProtiNX_P16473

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 413ExtracellularSequence analysisAdd BLAST393
Transmembranei414 – 441Helical; Name=1Sequence analysisAdd BLAST28
Topological domaini442 – 450CytoplasmicSequence analysis9
Transmembranei451 – 473Helical; Name=2Sequence analysisAdd BLAST23
Topological domaini474 – 494ExtracellularSequence analysisAdd BLAST21
Transmembranei495 – 517Helical; Name=3Sequence analysisAdd BLAST23
Topological domaini518 – 537CytoplasmicSequence analysisAdd BLAST20
Transmembranei538 – 560Helical; Name=4Sequence analysisAdd BLAST23
Topological domaini561 – 580ExtracellularSequence analysisAdd BLAST20
Transmembranei581 – 602Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini603 – 625CytoplasmicSequence analysisAdd BLAST23
Transmembranei626 – 649Helical; Name=6Sequence analysisAdd BLAST24
Topological domaini650 – 660ExtracellularSequence analysisAdd BLAST11
Transmembranei661 – 682Helical; Name=7Sequence analysisAdd BLAST22
Topological domaini683 – 764CytoplasmicSequence analysisAdd BLAST82

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in TSHR are found in patients affected by hyperthyroidism with different etiologies. Somatic, constitutively activating TSHR mutations and/or constitutively activating G(s)alpha mutations have been identified in toxic thyroid nodules (TTNs) that are the predominant cause of hyperthyroidism in iodine deficient areas. These mutations lead to TSH independent activation of the cAMP cascade resulting in thyroid growth and hormone production. TSHR mutations are found in autonomously functioning thyroid nodules (AFTN), toxic multinodular goiter (TMNG) and hyperfunctioning thyroid adenomas (HTA). TMNG encompasses a spectrum of different clinical entities, ranging from a single hyperfunctioning nodule within an enlarged thyroid, to multiple hyperfunctioning areas scattered throughout the gland. HTA are discrete encapsulated neoplasms characterized by TSH-independent autonomous growth, hypersecretion of thyroid hormones, and TSH suppression. Defects in TSHR are also a cause of thyroid neoplasms (papillary and follicular cancers).
Autoantibodies against TSHR are directly responsible for the pathogenesis and hyperthyroidism of Graves disease. Antibody interaction with TSHR results in an uncontrolled receptor stimulation.
Hypothyroidism, congenital, non-goitrous, 1 (CHNG1)12 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA non-autoimmune condition characterized by resistance to thyroid-stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. It presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland.
See also OMIM:275200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01151941C → S in CHNG1. 2 Publications1
Natural variantiVAR_011520109R → Q in CHNG1. 1 Publication1
Natural variantiVAR_011521162P → A in CHNG1. 5 PublicationsCorresponds to variant dbSNP:rs121908863EnsemblClinVar.1
Natural variantiVAR_011522167I → N in CHNG1. 1 Publication1
Natural variantiVAR_021495252L → P in CHNG1; displays a low expression at the cell surface and a reduced response to bovine TSH in terms of cAMP production. 1 Publication1
Natural variantiVAR_011524310R → C in CHNG1. 1 Publication1
Natural variantiVAR_011525390C → W in CHNG1; persistent hypothyroidism and defective thyroid development; abolishes high affinity hormone binding. 2 Publications1
Natural variantiVAR_011526410D → N in CHNG1; lack of adenylate cyclase activation. 1 Publication1
Natural variantiVAR_075585432N → D in CHNG1; abolishes cell membrane location; abolishes adenylate cyclase-activating G-protein coupled receptor signaling pathway; abolishes phospholipase C-activating G-protein coupled receptor signaling pathway. 1 Publication1
Natural variantiVAR_075586449P → L in CHNG1; no effect on cell membrane location; upon TSH stimulation decreases more phospholipase C-activating G-protein coupled receptor signaling pathway than adenylate cyclase-activating G-protein coupled receptor signaling pathway. 1 Publication1
Natural variantiVAR_011528450R → H in CHNG1. 1 Publication1
Natural variantiVAR_017295467L → P in CHNG1. 1 Publication1
Natural variantiVAR_017296477T → I in CHNG1; severe hypothyroidism. 1 Publication1
Natural variantiVAR_011533498G → S in CHNG1. 1 Publication1
Natural variantiVAR_011537525F → L in CHNG1; impairs adenylate cyclase activation. 1 Publication1
Natural variantiVAR_011538553A → T in CHNG1; severe hypothyroidism. 2 Publications1
Natural variantiVAR_017297600C → R in CHNG1. 1 Publication1
Familial gestational hyperthyroidism (HTFG)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition characterized by abnormally high levels of serum thyroid hormones occurring during early pregnancy.
See also OMIM:603373
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_003566183K → R in HTFG; enhances receptor response to chorionic gonadotropin. 1 Publication1
Hyperthyroidism, non-autoimmune (HTNA)16 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition characterized by abnormally high levels of serum thyroid hormones, thyroid hyperplasia, goiter and lack of anti-thyroid antibodies. Typical features of Graves disease such as exophthalmia, myxedema, antibodies anti-TSH receptor and lymphocytic infiltration of the thyroid gland are absent.
See also OMIM:609152
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_003570281S → N in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 5 Publications1
Natural variantiVAR_011527431G → S in HTNA; gain of function; constitutive activation of the G(s)/adenylyl cyclase system. 2 Publications1
Natural variantiVAR_011529453M → T in HTNA; sporadic; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 4 Publications1
Natural variantiVAR_011530463M → V in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011531486I → F in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas; also in hyperfunctioning follicular carcinoma. 4 Publications1
Natural variantiVAR_011532486I → M in HTNA; found in hyperfunctioning thyroid adenomas. 3 Publications1
Natural variantiVAR_003571505S → N in HTNA; found in toxic thyroid nodules. 3 Publications1
Natural variantiVAR_011534505S → R in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011535509V → A in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011539568I → T in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 3 Publications1
Natural variantiVAR_021499597V → F in HTNA; 11-fold increase in specific constitutive activity associated with reduction in receptor protein expression. 1 Publication1
Natural variantiVAR_003575629L → F in HTNA; also in hyperfunctioning thyroid adenomas and non-adenomatous nodules. 3 Publications1
Natural variantiVAR_011545631F → L in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 3 Publications1
Natural variantiVAR_011546632T → A in HTNA; found in toxic thyroid nodules and hyperfunctioning non-adenomatous nodules. 3 Publications1
Natural variantiVAR_011547632T → I in HTNA; gain of function; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 7 Publications1
Natural variantiVAR_011549633D → E in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 4 Publications1
Natural variantiVAR_011552639P → S in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011553647A → V in HTNA; found in non-adenomatous hyperfunctioning nodules. 1 Publication1
Natural variantiVAR_011554650N → Y in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011556670N → S in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011557672C → Y in HTNA; gain of function. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi283C → S: Abolishes cell surface expression. 1 Publication1
Mutagenesisi385 – 387YDY → EDE: Inhibits intracellular cAMP accumulation. 1 Publication3
Mutagenesisi385 – 387YDY → FDF: Abolishes sulfation. Inhibits intracellular cAMP accumulation. 1 Publication3
Mutagenesisi385Y → E: Reduces binding with thyrotropin. Inhibits intracellular cAMP accumulation. 1 Publication1 Publication1
Mutagenesisi385Y → F: Reduces sulfation. Reduces binding with thyrotropin. Inhibits intracellular cAMP accumulation. 1 Publication1 Publication1
Mutagenesisi387Y → E: No change in intracellular cAMP accumulation. 1 Publication1
Mutagenesisi387Y → F: Reduces sulfation. No change in intracellular cAMP accumulation. 1 Publication1

Keywords - Diseasei

Congenital hypothyroidism, Disease mutation

Organism-specific databases

DisGeNETi7253
MalaCardsiTSHR
MIMi275200 phenotype
603372 gene+phenotype
603373 phenotype
609152 phenotype
OpenTargetsiENSG00000165409
Orphaneti95713 Athyreosis
99819 Familial gestational hyperthyroidism
424 Familial hyperthyroidism due to mutations in TSH receptor
90673 Hypothyroidism due to TSH receptor mutations
95720 Thyroid hypoplasia
PharmGKBiPA37042

Chemistry databases

ChEMBLiCHEMBL1963
DrugBankiDB00024 Thyrotropin Alfa
GuidetoPHARMACOLOGYi255

Polymorphism and mutation databases

BioMutaiTSHR
DMDMi62298994

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Add BLAST20
ChainiPRO_000001278621 – 764Thyrotropin receptorAdd BLAST744

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 41
Glycosylationi77N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi99N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi113N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi177N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi198N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi302N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei385Sulfotyrosine1 Publication1
Disulfide bondi494 ↔ 569PROSITE-ProRule annotation

Post-translational modificationi

Glycosylated.1 Publication
Sulfated. Sulfation on Tyr-385 plays a role in thyrotropin receptor binding and activation.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Sulfation

Proteomic databases

PaxDbiP16473
PeptideAtlasiP16473
PRIDEiP16473
ProteomicsDBi53374
53375 [P16473-2]

PTM databases

iPTMnetiP16473
PhosphoSitePlusiP16473
SwissPalmiP16473

Expressioni

Tissue specificityi

Expressed in thyroide cells (at protein level) (PubMed:11847099). Expressed in the thyroid (PubMed:2610690).2 Publications

Gene expression databases

BgeeiENSG00000165409 Expressed in 90 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_TSHR
ExpressionAtlasiP16473 baseline and differential
GenevisibleiP16473 HS

Organism-specific databases

HPAiCAB000473

Interactioni

Subunit structurei

Interacts with heterodimer GPHA2:GPHB5; this interaction stimulates cAMP production (PubMed:12045258). Interacts (via the PDZ-binding motif) with SCRIB; regulates TSHR trafficking and function (PubMed:15775968).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SCRIBQ141603EBI-13939599,EBI-357345

Protein-protein interaction databases

BioGridi113104, 30 interactors
IntActiP16473, 2 interactors
STRINGi9606.ENSP00000298171

Chemistry databases

BindingDBiP16473

Structurei

Secondary structure

1764
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP16473
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16473

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati100 – 124LRR 1Add BLAST25
Repeati125 – 150LRR 2Add BLAST26
Repeati152 – 174LRR 3Add BLAST23
Repeati176 – 199LRR 4Add BLAST24
Repeati200 – 223LRR 5Add BLAST24
Repeati227 – 248LRR 6Add BLAST22
Repeati250 – 271LRR 7Add BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi762 – 764PDZ-binding3

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2087 Eukaryota
ENOG410XR1T LUCA
GeneTreeiENSGT00760000119088
HOVERGENiHBG052887
InParanoidiP16473
KOiK04249
PhylomeDBiP16473
TreeFamiTF316814

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR002131 Gphrmn_rcpt_fam
IPR026906 LRR_5
IPR032675 LRR_dom_sf
IPR002274 TSH_rcpt
IPR034298 TSHR/LHCGR/FSHR
PANTHERiPTHR24372 PTHR24372, 1 hit
PTHR24372:SF0 PTHR24372:SF0, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PF13306 LRR_5, 2 hits
PRINTSiPR00373 GLYCHORMONER
PR00237 GPCRRHODOPSN
PR01145 TSHRECEPTOR
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform Long (identifier: P16473-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MRPADLLQLV LLLDLPRDLG GMGCSSPPCE CHQEEDFRVT CKDIQRIPSL 
        60         70         80         90        100
PPSTQTLKLI ETHLRTIPSH AFSNLPNISR IYVSIDVTLQ QLESHSFYNL 
       110        120        130        140        150
SKVTHIEIRN TRNLTYIDPD ALKELPLLKF LGIFNTGLKM FPDLTKVYST 
       160        170        180        190        200
DIFFILEITD NPYMTSIPVN AFQGLCNETL TLKLYNNGFT SVQGYAFNGT 
       210        220        230        240        250
KLDAVYLNKN KYLTVIDKDA FGGVYSGPSL LDVSQTSVTA LPSKGLEHLK 
       260        270        280        290        300
ELIARNTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM 
       310        320        330        340        350
CNESSMQSLR QRKSVNALNS PLHQEYEENL GDSIVGYKEK SKFQDTHNNA 
       360        370        380        390        400
HYYVFFEEQE DEIIGFGQEL KNPQEETLQA FDSHYDYTIC GDSEDMVCTP 
       410        420        430        440        450
KSDEFNPCED IMGYKFLRIV VWFVSLLALL GNVFVLLILL TSHYKLNVPR 
       460        470        480        490        500
FLMCNLAFAD FCMGMYLLLI ASVDLYTHSE YYNHAIDWQT GPGCNTAGFF 
       510        520        530        540        550
TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHACA IMVGGWVCCF 
       560        570        580        590        600
LLALLPLVGI SSYAKVSICL PMDTETPLAL AYIVFVLTLN IVAFVIVCCC 
       610        620        630        640        650
YVKIYITVRN PQYNPGDKDT KIAKRMAVLI FTDFICMAPI SFYALSAILN 
       660        670        680        690        700
KPLITVSNSK ILLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGICK 
       710        720        730        740        750
RQAQAYRGQR VPPKNSTDIQ VQKVTHDMRQ GLHNMEDVYE LIENSHLTPK 
       760 
KQGQISEEYM QTVL
Length:764
Mass (Da):86,830
Last modified:March 29, 2005 - v2
Checksum:iD2EE9CEBFD64A65F
GO
Isoform Short (identifier: P16473-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     232-253: DVSQTSVTALPSKGLEHLKELI → LPLGRKSLSFETQKAPRSSMPS
     254-764: Missing.

Show »
Length:253
Mass (Da):28,427
Checksum:i69E12F0A7D8B5FD0
GO
Isoform 3 (identifier: P16473-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     232-274: DVSQTSVTAL...LSLSFLHLTR → VENVAVSGKG...QKAPRSSMPS
     275-764: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:274
Mass (Da):30,800
Checksum:iA8A8DBB061774F5C
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MTJ0A0A0A0MTJ0_HUMAN
Thyrotropin receptor
TSHR
764Annotation score:
A0A1B0GUJ5A0A1B0GUJ5_HUMAN
Thyrotropin receptor
TSHR
399Annotation score:
Q0VAP8Q0VAP8_HUMAN
TSHR protein
TSHR
231Annotation score:
G3V381G3V381_HUMAN
Thyrotropin receptor
TSHR
112Annotation score:
A0A2R8Y709A0A2R8Y709_HUMAN
Thyrotropin receptor
TSHR
89Annotation score:

Sequence cautioni

The sequence AAA70232 differs from that shown. Reason: Frameshift at positions 130, 135 and 612.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti87V → L no nucleotide entry (PubMed:2610690).Curated1
Sequence conflicti196 – 198AFN → DFF in AAA70232 (PubMed:2293030).Curated3
Sequence conflicti257T → S in AAA70232 (PubMed:2293030).Curated1
Sequence conflicti264P → A in AAA70232 (PubMed:2293030).Curated1
Sequence conflicti306 – 308MQS → IET in AAA70232 (PubMed:2293030).Curated3
Sequence conflicti528R → A in AAA70232 (PubMed:2293030).Curated1
Sequence conflicti601Y → H in AAA36783 (PubMed:2558651).Curated1
Sequence conflicti635I → T in AAA70232 (PubMed:2293030).Curated1
Sequence conflicti645L → V in AAA70232 (PubMed:2293030).Curated1
Sequence conflicti669L → I in AAA70232 (PubMed:2293030).Curated1
Sequence conflicti744N → K in AAA61236 (PubMed:2302212).Curated1
Isoform Short (identifier: P16473-2)
Sequence conflicti239L → F in AAB24246 (PubMed:1445355).Curated1
Sequence conflicti248R → S in AAB23390 (PubMed:1530609).Curated1
Sequence conflicti248R → S in AAH09237 (PubMed:15489334).Curated1
Sequence conflicti248R → S in AAI20974 (PubMed:15489334).Curated1
Sequence conflicti251M → T in AAB23390 (PubMed:1530609).Curated1
Isoform 3 (identifier: P16473-3)
Sequence conflicti269R → S in AAI27629 (PubMed:15489334).Curated1

Polymorphismi

The Asp727Glu polymorphism is associated with Graves disease in a Russian population. The Glu727 allele and the heterozygous Asp727Glu genotype are related to higher risk of the disease. The Asp727Glu polymorphism significantly ameliorates G(s)alpha protein activation in the presence of the gain-of-function mutation Ala593Asn although it is functionally inert in the context of the wild-type TSHR.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05592534E → K. Corresponds to variant dbSNP:rs45499704Ensembl.1
Natural variantiVAR_00356436D → H in a patient with Graves disease. 5 PublicationsCorresponds to variant dbSNP:rs61747482EnsemblClinVar.1
Natural variantiVAR_01151941C → S in CHNG1. 2 Publications1
Natural variantiVAR_00356552P → T Does not contribute to the genetic susceptibility to Graves disease. 7 PublicationsCorresponds to variant dbSNP:rs2234919EnsemblClinVar.1
Natural variantiVAR_011520109R → Q in CHNG1. 1 Publication1
Natural variantiVAR_011521162P → A in CHNG1. 5 PublicationsCorresponds to variant dbSNP:rs121908863EnsemblClinVar.1
Natural variantiVAR_011522167I → N in CHNG1. 1 Publication1
Natural variantiVAR_003566183K → R in HTFG; enhances receptor response to chorionic gonadotropin. 1 Publication1
Natural variantiVAR_003567197F → I in papillary cancer. 1 Publication1
Natural variantiVAR_003568219D → E in papillary cancer. 1 Publication1
Natural variantiVAR_021495252L → P in CHNG1; displays a low expression at the cell surface and a reduced response to bovine TSH in terms of cAMP production. 1 Publication1
Natural variantiVAR_003569281S → I in hyperthyroidism; congenital; due to a toxic adenoma. 1 Publication1
Natural variantiVAR_003570281S → N in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 5 Publications1
Natural variantiVAR_011523281S → T in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication1
Natural variantiVAR_011524310R → C in CHNG1. 1 Publication1
Natural variantiVAR_011525390C → W in CHNG1; persistent hypothyroidism and defective thyroid development; abolishes high affinity hormone binding. 2 Publications1
Natural variantiVAR_011526410D → N in CHNG1; lack of adenylate cyclase activation. 1 Publication1
Natural variantiVAR_021496425S → I Found in toxic thyroid nodules; 8 to 9 times higher levels of basal cAMP than wild-type TSHR and similar response to maximal TSH stimulation. 1 Publication1
Natural variantiVAR_011527431G → S in HTNA; gain of function; constitutive activation of the G(s)/adenylyl cyclase system. 2 Publications1
Natural variantiVAR_075585432N → D in CHNG1; abolishes cell membrane location; abolishes adenylate cyclase-activating G-protein coupled receptor signaling pathway; abolishes phospholipase C-activating G-protein coupled receptor signaling pathway. 1 Publication1
Natural variantiVAR_075586449P → L in CHNG1; no effect on cell membrane location; upon TSH stimulation decreases more phospholipase C-activating G-protein coupled receptor signaling pathway than adenylate cyclase-activating G-protein coupled receptor signaling pathway. 1 Publication1
Natural variantiVAR_011528450R → H in CHNG1. 1 Publication1
Natural variantiVAR_011529453M → T in HTNA; sporadic; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 4 Publications1
Natural variantiVAR_011530463M → V in HTNA; gain of function. 1 Publication1
Natural variantiVAR_017295467L → P in CHNG1. 1 Publication1
Natural variantiVAR_017296477T → I in CHNG1; severe hypothyroidism. 1 Publication1
Natural variantiVAR_011531486I → F in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas; also in hyperfunctioning follicular carcinoma. 4 Publications1
Natural variantiVAR_011532486I → M in HTNA; found in hyperfunctioning thyroid adenomas. 3 Publications1
Natural variantiVAR_011533498G → S in CHNG1. 1 Publication1
Natural variantiVAR_003571505S → N in HTNA; found in toxic thyroid nodules. 3 Publications1
Natural variantiVAR_011534505S → R in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011535509V → A in HTNA; gain of function. 1 Publication1
Natural variantiVAR_021497512L → Q Found in toxic thyroid nodules; 5 times higher levels of basal cAMP than wild-type TSHR and slightly less response to maximal TSH stimulation. 1 Publication1
Natural variantiVAR_011536512L → R in hyperthyroidism; associated with autonomously functioning thyroid nodules; 3.3-fold increase in basal cAMP level. 3 Publications1
Natural variantiVAR_011537525F → L in CHNG1; impairs adenylate cyclase activation. 1 Publication1
Natural variantiVAR_003572528R → H1 Publication1
Natural variantiVAR_011538553A → T in CHNG1; severe hypothyroidism. 2 Publications1
Natural variantiVAR_011539568I → T in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 3 Publications1
Natural variantiVAR_021498593A → N in toxic thyroid adenoma; requires 2 nucleotide substitutions; somatic mutation; constitutively activates the cAMP cascade. 1 Publication1
Natural variantiVAR_021499597V → F in HTNA; 11-fold increase in specific constitutive activity associated with reduction in receptor protein expression. 1 Publication1
Natural variantiVAR_011540597V → L in hyperthyroidism; congenital with severe thyrotoxicosis. 1 Publication1
Natural variantiVAR_017297600C → R in CHNG1. 1 Publication1
Natural variantiVAR_011541606I → M1 Publication1
Natural variantiVAR_003573619D → G in hyperthyroidism; found in toxic thyroid nodules; associated with hyperfunctioning thyroid adenomas. 3 Publications1
Natural variantiVAR_003574623A → I in hyperthyroidism; associated with hyperfunctioning thyroid adenomas; gain of function; requires 2 nucleotide substitutions. 2 Publications1
Natural variantiVAR_011542623A → V in hyperthyroidism; found in toxic thyroid nodules; associated with hyperfunctioning thyroid adenomas; gain of function. 2 Publications1
Natural variantiVAR_003575629L → F in HTNA; also in hyperfunctioning thyroid adenomas and non-adenomatous nodules. 3 Publications1
Natural variantiVAR_011543630I → L in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication1
Natural variantiVAR_011544631F → C in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication1
Natural variantiVAR_011545631F → L in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 3 Publications1
Natural variantiVAR_011546632T → A in HTNA; found in toxic thyroid nodules and hyperfunctioning non-adenomatous nodules. 3 Publications1
Natural variantiVAR_011547632T → I in HTNA; gain of function; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 7 Publications1
Natural variantiVAR_011548633D → A in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication1
Natural variantiVAR_011549633D → E in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 4 Publications1
Natural variantiVAR_011550633D → H in hyperthyroidism; found in toxic thyroid nodules; associated with hyperfunctioning thyroid adenomas; also in hyperfunctioning insular carcinoma; with severe thyrotoxicosis; gain of function. 3 PublicationsCorresponds to variant dbSNP:rs28937584EnsemblClinVar.1
Natural variantiVAR_011551633D → Y in hyperthyroidism; found in toxic thyroid nodules; associated with hyperfunctioning thyroid adenomas. 3 Publications1
Natural variantiVAR_021500639P → A Found in toxic thyroid nodules. 1 Publication1
Natural variantiVAR_011552639P → S in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011553647A → V in HTNA; found in non-adenomatous hyperfunctioning nodules. 1 Publication1
Natural variantiVAR_011554650N → Y in HTNA; gain of function. 1 Publication1
Natural variantiVAR_021501656V → F Found in toxic thyroid nodules. 1 Publication1
Natural variantiVAR_011555658 – 661Missing in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication4
Natural variantiVAR_011556670N → S in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011557672C → Y in HTNA; gain of function. 1 Publication1
Natural variantiVAR_011558677L → V in thyroid carcinoma; with thyrotoxicosis; gain of function. 1 Publication1
Natural variantiVAR_011559703A → G1 Publication1
Natural variantiVAR_003576715N → D in papillary cancer. 1 Publication1
Natural variantiVAR_011560720Q → E1 Publication1
Natural variantiVAR_003577723K → M in papillary cancer. 1 Publication1
Natural variantiVAR_003578727D → E May be a predisposing factor in toxic multinodular goiter pathogenesis; activation of the cAMP cascade does not differ from the wild-type. 7 PublicationsCorresponds to variant dbSNP:rs1991517Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044643232 – 274DVSQT…LHLTR → VENVAVSGKGFCKSLFSWLY RLPLGRKSLSFETQKAPRSS MPS in isoform 3. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_001981232 – 253DVSQT…LKELI → LPLGRKSLSFETQKAPRSSM PS in isoform Short. 3 PublicationsAdd BLAST22
Alternative sequenceiVSP_001982254 – 764Missing in isoform Short. 3 PublicationsAdd BLAST511
Alternative sequenceiVSP_044644275 – 764Missing in isoform 3. 1 PublicationAdd BLAST490

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31774 mRNA Translation: AAA36783.1
M32215 mRNA Translation: AAA61236.1
M73747 mRNA Translation: AAA70232.1 Frameshift.
S45272 mRNA Translation: AAB23390.2
S49816 mRNA Translation: AAB24246.1
AY429111 mRNA Translation: AAR07906.1
AC007262 Genomic DNA Translation: AAD31568.1
AC010072 Genomic DNA Translation: AAF09032.1
AC010582 Genomic DNA Translation: AAF26775.1
AL136040 Genomic DNA No translation available.
BC009237 mRNA Translation: AAH09237.1
BC024205 mRNA Translation: AAH24205.1
BC063613 mRNA Translation: AAH63613.1
BC108653 mRNA Translation: AAI08654.1
BC120973 mRNA Translation: AAI20974.1
BC127628 mRNA Translation: AAI27629.1
BC141970 mRNA Translation: AAI41971.1
CCDSiCCDS32131.1 [P16473-2]
CCDS55935.1 [P16473-3]
CCDS9872.1 [P16473-1]
PIRiA33789 QRHURH
JC1319
T01787
RefSeqiNP_000360.2, NM_000369.2
NP_001018046.1, NM_001018036.2 [P16473-2]
NP_001136098.1, NM_001142626.2 [P16473-3]
XP_005268096.1, XM_005268039.1 [P16473-2]
XP_006720308.1, XM_006720245.1 [P16473-3]
UniGeneiHs.160411

Genome annotation databases

EnsembliENST00000342443; ENSP00000340113; ENSG00000165409 [P16473-2]
ENST00000554435; ENSP00000450549; ENSG00000165409 [P16473-3]
GeneIDi7253
KEGGihsa:7253
UCSCiuc001xvc.4 human [P16473-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

TSH receptor database
SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

TSH receptor entry

Sequence-structure-function-analysis of glycoprotein hormone receptors
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31774 mRNA Translation: AAA36783.1
M32215 mRNA Translation: AAA61236.1
M73747 mRNA Translation: AAA70232.1 Frameshift.
S45272 mRNA Translation: AAB23390.2
S49816 mRNA Translation: AAB24246.1
AY429111 mRNA Translation: AAR07906.1
AC007262 Genomic DNA Translation: AAD31568.1
AC010072 Genomic DNA Translation: AAF09032.1
AC010582 Genomic DNA Translation: AAF26775.1
AL136040 Genomic DNA No translation available.
BC009237 mRNA Translation: AAH09237.1
BC024205 mRNA Translation: AAH24205.1
BC063613 mRNA Translation: AAH63613.1
BC108653 mRNA Translation: AAI08654.1
BC120973 mRNA Translation: AAI20974.1
BC127628 mRNA Translation: AAI27629.1
BC141970 mRNA Translation: AAI41971.1
CCDSiCCDS32131.1 [P16473-2]
CCDS55935.1 [P16473-3]
CCDS9872.1 [P16473-1]
PIRiA33789 QRHURH
JC1319
T01787
RefSeqiNP_000360.2, NM_000369.2
NP_001018046.1, NM_001018036.2 [P16473-2]
NP_001136098.1, NM_001142626.2 [P16473-3]
XP_005268096.1, XM_005268039.1 [P16473-2]
XP_006720308.1, XM_006720245.1 [P16473-3]
UniGeneiHs.160411

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XUMmodel-A54-236[»]
2XWTX-ray1.90C22-260[»]
3G04X-ray2.55C22-260[»]
ProteinModelPortaliP16473
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113104, 30 interactors
IntActiP16473, 2 interactors
STRINGi9606.ENSP00000298171

Chemistry databases

BindingDBiP16473
ChEMBLiCHEMBL1963
DrugBankiDB00024 Thyrotropin Alfa
GuidetoPHARMACOLOGYi255

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP16473
PhosphoSitePlusiP16473
SwissPalmiP16473

Polymorphism and mutation databases

BioMutaiTSHR
DMDMi62298994

Proteomic databases

PaxDbiP16473
PeptideAtlasiP16473
PRIDEiP16473
ProteomicsDBi53374
53375 [P16473-2]

Protocols and materials databases

DNASUi7253
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342443; ENSP00000340113; ENSG00000165409 [P16473-2]
ENST00000554435; ENSP00000450549; ENSG00000165409 [P16473-3]
GeneIDi7253
KEGGihsa:7253
UCSCiuc001xvc.4 human [P16473-1]

Organism-specific databases

CTDi7253
DisGeNETi7253
EuPathDBiHostDB:ENSG00000165409.15
GeneCardsiTSHR
H-InvDBiHIX0021925
HGNCiHGNC:12373 TSHR
HPAiCAB000473
MalaCardsiTSHR
MIMi275200 phenotype
603372 gene+phenotype
603373 phenotype
609152 phenotype
neXtProtiNX_P16473
OpenTargetsiENSG00000165409
Orphaneti95713 Athyreosis
99819 Familial gestational hyperthyroidism
424 Familial hyperthyroidism due to mutations in TSH receptor
90673 Hypothyroidism due to TSH receptor mutations
95720 Thyroid hypoplasia
PharmGKBiPA37042
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2087 Eukaryota
ENOG410XR1T LUCA
GeneTreeiENSGT00760000119088
HOVERGENiHBG052887
InParanoidiP16473
KOiK04249
PhylomeDBiP16473
TreeFamiTF316814

Enzyme and pathway databases

ReactomeiR-HSA-375281 Hormone ligand-binding receptors
R-HSA-418555 G alpha (s) signalling events
SignaLinkiP16473
SIGNORiP16473

Miscellaneous databases

ChiTaRSiTSHR human
EvolutionaryTraceiP16473
GeneWikiiThyrotropin_receptor
GenomeRNAii7253
PROiPR:P16473
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165409 Expressed in 90 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_TSHR
ExpressionAtlasiP16473 baseline and differential
GenevisibleiP16473 HS

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR002131 Gphrmn_rcpt_fam
IPR026906 LRR_5
IPR032675 LRR_dom_sf
IPR002274 TSH_rcpt
IPR034298 TSHR/LHCGR/FSHR
PANTHERiPTHR24372 PTHR24372, 1 hit
PTHR24372:SF0 PTHR24372:SF0, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PF13306 LRR_5, 2 hits
PRINTSiPR00373 GLYCHORMONER
PR00237 GPCRRHODOPSN
PR01145 TSHRECEPTOR
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTSHR_HUMAN
AccessioniPrimary (citable) accession number: P16473
Secondary accession number(s): A0PJU7
, F5GYU5, G3V2A9, Q16503, Q8TB90, Q96GT6, Q9P1V4, Q9ULA3, Q9UPH3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 29, 2005
Last modified: November 7, 2018
This is version 223 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  7. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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