Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - P16473 (TSHR_HUMAN)

Entry version 237 (12 Aug 2020)
Sequence version 2 (29 Mar 2005)
Previous versions | rss
Help videoAdd a publicationFeedback
Protein

Thyrotropin receptor

Gene

TSHR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P16473

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-375281, Hormone ligand-binding receptors
R-HSA-418555, G alpha (s) signalling events
R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P16473

SIGNOR Signaling Network Open Resource

More...SIGNORi		P16473

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Thyrotropin receptor
Alternative name(s):
Thyroid-stimulating hormone receptor
Short name:
TSH-R
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:TSHR
Synonyms:LGR3
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 14

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...EuPathDBi		HostDB:ENSG00000165409.15

Human Gene Nomenclature Database

More...HGNCi		HGNC:12373, TSHR

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		603372, gene+phenotype

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P16473

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini21 – 413ExtracellularSequence analysisAdd BLAST393
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>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

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>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.
Related information in OMIM
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.
Related information in OMIM
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
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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

DisGeNET

More...DisGeNETi		7253

MalaCards human disease database

More...MalaCardsi		TSHR
MIMi275200, phenotype
603372, gene+phenotype
603373, phenotype
609152, phenotype

Open Targets

More...OpenTargetsi		ENSG00000165409

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		95713, Athyreosis
99819, Familial gestational hyperthyroidism
424, Familial hyperthyroidism due to mutations in TSH receptor
90673, Hypothyroidism due to TSH receptor mutations
95720, Thyroid hypoplasia

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA37042

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P16473, Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL1963

Drug and drug target database

More...DrugBanki		DB00024, Thyrotropin alfa

DrugCentral

More...DrugCentrali		P16473

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		255

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		TSHR

Domain mapping of disease mutations (DMDM)

More...DMDMi		62298994

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 20Add BLAST20
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001278621 – 764Thyrotropin receptorAdd BLAST744

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi31 ↔ 41
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>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
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei385Sulfotyrosine1 Publication1
Disulfide bondi494 ↔ 569PROSITE-ProRule annotation

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P16473

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P16473

PeptideAtlas

More...PeptideAtlasi		P16473

PRoteomics IDEntifications database

More...PRIDEi		P16473

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		24847
32578
53374 [P16473-1]
53375 [P16473-2]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P16473, 6 sites

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P16473

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P16473

SwissPalm database of S-palmitoylation events

More...SwissPalmi		P16473

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000165409, Expressed in left lobe of thyroid gland and 116 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P16473, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P16473, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000165409, Tissue enriched (thyroid)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		113104, 31 interactors

Protein interaction database and analysis system

More...IntActi		P16473, 25 interactors

Molecular INTeraction database

More...MINTi		P16473

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000441235

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P16473

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P16473, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

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

3D structure databases

Database of comparative protein structure models

More...ModBasei		Search...

SWISS-MODEL Interactive Workspace

More...SWISS-MODEL-Workspacei		Submit a new modelling project...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P16473

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>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
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi762 – 764PDZ-binding3

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>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

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG2087, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000156510

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P16473

KEGG Orthology (KO)

More...KOi		K04249

Database for complete collections of gene phylogenies

More...PhylomeDBi		P16473

TreeFam database of animal gene trees

More...TreeFami		TF316814

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.80.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR000276, GPCR_Rhodpsn
IPR017452, GPCR_Rhodpsn_7TM
IPR002131, Gphrmn_rcpt_fam
IPR026906, LRR_5
IPR032675, LRR_dom_sf
IPR002274, TSH_rcpt

The PANTHER Classification System

More...PANTHERi		PTHR24372:SF0, PTHR24372:SF0, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00001, 7tm_1, 1 hit
PF13306, LRR_5, 2 hits

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00373, GLYCHORMONER
PR00237, GPCRRHODOPSN
PR01145, TSHRECEPTOR

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00237, G_PROTEIN_RECEP_F1_1, 1 hit
PS50262, G_PROTEIN_RECEP_F1_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> 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 <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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.

Show »
Length:274
Mass (Da):30,800
Checksum:iA8A8DBB061774F5C
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>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:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1B0GUJ5A0A1B0GUJ5_HUMAN
Thyrotropin receptor
TSHR
399Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
Q0VAP8Q0VAP8_HUMAN
TSHR protein
TSHR
231Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
G3V381G3V381_HUMAN
Thyrotropin receptor
TSHR
112Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A2R8Y709A0A2R8Y709_HUMAN
Thyrotropin receptor
TSHR
89Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAA70232 differs from that shown. Reason: Frameshift.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>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

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>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
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>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:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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

The Consensus CDS (CCDS) project

More...CCDSi		CCDS32131.1 [P16473-2]
CCDS55935.1 [P16473-3]
CCDS9872.1 [P16473-1]

Protein sequence database of the Protein Information Resource

More...PIRi		A33789, QRHURH
JC1319
T01787

NCBI Reference Sequences

More...RefSeqi		NP_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]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000342443; ENSP00000340113; ENSG00000165409 [P16473-2]
ENST00000554435; ENSP00000450549; ENSG00000165409 [P16473-3]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		7253

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:7253

UCSC genome browser

More...UCSCi		uc001xvc.4, human [P16473-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>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]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XUMmodel-A54-236[»]
2XWTX-ray1.90C22-260[»]
3G04X-ray2.55C22-260[»]
ModBaseiSearch...
SWISS-MODEL-WorkspaceiSubmit a new modelling project...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi113104, 31 interactors
IntActiP16473, 25 interactors
MINTiP16473
STRINGi9606.ENSP00000441235

Chemistry databases

BindingDBiP16473
ChEMBLiCHEMBL1963
DrugBankiDB00024, Thyrotropin alfa
DrugCentraliP16473
GuidetoPHARMACOLOGYi255

Protein family/group databases

Information system for G protein-coupled receptors (GPCRs)

More...GPCRDBi		Search...

PTM databases

GlyGeniP16473, 6 sites
iPTMnetiP16473
PhosphoSitePlusiP16473
SwissPalmiP16473

Polymorphism and mutation databases

BioMutaiTSHR
DMDMi62298994

Proteomic databases

MassIVEiP16473
PaxDbiP16473
PeptideAtlasiP16473
PRIDEiP16473
ProteomicsDBi24847
32578
53374 [P16473-1]
53375 [P16473-2]

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		P16473, 5 sequenced antibodies

Antibodypedia a portal for validated antibodies

More...Antibodypediai		4379, 1139 antibodies

The DNASU plasmid repository

More...DNASUi		7253

Genome annotation databases

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

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		7253
DisGeNETi7253
EuPathDBiHostDB:ENSG00000165409.15

GeneCards: human genes, protein and diseases

More...GeneCardsi		TSHR
HGNCiHGNC:12373, TSHR
HPAiENSG00000165409, Tissue enriched (thyroid)
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

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG2087, Eukaryota
GeneTreeiENSGT00940000156510
InParanoidiP16473
KOiK04249
PhylomeDBiP16473
TreeFamiTF316814

Enzyme and pathway databases

PathwayCommonsiP16473
ReactomeiR-HSA-375281, Hormone ligand-binding receptors
R-HSA-418555, G alpha (s) signalling events
R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production
SignaLinkiP16473
SIGNORiP16473

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		7253, 5 hits in 873 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		TSHR, human
EvolutionaryTraceiP16473

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Thyrotropin_receptor

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		7253
PharosiP16473, Tclin

Protein Ontology

More...PROi		PR:P16473
RNActiP16473, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000165409, Expressed in left lobe of thyroid gland and 116 other tissues
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
PANTHERiPTHR24372: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

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTSHR_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P16473
Secondary accession number(s): A0PJU7
, F5GYU5, G3V2A9, Q16503, Q8TB90, Q96GT6, Q9P1V4, Q9ULA3, Q9UPH3
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 29, 2005
Last modified: August 12, 2020
This is version 237 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  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. SIMILARITY comments
    Index of protein domains and families
  7. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again