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P16473 (TSHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 180. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thyrotropin receptor
Alternative name(s):
Thyroid-stimulating hormone receptor
Short name=TSH-R
Gene names
Name:TSHR
Synonyms:LGR3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length764 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for thyrothropin. Plays a central role in controlling thyroid cell metabolism. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Also acts as a receptor for thyrostimulin (GPA2+GPB5). Ref.11

Subunit structure

Interacts (via the PDZ-binding motif) with SCRIB; regulates TSHR trafficking and function. Ref.11 Ref.12

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Expressed in the thyroid. Ref.2

Polymorphism

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.

Involvement in disease

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). Ref.15 Ref.16 Ref.17

Autoantibodies against TSHR are directly responsible for the pathogenesis and hyperthyroidism of Graves disease. Antibody interaction with TSHR results in an uncontrolled receptor stimulation. Ref.15 Ref.16 Ref.17

Hypothyroidism, congenital, non-goitrous, 1 (CHNG1) [MIM:275200]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.16 Ref.17 Ref.27 Ref.32 Ref.34 Ref.36 Ref.39 Ref.50 Ref.53 Ref.61 Ref.63 Ref.67 Ref.69

Familial gestational hyperthyroidism (HTFG) [MIM:603373]: A condition characterized by abnormally high levels of serum thyroid hormones occurring during early pregnancy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.16 Ref.17 Ref.43

Hyperthyroidism, non-autoimmune (HTNA) [MIM:609152]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.16 Ref.17 Ref.24 Ref.26 Ref.30 Ref.31 Ref.37 Ref.38 Ref.41 Ref.42 Ref.44 Ref.51 Ref.54 Ref.55 Ref.57 Ref.58 Ref.59 Ref.68

Sequence similarities

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

Contains 7 LRR (leucine-rich) repeats.

Sequence caution

The sequence AAA70232.1 differs from that shown. Reason: Frameshift at positions 130, 135 and 612.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform Long (identifier: P16473-1)

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.
Isoform Short (identifier: P16473-2)

The sequence of this isoform differs from the canonical sequence as follows:
     232-253: DVSQTSVTALPSKGLEHLKELI → LPLGRKSLSFETQKAPRSSMPS
     254-764: Missing.
Isoform 3 (identifier: P16473-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020
Chain21 – 764744Thyrotropin receptor
PRO_0000012786

Regions

Topological domain21 – 413393Extracellular Potential
Transmembrane414 – 44128Helical; Name=1; Potential
Topological domain442 – 4509Cytoplasmic Potential
Transmembrane451 – 47323Helical; Name=2; Potential
Topological domain474 – 49421Extracellular Potential
Transmembrane495 – 51723Helical; Name=3; Potential
Topological domain518 – 53720Cytoplasmic Potential
Transmembrane538 – 56023Helical; Name=4; Potential
Topological domain561 – 58020Extracellular Potential
Transmembrane581 – 60222Helical; Name=5; Potential
Topological domain603 – 62523Cytoplasmic Potential
Transmembrane626 – 64924Helical; Name=6; Potential
Topological domain650 – 66011Extracellular Potential
Transmembrane661 – 68222Helical; Name=7; Potential
Topological domain683 – 76482Cytoplasmic Potential
Repeat100 – 12425LRR 1
Repeat125 – 15026LRR 2
Repeat152 – 17423LRR 3
Repeat176 – 19924LRR 4
Repeat200 – 22324LRR 5
Repeat227 – 24822LRR 6
Repeat250 – 27122LRR 7
Motif762 – 7643PDZ-binding

Amino acid modifications

Glycosylation771N-linked (GlcNAc...) Ref.10 Ref.14
Glycosylation991N-linked (GlcNAc...) Ref.14
Glycosylation1131N-linked (GlcNAc...) Ref.10 Ref.14
Glycosylation1771N-linked (GlcNAc...) Ref.14
Glycosylation1981N-linked (GlcNAc...) Ref.10 Ref.14
Glycosylation3021N-linked (GlcNAc...) Ref.10
Disulfide bond31 ↔ 41 Ref.14
Disulfide bond494 ↔ 569 By similarity

Natural variations

Alternative sequence232 – 27443DVSQT…LHLTR → VENVAVSGKGFCKSLFSWLY RLPLGRKSLSFETQKAPRSS MPS in isoform 3.
VSP_044643
Alternative sequence232 – 25322DVSQT…LKELI → LPLGRKSLSFETQKAPRSSM PS in isoform Short.
VSP_001981
Alternative sequence254 – 764511Missing in isoform Short.
VSP_001982
Alternative sequence275 – 764490Missing in isoform 3.
VSP_044644
Natural variant341E → K.
Corresponds to variant rs45499704 [ dbSNP | Ensembl ].
VAR_055925
Natural variant361D → H in a patient with Graves disease. Ref.17 Ref.19 Ref.25 Ref.65 Ref.66
Corresponds to variant rs61747482 [ dbSNP | Ensembl ].
VAR_003564
Natural variant411C → S in CHNG1. Ref.32 Ref.63
VAR_011519
Natural variant521P → T Does not contribute to the genetic susceptibility to Graves disease. Ref.17 Ref.21 Ref.27 Ref.29 Ref.49 Ref.65 Ref.66
Corresponds to variant rs2234919 [ dbSNP | Ensembl ].
VAR_003565
Natural variant1091R → Q in CHNG1. Ref.34
VAR_011520
Natural variant1621P → A in CHNG1. Ref.27 Ref.32 Ref.63 Ref.69
Corresponds to variant rs121908863 [ dbSNP | Ensembl ].
VAR_011521
Natural variant1671I → N in CHNG1. Ref.27
VAR_011522
Natural variant1831K → R in HTFG; enhances receptor response to chorionic gonadotropin. Ref.43
VAR_003566
Natural variant1971F → I in papillary cancer. Ref.28
VAR_003567
Natural variant2191D → E in papillary cancer. Ref.28
VAR_003568
Natural variant2521L → P in CHNG1; displays a low expression at the cell surface and a reduced response to bovine TSH in terms of cAMP production. Ref.69
VAR_021495
Natural variant2811S → I in hyperthyroidism; congenital; due to a toxic adenoma. Ref.40
VAR_003569
Natural variant2811S → N in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. Ref.35 Ref.42 Ref.51 Ref.54 Ref.60
VAR_003570
Natural variant2811S → T in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. Ref.35
VAR_011523
Natural variant3101R → C in CHNG1. Ref.53
VAR_011524
Natural variant3901C → W in CHNG1; persistent hypothyroidism and defective thyroid development; habolishes high affinity hormone binding. Ref.32 Ref.36
VAR_011525
Natural variant4101D → N in CHNG1; lack of adenylate cyclase activation. Ref.32
VAR_011526
Natural variant4251S → I in TTNs; 8 to 9 times higher levels of basal cAMP than wild-type TSHR and similar response to maximal TSH stimulation. Ref.60
VAR_021496
Natural variant4311G → S in HTNA; gain of function; constitutive activation of the G(s)/adenylyl cyclase system. Ref.54 Ref.59
VAR_011527
Natural variant4501R → H in CHNG1. Ref.61
VAR_011528
Natural variant4531M → T in HTNA; sporadic; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. Ref.31 Ref.35 Ref.60 Ref.62
VAR_011529
Natural variant4631M → V in HTNA; gain of function. Ref.57
VAR_011530
Natural variant4671L → P in CHNG1. Ref.63
VAR_017295
Natural variant4771T → I in CHNG1; severe hypothyroidism. Ref.50
VAR_017296
Natural variant4861I → F in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas; also in hyperfunctioning follicular carcinoma. Ref.35 Ref.51 Ref.56 Ref.60
VAR_011531
Natural variant4861I → M in HTNA; found in hyperfunctioning thyroid adenomas. Ref.35 Ref.51 Ref.62
VAR_011532
Natural variant4981G → S in CHNG1. Ref.61
VAR_011533
Natural variant5051S → N in HTNA; found in toxic thyroid nodules. Ref.37 Ref.60 Ref.68
VAR_003571
Natural variant5051S → R in HTNA; gain of function. Ref.30
VAR_011534
Natural variant5091V → A in HTNA; gain of function. Ref.24
VAR_011535
Natural variant5121L → Q in TTNs; 5 times higher levels of basal cAMP than wild-type TSHR and slightly less response to maximal TSH stimulation. Ref.60
VAR_021497
Natural variant5121L → R in hyperthyroidism and TTNs; associated with autonomously functioning thyroid nodules; 3.3-fold increase in basal cAMP level. Ref.48 Ref.60 Ref.62
VAR_011536
Natural variant5251F → L in CHNG1; impairs adenylate cyclase activation. Ref.32
VAR_011537
Natural variant5281R → H. Ref.42
VAR_003572
Natural variant5531A → T in CHNG1; severe hypothyroidism. Ref.39 Ref.67
VAR_011538
Natural variant5681I → T in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. Ref.35 Ref.55 Ref.60
VAR_011539
Natural variant5931A → N in toxic thyroid adenoma; requires 2 nucleotide substitutions; somatic mutation; N-593 and N-593/E-727 constitutively activate the cAMP cascade; double mutant's specific constitutive activity is 2.3-fold lower than the N-593 mutant. Ref.64
VAR_021498
Natural variant5971V → F in HTNA; 11-fold increase in specific constitutive activity associated with reduction in receptor protein expression. Ref.58
VAR_021499
Natural variant5971V → L in hyperthyroidism; congenital with severe thyrotoxicosis. Ref.47
VAR_011540
Natural variant6001C → R in CHNG1. Ref.63
VAR_017297
Natural variant6061I → M. Ref.45
VAR_011541
Natural variant6191D → G in hyperthyroidism and TTNs; associated with hyperfunctioning thyroid adenomas. Ref.20 Ref.35 Ref.60
VAR_003573
Natural variant6231A → I in hyperthyroidism; associated with hyperfunctioning thyroid adenomas; gain of function; requires 2 nucleotide substitutions. Ref.20 Ref.35
VAR_003574
Natural variant6231A → V in hyperthyroidism and TTNs; associated with hyperfunctioning thyroid adenomas; gain of function. Ref.23 Ref.60
VAR_011542
Natural variant6291L → F in HTNA; also in hyperfunctioning thyroid adenomas and non-adenomatous nodules. Ref.35 Ref.38 Ref.51
VAR_003575
Natural variant6301I → L in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. Ref.35
VAR_011543
Natural variant6311F → C in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. Ref.22
VAR_011544
Natural variant6311F → L in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. Ref.26 Ref.35 Ref.60
VAR_011545
Natural variant6321T → A in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning non-adenomatous nodules. Ref.51 Ref.60 Ref.62
VAR_011546
Natural variant6321T → I in HTNA; gain of function; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. Ref.22 Ref.23 Ref.35 Ref.41 Ref.51 Ref.54 Ref.60
VAR_011547
Natural variant6331D → A in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. Ref.35
VAR_011548
Natural variant6331D → E in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. Ref.22 Ref.35 Ref.51 Ref.60
VAR_011549
Natural variant6331D → H in hyperthyroidism and TTNs; associated with hyperfunctioning thyroid adenomas; also in hyperfunctioning insular carcinoma; with severe thyrotoxicosis; gain of function. Ref.33 Ref.35 Ref.60
Corresponds to variant rs28937584 [ dbSNP | Ensembl ].
VAR_011550
Natural variant6331D → Y in hyperthyroidism and TTNs; associated with hyperfunctioning thyroid adenomas. Ref.22 Ref.35 Ref.60
VAR_011551
Natural variant6391P → A in TTNs. Ref.60
VAR_021500
Natural variant6391P → S in HTNA; gain of function. Ref.44
VAR_011552
Natural variant6471A → V in HTNA; found in non-adenomatous hyperfunctioning nodules. Ref.51
VAR_011553
Natural variant6501N → Y in HTNA; gain of function. Ref.30
VAR_011554
Natural variant6561V → F in TTNs. Ref.60
VAR_021501
Natural variant658 – 6614Missing in hyperthyroidism; associated with hyperfunctioning thyroid adenomas.
VAR_011555
Natural variant6701N → S in HTNA; gain of function. Ref.30
VAR_011556
Natural variant6721C → Y in HTNA; gain of function. Ref.24
VAR_011557
Natural variant6771L → V in thyroid carcinoma; with thyrotoxicosis; gain of function. Ref.46
VAR_011558
Natural variant7031A → G. Ref.45
VAR_011559
Natural variant7151N → D in papillary cancer. Ref.28
VAR_003576
Natural variant7201Q → E. Ref.45
VAR_011560
Natural variant7231K → M in papillary cancer. Ref.28
VAR_003577
Natural variant7271D → E May be a predisposing factor in toxic multinodular goiter pathogenesis; activation of the cAMP cascade does not differ from the wild-type. Ref.3 Ref.8 Ref.15 Ref.16 Ref.17 Ref.28 Ref.45 Ref.52 Ref.64 Ref.65
Corresponds to variant rs1991517 [ dbSNP | Ensembl ].
VAR_003578

Experimental info

Sequence conflict871V → L no nucleotide entry Ref.2
Sequence conflict196 – 1983AFN → DFF in AAA70232. Ref.4
Sequence conflict2571T → S in AAA70232. Ref.4
Sequence conflict2641P → A in AAA70232. Ref.4
Sequence conflict306 – 3083MQS → IET in AAA70232. Ref.4
Sequence conflict5281R → A in AAA70232. Ref.4
Sequence conflict6011Y → H in AAA36783. Ref.1
Sequence conflict6351I → T in AAA70232. Ref.4
Sequence conflict6451L → V in AAA70232. Ref.4
Sequence conflict6691L → I in AAA70232. Ref.4
Sequence conflict7441N → K in AAA61236. Ref.3
Isoform Short:
Sequence conflict2391L → F in AAB24246. Ref.6
Sequence conflict2481R → S in AAB23390. Ref.5
Sequence conflict2481R → S in AAH09237. Ref.9
Sequence conflict2481R → S in AAI20974. Ref.9
Sequence conflict2511M → T in AAB23390. Ref.5
Isoform 3:
Sequence conflict2691R → S in AAI27629. Ref.9

Secondary structure

.......................................... 764
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified March 29, 2005. Version 2.
Checksum: D2EE9CEBFD64A65F

FASTA76486,830
        10         20         30         40         50         60 
MRPADLLQLV LLLDLPRDLG GMGCSSPPCE CHQEEDFRVT CKDIQRIPSL PPSTQTLKLI 

        70         80         90        100        110        120 
ETHLRTIPSH AFSNLPNISR IYVSIDVTLQ QLESHSFYNL SKVTHIEIRN TRNLTYIDPD 

       130        140        150        160        170        180 
ALKELPLLKF LGIFNTGLKM FPDLTKVYST DIFFILEITD NPYMTSIPVN AFQGLCNETL 

       190        200        210        220        230        240 
TLKLYNNGFT SVQGYAFNGT KLDAVYLNKN KYLTVIDKDA FGGVYSGPSL LDVSQTSVTA 

       250        260        270        280        290        300 
LPSKGLEHLK ELIARNTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM 

       310        320        330        340        350        360 
CNESSMQSLR QRKSVNALNS PLHQEYEENL GDSIVGYKEK SKFQDTHNNA HYYVFFEEQE 

       370        380        390        400        410        420 
DEIIGFGQEL KNPQEETLQA FDSHYDYTIC GDSEDMVCTP KSDEFNPCED IMGYKFLRIV 

       430        440        450        460        470        480 
VWFVSLLALL GNVFVLLILL TSHYKLNVPR FLMCNLAFAD FCMGMYLLLI ASVDLYTHSE 

       490        500        510        520        530        540 
YYNHAIDWQT GPGCNTAGFF TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHACA 

       550        560        570        580        590        600 
IMVGGWVCCF LLALLPLVGI SSYAKVSICL PMDTETPLAL AYIVFVLTLN IVAFVIVCCC 

       610        620        630        640        650        660 
YVKIYITVRN PQYNPGDKDT KIAKRMAVLI FTDFICMAPI SFYALSAILN KPLITVSNSK 

       670        680        690        700        710        720 
ILLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGICK RQAQAYRGQR VPPKNSTDIQ 

       730        740        750        760 
VQKVTHDMRQ GLHNMEDVYE LIENSHLTPK KQGQISEEYM QTVL 

« Hide

Isoform Short [UniParc].

Checksum: 69E12F0A7D8B5FD0
Show »

FASTA25328,427
Isoform 3 [UniParc].

Checksum: A8A8DBB061774F5C
Show »

FASTA27430,800

References

« Hide 'large scale' references
[1]"Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor."
Nagayama Y., Kaufman K.D., Seto P., Rapoport B.
Biochem. Biophys. Res. Commun. 165:1184-1190(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[2]"Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies."
Libert F., Lefort A., Gerard C., Parmentier M., Perret J., Ludgate M., Dumont J.E., Vassart G.
Biochem. Biophys. Res. Commun. 165:1250-1255(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), TISSUE SPECIFICITY.
Tissue: Thyroid.
[3]"Cloning, sequencing and expression of human TSH receptor."
Misrahi M., Loosfelt H., Atger M., Sar S., Guiochon-Mantel A., Milgrom E.
Biochem. Biophys. Res. Commun. 166:394-403(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANT GLU-727.
[4]"Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing."
Frazier A.L., Robbins L.S., Stork P.J., Sprengel R., Segaloff D.L., Cone R.D.
Mol. Endocrinol. 4:1264-1276(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
Tissue: Thyroid.
[5]"Cloning and sequencing of a 1.3 KB variant of human thyrotropin receptor mRNA lacking the transmembrane domain."
Graves P.N., Tomer Y., Davies T.F.
Biochem. Biophys. Res. Commun. 187:1135-1143(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[6]"Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript."
Takeshita A., Nagayama Y., Fujiyama K., Yokoyama N., Namba H., Yamashita S., Izumi M., Nagataki S.
Biochem. Biophys. Res. Commun. 188:1214-1219(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
Tissue: Thyroid.
[7]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
Tissue: Thyroid.
[8]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-727.
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SHORT AND 3).
Tissue: Ovarian adenocarcinoma.
[10]"Purification and characterization of a soluble bioactive amino-terminal extracellular domain of the human thyrotropin receptor."
Cornelis S., Uttenweiler-Joseph S., Panneels V., Vassart G., Costagliola S.
Biochemistry 40:9860-9869(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 66-80; 113-123; 184-210 AND 294-310, GLYCOSYLATION AT ASN-77; ASN-113; ASN-198 AND ASN-302.
[11]"Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor."
Nakabayashi K., Matsumi H., Bhalla A., Bae J., Mosselman S., Hsu S.Y., Hsueh A.J.W.
J. Clin. Invest. 109:1445-1452(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GPA2/GPB5.
[12]"Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway."
Lahuna O., Quellari M., Achard C., Nola S., Meduri G., Navarro C., Vitale N., Borg J.-P., Misrahi M.
EMBO J. 24:1364-1374(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SCRIB.
[13]"Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions."
Jiang X., Dreano M., Buckler D.R., Cheng S., Ythier A., Wu H., Hendrickson W.A., el Tayar N.
Structure 3:1341-1353(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING OF 54-236.
[14]"Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody."
Sanders J., Chirgadze D.Y., Sanders P., Baker S., Sullivan A., Bhardwaja A., Bolton J., Reeve M., Nakatake N., Evans M., Richards T., Powell M., Miguel R.N., Blundell T.L., Furmaniak J., Smith B.R.
Thyroid 17:395-410(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 22-260 IN COMPLEX WITH ANTIBODY, GLYCOSYLATION AT ASN-77; ASN-99; ASN-113; ASN-177 AND ASN-198, N-TERMINAL DISULFIDE BOND.
[15]"Further studies of genetic susceptibility to Graves' disease in a Russian population."
Chistiakov D.A., Savost'anov K.V., Turakulov R.I., Petunina N., Balabolkin M.I., Nosikov V.V.
Med. Sci. Monit. 8:CR180-CR184(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ANALYSIS OF INVOLVEMENT OF VARIANT GLU-727 IN GRAVES DISEASE.
[16]"A germline single nucleotide polymorphism at the intracellular domain of the human thyrotropin receptor does not have a major effect on the development of Graves' disease."
Ban Y., Greenberg D.A., Concepcion E.S., Tomer Y.
Thyroid 12:1079-1083(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ANALYSIS OF INVOLVEMENT OF VARIANT GLU-727 IN GRAVES DISEASE.
[17]"Association of Graves' disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic origins."
Ho S.-C., Goh S.-S., Khoo D.H.
Thyroid 13:523-528(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ANALYSIS OF INVOLVEMENT OF VARIANTS HIS-36; THR-52 AND GLU-727 IN GRAVES DISEASE.
[18]"The human thyrotropin receptor is highly mutable: a review of gain-of-function mutations."
Farid N.R., Kascur V., Balazs C.
Eur. J. Endocrinol. 143:25-30(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[19]"A somatic point mutation in a putative ligand binding domain of the TSH receptor in a patient with autoimmune hyperthyroidism."
Heldin N.-E., Gustavsson B., Westermark K., Westermark B.
J. Clin. Endocrinol. Metab. 73:1374-1376(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-36.
[20]"Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas."
Parma J., Duprez L., van Sande J., Cochaux P., Gervy C., Mockel J., Dumont J.E., Vassart G.
Nature 365:649-651(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPERTHYROIDISM GLY-619 AND ILE-623.
[21]"A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves' ophthalmopathy."
Bahn R.S., Dutton C.M., Heufelder A.E., Sarkar G.
J. Clin. Endocrinol. Metab. 78:256-260(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-52.
[22]"Novel mutations of thyrotropin receptor gene in thyroid hyperfunctioning adenomas. Rapid identification by fine needle aspiration biopsy."
Porcellini A., Ciullo I., Laviola L., Amabile G., Fenzi G., Avvedimento V.E.
J. Clin. Endocrinol. Metab. 79:657-661(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPERTHYROIDISM CYS-631; ILE-632; GLU-633 AND TYR-633.
[23]"Identification and functional characterization of two new somatic mutations causing constitutive activation of the thyrotropin receptor in hyperfunctioning autonomous adenomas of the thyroid."
Paschke R., Tonacchera M., van Sande J., Parma J., Vassart G.
J. Clin. Endocrinol. Metab. 79:1785-1789(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPERTHYROIDISM VAL-623 AND ILE-632.
[24]"Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism."
Duprez L., Parma J., van Sande J., Allgeier A., Leclere J., Schvartz C., Delisle M.-J., Decoulx M., Orgiazzi J., Dumont J.E., Vassart G.
Nat. Genet. 7:396-401(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HTNA ALA-509 AND TYR-672.
[25]"Functional analysis of a variant of the thyrotropin receptor gene in a family with Graves' disease."
Gustavsson B., Eklof C., Westermark K., Westermark B., Heldin N.-E.
Mol. Cell. Endocrinol. 111:167-173(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT HIS-36.
[26]"Congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene."
Kopp P., van Sande J., Parma J., Duprez L., Gerber H., Joss E., Jameson J.L., Dumont J.E., Vassart G.
N. Engl. J. Med. 332:150-154(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA LEU-631.
[27]"Resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene."
Sunthornthepvarakul T., Gottschalk M.E., Hayashi Y., Refetoff S.
N. Engl. J. Med. 332:155-160(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CHNG1 ALA-162 AND ASN-167, VARIANT THR-52.
[28]"Point mutations in the thyrotropin receptor in human thyroid tumors."
Ohno M., Endo T., Ohta K., Gunji K., Onaya T.
Thyroid 5:97-100(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PAPILLARY CANCER ILE-197; GLU-219; ASP-715 AND MET-723, VARIANT GLU-727.
[29]"Normal function in vivo of a homozygotic polymorphism in the human thyrotropin receptor."
Cuddihy R.M., Bryant W.P., Bahn R.S.
Thyroid 5:255-257(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-52.
[30]"Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia."
Tonacchera M., van Sande J., Cetani F., Swillens S., Schvartz C., Winiszewski P., Portmann L., Dumont J.E., Vassart G., Parma J.
J. Clin. Endocrinol. Metab. 81:547-554(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HTNA ARG-505; TYR-650 AND SER-670.
[31]"A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism."
de Roux N., Polak M., Couet J., Leger J., Czernichow P., Milgrom E., Misrahi M.
J. Clin. Endocrinol. Metab. 81:2023-2026(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA THR-453.
[32]"Four families with loss of function mutations of the thyrotropin receptor."
de Roux N., Misrahi M., Brauner R., Houang M., Carel J.-C., Granier M., Le Bouc Y., Ghinea N., Boumedienne A., Toublanc J.E., Milgrom E.
J. Clin. Endocrinol. Metab. 81:4229-4235(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CHNG1 SER-41; ALA-162; TRP-390; ASN-410 AND LEU-525.
[33]"Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma."
Russo D., Tumino S., Arturi F., Vigneri P., Grasso G., Pontecorvi A., Filetti S., Belfiore A.
J. Clin. Endocrinol. Metab. 82:735-738(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT INSULAR CARCINOMA HIS-633.
[34]"Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH."
Clifton-Bligh R.J., Gregory J.W., Ludgate M., John R., Persani L., Asteria C., Beck-Peccoz P., Chatterjee V.K.K.
J. Clin. Endocrinol. Metab. 82:1094-1100(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CHNG1 GLN-109.
[35]"Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas."
Parma J., Duprez L., van Sande J., Hermans J., Rocmans P., van Vliet G., Costagliola S., Rodien P., Dumont J.E., Vassart G.
J. Clin. Endocrinol. Metab. 82:2695-2701(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPERTHYROIDISM ASN-281; THR-281; THR-453; PHE-486; MET-486; THR-568; GLY-619; ILE-623; PHE-629; LEU-630; LEU-631; ILE-632; ALA-633; GLU-633; HIS-633; TYR-633 AND 658-ASN--ILE-661 DEL.
[36]"Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism."
Biebermann H., Schoeneberg T., Krude H., Schultz G., Gudermann T., Grueters A.
J. Clin. Endocrinol. Metab. 82:3471-3480(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CHNG1 TRP-390.
[37]"Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene."
Holzapfel H.P., Wonerow P., von Petrykowski W., Henschen M., Scherbaum W.A., Paschke R.
J. Clin. Endocrinol. Metab. 82:3879-3884(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA ASN-505.
[38]"Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism."
Fuhrer D., Wonerow P., Willgerodt H., Paschke R.
J. Clin. Endocrinol. Metab. 82:4234-4238(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA PHE-629.
[39]"Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland."
Abramowicz M.J., Duprez L., Parma J., Vassart G., Heinrichs C.
J. Clin. Invest. 99:3018-3024(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CHNG1 THR-553.
[40]"Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor."
Kopp P., Muirhead S., Jourdain N., Gu W.X., Jameson J.L., Rodd C.
J. Clin. Invest. 100:1634-1639(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPERTHYROIDISM ILE-281.
[41]"Congenital nonautoimmune hyperthyroidism in a nonidentical twin caused by a sporadic germline mutation in the thyrotropin receptor gene."
Kopp P., Jameson J.L., Roe T.F.
Thyroid 7:765-770(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA ILE-632.
[42]"Severe congenital hyperthyroidism caused by a germ-line neo mutation in the extracellular portion of the thyrotropin receptor."
Grueters A., Schoeneberg T., Biebermann H., Krude H., Krohn H.P., Dralle H., Gudermann T.
J. Clin. Endocrinol. Metab. 83:1431-1436(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA ASN-281, VARIANT HIS-528.
[43]"Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin."
Rodien P., Bremont C., Raffin Sanson M.-L., Parma J., van Sande J., Costagliola S., Luton J.-P., Vassart G., Duprez L.
N. Engl. J. Med. 339:1823-1826(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTFG ARG-183.
[44]"A germline mutation of the thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family."
Khoo D.H.C., Parma J., Rajasoorya C., Ho S.C., Vassart G.
J. Clin. Endocrinol. Metab. 84:1459-1462(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA SER-639.
[45]"Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter."
Gabriel E.M., Bergert E.R., Grant C.S., van Heerden J.A., Thompson G.B., Morris J.C.
J. Clin. Endocrinol. Metab. 84:3328-3335(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MET-606; GLY-703; GLU-720 AND GLU-727.
[46]"A Val 677 activating mutation of the thyrotropin receptor in a Hurthle cell thyroid carcinoma associated with thyrotoxicosis."
Russo D., Wong M.G., Costante G., Chiefari E., Treseler P.A., Arturi F., Filetti S., Clark O.H.
Thyroid 9:13-17(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THYROID CARCINOMA VAL-677.
[47]"A novel thyrotropin receptor mutation in an infant with severe thyrotoxicosis."
Esapa C.T., Duprez L., Ludgate M., Mustafa M.S., Kendall-Taylor P., Vassart G., Harris P.E.
Thyroid 9:1005-1010(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPERTHYROIDISM LEU-597.
[48]"A novel activating mutation in the thyrotropin receptor gene in an autonomously functioning thyroid nodule developed by a Japanese patient."
Kosugi S., Hai N., Okamoto H., Sugawa H., Mori T.
Eur. J. Endocrinol. 143:471-477(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPERTHYROIDISM ARG-512, CHARACTERIZATION OF VARIANT HYPERTHYROIDISM ARG-512.
[49]"Analysis of the genetic variability of the 1st (CCC/ACC, P52T) and the 10th exons (bp 1012-1704) of the TSH receptor gene in Graves' disease."
Kaczur V., Takacs M., Szalai C., Falus A., Nagy Z., Berencsi G., Balazs C.
Eur. J. Immunogenet. 27:17-23(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-52.
[50]"Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene."
Tonacchera M., Agretti P., Pinchera A., Rosellini V., Perri A., Collecchi P., Vitti P., Chiovato L.
J. Clin. Endocrinol. Metab. 85:1001-1008(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CHNG1 ILE-477.
[51]"Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter."
Tonacchera M., Agretti P., Chiovato L., Rosellini V., Ceccarini G., Perri A., Viacava P., Naccarato A.G., Miccoli P., Pinchera A., Vitti P.
J. Clin. Endocrinol. Metab. 85:2270-2274(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HTNA ASN-281; MET-486; PHE-486; PHE-629; ALA-632; ILE-632; GLU-633 AND VAL-647.
[52]"Lack of association of nonautoimmune hyperfunctioning thyroid disorders and a germline polymorphism of codon 727 of the human thyrotropin receptor in a European Caucasian population."
Muehlberg T., Herrmann K., Joba W., Kirchberger M., Heberling H.-J., Heufelder A.E.
J. Clin. Endocrinol. Metab. 85:2640-2643(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLU-727.
[53]"A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH."
Russo D., Betterle C., Arturi F., Chiefari E., Girelli M.E., Filetti S.
J. Clin. Endocrinol. Metab. 85:4238-4242(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CHNG1 CYS-310.
[54]"Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood."
Biebermann H., Schoeneberg T., Krude H., Gudermann T., Grueters A.
Langenbecks Arch. Surg. 385:390-392(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HTNA ASN-281; SER-431 AND ILE-632.
[55]"Sporadic nonautoimmune congenital hyperthyroidism due to a strong activating mutation of the thyrotropin receptor gene."
Tonacchera M., Agretti P., Rosellini V., Ceccarini G., Perri A., Zampolli M., Longhi R., Larizza D., Pinchera A., Vitti P., Chiovato L.
Thyroid 10:859-863(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA THR-568.
[56]"A Phe 486 thyrotropin receptor mutation in an autonomously functioning follicular carcinoma that was causing hyperthyroidism."
Camacho P., Gordon D., Chiefari E., Yong S., DeJong S., Pitale S., Russo D., Filetti S.
Thyroid 10:1009-1012(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FOLLICULAR CARCINOMA PHE-486.
[57]"Novel TSHR germline mutation (Met463Val) masquerading as Graves' disease in a large Welsh kindred with hyperthyroidism."
Fuhrer D., Warner J., Sequeira M., Paschke R., Gregory J.W., Ludgate M.
Thyroid 10:1035-1041(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA VAL-463.
[58]"A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism."
Alberti L., Proverbio M.C., Costagliola S., Weber G., Beck-Peccoz P., Chiumello G., Persani L.
Eur. J. Endocrinol. 145:249-254(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA PHE-597, CHARACTERIZATION OF VARIANT HTNA PHE-597.
[59]"The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism."
Biebermann H., Schoeneberg T., Hess C., Germak J., Gudermann T., Grueters A.
J. Clin. Endocrinol. Metab. 86:4429-4433(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA SER-431, CHARACTERIZATION OF VARIANT HTNA SER-431.
[60]"Detection of thyroid-stimulating hormone receptor and G(s)alpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis."
Truelzsch B., Krohn K., Wonerow P., Chey S., Holzapfel H.-P., Ackermann F., Fuehrer D., Paschke R.
J. Mol. Med. 78:684-691(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TTNS ASN-281; ILE-425; THR-453; PHE-486; ASN-505; ARG-512; GLN-512; THR-568; GLY-619; VAL-623; LEU-631; ALA-632; ILE-632; GLU-633; HIS-633; TYR-633; ALA-639 AND PHE-656, CHARACTERIZATION OF VARIANTS TTNS ILE-425 AND GLN-512.
[61]"Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin."
Nagashima T., Murakami M., Onigata K., Morimura T., Nagashima K., Mori M., Morikawa A.
Thyroid 11:551-559(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CHNG1 HIS-450 AND SER-498.
[62]"Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population."
Vanvooren V., Uchino S., Duprez L., Costa M.J., Vandekerckhove J., Parma J., Vassart G., Dumont J.E., van Sande J., Noguchi S.
Eur. J. Endocrinol. 147:287-291(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPERTHYROIDISM THR-453; MET-486; ARG-512 AND ALA-632.
[63]"Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism."
Alberti L., Proverbio M.C., Costagliola S., Romoli R., Boldrighini B., Vigone M.C., Weber G., Chiumello G., Beck-Peccoz P., Persani L.
J. Clin. Endocrinol. Metab. 87:2549-2555(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CHNG1 SER-41; ALA-162; PRO-467 AND ARG-600.
[64]"Functional significance of the thyrotropin receptor germline polymorphism D727E."
Sykiotis G.P., Neumann S., Georgopoulos N.A., Sgourou A., Papachatzopoulou A., Markou K.B., Kyriazopoulou V., Paschke R., Vagenakis A.G., Papavassiliou A.G.
Biochem. Biophys. Res. Commun. 301:1051-1056(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TOXIC THYROID ADENOMA ASN-593, VARIANT GLU-727, CHARACTERIZATION OF VARIANTS TOXIC THYROID ADENOMA ASN-593 AND ASN-593/GLU-727, CHARACTERIZATION OF VARIANT GLU-727.
[65]"Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects."
Peeters R.P., van Toor H., Klootwijk W., de Rijke Y.B., Kuiper G.G.J.M., Uitterlinden A.G., Visser T.J.
J. Clin. Endocrinol. Metab. 88:2880-2888(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-36; THR-52 AND GLU-727, ASSOCIATION WITH PLASMA TSH LEVEL.
[66]"TSH receptor and Gs(alpha) genetic analysis in children with Down's syndrome and subclinical hypothyroidism."
Tonacchera M., Perri A., De Marco G., Agretti P., Montanelli L., Banco M.E., Corrias A., Bellone J., Tosi M.T., Vitti P., Martino E., Pinchera A., Chiovato L.
J. Endocrinol. Invest. 26:997-1000(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-36 AND THR-52, RECEPTOR GENETIC ANALYSIS IN CHILDREN WITH DOWN'S SYNDROME.
[67]"Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor."
Park S.-M., Clifton-Bligh R.J., Betts P., Chatterjee V.K.K.
Clin. Endocrinol. (Oxf.) 60:220-227(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CHNG1 THR-553.
[68]"Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation."
Vaidya B., Campbell V., Tripp J.H., Spyer G., Hattersley A.T., Ellard S.
Clin. Endocrinol. (Oxf.) 60:711-718(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTNA ASN-505.
[69]"Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism."
Tonacchera M., Perri A., De Marco G., Agretti P., Banco M.E., Di Cosmo C., Grasso L., Vitti P., Chiovato L., Pinchera A.
J. Clin. Endocrinol. Metab. 89:5787-5793(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CHNG1 ALA-162 AND PRO-252, CHARACTERIZATION OF VARIANT CHNG1 PRO-252.
+Additional computationally mapped references.

Web resources

TSH receptor database
GRIS

Glycoprotein-hormone Receptors Information System

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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS32131.1. [P16473-2]
CCDS55935.1. [P16473-3]
CCDS9872.1. [P16473-1]
PIRQRHURH. A33789.
JC1319.
T01787.
RefSeqNP_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]
UniGeneHs.160411.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XUMmodel-A54-236[»]
2XWTX-ray1.90C22-260[»]
3G04X-ray2.55C22-260[»]
ProteinModelPortalP16473.
SMRP16473. Positions 24-305, 411-686.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113104. 10 interactions.
STRING9606.ENSP00000298171.

Chemistry

BindingDBP16473.
ChEMBLCHEMBL1963.
DrugBankDB00024. Thyrotropin Alfa.
GuidetoPHARMACOLOGY255.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP16473.

Polymorphism databases

DMDM62298994.

Proteomic databases

PaxDbP16473.
PRIDEP16473.

Protocols and materials databases

DNASU7253.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000298171; ENSP00000298171; ENSG00000165409.
ENST00000342443; ENSP00000340113; ENSG00000165409. [P16473-2]
ENST00000541158; ENSP00000441235; ENSG00000165409.
ENST00000554435; ENSP00000450549; ENSG00000165409. [P16473-3]
GeneID7253.
KEGGhsa:7253.
UCSCuc001xvc.3. human. [P16473-2]

Organism-specific databases

CTD7253.
GeneCardsGC14P081421.
H-InvDBHIX0021925.
HGNCHGNC:12373. TSHR.
HPACAB000473.
HPA026680.
MIM275200. phenotype.
603372. gene+phenotype.
603373. phenotype.
609152. phenotype.
neXtProtNX_P16473.
Orphanet95713. Athyreosis.
99819. Familial gestational hyperthyroidism.
424. Familial hyperthyroidism due to mutations in TSH receptor.
90673. Hypothyroidism due to TSH receptor mutations.
95720. Thyroid hypoplasia.
PharmGKBPA37042.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG285844.
HOVERGENHBG052887.
InParanoidP16473.
KOK04249.
OMASSATIHK.
OrthoDBEOG73BVCG.
PhylomeDBP16473.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkP16473.

Gene expression databases

ArrayExpressP16473.
BgeeP16473.
CleanExHS_TSHR.
GenevestigatorP16473.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR001611. Leu-rich_rpt.
IPR026906. LRR_5.
IPR002274. TSH_rcpt.
[Graphical view]
PANTHERPTHR24372. PTHR24372. 1 hit.
PTHR24372:SF0. PTHR24372:SF0. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 1 hit.
PF13855. LRR_8. 1 hit.
[Graphical view]
PRINTSPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01145. TSHRECEPTOR.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTSHR. human.
EvolutionaryTraceP16473.
GeneWikiThyrotropin_receptor.
GenomeRNAi7253.
NextBio28361.
PROP16473.
SOURCESearch...

Entry information

Entry nameTSHR_HUMAN
AccessionPrimary (citable) accession number: P16473
Secondary accession number(s): A0PJU7 expand/collapse secondary AC list , F5GYU5, G3V2A9, Q16503, Q8TB90, Q96GT6, Q9P1V4, Q9ULA3, Q9UPH3
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 29, 2005
Last modified: July 9, 2014
This is version 180 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries