P16473 (TSHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thyrotropin receptor

Alternative name(s):
Thyroid-stimulating hormone receptor
Short name=TSH-R

Gene names

Name:	TSHR
Synonyms:	LGR3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	764 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Congenital hypothyroidism Disease mutation
Domain	Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Traceable author statement PubMed 8552586. Source: ProtInc cell-cell signaling Traceable author statement Ref.24. Source: ProtInc positive regulation of cell proliferation Traceable author statement Ref.24. Source: ProtInc
Cellular_component	integral to plasma membrane Traceable author statement PubMed 8552586. Source: ProtInc
Molecular_function	thyroid-stimulating hormone receptor activity Traceable author statement PubMed 8552586. Source: ProtInc
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Chain

21 – 764

744

Thyrotropin receptor

PRO_0000012786

Regions

Topological domain

21 – 413

393

Extracellular Potential

Transmembrane

414 – 441

28

Helical; Name=1; Potential

Topological domain

442 – 450

9

Cytoplasmic Potential

Transmembrane

451 – 473

23

Helical; Name=2; Potential

Topological domain

474 – 494

21

Extracellular Potential

Transmembrane

495 – 517

23

Helical; Name=3; Potential

Topological domain

518 – 537

20

Cytoplasmic Potential

Transmembrane

538 – 560

23

Helical; Name=4; Potential

Topological domain

561 – 580

20

Extracellular Potential

Transmembrane

581 – 602

22

Helical; Name=5; Potential

Topological domain

603 – 625

23

Cytoplasmic Potential

Transmembrane

626 – 649

24

Helical; Name=6; Potential

Topological domain

650 – 660

11

Extracellular Potential

Transmembrane

661 – 682

22

Helical; Name=7; Potential

Topological domain

683 – 764

82

Cytoplasmic Potential

Repeat

100 – 124

25

LRR 1

Repeat

125 – 150

26

LRR 2

Repeat

152 – 174

23

LRR 3

Repeat

176 – 199

24

LRR 4

Repeat

200 – 223

24

LRR 5

Repeat

227 – 248

22

LRR 6

Repeat

250 – 271

22

LRR 7

Motif

762 – 764

3

PDZ-binding

Amino acid modifications

Glycosylation

77

1

N-linked (GlcNAc...) Ref.10 Ref.14

Glycosylation

99

1

N-linked (GlcNAc...) Ref.14

Glycosylation

113

1

N-linked (GlcNAc...) Ref.10 Ref.14

Glycosylation

177

1

N-linked (GlcNAc...) Ref.14

Glycosylation

198

1

N-linked (GlcNAc...) Ref.10 Ref.14

Glycosylation

302

1

N-linked (GlcNAc...) Ref.10

Disulfide bond

31 ↔ 41

Ref.14

Disulfide bond

494 ↔ 569

By similarity

Natural variations

Alternative sequence

232 – 274

43

DVSQT…LHLTR → VENVAVSGKGFCKSLFSWLY RLPLGRKSLSFETQKAPRSS MPS in isoform 3.

VSP_044643

Alternative sequence

232 – 253

22

DVSQT…LKELI → LPLGRKSLSFETQKAPRSSM PS in isoform Short.

VSP_001981

Alternative sequence

254 – 764

511

Missing in isoform Short.

VSP_001982

Alternative sequence

275 – 764

490

Missing in isoform 3.

VSP_044644

Natural variant

34

1

E → K.
Corresponds to variant rs45499704 [ dbSNP | Ensembl ].

VAR_055925

Natural variant

36

1

D → H in a patient with Graves disease. Ref.17 Ref.19 Ref.25 Ref.65 Ref.66

VAR_003564

Natural variant

41

1

C → S in CHNG1. Ref.32 Ref.63

VAR_011519

Natural variant

52

1

P → 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 variant

109

1

R → Q in CHNG1. Ref.34

VAR_011520

Natural variant

162

1

P → A in CHNG1. Ref.27 Ref.32 Ref.63 Ref.69

VAR_011521

Natural variant

167

1

I → N in CHNG1. Ref.27

VAR_011522

Natural variant

183

1

K → R in HTFG; enhances receptor response to chorionic gonadotropin. Ref.43

VAR_003566

Natural variant

197

1

F → I in papillary cancer. Ref.28

VAR_003567

Natural variant

219

1

D → E in papillary cancer. Ref.28

VAR_003568

Natural variant

252

1

L → 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 variant

281

1

S → I in hyperthyroidism; congenital; due to a toxic adenoma. Ref.40

VAR_003569

Natural variant

281

1

S → 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 variant

281

1

S → T in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. Ref.35

VAR_011523

Natural variant

310

1

R → C in CHNG1. Ref.53

VAR_011524

Natural variant

390

1

C → W in CHNG1; persistent hypothyroidism and defective thyroid development; habolishes high affinity hormone binding. Ref.32 Ref.36

VAR_011525

Natural variant

410

1

D → N in CHNG1; lack of adenylate cyclase activation. Ref.32

VAR_011526

Natural variant

425

1

S → 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 variant

431

1

G → S in HTNA; gain of function; constitutive activation of the G(s)/adenylyl cyclase system. Ref.54 Ref.59

VAR_011527

Natural variant

450

1

R → H in CHNG1. Ref.61

VAR_011528

Natural variant

453

1

M → T in HTNA; sporadic; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. Ref.31 Ref.35 Ref.60 Ref.62

VAR_011529

Natural variant

463

1

M → V in HTNA; gain of function. Ref.57

VAR_011530

Natural variant

467

1

L → P in CHNG1. Ref.63

VAR_017295

Natural variant

477

1

T → I in CHNG1; severe hypothyroidism. Ref.50

VAR_017296

Natural variant

486

1

I → 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 variant

486

1

I → M in HTNA; found in hyperfunctioning thyroid adenomas. Ref.35 Ref.51 Ref.62

VAR_011532

Natural variant

498

1

G → S in CHNG1. Ref.61

VAR_011533

Natural variant

505

1

S → N in HTNA; found in toxic thyroid nodules. Ref.37 Ref.60 Ref.68

VAR_003571

Natural variant

505

1

S → R in HTNA; gain of function. Ref.30

VAR_011534

Natural variant

509

1

V → A in HTNA; gain of function. Ref.24

VAR_011535

Natural variant

512

1

L → 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 variant

512

1

L → 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 variant

525

1

F → L in CHNG1; impairs adenylate cyclase activation. Ref.32

VAR_011537

Natural variant

528

1

R → H. Ref.42

VAR_003572

Natural variant

553

1

A → T in CHNG1; severe hypothyroidism. Ref.39 Ref.67

VAR_011538

Natural variant

568

1

I → T in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. Ref.35 Ref.55 Ref.60

VAR_011539

Natural variant

593

1

A → 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 variant

597

1

V → F in HTNA; 11-fold increase in specific constitutive activity associated with reduction in receptor protein expression. Ref.58

VAR_021499

Natural variant

597

1

V → L in hyperthyroidism; congenital with severe thyrotoxicosis. Ref.47

VAR_011540

Natural variant

600

1

C → R in CHNG1. Ref.63

VAR_017297

Natural variant

606

1

I → M. Ref.45

VAR_011541

Natural variant

619

1

D → G in hyperthyroidism and TTNs; associated with hyperfunctioning thyroid adenomas. Ref.20 Ref.35 Ref.60

VAR_003573

Natural variant

623

1

A → I in hyperthyroidism; associated with hyperfunctioning thyroid adenomas; gain of function; requires 2 nucleotide substitutions. Ref.20 Ref.35

VAR_003574

Natural variant

623

1

A → V in hyperthyroidism and TTNs; associated with hyperfunctioning thyroid adenomas; gain of function. Ref.23 Ref.60

VAR_011542

Natural variant

629

1

L → F in HTNA; also in hyperfunctioning thyroid adenomas and non-adenomatous nodules. Ref.35 Ref.38 Ref.51

VAR_003575

Natural variant

630

1

I → L in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. Ref.35

VAR_011543

Natural variant

631

1

F → C in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. Ref.22

VAR_011544

Natural variant

631

1

F → L in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. Ref.26 Ref.35 Ref.60

VAR_011545

Natural variant

632

1

T → 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 variant

632

1

T → 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 variant

633

1

D → A in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. Ref.35

VAR_011548

Natural variant

633

1

D → E in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. Ref.22 Ref.35 Ref.51 Ref.60

VAR_011549

Natural variant

633

1

D → 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 variant

633

1

D → Y in hyperthyroidism and TTNs; associated with hyperfunctioning thyroid adenomas. Ref.22 Ref.35 Ref.60

VAR_011551

Natural variant

639

1

P → A in TTNs. Ref.60

VAR_021500

Natural variant

639

1

P → S in HTNA; gain of function. Ref.44

VAR_011552

Natural variant

647

1

A → V in HTNA; found in non-adenomatous hyperfunctioning nodules. Ref.51

VAR_011553

Natural variant

650

1

N → Y in HTNA; gain of function. Ref.30

VAR_011554

Natural variant

656

1

V → F in TTNs. Ref.60

VAR_021501

Natural variant

658 – 661

4

Missing in hyperthyroidism; associated with hyperfunctioning thyroid adenomas.

VAR_011555

Natural variant

670

1

N → S in HTNA; gain of function. Ref.30

VAR_011556

Natural variant

672

1

C → Y in HTNA; gain of function. Ref.24

VAR_011557

Natural variant

677

1

L → V in thyroid carcinoma; with thyrotoxicosis; gain of function. Ref.46

VAR_011558

Natural variant

703

1

A → G. Ref.45

VAR_011559

Natural variant

715

1

N → D in papillary cancer. Ref.28

VAR_003576

Natural variant

720

1

Q → E. Ref.45

VAR_011560

Natural variant

723

1

K → M in papillary cancer. Ref.28

VAR_003577

Natural variant

727

1

D → 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 conflict

87

1

V → L no nucleotide entry Ref.2

Sequence conflict

196 – 198

3

AFN → DFF in AAA70232. Ref.4

Sequence conflict

257

1

T → S in AAA70232. Ref.4

Sequence conflict

264

1

P → A in AAA70232. Ref.4

Sequence conflict

306 – 308

3

MQS → IET in AAA70232. Ref.4

Sequence conflict

528

1

R → A in AAA70232. Ref.4

Sequence conflict

601

1

Y → H in AAA36783. Ref.1

Sequence conflict

635

1

I → T in AAA70232. Ref.4

Sequence conflict

645

1

L → V in AAA70232. Ref.4

Sequence conflict

669

1

L → I in AAA70232. Ref.4

Sequence conflict

744

1

N → K in AAA61236. Ref.3

Isoform Short:

Sequence conflict

239

1

L → F in AAB24246. Ref.6

Sequence conflict

248

1

R → S in AAB23390. Ref.5

Sequence conflict

248

1

R → S in AAH09237. Ref.9

Sequence conflict

248

1

R → S in AAI20974. Ref.9

Sequence conflict

251

1

M → T in AAB23390. Ref.5

Isoform 3:

Sequence conflict

269

1

R → S in AAI27629. Ref.9

Secondary structure

1

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764

Helix Strand Turn

Details...

Beta strand

26 – 28

3

Beta strand

30 – 33

4

Turn

35 – 37

3

Beta strand

38 – 41

4

Beta strand

56 – 61

6

Beta strand

65 – 67

3

Turn

69 – 74

6

Beta strand

80 – 84

5

Turn

94 – 96

3

Beta strand

97 – 99

3

Beta strand

105 – 111

7

Beta strand

121 – 123

3

Beta strand

130 – 136

7

Beta strand

152 – 160

9

Turn

169 – 174

6

Beta strand

175 – 183

9

Beta strand

190 – 192

3

Turn

194 – 199

6

Beta strand

201 – 206

6

Turn

218 – 223

6

Beta strand

229 – 232

4

Beta strand

250 – 253

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified March 29, 2005. Version 2. Checksum: D2EE9CEBFD64A65F	FASTA	764	86,830
	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
	Isoform Short [UniParc]. Checksum: 69E12F0A7D8B5FD0	FASTA	253	28,427
	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 LLPLGRKSLS 250 FETQKAPRSS MPS
	Isoform 3 [UniParc]. Checksum: A8A8DBB061774F5C	FASTA	274	30,800
	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 LVENVAVSGK 250 260 270 GFCKSLFSWL YRLPLGRKSL SFETQKAPRS SMPS

References

	« Hide 'large scale' referencesShow '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. , 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

GeneReviews

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.

IPI

IPI00028642.
IPI00744312.
IPI00902935.

PIR

QRHURH. A33789.
JC1319.
T01787.

RefSeq

NP_000360.2. NM_000369.2.
NP_001018046.1. NM_001018036.2.
NP_001136098.1. NM_001142626.2.

UniGene

Hs.160411.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XUM	model	-	A	54-236	[»]
2XWT	X-ray	1.90	C	22-260	[»]
3G04	X-ray	2.55	C	22-260	[»]

ProteinModelPortal

P16473.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000298171.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P16473.

Polymorphism databases

DMDM

62298994.

Proteomic databases

PaxDb

P16473.

PRIDE

P16473.

Protocols and materials databases

DNASU

7253.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000342443; ENSP00000340113; ENSG00000165409.
ENST00000554435; ENSP00000450549; ENSG00000165409.

GeneID

7253.

KEGG

hsa:7253.

UCSC

uc001xvc.3. human.
uc001xvd.1. human.
uc010tvs.2. human.

Organism-specific databases

CTD

7253.

GeneCards

GC14P081421.

H-InvDB

HIX0021925.

HGNC

HGNC:12373. TSHR.

HPA

CAB000473.
HPA026680.

MIM

275200. phenotype.
603372. gene+phenotype.
603373. phenotype.
609152. phenotype.

neXtProt

NX_P16473.

Orphanet

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.

PharmGKB

PA37042.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG285844.

HOVERGEN

HBG052887.

InParanoid

P16473.

KO

K04249.

OrthoDB

EOG4S1T6J.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6cyclingpathway. Arf6 signaling events.
arf6_traffickingpathway. Arf6 trafficking events.

Reactome

REACT_111102. Signal Transduction.

SignaLink

P16473.

Gene expression databases

ArrayExpress

P16473.

Bgee

P16473.

CleanEx

HS_TSHR.

Genevestigator

P16473.

GermOnline

ENSG00000165409. Homo sapiens.

Family and domain databases

InterPro

IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt.
IPR026906. LRR_5.
IPR002274. TSH_rcpt.
[Graphical view]

PANTHER

PTHR24372:SF0. PTHR24372:SF0. 1 hit.

Pfam

PF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 1 hit.
[Graphical view]

PRINTS

PR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01145. TSHRECEPTOR.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P16473.

ChEMBL

CHEMBL1963.

ChiTaRS

TSHR. human.

DrugBank

DB00024. Thyrotropin Alfa.

EvolutionaryTrace

P16473.

GenomeRNAi

7253.

NextBio

28361.

SOURCE

Search...

Entry information

Entry name

TSHR_HUMAN

Accession

Primary (citable) accession number: P16473
Secondary accession number(s): A0PJU7 , 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:	May 29, 2013
This is version 167 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.