UniProtKB - P16473 (TSHR_HUMAN)
Thyrotropin receptor
TSHR
Functioni
Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258).
Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin (PubMed:12045258).
The activity of this receptor is mediated by G proteins which activate adenylate cyclase (PubMed:11847099).
Plays a central role in controlling thyroid cell metabolism (By similarity).
By similarity2 PublicationsGO - Molecular functioni
- G protein-coupled peptide receptor activity Source: GO_Central
- protein-containing complex binding Source: UniProtKB
- signaling receptor activity Source: UniProtKB
- thyroid-stimulating hormone receptor activity Source: UniProtKB
GO - Biological processi
- activation of adenylate cyclase activity Source: GO_Central
- adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: UniProtKB
- cell-cell signaling Source: ProtInc
- cell surface receptor signaling pathway Source: UniProtKB
- cellular response to glycoprotein Source: UniProtKB
- cellular response to thyrotropin-releasing hormone Source: UniProtKB
- G protein-coupled receptor signaling pathway Source: ProtInc
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
- hormone-mediated signaling pathway Source: GO_Central
- positive regulation of cell population proliferation Source: ProtInc
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- thyroid-stimulating hormone signaling pathway Source: UniProtKB
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Enzyme and pathway databases
PathwayCommonsi | P16473 |
Reactomei | R-HSA-375281, Hormone ligand-binding receptors R-HSA-418555, G alpha (s) signalling events R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SignaLinki | P16473 |
SIGNORi | P16473 |
Names & Taxonomyi
Protein namesi | Recommended name: Thyrotropin receptorAlternative name(s): Thyroid-stimulating hormone receptor Short name: TSH-R |
Gene namesi | Name:TSHR Synonyms:LGR3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:12373, TSHR |
MIMi | 603372, gene+phenotype |
neXtProti | NX_P16473 |
VEuPathDBi | HostDB:ENSG00000165409 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein Curated
- Basolateral cell membrane 1 Publication; Multi-pass membrane protein Curated
Plasma Membrane
- basolateral plasma membrane Source: UniProtKB
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: UniProtKB
Other locations
- cell surface Source: UniProtKB
- receptor complex Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 21 – 413 | ExtracellularSequence analysisAdd BLAST | 393 | |
Transmembranei | 414 – 441 | Helical; Name=1Sequence analysisAdd BLAST | 28 | |
Topological domaini | 442 – 450 | CytoplasmicSequence analysis | 9 | |
Transmembranei | 451 – 473 | Helical; Name=2Sequence analysisAdd BLAST | 23 | |
Topological domaini | 474 – 494 | ExtracellularSequence analysisAdd BLAST | 21 | |
Transmembranei | 495 – 517 | Helical; Name=3Sequence analysisAdd BLAST | 23 | |
Topological domaini | 518 – 537 | CytoplasmicSequence analysisAdd BLAST | 20 | |
Transmembranei | 538 – 560 | Helical; Name=4Sequence analysisAdd BLAST | 23 | |
Topological domaini | 561 – 580 | ExtracellularSequence analysisAdd BLAST | 20 | |
Transmembranei | 581 – 602 | Helical; Name=5Sequence analysisAdd BLAST | 22 | |
Topological domaini | 603 – 625 | CytoplasmicSequence analysisAdd BLAST | 23 | |
Transmembranei | 626 – 649 | Helical; Name=6Sequence analysisAdd BLAST | 24 | |
Topological domaini | 650 – 660 | ExtracellularSequence analysisAdd BLAST | 11 | |
Transmembranei | 661 – 682 | Helical; Name=7Sequence analysisAdd BLAST | 22 | |
Topological domaini | 683 – 764 | CytoplasmicSequence analysisAdd BLAST | 82 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Hypothyroidism, congenital, non-goitrous, 1 (CHNG1)12 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_011519 | 41 | C → S in CHNG1. 2 Publications | 1 | |
Natural variantiVAR_011520 | 109 | R → Q in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_011521 | 162 | P → A in CHNG1. 5 PublicationsCorresponds to variant dbSNP:rs121908863EnsemblClinVar. | 1 | |
Natural variantiVAR_011522 | 167 | I → N in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_021495 | 252 | L → P in CHNG1; displays a low expression at the cell surface and a reduced response to bovine TSH in terms of cAMP production. 1 Publication | 1 | |
Natural variantiVAR_011524 | 310 | R → C in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_011525 | 390 | C → W in CHNG1; persistent hypothyroidism and defective thyroid development; abolishes high affinity hormone binding. 2 Publications | 1 | |
Natural variantiVAR_011526 | 410 | D → N in CHNG1; lack of adenylate cyclase activation. 1 Publication | 1 | |
Natural variantiVAR_075585 | 432 | N → D in CHNG1; abolishes cell membrane location; abolishes adenylate cyclase-activating G-protein coupled receptor signaling pathway; abolishes phospholipase C-activating G-protein coupled receptor signaling pathway. 1 Publication | 1 | |
Natural variantiVAR_075586 | 449 | P → L in CHNG1; no effect on cell membrane location; upon TSH stimulation decreases more phospholipase C-activating G-protein coupled receptor signaling pathway than adenylate cyclase-activating G-protein coupled receptor signaling pathway. 1 Publication | 1 | |
Natural variantiVAR_011528 | 450 | R → H in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_017295 | 467 | L → P in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_017296 | 477 | T → I in CHNG1; severe hypothyroidism. 1 Publication | 1 | |
Natural variantiVAR_011533 | 498 | G → S in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_011537 | 525 | F → L in CHNG1; impairs adenylate cyclase activation. 1 Publication | 1 | |
Natural variantiVAR_011538 | 553 | A → T in CHNG1; severe hypothyroidism. 2 Publications | 1 | |
Natural variantiVAR_017297 | 600 | C → R in CHNG1. 1 Publication | 1 |
Familial gestational hyperthyroidism (HTFG)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_003566 | 183 | K → R in HTFG; enhances receptor response to chorionic gonadotropin. 1 Publication | 1 |
Hyperthyroidism, non-autoimmune (HTNA)16 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_003570 | 281 | S → N in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 5 Publications | 1 | |
Natural variantiVAR_011527 | 431 | G → S in HTNA; gain of function; constitutive activation of the G(s)/adenylyl cyclase system. 2 Publications | 1 | |
Natural variantiVAR_011529 | 453 | M → T in HTNA; sporadic; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 4 Publications | 1 | |
Natural variantiVAR_011530 | 463 | M → V in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011531 | 486 | I → F in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas; also in hyperfunctioning follicular carcinoma. 4 Publications | 1 | |
Natural variantiVAR_011532 | 486 | I → M in HTNA; found in hyperfunctioning thyroid adenomas. 3 Publications | 1 | |
Natural variantiVAR_003571 | 505 | S → N in HTNA; found in toxic thyroid nodules. 3 Publications | 1 | |
Natural variantiVAR_011534 | 505 | S → R in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011535 | 509 | V → A in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011539 | 568 | I → T in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 3 Publications | 1 | |
Natural variantiVAR_021499 | 597 | V → F in HTNA; 11-fold increase in specific constitutive activity associated with reduction in receptor protein expression. 1 Publication | 1 | |
Natural variantiVAR_003575 | 629 | L → F in HTNA; also in hyperfunctioning thyroid adenomas and non-adenomatous nodules. 3 Publications | 1 | |
Natural variantiVAR_011545 | 631 | F → L in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 3 Publications | 1 | |
Natural variantiVAR_011546 | 632 | T → A in HTNA; found in toxic thyroid nodules and hyperfunctioning non-adenomatous nodules. 3 Publications | 1 | |
Natural variantiVAR_011547 | 632 | T → I in HTNA; gain of function; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 7 Publications | 1 | |
Natural variantiVAR_011549 | 633 | D → E in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 4 Publications | 1 | |
Natural variantiVAR_011552 | 639 | P → S in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011553 | 647 | A → V in HTNA; found in non-adenomatous hyperfunctioning nodules. 1 Publication | 1 | |
Natural variantiVAR_011554 | 650 | N → Y in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011556 | 670 | N → S in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011557 | 672 | C → Y in HTNA; gain of function. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 283 | C → S: Abolishes cell surface expression. 1 Publication | 1 | |
Mutagenesisi | 385 – 387 | YDY → EDE: Inhibits intracellular cAMP accumulation. 1 Publication | 3 | |
Mutagenesisi | 385 – 387 | YDY → FDF: Abolishes sulfation. Inhibits intracellular cAMP accumulation. 1 Publication | 3 | |
Mutagenesisi | 385 | Y → E: Reduces binding with thyrotropin. Inhibits intracellular cAMP accumulation. 1 Publication1 Publication | 1 | |
Mutagenesisi | 385 | Y → F: Reduces sulfation. Reduces binding with thyrotropin. Inhibits intracellular cAMP accumulation. 1 Publication1 Publication | 1 | |
Mutagenesisi | 387 | Y → E: No change in intracellular cAMP accumulation. 1 Publication | 1 | |
Mutagenesisi | 387 | Y → F: Reduces sulfation. No change in intracellular cAMP accumulation. 1 Publication | 1 |
Keywords - Diseasei
Congenital hypothyroidism, Disease variantOrganism-specific databases
DisGeNETi | 7253 |
MalaCardsi | TSHR |
MIMi | 275200, phenotype 603372, gene+phenotype 603373, phenotype 609152, phenotype |
OpenTargetsi | ENSG00000165409 |
Orphaneti | 95713, Athyreosis 99819, Familial gestational hyperthyroidism 424, Familial hyperthyroidism due to mutations in TSH receptor 90673, Hypothyroidism due to TSH receptor mutations 95720, Thyroid hypoplasia |
PharmGKBi | PA37042 |
Miscellaneous databases
Pharosi | P16473, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1963 |
DrugBanki | DB00024, Thyrotropin alfa |
DrugCentrali | P16473 |
GuidetoPHARMACOLOGYi | 255 |
Genetic variation databases
BioMutai | TSHR |
DMDMi | 62298994 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Add BLAST | 20 | |
ChainiPRO_0000012786 | 21 – 764 | Thyrotropin receptorAdd BLAST | 744 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 31 ↔ 41 | |||
Glycosylationi | 77 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 99 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 113 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 177 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 198 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 302 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Modified residuei | 385 | Sulfotyrosine1 Publication | 1 | |
Disulfide bondi | 494 ↔ 569 | PROSITE-ProRule annotation |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, SulfationProteomic databases
MassIVEi | P16473 |
PaxDbi | P16473 |
PeptideAtlasi | P16473 |
PRIDEi | P16473 |
ProteomicsDBi | 24847 32578 53374 [P16473-1] 53375 [P16473-2] |
PTM databases
GlyGeni | P16473, 6 sites |
iPTMneti | P16473 |
PhosphoSitePlusi | P16473 |
SwissPalmi | P16473 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000165409, Expressed in left lobe of thyroid gland and 118 other tissues |
ExpressionAtlasi | P16473, baseline and differential |
Genevisiblei | P16473, HS |
Organism-specific databases
HPAi | ENSG00000165409, Tissue enriched (thyroid) |
Interactioni
Subunit structurei
Binary interactionsi
P16473
With | #Exp. | IntAct |
---|---|---|
ADORA1 [P30542] | 2 | EBI-13939599,EBI-2903663 |
MID1IP1 [Q9NPA3] | 2 | EBI-13939599,EBI-750096 |
SCRIB [Q14160] | 3 | EBI-13939599,EBI-357345 |
SYT1 [P21579] | 2 | EBI-13939599,EBI-524909 |
Protein-protein interaction databases
BioGRIDi | 113104, 83 interactors |
IntActi | P16473, 25 interactors |
MINTi | P16473 |
STRINGi | 9606.ENSP00000441235 |
Chemistry databases
BindingDBi | P16473 |
Miscellaneous databases
RNActi | P16473, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P16473 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P16473 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 100 – 124 | LRR 1Add BLAST | 25 | |
Repeati | 125 – 150 | LRR 2Add BLAST | 26 | |
Repeati | 152 – 174 | LRR 3Add BLAST | 23 | |
Repeati | 176 – 199 | LRR 4Add BLAST | 24 | |
Repeati | 200 – 223 | LRR 5Add BLAST | 24 | |
Repeati | 227 – 248 | LRR 6Add BLAST | 22 | |
Repeati | 250 – 271 | LRR 7Add BLAST | 22 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 762 – 764 | PDZ-binding | 3 |
Sequence similaritiesi
Keywords - Domaini
Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2087, Eukaryota |
GeneTreei | ENSGT00940000156510 |
InParanoidi | P16473 |
PhylomeDBi | P16473 |
TreeFami | TF316814 |
Family and domain databases
Gene3Di | 3.80.10.10, 1 hit |
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR002131, Gphrmn_rcpt_fam IPR026906, LRR_5 IPR032675, LRR_dom_sf IPR002274, TSH_rcpt |
PANTHERi | PTHR24372:SF0, PTHR24372:SF0, 1 hit |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit PF13306, LRR_5, 2 hits |
PRINTSi | PR00373, GLYCHORMONER PR00237, GPCRRHODOPSN PR01145, TSHRECEPTOR |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MRPADLLQLV LLLDLPRDLG GMGCSSPPCE CHQEEDFRVT CKDIQRIPSL
60 70 80 90 100
PPSTQTLKLI ETHLRTIPSH AFSNLPNISR IYVSIDVTLQ QLESHSFYNL
110 120 130 140 150
SKVTHIEIRN TRNLTYIDPD ALKELPLLKF LGIFNTGLKM FPDLTKVYST
160 170 180 190 200
DIFFILEITD NPYMTSIPVN AFQGLCNETL TLKLYNNGFT SVQGYAFNGT
210 220 230 240 250
KLDAVYLNKN KYLTVIDKDA FGGVYSGPSL LDVSQTSVTA LPSKGLEHLK
260 270 280 290 300
ELIARNTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM
310 320 330 340 350
CNESSMQSLR QRKSVNALNS PLHQEYEENL GDSIVGYKEK SKFQDTHNNA
360 370 380 390 400
HYYVFFEEQE DEIIGFGQEL KNPQEETLQA FDSHYDYTIC GDSEDMVCTP
410 420 430 440 450
KSDEFNPCED IMGYKFLRIV VWFVSLLALL GNVFVLLILL TSHYKLNVPR
460 470 480 490 500
FLMCNLAFAD FCMGMYLLLI ASVDLYTHSE YYNHAIDWQT GPGCNTAGFF
510 520 530 540 550
TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHACA IMVGGWVCCF
560 570 580 590 600
LLALLPLVGI SSYAKVSICL PMDTETPLAL AYIVFVLTLN IVAFVIVCCC
610 620 630 640 650
YVKIYITVRN PQYNPGDKDT KIAKRMAVLI FTDFICMAPI SFYALSAILN
660 670 680 690 700
KPLITVSNSK ILLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGICK
710 720 730 740 750
RQAQAYRGQR VPPKNSTDIQ VQKVTHDMRQ GLHNMEDVYE LIENSHLTPK
760
KQGQISEEYM QTVL
The sequence of this isoform differs from the canonical sequence as follows:
232-253: DVSQTSVTALPSKGLEHLKELI → LPLGRKSLSFETQKAPRSSMPS
254-764: Missing.
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0A0MTJ0 | A0A0A0MTJ0_HUMAN | Thyrotropin receptor | TSHR | 764 | Annotation score: | ||
A0A1B0GUJ5 | A0A1B0GUJ5_HUMAN | Thyrotropin receptor | TSHR | 399 | Annotation score: | ||
Q0VAP8 | Q0VAP8_HUMAN | TSHR protein | TSHR | 231 | Annotation score: | ||
G3V381 | G3V381_HUMAN | Thyrotropin receptor | TSHR | 112 | Annotation score: | ||
A0A2R8Y709 | A0A2R8Y709_HUMAN | Thyrotropin receptor | TSHR | 89 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 87 | V → L no nucleotide entry (PubMed:2610690).Curated | 1 | ||
Sequence conflicti | 196 – 198 | AFN → DFF in AAA70232 (PubMed:2293030).Curated | 3 | ||
Sequence conflicti | 257 | T → S in AAA70232 (PubMed:2293030).Curated | 1 | ||
Sequence conflicti | 264 | P → A in AAA70232 (PubMed:2293030).Curated | 1 | ||
Sequence conflicti | 306 – 308 | MQS → IET in AAA70232 (PubMed:2293030).Curated | 3 | ||
Sequence conflicti | 528 | R → A in AAA70232 (PubMed:2293030).Curated | 1 | ||
Sequence conflicti | 601 | Y → H in AAA36783 (PubMed:2558651).Curated | 1 | ||
Sequence conflicti | 635 | I → T in AAA70232 (PubMed:2293030).Curated | 1 | ||
Sequence conflicti | 645 | L → V in AAA70232 (PubMed:2293030).Curated | 1 | ||
Sequence conflicti | 669 | L → I in AAA70232 (PubMed:2293030).Curated | 1 | ||
Sequence conflicti | 744 | N → K in AAA61236 (PubMed:2302212).Curated | 1 | ||
Isoform Short (identifier: P16473-2) | |||||
Sequence conflicti | 239 | L → F in AAB24246 (PubMed:1445355).Curated | 1 | ||
Sequence conflicti | 248 | R → S in AAB23390 (PubMed:1530609).Curated | 1 | ||
Sequence conflicti | 248 | R → S in AAH09237 (PubMed:15489334).Curated | 1 | ||
Sequence conflicti | 248 | R → S in AAI20974 (PubMed:15489334).Curated | 1 | ||
Sequence conflicti | 251 | M → T in AAB23390 (PubMed:1530609).Curated | 1 | ||
Isoform 3 (identifier: P16473-3) | |||||
Sequence conflicti | 269 | R → S in AAI27629 (PubMed:15489334).Curated | 1 |
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_055925 | 34 | E → K. Corresponds to variant dbSNP:rs45499704EnsemblClinVar. | 1 | |
Natural variantiVAR_003564 | 36 | D → H in a patient with Graves disease. 5 PublicationsCorresponds to variant dbSNP:rs61747482EnsemblClinVar. | 1 | |
Natural variantiVAR_011519 | 41 | C → S in CHNG1. 2 Publications | 1 | |
Natural variantiVAR_003565 | 52 | P → T Does not contribute to the genetic susceptibility to Graves disease. 7 PublicationsCorresponds to variant dbSNP:rs2234919EnsemblClinVar. | 1 | |
Natural variantiVAR_011520 | 109 | R → Q in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_011521 | 162 | P → A in CHNG1. 5 PublicationsCorresponds to variant dbSNP:rs121908863EnsemblClinVar. | 1 | |
Natural variantiVAR_011522 | 167 | I → N in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_003566 | 183 | K → R in HTFG; enhances receptor response to chorionic gonadotropin. 1 Publication | 1 | |
Natural variantiVAR_003567 | 197 | F → I in papillary cancer. 1 Publication | 1 | |
Natural variantiVAR_003568 | 219 | D → E in papillary cancer. 1 Publication | 1 | |
Natural variantiVAR_021495 | 252 | L → P in CHNG1; displays a low expression at the cell surface and a reduced response to bovine TSH in terms of cAMP production. 1 Publication | 1 | |
Natural variantiVAR_003569 | 281 | S → I in hyperthyroidism; congenital; due to a toxic adenoma. 1 Publication | 1 | |
Natural variantiVAR_003570 | 281 | S → N in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 5 Publications | 1 | |
Natural variantiVAR_011523 | 281 | S → T in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication | 1 | |
Natural variantiVAR_011524 | 310 | R → C in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_011525 | 390 | C → W in CHNG1; persistent hypothyroidism and defective thyroid development; abolishes high affinity hormone binding. 2 Publications | 1 | |
Natural variantiVAR_011526 | 410 | D → N in CHNG1; lack of adenylate cyclase activation. 1 Publication | 1 | |
Natural variantiVAR_021496 | 425 | S → I Found in toxic thyroid nodules; 8 to 9 times higher levels of basal cAMP than wild-type TSHR and similar response to maximal TSH stimulation. 1 Publication | 1 | |
Natural variantiVAR_011527 | 431 | G → S in HTNA; gain of function; constitutive activation of the G(s)/adenylyl cyclase system. 2 Publications | 1 | |
Natural variantiVAR_075585 | 432 | N → D in CHNG1; abolishes cell membrane location; abolishes adenylate cyclase-activating G-protein coupled receptor signaling pathway; abolishes phospholipase C-activating G-protein coupled receptor signaling pathway. 1 Publication | 1 | |
Natural variantiVAR_075586 | 449 | P → L in CHNG1; no effect on cell membrane location; upon TSH stimulation decreases more phospholipase C-activating G-protein coupled receptor signaling pathway than adenylate cyclase-activating G-protein coupled receptor signaling pathway. 1 Publication | 1 | |
Natural variantiVAR_011528 | 450 | R → H in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_011529 | 453 | M → T in HTNA; sporadic; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 4 Publications | 1 | |
Natural variantiVAR_011530 | 463 | M → V in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_017295 | 467 | L → P in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_017296 | 477 | T → I in CHNG1; severe hypothyroidism. 1 Publication | 1 | |
Natural variantiVAR_011531 | 486 | I → F in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas; also in hyperfunctioning follicular carcinoma. 4 Publications | 1 | |
Natural variantiVAR_011532 | 486 | I → M in HTNA; found in hyperfunctioning thyroid adenomas. 3 Publications | 1 | |
Natural variantiVAR_011533 | 498 | G → S in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_003571 | 505 | S → N in HTNA; found in toxic thyroid nodules. 3 Publications | 1 | |
Natural variantiVAR_011534 | 505 | S → R in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011535 | 509 | V → A in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_021497 | 512 | L → Q Found in toxic thyroid nodules; 5 times higher levels of basal cAMP than wild-type TSHR and slightly less response to maximal TSH stimulation. 1 Publication | 1 | |
Natural variantiVAR_011536 | 512 | L → R in hyperthyroidism; associated with autonomously functioning thyroid nodules; 3.3-fold increase in basal cAMP level. 3 Publications | 1 | |
Natural variantiVAR_011537 | 525 | F → L in CHNG1; impairs adenylate cyclase activation. 1 Publication | 1 | |
Natural variantiVAR_003572 | 528 | R → H1 Publication | 1 | |
Natural variantiVAR_011538 | 553 | A → T in CHNG1; severe hypothyroidism. 2 Publications | 1 | |
Natural variantiVAR_011539 | 568 | I → T in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 3 Publications | 1 | |
Natural variantiVAR_021498 | 593 | A → N in toxic thyroid adenoma; requires 2 nucleotide substitutions; somatic mutation; constitutively activates the cAMP cascade. 1 Publication | 1 | |
Natural variantiVAR_021499 | 597 | V → F in HTNA; 11-fold increase in specific constitutive activity associated with reduction in receptor protein expression. 1 Publication | 1 | |
Natural variantiVAR_011540 | 597 | V → L in hyperthyroidism; congenital with severe thyrotoxicosis. 1 Publication | 1 | |
Natural variantiVAR_017297 | 600 | C → R in CHNG1. 1 Publication | 1 | |
Natural variantiVAR_011541 | 606 | I → M1 Publication | 1 | |
Natural variantiVAR_003573 | 619 | D → G in hyperthyroidism; found in toxic thyroid nodules; associated with hyperfunctioning thyroid adenomas. 3 Publications | 1 | |
Natural variantiVAR_003574 | 623 | A → I in hyperthyroidism; associated with hyperfunctioning thyroid adenomas; gain of function; requires 2 nucleotide substitutions. 2 Publications | 1 | |
Natural variantiVAR_011542 | 623 | A → V in hyperthyroidism; found in toxic thyroid nodules; associated with hyperfunctioning thyroid adenomas; gain of function. 2 Publications | 1 | |
Natural variantiVAR_003575 | 629 | L → F in HTNA; also in hyperfunctioning thyroid adenomas and non-adenomatous nodules. 3 Publications | 1 | |
Natural variantiVAR_011543 | 630 | I → L in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication | 1 | |
Natural variantiVAR_011544 | 631 | F → C in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication | 1 | |
Natural variantiVAR_011545 | 631 | F → L in HTNA; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas. 3 Publications | 1 | |
Natural variantiVAR_011546 | 632 | T → A in HTNA; found in toxic thyroid nodules and hyperfunctioning non-adenomatous nodules. 3 Publications | 1 | |
Natural variantiVAR_011547 | 632 | T → I in HTNA; gain of function; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 7 Publications | 1 | |
Natural variantiVAR_011548 | 633 | D → A in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication | 1 | |
Natural variantiVAR_011549 | 633 | D → E in HTNA; found in thyroid toxic nodules and hyperfunctioning thyroid adenomas. 4 Publications | 1 | |
Natural variantiVAR_011550 | 633 | D → H in hyperthyroidism; found in toxic thyroid nodules; associated with hyperfunctioning thyroid adenomas; also in hyperfunctioning insular carcinoma; with severe thyrotoxicosis; gain of function. 3 PublicationsCorresponds to variant dbSNP:rs28937584EnsemblClinVar. | 1 | |
Natural variantiVAR_011551 | 633 | D → Y in hyperthyroidism; found in toxic thyroid nodules; associated with hyperfunctioning thyroid adenomas. 3 Publications | 1 | |
Natural variantiVAR_021500 | 639 | P → A Found in toxic thyroid nodules. 1 Publication | 1 | |
Natural variantiVAR_011552 | 639 | P → S in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011553 | 647 | A → V in HTNA; found in non-adenomatous hyperfunctioning nodules. 1 Publication | 1 | |
Natural variantiVAR_011554 | 650 | N → Y in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_021501 | 656 | V → F Found in toxic thyroid nodules. 1 Publication | 1 | |
Natural variantiVAR_011555 | 658 – 661 | Missing in hyperthyroidism; associated with hyperfunctioning thyroid adenomas. 1 Publication | 4 | |
Natural variantiVAR_011556 | 670 | N → S in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011557 | 672 | C → Y in HTNA; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011558 | 677 | L → V in thyroid carcinoma; with thyrotoxicosis; gain of function. 1 Publication | 1 | |
Natural variantiVAR_011559 | 703 | A → G1 Publication | 1 | |
Natural variantiVAR_003576 | 715 | N → D in papillary cancer. 1 Publication | 1 | |
Natural variantiVAR_011560 | 720 | Q → E1 Publication | 1 | |
Natural variantiVAR_003577 | 723 | K → M in papillary cancer. 1 Publication | 1 | |
Natural variantiVAR_003578 | 727 | D → E May be a predisposing factor in toxic multinodular goiter pathogenesis; activation of the cAMP cascade does not differ from the wild-type. 7 PublicationsCorresponds to variant dbSNP:rs1991517Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044643 | 232 – 274 | DVSQT…LHLTR → VENVAVSGKGFCKSLFSWLY RLPLGRKSLSFETQKAPRSS MPS in isoform 3. 1 PublicationAdd BLAST | 43 | |
Alternative sequenceiVSP_001981 | 232 – 253 | DVSQT…LKELI → LPLGRKSLSFETQKAPRSSM PS in isoform Short. 3 PublicationsAdd BLAST | 22 | |
Alternative sequenceiVSP_001982 | 254 – 764 | Missing in isoform Short. 3 PublicationsAdd BLAST | 511 | |
Alternative sequenceiVSP_044644 | 275 – 764 | Missing in isoform 3. 1 PublicationAdd BLAST | 490 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000342443; ENSP00000340113; ENSG00000165409 [P16473-2] ENST00000554435; ENSP00000450549; ENSG00000165409 [P16473-3] |
GeneIDi | 7253 |
KEGGi | hsa:7253 |
UCSCi | uc001xvc.4, human [P16473-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
TSH receptor database |
SHMPD The Singapore human mutation and polymorphism database |
Wikipedia TSH receptor entry |
Sequence-structure-function-analysis of glycoprotein hormone receptors |
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2XWT | X-ray | 1.90 | C | 22-260 | [»] | |
3G04 | X-ray | 2.55 | C | 22-260 | [»] | |
SMRi | P16473 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 113104, 83 interactors |
IntActi | P16473, 25 interactors |
MINTi | P16473 |
STRINGi | 9606.ENSP00000441235 |
Chemistry databases
BindingDBi | P16473 |
ChEMBLi | CHEMBL1963 |
DrugBanki | DB00024, Thyrotropin alfa |
DrugCentrali | P16473 |
GuidetoPHARMACOLOGYi | 255 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | P16473, 6 sites |
iPTMneti | P16473 |
PhosphoSitePlusi | P16473 |
SwissPalmi | P16473 |
Genetic variation databases
BioMutai | TSHR |
DMDMi | 62298994 |
Proteomic databases
MassIVEi | P16473 |
PaxDbi | P16473 |
PeptideAtlasi | P16473 |
PRIDEi | P16473 |
ProteomicsDBi | 24847 32578 53374 [P16473-1] 53375 [P16473-2] |
Protocols and materials databases
ABCDi | P16473, 14 sequenced antibodies |
Antibodypediai | 4379, 1161 antibodies from 38 providers |
DNASUi | 7253 |
Genome annotation databases
Ensembli | ENST00000342443; ENSP00000340113; ENSG00000165409 [P16473-2] ENST00000554435; ENSP00000450549; ENSG00000165409 [P16473-3] |
GeneIDi | 7253 |
KEGGi | hsa:7253 |
UCSCi | uc001xvc.4, human [P16473-1] |
Organism-specific databases
CTDi | 7253 |
DisGeNETi | 7253 |
GeneCardsi | TSHR |
HGNCi | HGNC:12373, TSHR |
HPAi | ENSG00000165409, Tissue enriched (thyroid) |
MalaCardsi | TSHR |
MIMi | 275200, phenotype 603372, gene+phenotype 603373, phenotype 609152, phenotype |
neXtProti | NX_P16473 |
OpenTargetsi | ENSG00000165409 |
Orphaneti | 95713, Athyreosis 99819, Familial gestational hyperthyroidism 424, Familial hyperthyroidism due to mutations in TSH receptor 90673, Hypothyroidism due to TSH receptor mutations 95720, Thyroid hypoplasia |
PharmGKBi | PA37042 |
VEuPathDBi | HostDB:ENSG00000165409 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2087, Eukaryota |
GeneTreei | ENSGT00940000156510 |
InParanoidi | P16473 |
PhylomeDBi | P16473 |
TreeFami | TF316814 |
Enzyme and pathway databases
PathwayCommonsi | P16473 |
Reactomei | R-HSA-375281, Hormone ligand-binding receptors R-HSA-418555, G alpha (s) signalling events R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SignaLinki | P16473 |
SIGNORi | P16473 |
Miscellaneous databases
BioGRID-ORCSi | 7253, 7 hits in 1037 CRISPR screens |
ChiTaRSi | TSHR, human |
EvolutionaryTracei | P16473 |
GeneWikii | Thyrotropin_receptor |
GenomeRNAii | 7253 |
Pharosi | P16473, Tclin |
PROi | PR:P16473 |
RNActi | P16473, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000165409, Expressed in left lobe of thyroid gland and 118 other tissues |
ExpressionAtlasi | P16473, baseline and differential |
Genevisiblei | P16473, HS |
Family and domain databases
Gene3Di | 3.80.10.10, 1 hit |
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR002131, Gphrmn_rcpt_fam IPR026906, LRR_5 IPR032675, LRR_dom_sf IPR002274, TSH_rcpt |
PANTHERi | PTHR24372:SF0, PTHR24372:SF0, 1 hit |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit PF13306, LRR_5, 2 hits |
PRINTSi | PR00373, GLYCHORMONER PR00237, GPCRRHODOPSN PR01145, TSHRECEPTOR |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TSHR_HUMAN | |
Accessioni | P16473Primary (citable) accession number: P16473 Secondary accession number(s): A0PJU7 Q9UPH3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | March 29, 2005 | |
Last modified: | February 23, 2022 | |
This is version 243 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries - Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families