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Protein

Thyrotropin receptor

Gene

Tshr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

GO - Biological processi

  • activation of adenylate cyclase activity Source: GO_Central
  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: MGI
  • adult locomotory behavior Source: MGI
  • B cell differentiation Source: MGI
  • cell surface receptor signaling pathway Source: UniProtKB
  • cellular response to glycoprotein Source: UniProtKB
  • cellular response to thyrotropin-releasing hormone Source: UniProtKB
  • cochlea morphogenesis Source: MGI
  • dopaminergic neuron differentiation Source: MGI
  • hormone-mediated signaling pathway Source: GO_Central
  • inner ear receptor cell development Source: MGI
  • inner ear receptor stereocilium organization Source: MGI
  • positive regulation of adenylate cyclase activity Source: UniProtKB
  • positive regulation of cAMP biosynthetic process Source: UniProtKB
  • positive regulation of multicellular organism growth Source: MGI
  • regulation of locomotion Source: MGI

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-MMU-375281. Hormone ligand-binding receptors.
R-MMU-418555. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Thyrotropin receptor
Alternative name(s):
Thyroid-stimulating hormone receptor
Short name:
TSH-R
Gene namesi
Name:Tshr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:98849. Tshr.

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein By similarity
  • Basolateral cell membrane By similarity; Multi-pass membrane protein By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 413ExtracellularSequence analysisAdd BLAST392
Transmembranei414 – 441Helical; Name=1Sequence analysisAdd BLAST28
Topological domaini442 – 450CytoplasmicSequence analysis9
Transmembranei451 – 473Helical; Name=2Sequence analysisAdd BLAST23
Topological domaini474 – 494ExtracellularSequence analysisAdd BLAST21
Transmembranei495 – 517Helical; Name=3Sequence analysisAdd BLAST23
Topological domaini518 – 537CytoplasmicSequence analysisAdd BLAST20
Transmembranei538 – 560Helical; Name=4Sequence analysisAdd BLAST23
Topological domaini561 – 580ExtracellularSequence analysisAdd BLAST20
Transmembranei581 – 602Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini603 – 625CytoplasmicSequence analysisAdd BLAST23
Transmembranei626 – 649Helical; Name=6Sequence analysisAdd BLAST24
Topological domaini650 – 660ExtracellularSequence analysisAdd BLAST11
Transmembranei661 – 682Helical; Name=7Sequence analysisAdd BLAST22
Topological domaini683 – 764CytoplasmicSequence analysisAdd BLAST82

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Tshr are the cause of hyt/hyt hypothyroidism, an autosomal recessive, fetal-onset, severe hypothyroidism related to TSH hyporesponsiveness and associated with elevated TSH.1 Publication

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21By similarityAdd BLAST21
ChainiPRO_000001278722 – 764Thyrotropin receptorAdd BLAST743

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 41PROSITE-ProRule annotation
Glycosylationi77N-linked (GlcNAc...)Sequence analysis1
Glycosylationi99N-linked (GlcNAc...)Sequence analysis1
Glycosylationi177N-linked (GlcNAc...)Sequence analysis1
Glycosylationi198N-linked (GlcNAc...)Sequence analysis1
Glycosylationi302N-linked (GlcNAc...)Sequence analysis1
Modified residuei385SulfotyrosineBy similarity1
Disulfide bondi494 ↔ 569PROSITE-ProRule annotation

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Sulfation

Proteomic databases

PaxDbiP47750.
PRIDEiP47750.

PTM databases

iPTMnetiP47750.
PhosphoSitePlusiP47750.

Expressioni

Gene expression databases

BgeeiENSMUSG00000020963.
CleanExiMM_TSHR.
ExpressionAtlasiP47750. baseline and differential.
GenevisibleiP47750. MM.

Interactioni

Subunit structurei

Interacts with heterodimer GPHA2:GPHB5; this interaction stimulates cAMP production. Interacts (via the PDZ-binding motif) with SCRIB; regulates TSHR trafficking and function.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000021346.

Structurei

3D structure databases

ProteinModelPortaliP47750.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati100 – 124LRR 1Add BLAST25
Repeati125 – 150LRR 2Add BLAST26
Repeati151 – 174LRR 3Add BLAST24
Repeati176 – 199LRR 4Add BLAST24
Repeati200 – 223LRR 5Add BLAST24
Repeati225 – 248LRR 6Add BLAST24
Repeati264 – 288LRR 7Add BLAST25

Motif

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

Sequence similaritiesi

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

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG2087. Eukaryota.
ENOG410XR1T. LUCA.
GeneTreeiENSGT00760000119088.
HOGENOMiHOG000045902.
HOVERGENiHBG003521.
InParanoidiP47750.
KOiK04249.
OMAiCSCYVKI.
OrthoDBiEOG091G02BV.
PhylomeDBiP47750.
TreeFamiTF316814.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiView protein in InterPro
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR032675. L_dom-like.
IPR026906. LRR_5.
IPR002274. TSH_rcpt.
IPR034298. TSHR/LHCGR/FSHR.
PANTHERiPTHR24372. PTHR24372. 1 hit.
PTHR24372:SF63. PTHR24372:SF63. 1 hit.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 2 hits.
PRINTSiPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01145. TSHRECEPTOR.
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P47750-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRPGSLLLLV LLLALSRSLR GKECASPPCE CHQEDDFRVT CKELHRIPSL
60 70 80 90 100
PPSTQTLKLI ETHLKTIPSL AFSSLPNISR IYLSIDATLQ RLEPHSFYNL
110 120 130 140 150
SKMTHIEIRN TRSLTYIDPD ALTELPLLKF LGIFNTGLRI FPDLTKIYST
160 170 180 190 200
DIFFILEITD NPYMTSVPEN AFQGLCNETL TLKLYNNGFT SVQGHAFNGT
210 220 230 240 250
KLDAVYLNKN KYLTAIDNDA FGGVYSGPTL LDVSSTSVTA LPSKGLEHLK
260 270 280 290 300
ELIAKDTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM
310 320 330 340 350
CNESSIRNLR QRKSVNILRG PIYQEYEEDP GDNSVGYKQN SKFQESPSNS
360 370 380 390 400
HYYVFFEEQE DEVVGFGQEL KNPQEETLQA FESHYDYTVC GDNEDMVCTP
410 420 430 440 450
KSDEFNPCED IMGYRFLRIV VWFVSLLALL GNIFVLLILL TSHYKLTVPR
460 470 480 490 500
FLMCNLAFAD FCMGVYLLLI ASVDLYTHSE YYNHAIDWQT GPGCNTAGFF
510 520 530 540 550
TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHAYT IMAGGWVSCF
560 570 580 590 600
LLALLPMVGI SSYAKVSICL PMDTDTPLAL AYIVLVLLLN VVAFVVVCSC
610 620 630 640 650
YVKIYITVRN PQYNPRDKDT KIAKRMAVLI FTDFMCMAPI SFYALSALMN
660 670 680 690 700
KPLITVTNSK ILLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGICK
710 720 730 740 750
RQAQAYQGQR VCPNNSTGIQ IQKIPQDTRQ SLPNMQDTYE LLGNSQLAPK
760
LQGQISEEYK QTAL
Length:764
Mass (Da):86,583
Last modified:October 1, 1996 - v2
Checksum:i6ADD2CC72F018317
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti312R → S in BAB29408 (PubMed:16141072).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti556P → L in hypothyroidism. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02601 mRNA. Translation: AAA53209.1.
U02602 mRNA. Translation: AAB60455.1.
AK014519 mRNA. Translation: BAB29408.1.
AK029084 mRNA. Translation: BAC26286.1.
BC086691 mRNA. Translation: AAH86691.1.
BC092523 mRNA. Translation: AAH92523.1.
CCDSiCCDS26088.1.
PIRiI48882.
RefSeqiNP_035778.3. NM_011648.5.
UniGeneiMm.173847.

Genome annotation databases

EnsembliENSMUST00000021346; ENSMUSP00000021346; ENSMUSG00000020963.
GeneIDi22095.
KEGGimmu:22095.
UCSCiuc007okq.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02601 mRNA. Translation: AAA53209.1.
U02602 mRNA. Translation: AAB60455.1.
AK014519 mRNA. Translation: BAB29408.1.
AK029084 mRNA. Translation: BAC26286.1.
BC086691 mRNA. Translation: AAH86691.1.
BC092523 mRNA. Translation: AAH92523.1.
CCDSiCCDS26088.1.
PIRiI48882.
RefSeqiNP_035778.3. NM_011648.5.
UniGeneiMm.173847.

3D structure databases

ProteinModelPortaliP47750.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000021346.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP47750.
PhosphoSitePlusiP47750.

Proteomic databases

PaxDbiP47750.
PRIDEiP47750.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021346; ENSMUSP00000021346; ENSMUSG00000020963.
GeneIDi22095.
KEGGimmu:22095.
UCSCiuc007okq.2. mouse.

Organism-specific databases

CTDi7253.
MGIiMGI:98849. Tshr.

Phylogenomic databases

eggNOGiKOG2087. Eukaryota.
ENOG410XR1T. LUCA.
GeneTreeiENSGT00760000119088.
HOGENOMiHOG000045902.
HOVERGENiHBG003521.
InParanoidiP47750.
KOiK04249.
OMAiCSCYVKI.
OrthoDBiEOG091G02BV.
PhylomeDBiP47750.
TreeFamiTF316814.

Enzyme and pathway databases

ReactomeiR-MMU-375281. Hormone ligand-binding receptors.
R-MMU-418555. G alpha (s) signalling events.

Miscellaneous databases

PROiPR:P47750.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020963.
CleanExiMM_TSHR.
ExpressionAtlasiP47750. baseline and differential.
GenevisibleiP47750. MM.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiView protein in InterPro
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR032675. L_dom-like.
IPR026906. LRR_5.
IPR002274. TSH_rcpt.
IPR034298. TSHR/LHCGR/FSHR.
PANTHERiPTHR24372. PTHR24372. 1 hit.
PTHR24372:SF63. PTHR24372:SF63. 1 hit.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 2 hits.
PRINTSiPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01145. TSHRECEPTOR.
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiTSHR_MOUSE
AccessioniPrimary (citable) accession number: P47750
Secondary accession number(s): Q562E4, Q9D697
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: October 1, 1996
Last modified: April 12, 2017
This is version 151 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.