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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 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).

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
  • 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 multicellular organism growth Source: MGI
  • regulation of locomotion Source: MGI
  • thyroid-stimulating hormone signaling pathway Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_295506. Hormone ligand-binding receptors.
REACT_313192. 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
ProteomesiUP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:98849. Tshr.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 413392ExtracellularSequence AnalysisAdd
BLAST
Transmembranei414 – 44128Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini442 – 4509CytoplasmicSequence Analysis
Transmembranei451 – 47323Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini474 – 49421ExtracellularSequence AnalysisAdd
BLAST
Transmembranei495 – 51723Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini518 – 53720CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei538 – 56023Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini561 – 58020ExtracellularSequence AnalysisAdd
BLAST
Transmembranei581 – 60222Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini603 – 62523CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei626 – 64924Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini650 – 66011ExtracellularSequence AnalysisAdd
BLAST
Transmembranei661 – 68222Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini683 – 76482CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: MGI
  • receptor complex Source: MGI
Complete GO annotation...

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.

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121By similarityAdd
BLAST
Chaini22 – 764743Thyrotropin receptorPRO_0000012787Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi31 ↔ 41PROSITE-ProRule annotation
Glycosylationi77 – 771N-linked (GlcNAc...)Sequence Analysis
Glycosylationi99 – 991N-linked (GlcNAc...)Sequence Analysis
Glycosylationi177 – 1771N-linked (GlcNAc...)Sequence Analysis
Glycosylationi198 – 1981N-linked (GlcNAc...)Sequence Analysis
Glycosylationi302 – 3021N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi494 ↔ 569PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP47750.
PRIDEiP47750.

PTM databases

PhosphoSiteiP47750.

Expressioni

Gene expression databases

BgeeiP47750.
CleanExiMM_TSHR.
ExpressionAtlasiP47750. baseline and differential.
GenevisibleiP47750. MM.

Interactioni

Subunit structurei

Interacts (via the PDZ-binding motif) with SCRIB; regulates TSHR trafficking and function.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000021346.

Structurei

3D structure databases

ProteinModelPortaliP47750.
SMRiP47750. Positions 24-257, 411-686.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati100 – 12425LRR 1Add
BLAST
Repeati125 – 15026LRR 2Add
BLAST
Repeati151 – 17424LRR 3Add
BLAST
Repeati176 – 19924LRR 4Add
BLAST
Repeati200 – 22324LRR 5Add
BLAST
Repeati225 – 24824LRR 6Add
BLAST
Repeati264 – 28825LRR 7Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi762 – 7643PDZ-binding

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.PROSITE-ProRule annotation
Contains 7 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

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

Phylogenomic databases

eggNOGiNOG285844.
GeneTreeiENSGT00760000119088.
HOGENOMiHOG000045902.
HOVERGENiHBG003521.
InParanoidiP47750.
OMAiPRDKDTK.
OrthoDBiEOG73BVCG.
PhylomeDBiP47750.
TreeFamiTF316814.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR026906. LRR_5.
IPR002274. TSH_rcpt.
[Graphical view]
PANTHERiPTHR24372. PTHR24372. 1 hit.
PTHR24372:SF0. PTHR24372:SF0. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 2 hits.
[Graphical view]
PRINTSiPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01145. TSHRECEPTOR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti312 – 3121R → S in BAB29408 (PubMed:16141072).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti556 – 5561P → L in hypothyroidism.

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.
UCSCiuc007okq.2. mouse.

Cross-referencesi

Web resourcesi

GRIS

Glycoprotein-hormone Receptors Information System

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.
SMRiP47750. Positions 24-257, 411-686.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000021346.

Chemistry

GuidetoPHARMACOLOGYi255.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP47750.

Proteomic databases

PaxDbiP47750.
PRIDEiP47750.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021346; ENSMUSP00000021346; ENSMUSG00000020963.
GeneIDi22095.
UCSCiuc007okq.2. mouse.

Organism-specific databases

CTDi7253.
MGIiMGI:98849. Tshr.

Phylogenomic databases

eggNOGiNOG285844.
GeneTreeiENSGT00760000119088.
HOGENOMiHOG000045902.
HOVERGENiHBG003521.
InParanoidiP47750.
OMAiPRDKDTK.
OrthoDBiEOG73BVCG.
PhylomeDBiP47750.
TreeFamiTF316814.

Enzyme and pathway databases

ReactomeiREACT_295506. Hormone ligand-binding receptors.
REACT_313192. G alpha (s) signalling events.

Miscellaneous databases

NextBioi301940.
PROiP47750.
SOURCEiSearch...

Gene expression databases

BgeeiP47750.
CleanExiMM_TSHR.
ExpressionAtlasiP47750. baseline and differential.
GenevisibleiP47750. MM.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR026906. LRR_5.
IPR002274. TSH_rcpt.
[Graphical view]
PANTHERiPTHR24372. PTHR24372. 1 hit.
PTHR24372:SF0. PTHR24372:SF0. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 2 hits.
[Graphical view]
PRINTSiPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01145. TSHRECEPTOR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse."
    Stein S.A., Oates E.L., Hall C.R., Grumbles R.M., Fernandez L.M., Taylor N.A., Puett D., Jin S.
    Mol. Endocrinol. 8:129-138(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
    Tissue: Thyroid.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Skin.
  3. "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].
    Strain: C57BL/6.
    Tissue: Eye.

Entry informationi

Entry nameiTSHR_MOUSE
AccessioniPrimary (citable) accession number: P47750
Secondary accession number(s): Q562E4, Q9D697
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: October 1, 1996
Last modified: July 22, 2015
This is version 138 of the entry and version 2 of the sequence. [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

External Data

Dasty 3

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 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.