P47750 (TSHR_MOUSE) 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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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).
Subunit structure	Interacts (via the PDZ-binding motif) with SCRIB; regulates TSHR trafficking and function By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Involvement in disease	Note=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.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily. Contains 7 LRR (leucine-rich) repeats.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Disease	Disease mutation
Domain	Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	B cell differentiation Inferred from mutant phenotype. Source: MGI activation of adenylate cyclase activity by G-protein signaling pathway Inferred from direct assay. Source: MGI adult locomotory behavior Inferred from mutant phenotype. Source: MGI positive regulation of multicellular organism growth Inferred from mutant phenotype. Source: MGI regulation of locomotion Inferred from mutant phenotype. Source: MGI
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay. Source: MGI
Molecular function	thyroid-stimulating hormone receptor activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	By similarity
	Chain	22 – 764	743	Thyrotropin receptor		PRO_0000012787
Regions
	Topological domain	22 – 413	392	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	151 – 174	24	LRR 3
	Repeat	176 – 199	24	LRR 4
	Repeat	200 – 223	24	LRR 5
	Repeat	225 – 248	24	LRR 6
	Repeat	264 – 288	25	LRR 7
	Motif	762 – 764	3	PDZ-binding
Amino acid modifications
	Glycosylation	77	1	N-linked (GlcNAc...) Potential
	Glycosylation	99	1	N-linked (GlcNAc...) Potential
	Glycosylation	177	1	N-linked (GlcNAc...) Potential
	Glycosylation	198	1	N-linked (GlcNAc...) Potential
	Glycosylation	302	1	N-linked (GlcNAc...) Potential
	Disulfide bond	31 ↔ 41		By similarity
	Disulfide bond	494 ↔ 569		By similarity
Natural variations
	Natural variant	556	1	P → L in hypothyroidism.
Experimental info
	Sequence conflict	312	1	R → S in BAB29408. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P47750 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 6ADD2CC72F018317	FASTA	764	86,583
	10 20 30 40 50 60 MRPGSLLLLV LLLALSRSLR GKECASPPCE CHQEDDFRVT CKELHRIPSL PPSTQTLKLI 70 80 90 100 110 120 ETHLKTIPSL AFSSLPNISR IYLSIDATLQ RLEPHSFYNL SKMTHIEIRN TRSLTYIDPD 130 140 150 160 170 180 ALTELPLLKF LGIFNTGLRI FPDLTKIYST DIFFILEITD NPYMTSVPEN AFQGLCNETL 190 200 210 220 230 240 TLKLYNNGFT SVQGHAFNGT KLDAVYLNKN KYLTAIDNDA FGGVYSGPTL LDVSSTSVTA 250 260 270 280 290 300 LPSKGLEHLK ELIAKDTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM 310 320 330 340 350 360 CNESSIRNLR QRKSVNILRG PIYQEYEEDP GDNSVGYKQN SKFQESPSNS HYYVFFEEQE 370 380 390 400 410 420 DEVVGFGQEL KNPQEETLQA FESHYDYTVC GDNEDMVCTP KSDEFNPCED IMGYRFLRIV 430 440 450 460 470 480 VWFVSLLALL GNIFVLLILL TSHYKLTVPR FLMCNLAFAD FCMGVYLLLI ASVDLYTHSE 490 500 510 520 530 540 YYNHAIDWQT GPGCNTAGFF TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHAYT 550 560 570 580 590 600 IMAGGWVSCF LLALLPMVGI SSYAKVSICL PMDTDTPLAL AYIVLVLLLN VVAFVVVCSC 610 620 630 640 650 660 YVKIYITVRN PQYNPRDKDT KIAKRMAVLI FTDFMCMAPI SFYALSALMN KPLITVTNSK 670 680 690 700 710 720 ILLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGICK RQAQAYQGQR VCPNNSTGIQ 730 740 750 760 IQKIPQDTRQ SLPNMQDTYE LLGNSQLAPK LQGQISEEYK QTAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 8170469] [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: 16141072] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Eye.
+	Additional computationally mapped references.

Web resources

GRIS

Glycoprotein-hormone Receptors Information System

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00111260.
PIR	I48882.
RefSeq	NP_035778.3. NM_011648.5.
UniGene	Mm.173847.
3D structure databases
ProteinModelPortal	P47750.
SMR	P47750. Positions 24-257, 415-694.
ModBase	Search...
Protein-protein interaction databases
STRING	P47750.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P47750.
Proteomic databases
PRIDE	P47750.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021346; ENSMUSP00000021346; ENSMUSG00000020963.
GeneID	22095.
KEGG	mmu:22095.
UCSC	uc007okq.2. mouse.
Organism-specific databases
CTD	7253.
MGI	MGI:98849. Tshr.
Phylogenomic databases
eggNOG	roNOG08925.
GeneTree	ENSGT00600000084134.
HOGENOM	HBG444089.
HOVERGEN	HBG003521.
InParanoid	P47750.
OMA	TVRNPQY.
OrthoDB	EOG4S1T6J.
PhylomeDB	P47750.
Gene expression databases
ArrayExpress	P47750.
Bgee	P47750.
CleanEx	MM_TSHR.
Genevestigator	P47750.
GermOnline	ENSMUSG00000020963. Mus musculus.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. IPR002131. Gphrmn_rcpt. IPR002274. TSH_rcpt. [Graphical view]
KO	K04249.
Pfam	PF00001. 7tm_1. 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
NextBio	301940.
SOURCE	Search...

Entry information

Entry name

TSHR_MOUSE

Accession

Primary (citable) accession number: P47750
Secondary accession number(s): Q562E4, Q9D697

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 16, 2011
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program