TSHR_MOUSE
ID TSHR_MOUSE Reviewed; 764 AA.
AC P47750; Q562E4; Q9D697;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Thyrotropin receptor;
DE AltName: Full=Thyroid-stimulating hormone receptor;
DE Short=TSH-R;
DE Flags: Precursor;
GN Name=Tshr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INVOLVEMENT IN HYPOTHYROIDISM.
RC STRAIN=BALB/cJ; TISSUE=Thyroid;
RX PubMed=8170469; DOI=10.1210/mend.8.2.8170469;
RA Stein S.A., Oates E.L., Hall C.R., Grumbles R.M., Fernandez L.M.,
RA Taylor N.A., Puett D., Jin S.;
RT "Identification of a point mutation in the thyrotropin receptor of the
RT hyt/hyt hypothyroid mouse.";
RL Mol. Endocrinol. 8:129-138(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Receptor for the thyroid-stimulating hormone (TSH) or
CC thyrotropin. Also acts as a receptor for the heterodimeric glycoprotein
CC hormone (GPHA2:GPHB5) or thyrostimulin. The activity of this receptor
CC is mediated by G proteins which activate adenylate cyclase. Plays a
CC central role in controlling thyroid cell metabolism.
CC {ECO:0000250|UniProtKB:P16473, ECO:0000250|UniProtKB:P21463}.
CC -!- SUBUNIT: Interacts with heterodimer GPHA2:GPHB5; this interaction
CC stimulates cAMP production. Interacts (via the PDZ-binding motif) with
CC SCRIB; regulates TSHR trafficking and function.
CC {ECO:0000250|UniProtKB:P16473}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P16473};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P16473}. Basolateral
CC cell membrane {ECO:0000250|UniProtKB:P16473}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P16473}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P16473}.
CC -!- PTM: Sulfated. Sulfation on Tyr-385 plays a role in thyrotropin
CC receptor binding and activation. {ECO:0000250|UniProtKB:P16473}.
CC -!- DISEASE: Note=Defects in Tshr are the cause of hyt/hyt hypothyroidism,
CC an autosomal recessive, fetal-onset, severe hypothyroidism related to
CC TSH hyporesponsiveness and associated with elevated TSH.
CC {ECO:0000305|PubMed:8170469}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC FSH/LSH/TSH subfamily. {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U02601; AAA53209.1; -; mRNA.
DR EMBL; U02602; AAB60455.1; -; mRNA.
DR EMBL; AK014519; BAB29408.1; -; mRNA.
DR EMBL; AK029084; BAC26286.1; -; mRNA.
DR EMBL; BC086691; AAH86691.1; -; mRNA.
DR EMBL; BC092523; AAH92523.1; -; mRNA.
DR CCDS; CCDS26088.1; -.
DR PIR; I48882; I48882.
DR RefSeq; NP_035778.3; NM_011648.5.
DR AlphaFoldDB; P47750; -.
DR SMR; P47750; -.
DR STRING; 10090.ENSMUSP00000021346; -.
DR GlyGen; P47750; 5 sites.
DR iPTMnet; P47750; -.
DR PhosphoSitePlus; P47750; -.
DR jPOST; P47750; -.
DR PaxDb; P47750; -.
DR PRIDE; P47750; -.
DR ProteomicsDB; 300047; -.
DR Antibodypedia; 4379; 1130 antibodies from 38 providers.
DR DNASU; 22095; -.
DR Ensembl; ENSMUST00000021346; ENSMUSP00000021346; ENSMUSG00000020963.
DR GeneID; 22095; -.
DR KEGG; mmu:22095; -.
DR UCSC; uc007okq.2; mouse.
DR CTD; 7253; -.
DR MGI; MGI:98849; Tshr.
DR VEuPathDB; HostDB:ENSMUSG00000020963; -.
DR eggNOG; KOG2087; Eukaryota.
DR GeneTree; ENSGT00940000156510; -.
DR HOGENOM; CLU_006130_1_1_1; -.
DR InParanoid; P47750; -.
DR OMA; HAGYKDN; -.
DR OrthoDB; 257031at2759; -.
DR PhylomeDB; P47750; -.
DR TreeFam; TF316814; -.
DR Reactome; R-MMU-375281; Hormone ligand-binding receptors.
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR BioGRID-ORCS; 22095; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Tshr; mouse.
DR PRO; PR:P47750; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P47750; protein.
DR Bgee; ENSMUSG00000020963; Expressed in gonadal fat pad and 66 other tissues.
DR ExpressionAtlas; P47750; baseline and differential.
DR Genevisible; P47750; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; ISS:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; ISO:MGI.
DR GO; GO:0004996; F:thyroid-stimulating hormone receptor activity; IDA:MGI.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:0030183; P:B cell differentiation; IMP:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:1904588; P:cellular response to glycoprotein; ISS:UniProtKB.
DR GO; GO:1905229; P:cellular response to thyrotropin-releasing hormone; ISS:UniProtKB.
DR GO; GO:0090103; P:cochlea morphogenesis; IMP:MGI.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IMP:MGI.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0060119; P:inner ear receptor cell development; IMP:MGI.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0040012; P:regulation of locomotion; IMP:MGI.
DR GO; GO:0038194; P:thyroid-stimulating hormone signaling pathway; ISO:MGI.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR002131; Gphrmn_rcpt_fam.
DR InterPro; IPR026906; LRR_5.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR002274; TSH_rcpt.
DR PANTHER; PTHR24372:SF0; PTHR24372:SF0; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF13306; LRR_5; 2.
DR PRINTS; PR00373; GLYCHORMONER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01145; TSHRECEPTOR.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Leucine-rich repeat; Membrane; Receptor; Reference proteome;
KW Repeat; Signal; Sulfation; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000250"
FT CHAIN 22..764
FT /note="Thyrotropin receptor"
FT /id="PRO_0000012787"
FT TOPO_DOM 22..413
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..441
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 442..450
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..473
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 474..494
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..517
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 518..537
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 538..560
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 561..580
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 581..602
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 603..625
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 626..649
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 650..660
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 661..682
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 683..764
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 100..124
FT /note="LRR 1"
FT REPEAT 125..150
FT /note="LRR 2"
FT REPEAT 151..174
FT /note="LRR 3"
FT REPEAT 176..199
FT /note="LRR 4"
FT REPEAT 200..223
FT /note="LRR 5"
FT REPEAT 225..248
FT /note="LRR 6"
FT REPEAT 264..288
FT /note="LRR 7"
FT MOTIF 762..764
FT /note="PDZ-binding"
FT MOD_RES 385
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P16473"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..41
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 494..569
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 556
FT /note="P -> L (in hypothyroidism)"
FT CONFLICT 312
FT /note="R -> S (in Ref. 2; BAB29408)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 764 AA; 86583 MW; 6ADD2CC72F018317 CRC64;
MRPGSLLLLV LLLALSRSLR GKECASPPCE CHQEDDFRVT CKELHRIPSL PPSTQTLKLI
ETHLKTIPSL AFSSLPNISR IYLSIDATLQ RLEPHSFYNL SKMTHIEIRN TRSLTYIDPD
ALTELPLLKF LGIFNTGLRI FPDLTKIYST DIFFILEITD NPYMTSVPEN AFQGLCNETL
TLKLYNNGFT SVQGHAFNGT KLDAVYLNKN KYLTAIDNDA FGGVYSGPTL LDVSSTSVTA
LPSKGLEHLK ELIAKDTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM
CNESSIRNLR QRKSVNILRG PIYQEYEEDP GDNSVGYKQN SKFQESPSNS HYYVFFEEQE
DEVVGFGQEL KNPQEETLQA FESHYDYTVC GDNEDMVCTP KSDEFNPCED IMGYRFLRIV
VWFVSLLALL GNIFVLLILL TSHYKLTVPR FLMCNLAFAD FCMGVYLLLI ASVDLYTHSE
YYNHAIDWQT GPGCNTAGFF TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHAYT
IMAGGWVSCF LLALLPMVGI SSYAKVSICL PMDTDTPLAL AYIVLVLLLN VVAFVVVCSC
YVKIYITVRN PQYNPRDKDT KIAKRMAVLI FTDFMCMAPI SFYALSALMN KPLITVTNSK
ILLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGICK RQAQAYQGQR VCPNNSTGIQ
IQKIPQDTRQ SLPNMQDTYE LLGNSQLAPK LQGQISEEYK QTAL
