TSHB_HUMAN
ID TSHB_HUMAN Reviewed; 138 AA.
AC P01222; B1AKP0; Q16163;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Thyrotropin subunit beta;
DE AltName: Full=Thyroid-stimulating hormone subunit beta;
DE Short=TSH-B;
DE Short=TSH-beta;
DE AltName: Full=Thyrotropin beta chain;
DE AltName: INN=Thyrotropin alfa;
DE Flags: Precursor;
GN Name=TSHB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-14.
RX PubMed=3839756; DOI=10.1016/0014-5793(85)80409-9;
RA Hayashizaki Y., Miyai K., Kato K., Matsubara K.;
RT "Molecular cloning of the human thyrotropin-beta subunit gene.";
RL FEBS Lett. 188:394-400(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-14.
RX PubMed=3234176; DOI=10.1089/dna.1988.7.691;
RA Guidon P.T. Jr., Whitfield G.K., Porti D., Kourides I.A.;
RT "The human thyrotropin beta-subunit gene differs in 5' structure from
RT murine TSH-beta genes.";
RL DNA 7:691-699(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-14.
RX PubMed=3243440; DOI=10.1016/0378-1119(88)90513-6;
RA Tatsumi K., Hayashizaki Y., Hiraoka Y., Miyai K., Matsubara K.;
RT "The structure of the human thyrotropin beta-subunit gene.";
RL Gene 73:489-497(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-14.
RX PubMed=2457586; DOI=10.1016/s0021-9258(18)37788-3;
RA Wondisford F.E., Radovick S., Moates J.M., Usala S.J., Weintraub B.D.;
RT "Isolation and characterization of the human thyrotropin beta-subunit gene.
RT Differences in gene structure and promoter function from murine species.";
RL J. Biol. Chem. 263:12538-12542(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-14.
RX PubMed=8196184;
RA Miyoshi I., Kasai N., Hayashizaki Y.;
RT "Structure and regulation of human thyroid-stimulating hormone (TSH)
RT gene.";
RL Nippon Rinsho 52:940-947(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-14.
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).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=19364510; DOI=10.1016/j.ygcen.2009.04.006;
RA Schaefer J.S., Klein J.R.;
RT "A novel thyroid stimulating hormone beta-subunit isoform in human
RT pituitary, peripheral blood leukocytes, and thyroid.";
RL Gen. Comp. Endocrinol. 162:241-244(2009).
RN [9]
RP PROTEIN SEQUENCE OF 21-132.
RX PubMed=890569; DOI=10.1139/o77-108;
RA Sairam M.R., Li C.H.;
RT "Human pituitary thyrotropin. The primary structure of the alpha and beta
RT subunits.";
RL Can. J. Biochem. 55:755-760(1977).
CC -!- FUNCTION: Indispensable for the control of thyroid structure and
CC metabolism.
CC -!- SUBUNIT: Heterodimer of a common alpha chain and a unique beta chain
CC which confers biological specificity to thyrotropin, lutropin,
CC follitropin and gonadotropin.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P01222-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P01222-2; Sequence=VSP_053387;
CC -!- PHARMACEUTICAL: Available under the name Thyrogen (Genzyme). Used in
CC combination with other tests to detect recurring or leftover thyroid
CC cancer cells in patients with a history of certain types of thyroid
CC cancer.
CC -!- MISCELLANEOUS: [Isoform 2]: Major isoform in peripheral blood
CC leukocytes and thyroid, may form heterodimers with isoform 1.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the glycoprotein hormones subunit beta family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Thyroid-stimulating hormone entry;
CC URL="https://en.wikipedia.org/wiki/Thyroid-stimulating_hormone";
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DR EMBL; X02866; CAA26618.1; -; Genomic_DNA.
DR EMBL; X02867; CAA26619.1; -; Genomic_DNA.
DR EMBL; M23671; AAB05845.1; -; Genomic_DNA.
DR EMBL; M23670; AAB05845.1; JOINED; Genomic_DNA.
DR EMBL; M25164; AAA61235.1; -; Genomic_DNA.
DR EMBL; M21024; AAA36782.1; -; Genomic_DNA.
DR EMBL; S70587; AAB30828.2; -; Genomic_DNA.
DR EMBL; AL109660; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069298; AAH69298.1; -; mRNA.
DR CCDS; CCDS880.1; -. [P01222-1]
DR PIR; A23997; TTHUB.
DR RefSeq; NP_000540.2; NM_000549.4. [P01222-1]
DR RefSeq; NP_001264920.1; NM_001277991.1. [P01222-2]
DR RefSeq; XP_011540367.1; XM_011542065.2. [P01222-1]
DR AlphaFoldDB; P01222; -.
DR SMR; P01222; -.
DR BioGRID; 113103; 51.
DR ComplexPortal; CPX-6096; Thyroid-stimulating hormone complex.
DR IntAct; P01222; 16.
DR STRING; 9606.ENSP00000256592; -.
DR GlyGen; P01222; 1 site, 7 N-linked glycans (1 site).
DR BioMuta; TSHB; -.
DR DMDM; 311033515; -.
DR CPTAC; CPTAC-691; -.
DR CPTAC; CPTAC-729; -.
DR MassIVE; P01222; -.
DR PaxDb; P01222; -.
DR PeptideAtlas; P01222; -.
DR PRIDE; P01222; -.
DR Antibodypedia; 20170; 1049 antibodies from 40 providers.
DR CPTC; P01222; 2 antibodies.
DR DNASU; 7252; -.
DR Ensembl; ENST00000256592.3; ENSP00000256592.1; ENSG00000134200.4. [P01222-1]
DR GeneID; 7252; -.
DR KEGG; hsa:7252; -.
DR MANE-Select; ENST00000256592.3; ENSP00000256592.1; NM_000549.5; NP_000540.2.
DR UCSC; uc001efs.2; human. [P01222-1]
DR CTD; 7252; -.
DR DisGeNET; 7252; -.
DR GeneCards; TSHB; -.
DR HGNC; HGNC:12372; TSHB.
DR HPA; ENSG00000134200; Tissue enriched (pituitary).
DR MalaCards; TSHB; -.
DR MIM; 188540; gene.
DR MIM; 275100; phenotype.
DR neXtProt; NX_P01222; -.
DR OpenTargets; ENSG00000134200; -.
DR Orphanet; 90674; Isolated thyroid-stimulating hormone deficiency.
DR PharmGKB; PA37041; -.
DR VEuPathDB; HostDB:ENSG00000134200; -.
DR eggNOG; ENOG502S2JW; Eukaryota.
DR GeneTree; ENSGT00940000158152; -.
DR HOGENOM; CLU_126319_0_2_1; -.
DR InParanoid; P01222; -.
DR OMA; PTEYMMH; -.
DR OrthoDB; 1362225at2759; -.
DR PhylomeDB; P01222; -.
DR TreeFam; TF332940; -.
DR PathwayCommons; P01222; -.
DR Reactome; R-HSA-209822; Glycoprotein hormones.
DR Reactome; R-HSA-209968; Thyroxine biosynthesis.
DR Reactome; R-HSA-375281; Hormone ligand-binding receptors.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P01222; -.
DR SIGNOR; P01222; -.
DR BioGRID-ORCS; 7252; 21 hits in 1028 CRISPR screens.
DR GeneWiki; TSHB; -.
DR GenomeRNAi; 7252; -.
DR Pharos; P01222; Tbio.
DR PRO; PR:P01222; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P01222; protein.
DR Bgee; ENSG00000134200; Expressed in adenohypophysis and 110 other tissues.
DR Genevisible; P01222; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0061696; C:pituitary gonadotropin complex; IC:ComplexPortal.
DR GO; GO:0005179; F:hormone activity; TAS:ProtInc.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IC:ComplexPortal.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl.
DR CDD; cd00069; GHB_like; 1.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR006208; Glyco_hormone_CN.
DR InterPro; IPR001545; Gonadotropin_bsu.
DR InterPro; IPR018245; Gonadotropin_bsu_CS.
DR PANTHER; PTHR11515; PTHR11515; 1.
DR Pfam; PF00007; Cys_knot; 1.
DR SMART; SM00068; GHB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00261; GLYCO_HORMONE_BETA_1; 1.
DR PROSITE; PS00689; GLYCO_HORMONE_BETA_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hormone; Pharmaceutical; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:890569"
FT CHAIN 21..132
FT /note="Thyrotropin subunit beta"
FT /id="PRO_0000011746"
FT PROPEP 133..138
FT /id="PRO_0000011747"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 22..72
FT /evidence="ECO:0000250"
FT DISULFID 36..87
FT /evidence="ECO:0000250"
FT DISULFID 39..125
FT /evidence="ECO:0000250"
FT DISULFID 47..103
FT /evidence="ECO:0000250"
FT DISULFID 51..105
FT /evidence="ECO:0000250"
FT DISULFID 108..115
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..54
FT /note="MTALFLMSMLFGLTCGQAMSFCIPTEYTMHIERRECAYCLTINTTICAGYCM
FT TR -> MLSFLFFPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19364510"
FT /id="VSP_053387"
FT VARIANT 14
FT /note="T -> A (in dbSNP:rs10776792)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2457586, ECO:0000269|PubMed:3234176,
FT ECO:0000269|PubMed:3243440, ECO:0000269|PubMed:3839756,
FT ECO:0000269|PubMed:8196184"
FT /id="VAR_054769"
FT CONFLICT 46
FT /note="I -> M (in Ref. 5; AAB30828)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 138 AA; 15639 MW; 6A367538D8393DB7 CRC64;
MTALFLMSML FGLTCGQAMS FCIPTEYTMH IERRECAYCL TINTTICAGY CMTRDINGKL
FLPKYALSQD VCTYRDFIYR TVEIPGCPLH VAPYFSYPVA LSCKCGKCNT DYSDCIHEAI
KTNYCTKPQK SYLVGFSV
