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   13-FEB-2019, entry version 168.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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;
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
RT   gene. Differences in gene structure and promoter function from murine
RT   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.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   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.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   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.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   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
RP   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
RT   project: 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;
RA   Sairam M.R., Li C.H.;
RT   "Human pituitary thyrotropin. The primary structure of the alpha and
RT   beta 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
CC       chain which confers biological specificity to thyrotropin,
CC       lutropin, 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         Note=Major isoform in peripheral blood leukocytes and thyroid,
CC         may form heterodimers with isoform 1.;
CC   -!- PHARMACEUTICAL: Available under the name Thyrogen (Genzyme). Used
CC       in combination with other tests to detect recurring or leftover
CC       thyroid cancer cells in patients with a history of certain types
CC       of thyroid cancer.
CC   -!- SIMILARITY: Belongs to the glycoprotein hormones subunit beta
CC       family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Thyroid-stimulating hormone
CC       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   UniGene; Hs.406687; -.
DR   ProteinModelPortal; P01222; -.
DR   SMR; P01222; -.
DR   BioGrid; 113103; 15.
DR   IntAct; P01222; 1.
DR   STRING; 9606.ENSP00000256592; -.
DR   UniCarbKB; P01222; -.
DR   BioMuta; TSHB; -.
DR   DMDM; 311033515; -.
DR   jPOST; P01222; -.
DR   PaxDb; P01222; -.
DR   PeptideAtlas; P01222; -.
DR   PRIDE; P01222; -.
DR   ProteomicsDB; 51347; -.
DR   DNASU; 7252; -.
DR   Ensembl; ENST00000256592; ENSP00000256592; ENSG00000134200. [P01222-1]
DR   Ensembl; ENST00000369517; ENSP00000358530; ENSG00000134200. [P01222-1]
DR   GeneID; 7252; -.
DR   KEGG; hsa:7252; -.
DR   UCSC; uc001efs.2; human. [P01222-1]
DR   CTD; 7252; -.
DR   DisGeNET; 7252; -.
DR   EuPathDB; HostDB:ENSG00000134200.3; -.
DR   GeneCards; TSHB; -.
DR   H-InvDB; HIX0028781; -.
DR   HGNC; HGNC:12372; TSHB.
DR   HPA; CAB022202; -.
DR   HPA; HPA042681; -.
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   eggNOG; ENOG410IXJG; Eukaryota.
DR   eggNOG; ENOG410YSY0; LUCA.
DR   GeneTree; ENSGT00940000158152; -.
DR   HOGENOM; HOG000116098; -.
DR   HOVERGEN; HBG006698; -.
DR   InParanoid; P01222; -.
DR   KO; K05251; -.
DR   OMA; DVCTYRD; -.
DR   OrthoDB; 1362225at2759; -.
DR   PhylomeDB; P01222; -.
DR   TreeFam; TF332940; -.
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   SIGNOR; P01222; -.
DR   GeneWiki; TSHB; -.
DR   GenomeRNAi; 7252; -.
DR   PRO; PR:P01222; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000134200; Expressed in 79 organ(s), highest expression level in pituitary gland.
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: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; IBA:GO_Central.
DR   GO; GO:0016486; P:peptide hormone processing; TAS:Reactome.
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; Complete proteome; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Hormone; Pharmaceutical; Polymorphism;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     20       {ECO:0000269|PubMed:890569}.
FT   CHAIN        21    132       Thyrotropin subunit beta.
FT                                /FTId=PRO_0000011746.
FT   PROPEP      133    138
FT                                /FTId=PRO_0000011747.
FT   CARBOHYD     43     43       N-linked (GlcNAc...) asparagine.
FT   DISULFID     22     72       {ECO:0000250}.
FT   DISULFID     36     87       {ECO:0000250}.
FT   DISULFID     39    125       {ECO:0000250}.
FT   DISULFID     47    103       {ECO:0000250}.
FT   DISULFID     51    105       {ECO:0000250}.
FT   DISULFID    108    115       {ECO:0000250}.
FT   VAR_SEQ       1     54       MTALFLMSMLFGLTCGQAMSFCIPTEYTMHIERRECAYCLT
FT                                INTTICAGYCMTR -> MLSFLFFPQ (in isoform
FT                                2). {ECO:0000303|PubMed:19364510}.
FT                                /FTId=VSP_053387.
FT   VARIANT      14     14       T -> A (in dbSNP:rs10776792).
FT                                {ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:2457586,
FT                                ECO:0000269|PubMed:3234176,
FT                                ECO:0000269|PubMed:3243440,
FT                                ECO:0000269|PubMed:3839756,
FT                                ECO:0000269|PubMed:8196184}.
FT                                /FTId=VAR_054769.
FT   CONFLICT     46     46       I -> M (in Ref. 5; AAB30828).
FT                                {ECO:0000305}.
SQ   SEQUENCE   138 AA;  15639 MW;  6A367538D8393DB7 CRC64;
     MTALFLMSML FGLTCGQAMS FCIPTEYTMH IERRECAYCL TINTTICAGY CMTRDINGKL
     FLPKYALSQD VCTYRDFIYR TVEIPGCPLH VAPYFSYPVA LSCKCGKCNT DYSDCIHEAI
     KTNYCTKPQK SYLVGFSV
//