ID PERT_HUMAN Reviewed; 933 AA. AC P07202; P09934; P09935; Q8IUL0; Q8NF94; Q8NF95; Q8NF96; Q8NF97; Q8TCI9; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 4. DT 24-JAN-2024, entry version 258. DE RecName: Full=Thyroid peroxidase {ECO:0000305}; DE Short=TPO; DE EC=1.11.1.8 {ECO:0000250|UniProtKB:P09933}; DE Flags: Precursor; GN Name=TPO {ECO:0000312|HGNC:HGNC:12015}; 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 [MRNA] (ISOFORMS 1 AND 2), AND VARIANTS PRO-725 AND RP ALA-847. RX PubMed=3475693; DOI=10.1073/pnas.84.16.5555; RA Kimura S., Kotani T., McBride O.W., Umeki K., Hirai K., Nakayama T., RA Ohtaki S.; RT "Human thyroid peroxidase: complete cDNA and protein sequence, chromosome RT mapping, and identification of two alternately spliced mRNAs."; RL Proc. Natl. Acad. Sci. U.S.A. 84:5555-5559(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS PRO-725 AND ALA-847. RC TISSUE=Thyroid; RX PubMed=3453124; DOI=10.1093/nar/15.16.6735; RA Libert F., Ruel J., Ludgate M., Swillens S., Alexander N., Vassart G., RA Dinsart C.; RT "Complete nucleotide sequence of the human thyroperoxidase-microsomal RT antigen cDNA."; RL Nucleic Acids Res. 15:6735-6735(1987). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=2548579; DOI=10.1021/bi00436a054; RA Kimura S., Hong Y.S., Kotani T., Ohtaki S., Kikkawa F.; RT "Structure of the human thyroid peroxidase gene: comparison and RT relationship to the human myeloperoxidase gene."; RL Biochemistry 28:4481-4489(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Thyroid; RX PubMed=2308857; DOI=10.1093/nar/18.3.670; RA Barnett P.S., Banga J.P., Watkins J., Huang G.C., Gluckman D.R.B., RA Page M.J., McGregor A.M.; RT "Nucleotide sequence of the alternatively spliced human thyroid peroxidase RT cDNA, TPO-2."; RL Nucleic Acids Res. 18:670-670(1990). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-257. RC TISSUE=Thyroid; RA Rapoport B.; RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND VARIANTS SER-257; PRO-725 AND RP ALA-847. RC TISSUE=Thyroid; RA Hennen G.P., Igout A., Melen L.B.; RT "Homo sapiens thyroid peroxidase (TPO) variant mRNA, alternatively spliced RT sequence."; RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6; 2-3 AND 2-4), AND RP VARIANTS PRO-725 AND ALA-847. RC TISSUE=Thyroid; RX PubMed=12454013; DOI=10.1074/jbc.m209513200; RA Ferrand M., Le Fourn V., Franc J.-L.; RT "Increasing diversity of human thyroperoxidase generated by alternative RT splicing. Characterization by molecular cloning of new transcripts with RT single- and multispliced mRNAs."; RL J. Biol. Chem. 278:3793-3800(2003). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 217-496. RX PubMed=3654979; DOI=10.1172/jci113181; RA Seto P., Hirayu H., Magnusson R.P., Gestautas J., Portmann L., RA Degroot L.J., Rapoport B.; RT "Isolation of a complementary DNA clone for thyroid microsomal antigen. RT Homology with the gene for thyroid peroxidase."; RL J. Clin. Invest. 80:1205-1208(1987). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 670-933 (ISOFORM 3), AND ALTERNATIVE SPLICING RP IN GRAVES' DISEASE. RC TISSUE=Thyroid; RX PubMed=2383265; DOI=10.1016/0006-291x(90)92152-p; RA Zanelli E., Henry M., Charvet B., Malthiery Y.; RT "Evidence for an alternate splicing in the thyroperoxidase messenger from RT patients with Graves' disease."; RL Biochem. Biophys. Res. Commun. 170:735-741(1990). RN [10] RP INTERACTION WITH DUOX1; DUOX2 AND CYBA. RX PubMed=15561711; DOI=10.1074/jbc.m407709200; RA Wang D., De Deken X., Milenkovic M., Song Y., Pirson I., Dumont J.E., RA Miot F.; RT "Identification of a novel partner of duox: EFP1, a thioredoxin-related RT protein."; RL J. Biol. Chem. 280:3096-3103(2005). RN [11] RP VARIANTS TDH2A ASP-453; SER-590 AND LYS-799, AND VARIANTS SER-257; SER-373; RP THR-398 AND PRO-725. RX PubMed=7550241; DOI=10.1002/humu.1380060104; RA Bikker H., Vulsma T., Baas F., de Vijlder J.J.M.; RT "Identification of five novel inactivating mutations in the human thyroid RT peroxidase gene by denaturing gradient gel electrophoresis."; RL Hum. Mutat. 6:9-16(1995). RN [12] RP VARIANT TDH2A PHE-447. RX PubMed=9024270; DOI=10.1210/jcem.82.2.3729; RA Bikker H., Baas F., De Vijlder J.J.M.; RT "Molecular analysis of mutated thyroid peroxidase detected in patients with RT total iodide organification defects."; RL J. Clin. Endocrinol. Metab. 82:649-653(1997). RN [13] RP VARIANT TDH2A GLU-660. RX PubMed=10468986; DOI=10.1046/j.1365-2265.1999.00746.x; RA Santos C.L.S., Bikker H., Rego K.G.M., Nascimento A.C., Tambascia M., RA De Vijlder J.J.M., Medeiros-Neto G.; RT "A novel mutation in the TPO gene in goitrous hypothyroid patients with RT iodide organification defect."; RL Clin. Endocrinol. (Oxf.) 51:165-172(1999). RN [14] RP VARIANTS TDH2A GLN-648 AND LYS-799. RX PubMed=10084596; DOI=10.1210/jcem.84.3.5541; RA Pannain S., Weiss R.E., Jackson C.E., Dian D., Beck J.C., Sheffield V.C., RA Cox N., Refetoff S.; RT "Two different mutations in the thyroid peroxidase gene of a large inbred RT Amish kindred: power and limits of homozygosity mapping."; RL J. Clin. Endocrinol. Metab. 84:1061-1071(1999). RN [15] RP VARIANT TDH2A ASN-240, AND CHARACTERIZATION OF VARIANT TDH2A ASN-240. RX PubMed=9924196; DOI=10.1677/joe.0.1600267; RA Kotani T., Umeki K., Yamamoto I., Maesaka H., Tachibana K., Ohtaki S.; RT "A novel mutation in the human thyroid peroxidase gene resulting in a total RT iodide organification defect."; RL J. Endocrinol. 160:267-273(1999). RN [16] RP VARIANTS TDH2A THR-326; PHE-447; ASP-453; CYS-527; TRP-693 AND LYS-799. RX PubMed=11061528; DOI=10.1210/jcem.85.10.6878; RA Bakker B., Bikker H., Vulsma T., de Randamie J.S.E., Wiedijk B.M., RA De Vijlder J.J.M.; RT "Two decades of screening for congenital hypothyroidism in The Netherlands: RT TPO gene mutations in total iodide organification defects (an update)."; RL J. Clin. Endocrinol. Metab. 85:3708-3712(2000). RN [17] RP VARIANTS TDH2A PRO-458 AND HIS-491. RX PubMed=11415848; DOI=10.1530/eje.0.1450019; RA Ambrugger P., Stoeva I., Biebermann H., Torresani T., Leitner C., RA Grueters A.; RT "Novel mutations of the thyroid peroxidase gene in patients with permanent RT congenital hypothyroidism."; RL Eur. J. Endocrinol. 145:19-24(2001). RN [18] RP VARIANTS TDH2A TRP-665 AND ARG-771, AND CHARACTERIZATION OF VARIANTS TDH2A RP TRP-665 AND ARG-771. RX PubMed=11916616; DOI=10.1530/eje.0.1460491; RA Umeki K., Kotani T., Kawano J., Suganuma T., Yamamoto I., Aratake Y., RA Furujo M., Ichiba Y.; RT "Two novel missense mutations in the thyroid peroxidase gene, R665W and RT G771R, result in a localization defect and cause congenital RT hypothyroidism."; RL Eur. J. Endocrinol. 146:491-498(2002). RN [19] RP VARIANT TDH2A PRO-53. RX PubMed=12213873; DOI=10.1210/jc.2002-020153; RA Niu D.-M., Hwang B., Chu Y.-K., Liao C.-J., Wang P.-L., Lin C.-Y.; RT "High prevalence of a novel mutation (2268 insT) of the thyroid peroxidase RT gene in Taiwanese patients with total iodide organification defect, and RT evidence for a founder effect."; RL J. Clin. Endocrinol. Metab. 87:4208-4212(2002). RN [20] RP VARIANTS TDH2A SER-493 AND TYR-796. RX PubMed=11874711; DOI=10.1677/joe.0.1720627; RA Wu J.-Y., Shu S.-G., Yang C.-F., Lee C.-C., Tsai F.-J.; RT "Mutation analysis of thyroid peroxidase gene in Chinese patients with RT total iodide organification defect: identification of five novel RT mutations."; RL J. Endocrinol. 172:627-635(2002). RN [21] RP VARIANT TDH2A ILE-839. RX PubMed=12490071; DOI=10.1089/105072502320908277; RA Calaciura F., Miscio G., Coco A., Leonardi D., Cisternino C., Regalbuto C., RA Bozzali M., Maiorana R., Ranieri A., Carta A., Buscema M., Trischitta V., RA Sava L., Tassi V.; RT "Genetics of specific phenotypes of congenital hypothyroidism: a RT population-based approach."; RL Thyroid 12:945-951(2002). RN [22] RP VARIANTS TDH2A CYS-533 AND 574-ASP-LEU-575 DEL, AND CHARACTERIZATION OF RP VARIANTS TDH2A CYS-533 AND 574-ASP-LEU-575 DEL. RX PubMed=12864797; DOI=10.1046/j.1365-2265.2003.01823.x; RA Kotani T., Umeki K., Kawano J., Suganuma T., Hishinuma A., Ieiri T., RA Harada S.; RT "Partial iodide organification defect caused by a novel mutation of the RT thyroid peroxidase gene in three siblings."; RL Clin. Endocrinol. (Oxf.) 59:198-206(2003). RN [23] RP VARIANTS TDH2A THR-307; MET-433; LEU-499 AND ARG-808. RX PubMed=12938097; DOI=10.1002/humu.9175; RA Rivolta C.M., Esperante S.A., Gruneiro-Papendieck L., Chiesa A., Moya C.M., RA Domene S., Varela V., Targovnik H.M.; RT "Five novel inactivating mutations in the thyroid peroxidase gene RT responsible for congenital goiter and iodide organification defect."; RL Hum. Mutat. 22:259-259(2003). RN [24] RP VARIANT TDH2A TRP-693. RX PubMed=12843174; DOI=10.1210/jc.2002-021377; RA Fugazzola L., Cerutti N., Mannavola D., Vannucchi G., Fallini C., RA Persani L., Beck-Peccoz P.; RT "Monoallelic expression of mutant thyroid peroxidase allele causing total RT iodide organification defect."; RL J. Clin. Endocrinol. Metab. 88:3264-3271(2003). RN [25] RP VARIANT TDH2A LYS-378. RX PubMed=16284446; DOI=10.1507/endocrj.52.643; RA Tajima T., Tsubaki J., Fujieda K.; RT "Two novel mutations in the thyroid peroxidase gene with goitrous RT hypothyroidism."; RL Endocr. J. 52:643-645(2005). RN [26] RP VARIANT TDH2A ASP-453. RX PubMed=16684826; DOI=10.1210/jc.2006-0142; RA Pfarr N., Borck G., Turk A., Napiontek U., Keilmann A., Mueller-Forell W., RA Kopp P., Pohlenz J.; RT "Goitrous congenital hypothyroidism and hearing impairment associated with RT mutations in the TPO and SLC26A4/PDS genes."; RL J. Clin. Endocrinol. Metab. 91:2678-2681(2006). RN [27] RP VARIANTS TDH2A HIS-412 AND 596-GLU--LEU-933 DEL. RX PubMed=27305979; DOI=10.1038/jhg.2016.62; RA Mittal K., Rafiq M.A., Rafiullah R., Harripaul R., Ali H., Ayaz M., RA Aslam M., Naeem F., Amin-Ud-Din M., Waqas A., So J., Rappold G.A., RA Vincent J.B., Ayub M.; RT "Mutations in the genes for thyroglobulin and thyroid peroxidase cause RT thyroid dyshormonogenesis and autosomal-recessive intellectual RT disability."; RL J. Hum. Genet. 61:867-872(2016). CC -!- FUNCTION: Iodination and coupling of the hormonogenic tyrosines in CC thyroglobulin to yield the thyroid hormones T(3) and T(4). CC {ECO:0000250|UniProtKB:P09933}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 H(+) + H2O2 + 2 iodide = diiodine + 2 H2O; CC Xref=Rhea:RHEA:23336, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:17606; EC=1.11.1.8; CC Evidence={ECO:0000250|UniProtKB:P09933}; CC -!- CATALYTIC ACTIVITY: CC Reaction=[thyroglobulin]-L-tyrosine + H(+) + H2O2 + iodide = CC [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48956, CC Rhea:RHEA-COMP:12274, Rhea:RHEA-COMP:12275, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, CC ChEBI:CHEBI:46858, ChEBI:CHEBI:90870; EC=1.11.1.8; CC Evidence={ECO:0000250|UniProtKB:P09933}; CC -!- CATALYTIC ACTIVITY: CC Reaction=[thyroglobulin]-3-iodo-L-tyrosine + H(+) + H2O2 + iodide = CC [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48960, CC Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, CC ChEBI:CHEBI:90870, ChEBI:CHEBI:90871; EC=1.11.1.8; CC Evidence={ECO:0000250|UniProtKB:P09933}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = CC [thyroglobulin]-dehydroalanine + [thyroglobulin]-L-thyroxine + 2 H2O; CC Xref=Rhea:RHEA:48964, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12277, CC Rhea:RHEA-COMP:12278, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, CC ChEBI:CHEBI:90871, ChEBI:CHEBI:90872, ChEBI:CHEBI:90873; EC=1.11.1.8; CC Evidence={ECO:0000250|UniProtKB:P09933}; CC -!- CATALYTIC ACTIVITY: CC Reaction=[thyroglobulin]-3,5-diiodo-L-tyrosine + [thyroglobulin]-3- CC iodo-L-tyrosine + H2O2 = [thyroglobulin]-3,3',5-triiodo-L-thyronine + CC [thyroglobulin]-dehydroalanine + 2 H2O; Xref=Rhea:RHEA:48968, CC Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12278, CC Rhea:RHEA-COMP:12279, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, CC ChEBI:CHEBI:90870, ChEBI:CHEBI:90871, ChEBI:CHEBI:90873, CC ChEBI:CHEBI:90874; EC=1.11.1.8; CC Evidence={ECO:0000250|UniProtKB:P09933}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00298}; CC Note=Binds 1 Ca(2+) ion per heterodimer. {ECO:0000255|PROSITE- CC ProRule:PRU00298}; CC -!- COFACTOR: CC Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00298}; CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per CC heterodimer. {ECO:0000255|PROSITE-ProRule:PRU00298}; CC -!- PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis. CC -!- SUBUNIT: Interacts with DUOX1, DUOX2 and CYBA. CC {ECO:0000269|PubMed:15561711}. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell surface. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Comment=Additional isoforms seem to exist.; CC Name=1; Synonyms=TPO1; CC IsoId=P07202-1; Sequence=Displayed; CC Name=2; Synonyms=TPO2; CC IsoId=P07202-2; Sequence=VSP_004665; CC Name=3; Synonyms=TPO3, Graves' disease, TPOzaninelli; CC IsoId=P07202-3; Sequence=VSP_004666; CC Name=4; Synonyms=TPO4; CC IsoId=P07202-4; Sequence=VSP_007269; CC Name=5; Synonyms=TPO5; CC IsoId=P07202-5; Sequence=VSP_007268; CC Name=6; Synonyms=TPO6; CC IsoId=P07202-6; Sequence=VSP_004665, VSP_007270; CC Name=2-3; CC IsoId=P07202-7; Sequence=VSP_004665, VSP_004666; CC Name=2-4; CC IsoId=P07202-8; Sequence=VSP_004665, VSP_007269; CC -!- PTM: Glycosylated. CC -!- PTM: Heme is covalently bound through a H(2)O(2)-dependent CC autocatalytic process. Heme insertion is important for the delivery of CC protein at the cell surface. CC -!- PTM: Cleaved in its N-terminal part. CC -!- DISEASE: Note=An alternative splicing in the thyroperoxidase mRNA can CC cause Graves' disease. CC -!- DISEASE: Thyroid dyshormonogenesis 2A (TDH2A) [MIM:274500]: A disorder CC due to defective conversion of accumulated iodide to organically bound CC iodine. The iodide organification defect can be partial or complete. CC {ECO:0000269|PubMed:10084596, ECO:0000269|PubMed:10468986, CC ECO:0000269|PubMed:11061528, ECO:0000269|PubMed:11415848, CC ECO:0000269|PubMed:11874711, ECO:0000269|PubMed:11916616, CC ECO:0000269|PubMed:12213873, ECO:0000269|PubMed:12490071, CC ECO:0000269|PubMed:12843174, ECO:0000269|PubMed:12864797, CC ECO:0000269|PubMed:12938097, ECO:0000269|PubMed:16284446, CC ECO:0000269|PubMed:16684826, ECO:0000269|PubMed:27305979, CC ECO:0000269|PubMed:7550241, ECO:0000269|PubMed:9024270, CC ECO:0000269|PubMed:9924196}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: Lacks exon 10. Found in normal thyroid CC tissues as well as Graves'tissues. Rapidly degraded after synthesis, CC does not reach the cell surface. Inactive. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Lacks exon 16. Found in normal thyroid CC tissues as well as Graves'tissues. Active. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Lacks exon 14. Active. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Lacks exon 8. Does not fold correctly. Does CC not reach the cell surface. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 6]: Lacks exons 10, 12, 13, 14 and 16. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 2-3]: Lacks exons 10 and 16. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 2-4]: Lacks exons 10 and 14. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00298}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Thyroid peroxidase entry; CC URL="https://en.wikipedia.org/wiki/Thyroid_peroxidase"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J02969; AAA61215.1; -; mRNA. DR EMBL; J02970; AAA61216.1; -; mRNA. DR EMBL; Y00406; CAA68467.1; -; mRNA. DR EMBL; M25715; AAA97517.1; -; Genomic_DNA. DR EMBL; M25702; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25703; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25704; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25705; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25706; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25707; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25708; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25709; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25710; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25711; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25712; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25713; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; M25714; AAA97517.1; JOINED; Genomic_DNA. DR EMBL; X17358; CAA35235.1; -; mRNA. DR EMBL; M17755; AAA61217.2; -; mRNA. DR EMBL; AF439430; AAL74416.1; -; mRNA. DR EMBL; AF533528; AAN04471.1; -; mRNA. DR EMBL; AY136822; AAN11302.1; -; mRNA. DR EMBL; AF533529; AAN04472.1; -; mRNA. DR EMBL; AF533530; AAN04473.1; -; mRNA. DR EMBL; AF533531; AAN04474.1; -; mRNA. DR EMBL; M55702; AAA61219.1; -; mRNA. DR EMBL; M55702; AAA61218.1; -; mRNA. DR CCDS; CCDS1643.1; -. [P07202-1] DR CCDS; CCDS1644.1; -. [P07202-2] DR CCDS; CCDS1646.1; -. [P07202-5] DR PIR; A32413; OPHUIT. DR RefSeq; NP_000538.3; NM_000547.5. [P07202-1] DR RefSeq; NP_001193673.1; NM_001206744.1. [P07202-1] DR RefSeq; NP_001193674.1; NM_001206745.1. [P07202-2] DR RefSeq; NP_783650.1; NM_175719.3. [P07202-2] DR RefSeq; NP_783652.1; NM_175721.3. [P07202-4] DR RefSeq; NP_783653.1; NM_175722.3. [P07202-5] DR RefSeq; XP_011508683.1; XM_011510381.2. DR AlphaFoldDB; P07202; -. DR SMR; P07202; -. DR BioGRID; 113026; 6. DR STRING; 9606.ENSP00000329869; -. DR BindingDB; P07202; -. DR ChEMBL; CHEMBL1839; -. DR DrugBank; DB11496; 2-mercaptobenzothiazole. DR DrugBank; DB00389; Carbimazole. DR DrugBank; DB00509; Dextrothyroxine. DR DrugBank; DB05382; Iodine. DR DrugBank; DB00763; Methimazole. DR DrugBank; DB00550; Propylthiouracil. DR DrugBank; DB11085; Resorcinol. DR DrugBank; DB08604; Triclosan. DR DrugCentral; P07202; -. DR GuidetoPHARMACOLOGY; 2526; -. DR Allergome; 9554; Hom s TPO. DR PeroxiBase; 3318; HsTPO01. DR GlyCosmos; P07202; 4 sites, No reported glycans. DR GlyGen; P07202; 5 sites, 1 O-linked glycan (1 site). DR iPTMnet; P07202; -. DR PhosphoSitePlus; P07202; -. DR BioMuta; TPO; -. DR DMDM; 160281455; -. DR MassIVE; P07202; -. DR PaxDb; 9606-ENSP00000318820; -. DR PeptideAtlas; P07202; -. DR ProteomicsDB; 51964; -. [P07202-1] DR ProteomicsDB; 51965; -. [P07202-2] DR ProteomicsDB; 51966; -. [P07202-3] DR ProteomicsDB; 51967; -. [P07202-4] DR ProteomicsDB; 51968; -. [P07202-5] DR ProteomicsDB; 51969; -. [P07202-6] DR ProteomicsDB; 51970; -. [P07202-7] DR ProteomicsDB; 51971; -. [P07202-8] DR ABCD; P07202; 56 sequenced antibodies. DR Antibodypedia; 2364; 739 antibodies from 35 providers. DR DNASU; 7173; -. DR Ensembl; ENST00000329066.9; ENSP00000329869.4; ENSG00000115705.22. [P07202-1] DR Ensembl; ENST00000345913.8; ENSP00000318820.7; ENSG00000115705.22. [P07202-1] DR Ensembl; ENST00000346956.7; ENSP00000263886.6; ENSG00000115705.22. [P07202-4] DR Ensembl; ENST00000382198.5; ENSP00000371633.1; ENSG00000115705.22. [P07202-5] DR Ensembl; ENST00000382201.7; ENSP00000371636.3; ENSG00000115705.22. [P07202-2] DR GeneID; 7173; -. DR KEGG; hsa:7173; -. DR MANE-Select; ENST00000329066.9; ENSP00000329869.4; NM_001206744.2; NP_001193673.1. DR UCSC; uc002qwr.4; human. [P07202-1] DR AGR; HGNC:12015; -. DR CTD; 7173; -. DR DisGeNET; 7173; -. DR GeneCards; TPO; -. DR HGNC; HGNC:12015; TPO. DR HPA; ENSG00000115705; Tissue enriched (thyroid). DR MalaCards; TPO; -. DR MIM; 274500; phenotype. DR MIM; 606765; gene. DR neXtProt; NX_P07202; -. DR OpenTargets; ENSG00000115705; -. DR Orphanet; 95716; Familial thyroid dyshormonogenesis. DR PharmGKB; PA36694; -. DR VEuPathDB; HostDB:ENSG00000115705; -. DR eggNOG; KOG2408; Eukaryota. DR GeneTree; ENSGT00940000158104; -. DR InParanoid; P07202; -. DR OMA; HPCFPIE; -. DR OrthoDB; 4560at2759; -. DR PhylomeDB; P07202; -. DR TreeFam; TF314316; -. DR BRENDA; 1.11.1.8; 2681. DR BRENDA; 3.6.1.52; 2681. DR PathwayCommons; P07202; -. DR Reactome; R-HSA-209968; Thyroxine biosynthesis. DR SignaLink; P07202; -. DR SIGNOR; P07202; -. DR UniPathway; UPA00194; -. DR BioGRID-ORCS; 7173; 8 hits in 1150 CRISPR screens. DR ChiTaRS; TPO; human. DR GenomeRNAi; 7173; -. DR Pharos; P07202; Tclin. DR PRO; PR:P07202; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P07202; Protein. DR Bgee; ENSG00000115705; Expressed in left lobe of thyroid gland and 94 other cell types or tissues. DR ExpressionAtlas; P07202; baseline and differential. DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0020037; F:heme binding; IEA:InterPro. DR GO; GO:0004447; F:iodide peroxidase activity; IEA:UniProtKB-EC. DR GO; GO:0004601; F:peroxidase activity; IBA:GO_Central. DR GO; GO:0035162; P:embryonic hemopoiesis; IDA:DFLAT. DR GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW. DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro. DR GO; GO:0006590; P:thyroid hormone generation; TAS:Reactome. DR CDD; cd00033; CCP; 1. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd09825; thyroid_peroxidase; 1. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 1. DR Gene3D; 1.10.640.10; Haem peroxidase domain superfamily, animal type; 1. DR Gene3D; 2.10.25.10; Laminin; 1. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR019791; Haem_peroxidase_animal. DR InterPro; IPR010255; Haem_peroxidase_sf. DR InterPro; IPR037120; Haem_peroxidase_sf_animal. DR InterPro; IPR035976; Sushi/SCR/CCP_sf. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR InterPro; IPR029589; TPO. DR PANTHER; PTHR11475; OXIDASE/PEROXIDASE; 1. DR PANTHER; PTHR11475:SF60; THYROID PEROXIDASE; 1. DR Pfam; PF03098; An_peroxidase; 1. DR Pfam; PF07645; EGF_CA; 1. DR Pfam; PF00084; Sushi; 1. DR PRINTS; PR00457; ANPEROXIDASE. DR SMART; SM00032; CCP; 1. DR SMART; SM00181; EGF; 1. DR SMART; SM00179; EGF_CA; 1. DR SUPFAM; SSF57535; Complement control module/SCR domain; 1. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF48113; Heme-dependent peroxidases; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 1. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 1. DR PROSITE; PS01187; EGF_CA; 1. DR PROSITE; PS00435; PEROXIDASE_1; 1. DR PROSITE; PS50292; PEROXIDASE_3; 1. DR PROSITE; PS50923; SUSHI; 1. DR Genevisible; P07202; HS. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Congenital hypothyroidism; Disease variant; KW Disulfide bond; EGF-like domain; Glycoprotein; Heme; Hydrogen peroxide; KW Iron; Membrane; Metal-binding; Oxidoreductase; Peroxidase; KW Reference proteome; Signal; Sushi; Thyroid hormones biosynthesis; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..933 FT /note="Thyroid peroxidase" FT /id="PRO_0000023662" FT TOPO_DOM 19..846 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 847..871 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 872..933 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 740..795 FT /note="Sushi" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 796..839 FT /note="EGF-like; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 881..933 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 918..933 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 239 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 238 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /note="covalent" FT /evidence="ECO:0000250" FT BINDING 240 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 321 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 323 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 325 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 327 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 399 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /note="covalent" FT /evidence="ECO:0000250" FT BINDING 494 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT SITE 396 FT /note="Transition state stabilizer" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT CARBOHYD 129 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 307 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 342 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 569 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 142..158 FT /evidence="ECO:0000250" FT DISULFID 259..269 FT /evidence="ECO:0000250" FT DISULFID 263..286 FT /evidence="ECO:0000250" FT DISULFID 598..655 FT /evidence="ECO:0000250" FT DISULFID 696..721 FT /evidence="ECO:0000250" FT DISULFID 800..814 FT /evidence="ECO:0000250" FT DISULFID 808..823 FT /evidence="ECO:0000250" FT DISULFID 825..838 FT /evidence="ECO:0000250" FT VAR_SEQ 274..446 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_007268" FT VAR_SEQ 534..590 FT /note="Missing (in isoform 2, isoform 2-3, isoform 2-4 and FT isoform 6)" FT /evidence="ECO:0000303|PubMed:2308857, FT ECO:0000303|PubMed:3475693" FT /id="VSP_004665" FT VAR_SEQ 669..933 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000305" FT /id="VSP_007270" FT VAR_SEQ 796..839 FT /note="Missing (in isoform 4 and isoform 2-4)" FT /evidence="ECO:0000305" FT /id="VSP_007269" FT VAR_SEQ 874..933 FT /note="TRTGTKSTLPISETGGGTPELRCGKHQAVGTSPQRAAAQDSEQESAGMEGRD FT THRLPRAL -> RVLGWKAGILTGCREPSEGKVAGHCRTASCSQNHRTTLFQTQANRKS FT AGRLFSQHG (in isoform 3 and isoform 2-3)" FT /evidence="ECO:0000303|PubMed:2383265" FT /id="VSP_004666" FT VARIANT 53 FT /note="A -> P (in TDH2A)" FT /evidence="ECO:0000269|PubMed:12213873" FT /id="VAR_021622" FT VARIANT 240 FT /note="D -> N (in TDH2A; loss of activity; FT dbSNP:rs1427024341)" FT /evidence="ECO:0000269|PubMed:9924196" FT /id="VAR_021623" FT VARIANT 257 FT /note="A -> S (in dbSNP:rs4927611)" FT /evidence="ECO:0000269|PubMed:7550241, ECO:0000269|Ref.5, FT ECO:0000269|Ref.6" FT /id="VAR_006057" FT VARIANT 307 FT /note="N -> T (in TDH2A)" FT /evidence="ECO:0000269|PubMed:12938097" FT /id="VAR_021624" FT VARIANT 326 FT /note="A -> T (in TDH2A; dbSNP:rs371367459)" FT /evidence="ECO:0000269|PubMed:11061528" FT /id="VAR_021625" FT VARIANT 373 FT /note="A -> S (in dbSNP:rs2280132)" FT /evidence="ECO:0000269|PubMed:7550241" FT /id="VAR_006058" FT VARIANT 378 FT /note="E -> K (in TDH2A; dbSNP:rs1297312788)" FT /evidence="ECO:0000269|PubMed:16284446" FT /id="VAR_025784" FT VARIANT 398 FT /note="S -> T (in dbSNP:rs2175977)" FT /evidence="ECO:0000269|PubMed:7550241" FT /id="VAR_006059" FT VARIANT 412 FT /note="R -> H (in TDH2A; uncertain significance; FT dbSNP:rs1173922703)" FT /evidence="ECO:0000269|PubMed:27305979" FT /id="VAR_078336" FT VARIANT 433 FT /note="V -> M (in TDH2A; dbSNP:rs1035791118)" FT /evidence="ECO:0000269|PubMed:12938097" FT /id="VAR_021626" FT VARIANT 447 FT /note="I -> F (in TDH2A; dbSNP:rs104893669)" FT /evidence="ECO:0000269|PubMed:11061528, FT ECO:0000269|PubMed:9024270" FT /id="VAR_015375" FT VARIANT 453 FT /note="Y -> D (in TDH2A; dbSNP:rs121908083)" FT /evidence="ECO:0000269|PubMed:11061528, FT ECO:0000269|PubMed:16684826, ECO:0000269|PubMed:7550241" FT /id="VAR_006060" FT VARIANT 458 FT /note="L -> P (in TDH2A; dbSNP:rs1231870370)" FT /evidence="ECO:0000269|PubMed:11415848" FT /id="VAR_021627" FT VARIANT 491 FT /note="R -> H (in TDH2A; dbSNP:rs201165648)" FT /evidence="ECO:0000269|PubMed:11415848" FT /id="VAR_021628" FT VARIANT 493 FT /note="G -> S (in TDH2A; dbSNP:rs778515113)" FT /evidence="ECO:0000269|PubMed:11874711" FT /id="VAR_021629" FT VARIANT 499 FT /note="P -> L (in TDH2A; dbSNP:rs1169072188)" FT /evidence="ECO:0000269|PubMed:12938097" FT /id="VAR_021630" FT VARIANT 527 FT /note="W -> C (in TDH2A; dbSNP:rs779434941)" FT /evidence="ECO:0000269|PubMed:11061528" FT /id="VAR_021631" FT VARIANT 533 FT /note="G -> C (in TDH2A; partial defect; expression FT slightly lower in efficiency and more degenerative than FT wild-type enzyme)" FT /evidence="ECO:0000269|PubMed:12864797" FT /id="VAR_027229" FT VARIANT 574..575 FT /note="Missing (in TDH2A; partial defect; expressed on the FT plasma membrane surface at less than half the rate of FT wild-type enzyme)" FT /id="VAR_027230" FT VARIANT 590 FT /note="G -> S (in TDH2A; dbSNP:rs121908084)" FT /evidence="ECO:0000269|PubMed:7550241" FT /id="VAR_027231" FT VARIANT 596..933 FT /note="Missing (in TDH2A; uncertain significance)" FT /evidence="ECO:0000269|PubMed:27305979" FT /id="VAR_078337" FT VARIANT 618 FT /note="V -> M (in dbSNP:rs10189135)" FT /id="VAR_027232" FT VARIANT 648 FT /note="R -> Q (in TDH2A; dbSNP:rs121908086)" FT /evidence="ECO:0000269|PubMed:10084596" FT /id="VAR_013138" FT VARIANT 660 FT /note="Q -> E (in TDH2A; dbSNP:rs121908088)" FT /evidence="ECO:0000269|PubMed:10468986" FT /id="VAR_021632" FT VARIANT 665 FT /note="R -> W (in TDH2A; fails to localize to the plasma FT membrane; dbSNP:rs776742629)" FT /evidence="ECO:0000269|PubMed:11916616" FT /id="VAR_021633" FT VARIANT 693 FT /note="R -> W (in TDH2A; dbSNP:rs121908087)" FT /evidence="ECO:0000269|PubMed:11061528, FT ECO:0000269|PubMed:12843174" FT /id="VAR_021634" FT VARIANT 706 FT /note="M -> V (in dbSNP:rs13431173)" FT /id="VAR_027233" FT VARIANT 725 FT /note="T -> P (in dbSNP:rs732609)" FT /evidence="ECO:0000269|PubMed:12454013, FT ECO:0000269|PubMed:3453124, ECO:0000269|PubMed:3475693, FT ECO:0000269|PubMed:7550241, ECO:0000269|Ref.6" FT /id="VAR_006061" FT VARIANT 771 FT /note="G -> R (in TDH2A; fails to localize to the plasma FT membrane; dbSNP:rs138931129)" FT /evidence="ECO:0000269|PubMed:11916616" FT /id="VAR_021635" FT VARIANT 793 FT /note="L -> P (in dbSNP:rs28991293)" FT /id="VAR_027234" FT VARIANT 796 FT /note="D -> Y (in TDH2A)" FT /evidence="ECO:0000269|PubMed:11874711" FT /id="VAR_021636" FT VARIANT 799 FT /note="E -> K (in TDH2A; dbSNP:rs121908085)" FT /evidence="ECO:0000269|PubMed:10084596, FT ECO:0000269|PubMed:11061528, ECO:0000269|PubMed:7550241" FT /id="VAR_006062" FT VARIANT 808 FT /note="C -> R (in TDH2A; dbSNP:rs935058009)" FT /evidence="ECO:0000269|PubMed:12938097" FT /id="VAR_021637" FT VARIANT 839 FT /note="V -> I (in TDH2A; dbSNP:rs146351101)" FT /evidence="ECO:0000269|PubMed:12490071" FT /id="VAR_027235" FT VARIANT 846 FT /note="R -> W (in dbSNP:rs28913014)" FT /id="VAR_027236" FT VARIANT 847 FT /note="V -> A (in dbSNP:rs1126799)" FT /evidence="ECO:0000269|PubMed:12454013, FT ECO:0000269|PubMed:3453124, ECO:0000269|PubMed:3475693, FT ECO:0000269|Ref.6" FT /id="VAR_027237" FT CONFLICT 70 FT /note="P -> G (in Ref. 5; AAA61217)" FT /evidence="ECO:0000305" FT CONFLICT 354 FT /note="A -> G (in Ref. 5 and 8)" FT /evidence="ECO:0000305" FT CONFLICT 371 FT /note="A -> R (in Ref. 1; AAA61215/AAA61216)" FT /evidence="ECO:0000305" FT CONFLICT 381 FT /note="I -> N (in Ref. 5 and 8)" FT /evidence="ECO:0000305" FT CONFLICT 574 FT /note="D -> N (in Ref. 2; CAA68467)" FT /evidence="ECO:0000305" FT CONFLICT 732 FT /note="W -> C (in Ref. 7; AAN11302)" FT /evidence="ECO:0000305" FT CONFLICT 748 FT /note="V -> M (in Ref. 2 and 7)" FT /evidence="ECO:0000305" FT CONFLICT 816 FT /note="N -> S (in Ref. 6; AAL74416)" FT /evidence="ECO:0000305" FT CONFLICT 872 FT /note="R -> K (in Ref. 2 and 7)" FT /evidence="ECO:0000305" SQ SEQUENCE 933 AA; 102963 MW; F67C5F1A4AEE0B29 CRC64; MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGGLDPLIR GLLARPAKLQ VQDQLMNEEL TERLFVLSNS STLDLASINL QRGRDHGLPG YNEWREFCGL PRLETPADLS TAIASRSVAD KILDLYKHPD NIDVWLGGLA ENFLPRARTG PLFACLIGKQ MKALRDGDWF WWENSHVFTD AQRRELEKHS LSRVICDNTG LTRVPMDAFQ VGKFPEDFES CDSITGMNLE AWRETFPQDD KCGFPESVEN GDFVHCEESG RRVLVYSCRH GYELQGREQL TCTQEGWDFQ PPLCKDVNEC ADGAHPPCHA SARCRNTKGG FQCLCADPYE LGDDGRTCVD SGRLPRVTWI SMSLAALLIG GFAGLTSTVI CRWTRTGTKS TLPISETGGG TPELRCGKHQ AVGTSPQRAA AQDSEQESAG MEGRDTHRLP RAL //