ID PERT_HUMAN Reviewed; 933 AA. AC P07202; P09934; P09935; Q8IUL0; Q8NF94; Q8NF95; Q8NF96; Q8NF97; AC Q8TCI9; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 4. DT 11-NOV-2015, entry version 201. DE RecName: Full=Thyroid peroxidase; DE Short=TPO; DE EC=1.11.1.8; DE Flags: Precursor; GN Name=TPO; 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 [MRNA] (ISOFORMS 1 AND 2), AND VARIANTS PRO-725 RP AND 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, RT chromosome mapping, and identification of two alternately spliced RT 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 RP 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 RT peroxidase 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 RP AND ALA-847. RC TISSUE=Thyroid; RA Hennen G.P., Igout A., Melen L.B.; RT "Homo sapiens thyroid peroxidase (TPO) variant mRNA, alternatively RT spliced 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), RP AND 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 RT alternative splicing. Characterization by molecular cloning of new RT transcripts with 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 RT antigen. 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 RP SPLICING 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 RT from 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- RT related 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; RP SER-373; 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 RT thyroid 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/jc.82.2.649; RA Bikker H., Baas F., De Vijlder J.J.M.; RT "Molecular analysis of mutated thyroid peroxidase detected in patients RT with 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 RT with 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/jc.84.3.1061; RA Pannain S., Weiss R.E., Jackson C.E., Dian D., Beck J.C., RA Sheffield V.C., Cox N., Refetoff S.; RT "Two different mutations in the thyroid peroxidase gene of a large RT inbred 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 RT total 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 RP LYS-799. RX PubMed=11061528; DOI=10.1210/jc.85.10.3708; 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 RT Netherlands: TPO gene mutations in total iodide organification defects RT (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 RT permanent congenital hypothyroidism."; RL Eur. J. Endocrinol. 145:19-24(2001). RN [18] RP VARIANTS TDH2A TRP-665 AND ARG-771, AND CHARACTERIZATION OF VARIANTS RP TDH2A 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 RT and 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 RT peroxidase gene in Taiwanese patients with total iodide organification RT defect, and 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., RA Regalbuto C., Bozzali M., Maiorana R., Ranieri A., Carta A., RA Buscema M., Trischitta V., 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 ASP-574-575-LEU DEL, AND CHARACTERIZATION RP OF VARIANTS TDH2A CYS-533 AND ASP-574-575-LEU 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 RT the 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., RA Moya C.M., 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 RT total 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., RA Mueller-Forell W., Kopp P., Pohlenz J.; RT "Goitrous congenital hypothyroidism and hearing impairment associated RT with mutations in the TPO and SLC26A4/PDS genes."; RL J. Clin. Endocrinol. Metab. 91:2678-2681(2006). CC -!- FUNCTION: Iodination and coupling of the hormonogenic tyrosines in CC thyroglobulin to yield the thyroid hormones T(3) and T(4). CC -!- CATALYTIC ACTIVITY: 2 iodide + H(2)O(2) + 2 H(+) = 2 iodine + 2 CC H(2)O. CC -!- CATALYTIC ACTIVITY: [Thyroglobulin]-L-tyrosine + iodide + H(2)O(2) CC = [thyroglobulin]-3-iodo-L-tyrosine + 2 H(2)O. CC -!- CATALYTIC ACTIVITY: [Thyroglobulin]-3-iodo-L-tyrosine + iodide + CC H(2)O(2) = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H(2)O. CC -!- CATALYTIC ACTIVITY: 2 [thyroglobulin]-3,5-diiodo-L-tyrosine + CC H(2)O(2) = [thyroglobulin]-L-thyroxine + [thyroglobulin]- CC aminoacrylate + 2 H(2)O. CC -!- CATALYTIC ACTIVITY: [Thyroglobulin]-3-iodo-L-tyrosine + CC [thyroglobulin]-3,5-diiodo-L-tyrosine + H(2)O(2) = CC [thyroglobulin]-3,5,3'-triiodo-L-thyronine + [thyroglobulin]- CC aminoacrylate + 2 H(2)O. CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000255|PROSITE-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; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00298}; CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently CC per 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 CC 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 Note=Lacks exon 10. Found in normal thyroid tissues as well as CC Graves'tissues. Rapidly degraded after synthesis, does not reach CC the cell surface. Inactive.; CC Name=3; Synonyms=TPO3, Graves' disease, TPOzaninelli; CC IsoId=P07202-3; Sequence=VSP_004666; CC Note=Lacks exon 16. Found in normal thyroid tissues as well as CC Graves'tissues. Active.; CC Name=4; Synonyms=TPO4; CC IsoId=P07202-4; Sequence=VSP_007269; CC Note=Lacks exon 14. Active.; CC Name=5; Synonyms=TPO5; CC IsoId=P07202-5; Sequence=VSP_007268; CC Note=Lacks exon 8. Does not fold correctly. Does not reach the CC cell surface.; CC Name=6; Synonyms=TPO6; CC IsoId=P07202-6; Sequence=VSP_004665, VSP_007270; CC Note=Lacks exons 10, 12, 13, 14 and 16.; CC Name=2-3; CC IsoId=P07202-7; Sequence=VSP_004665, VSP_004666; CC Note=Lacks exons 10 and 16.; CC Name=2-4; CC IsoId=P07202-8; Sequence=VSP_004665, VSP_007269; CC Note=Lacks exons 10 and 14.; 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 CC delivery of protein at the cell surface. CC -!- PTM: Cleaved in its N-terminal part. CC -!- DISEASE: Note=An alternative splicing in the thyroperoxidase mRNA CC can cause Graves' disease. CC -!- DISEASE: Thyroid dyshormonogenesis 2A (TDH2A) [MIM:274500]: A CC disorder due to defective conversion of accumulated iodide to CC organically bound iodine. The iodide organification defect can be CC partial or complete. {ECO:0000269|PubMed:10084596, CC ECO:0000269|PubMed:10468986, ECO:0000269|PubMed:11061528, CC ECO:0000269|PubMed:11415848, ECO:0000269|PubMed:11874711, CC ECO:0000269|PubMed:11916616, ECO:0000269|PubMed:12213873, CC ECO:0000269|PubMed:12490071, ECO:0000269|PubMed:12843174, CC ECO:0000269|PubMed:12864797, ECO:0000269|PubMed:12938097, CC ECO:0000269|PubMed:16284446, ECO:0000269|PubMed:16684826, CC ECO:0000269|PubMed:7550241, ECO:0000269|PubMed:9024270, CC ECO:0000269|PubMed:9924196}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00298}. CC -!- SIMILARITY: Contains 1 EGF-like domain. {ECO:0000255|PROSITE- CC ProRule:PRU00076}. CC -!- SIMILARITY: Contains 1 Sushi (CCP/SCR) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00302}. 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_011510381.1. [P07202-8] DR UniGene; Hs.467554; -. DR ProteinModelPortal; P07202; -. DR SMR; P07202; 149-732, 792-842. DR STRING; 9606.ENSP00000318820; -. DR ChEMBL; CHEMBL1839; -. DR DrugBank; DB00389; Carbimazole. DR DrugBank; DB00509; Dextrothyroxine. DR DrugBank; DB00763; Methimazole. DR DrugBank; DB00550; Propylthiouracil. DR GuidetoPHARMACOLOGY; 2526; -. DR Allergome; 9554; Hom s TPO. DR PeroxiBase; 3318; HsTPO01. DR PhosphoSite; P07202; -. DR BioMuta; TPO; -. DR DMDM; 160281455; -. DR PaxDb; P07202; -. DR PRIDE; P07202; -. DR Ensembl; ENST00000329066; ENSP00000329869; ENSG00000115705. [P07202-1] DR Ensembl; ENST00000345913; ENSP00000318820; ENSG00000115705. [P07202-1] DR Ensembl; ENST00000346956; ENSP00000263886; ENSG00000115705. [P07202-4] DR Ensembl; ENST00000382198; ENSP00000371633; ENSG00000115705. [P07202-5] DR Ensembl; ENST00000382201; ENSP00000371636; ENSG00000115705. [P07202-2] DR GeneID; 7173; -. DR KEGG; hsa:7173; -. DR UCSC; uc002qwr.3; human. [P07202-1] DR UCSC; uc002qwu.3; human. [P07202-2] DR UCSC; uc010yio.2; human. [P07202-5] DR UCSC; uc010yip.2; human. [P07202-4] DR CTD; 7173; -. DR GeneCards; TPO; -. DR H-InvDB; HIX0029848; -. DR HGNC; HGNC:12015; TPO. DR HPA; CAB009587; -. DR HPA; HPA007987; -. DR MIM; 274500; phenotype. DR MIM; 606765; gene. DR neXtProt; NX_P07202; -. DR Orphanet; 95716; Familial thyroid dyshormonogenesis. DR PharmGKB; PA36694; -. DR eggNOG; KOG2408; Eukaryota. DR eggNOG; ENOG410XPZ3; LUCA. DR GeneTree; ENSGT00550000074325; -. DR HOVERGEN; HBG000071; -. DR InParanoid; P07202; -. DR KO; K00431; -. DR OMA; CDSIPGM; -. DR OrthoDB; EOG7D2FD6; -. DR PhylomeDB; P07202; -. DR TreeFam; TF314316; -. DR BRENDA; 3.6.1.52; 2681. DR Reactome; R-HSA-209968; Thyroxine biosynthesis. DR UniPathway; UPA00194; -. DR ChiTaRS; TPO; human. DR GenomeRNAi; 7173; -. DR NextBio; 28112; -. DR PRO; PR:P07202; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; P07202; -. DR ExpressionAtlas; P07202; baseline and differential. DR Genevisible; P07202; HS. DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. 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; TAS:ProtInc. DR GO; GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome. DR GO; GO:0071732; P:cellular response to nitric oxide; IEA:Ensembl. 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:0033993; P:response to lipid; IEA:Ensembl. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006590; P:thyroid hormone generation; TAS:Reactome. DR Gene3D; 1.10.640.10; -; 2. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR010255; Haem_peroxidase. DR InterPro; IPR019791; Haem_peroxidase_animal. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR InterPro; IPR029589; TPO. DR PANTHER; PTHR11475:SF60; PTHR11475:SF60; 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; SM00179; EGF_CA; 1. DR SUPFAM; SSF48113; SSF48113; 1. DR SUPFAM; SSF57535; SSF57535; 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. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Complete proteome; KW Congenital hypothyroidism; Disease mutation; Disulfide bond; KW EGF-like domain; Glycoprotein; Heme; Hydrogen peroxide; Iron; KW Membrane; Metal-binding; Oxidoreductase; Peroxidase; Polymorphism; KW Reference proteome; Signal; Sushi; Thyroid hormones biosynthesis; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 18 {ECO:0000255}. FT CHAIN 19 933 Thyroid peroxidase. FT /FTId=PRO_0000023662. FT TOPO_DOM 19 846 Extracellular. {ECO:0000255}. FT TRANSMEM 847 871 Helical. {ECO:0000255}. FT TOPO_DOM 872 933 Cytoplasmic. {ECO:0000255}. FT DOMAIN 740 795 Sushi. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 796 839 EGF-like; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT ACT_SITE 239 239 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00298}. FT METAL 240 240 Calcium. {ECO:0000255|PROSITE- FT ProRule:PRU00298}. FT METAL 321 321 Calcium. {ECO:0000255|PROSITE- FT ProRule:PRU00298}. FT METAL 323 323 Calcium; via carbonyl oxygen. FT {ECO:0000255|PROSITE-ProRule:PRU00298}. FT METAL 325 325 Calcium. {ECO:0000255|PROSITE- FT ProRule:PRU00298}. FT METAL 327 327 Calcium. {ECO:0000255|PROSITE- FT ProRule:PRU00298}. FT METAL 494 494 Iron (heme axial ligand). FT {ECO:0000255|PROSITE-ProRule:PRU00298}. FT BINDING 238 238 Heme (covalent; via 2 links). FT {ECO:0000250}. FT BINDING 399 399 Heme (covalent; via 2 links). FT {ECO:0000250}. FT SITE 396 396 Transition state stabilizer. FT {ECO:0000255|PROSITE-ProRule:PRU00298}. FT CARBOHYD 129 129 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 307 307 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 342 342 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 569 569 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 142 158 {ECO:0000250}. FT DISULFID 259 269 {ECO:0000250}. FT DISULFID 263 286 {ECO:0000250}. FT DISULFID 598 655 {ECO:0000250}. FT DISULFID 696 721 {ECO:0000250}. FT DISULFID 800 814 {ECO:0000250}. FT DISULFID 808 823 {ECO:0000250}. FT DISULFID 825 838 {ECO:0000250}. FT VAR_SEQ 274 446 Missing (in isoform 5). FT {ECO:0000303|Ref.6}. FT /FTId=VSP_007268. FT VAR_SEQ 534 590 Missing (in isoform 2, isoform 2-3, FT isoform 2-4 and isoform 6). FT {ECO:0000303|PubMed:2308857, FT ECO:0000303|PubMed:3475693}. FT /FTId=VSP_004665. FT VAR_SEQ 669 933 Missing (in isoform 6). {ECO:0000305}. FT /FTId=VSP_007270. FT VAR_SEQ 796 839 Missing (in isoform 4 and isoform 2-4). FT {ECO:0000305}. FT /FTId=VSP_007269. FT VAR_SEQ 874 933 TRTGTKSTLPISETGGGTPELRCGKHQAVGTSPQRAAAQDS FT EQESAGMEGRDTHRLPRAL -> RVLGWKAGILTGCREPSE FT GKVAGHCRTASCSQNHRTTLFQTQANRKSAGRLFSQHG FT (in isoform 3 and isoform 2-3). FT {ECO:0000303|PubMed:2383265}. FT /FTId=VSP_004666. FT VARIANT 53 53 A -> P (in TDH2A). FT {ECO:0000269|PubMed:12213873}. FT /FTId=VAR_021622. FT VARIANT 240 240 D -> N (in TDH2A; loss of activity). FT {ECO:0000269|PubMed:9924196}. FT /FTId=VAR_021623. FT VARIANT 257 257 A -> S (in dbSNP:rs4927611). FT {ECO:0000269|PubMed:7550241, FT ECO:0000269|Ref.5, ECO:0000269|Ref.6}. FT /FTId=VAR_006057. FT VARIANT 307 307 N -> T (in TDH2A). FT {ECO:0000269|PubMed:12938097}. FT /FTId=VAR_021624. FT VARIANT 326 326 A -> T (in TDH2A). FT {ECO:0000269|PubMed:11061528}. FT /FTId=VAR_021625. FT VARIANT 373 373 A -> S (in dbSNP:rs2280132). FT {ECO:0000269|PubMed:7550241}. FT /FTId=VAR_006058. FT VARIANT 378 378 E -> K (in TDH2A). FT {ECO:0000269|PubMed:16284446}. FT /FTId=VAR_025784. FT VARIANT 398 398 S -> T (in dbSNP:rs2175977). FT {ECO:0000269|PubMed:7550241}. FT /FTId=VAR_006059. FT VARIANT 433 433 V -> M (in TDH2A). FT {ECO:0000269|PubMed:12938097}. FT /FTId=VAR_021626. FT VARIANT 447 447 I -> F (in TDH2A). FT {ECO:0000269|PubMed:11061528, FT ECO:0000269|PubMed:9024270}. FT /FTId=VAR_015375. FT VARIANT 453 453 Y -> D (in TDH2A). FT {ECO:0000269|PubMed:11061528, FT ECO:0000269|PubMed:16684826, FT ECO:0000269|PubMed:7550241}. FT /FTId=VAR_006060. FT VARIANT 458 458 L -> P (in TDH2A). FT {ECO:0000269|PubMed:11415848}. FT /FTId=VAR_021627. FT VARIANT 491 491 R -> H (in TDH2A; dbSNP:rs201165648). FT {ECO:0000269|PubMed:11415848}. FT /FTId=VAR_021628. FT VARIANT 493 493 G -> S (in TDH2A). FT {ECO:0000269|PubMed:11874711}. FT /FTId=VAR_021629. FT VARIANT 499 499 P -> L (in TDH2A). FT {ECO:0000269|PubMed:12938097}. FT /FTId=VAR_021630. FT VARIANT 527 527 W -> C (in TDH2A). FT {ECO:0000269|PubMed:11061528}. FT /FTId=VAR_021631. FT VARIANT 533 533 G -> C (in TDH2A; partial defect; FT expression slightly lower in efficiency FT and more degenerative than wild-type FT enzyme). {ECO:0000269|PubMed:12864797}. FT /FTId=VAR_027229. FT VARIANT 574 575 Missing (in TDH2A; partial defect; FT expressed on the plasma membrane surface FT at less than half the rate of wild-type FT enzyme). FT /FTId=VAR_027230. FT VARIANT 590 590 G -> S (in TDH2A). FT {ECO:0000269|PubMed:7550241}. FT /FTId=VAR_027231. FT VARIANT 618 618 V -> M (in dbSNP:rs10189135). FT /FTId=VAR_027232. FT VARIANT 648 648 R -> Q (in TDH2A). FT {ECO:0000269|PubMed:10084596}. FT /FTId=VAR_013138. FT VARIANT 660 660 Q -> E (in TDH2A; dbSNP:rs121908088). FT {ECO:0000269|PubMed:10468986}. FT /FTId=VAR_021632. FT VARIANT 665 665 R -> W (in TDH2A; fails to localize to FT the plasma membrane). FT {ECO:0000269|PubMed:11916616}. FT /FTId=VAR_021633. FT VARIANT 693 693 R -> W (in TDH2A). FT {ECO:0000269|PubMed:11061528, FT ECO:0000269|PubMed:12843174}. FT /FTId=VAR_021634. FT VARIANT 706 706 M -> V (in dbSNP:rs13431173). FT /FTId=VAR_027233. FT VARIANT 725 725 T -> P (in dbSNP:rs732609). FT {ECO:0000269|PubMed:12454013, FT ECO:0000269|PubMed:3453124, FT ECO:0000269|PubMed:3475693, FT ECO:0000269|PubMed:7550241, FT ECO:0000269|Ref.6}. FT /FTId=VAR_006061. FT VARIANT 771 771 G -> R (in TDH2A; fails to localize to FT the plasma membrane). FT {ECO:0000269|PubMed:11916616}. FT /FTId=VAR_021635. FT VARIANT 793 793 L -> P (in dbSNP:rs28991293). FT /FTId=VAR_027234. FT VARIANT 796 796 D -> Y (in TDH2A). FT {ECO:0000269|PubMed:11874711}. FT /FTId=VAR_021636. FT VARIANT 799 799 E -> K (in TDH2A; dbSNP:rs121908085). FT {ECO:0000269|PubMed:10084596, FT ECO:0000269|PubMed:11061528, FT ECO:0000269|PubMed:7550241}. FT /FTId=VAR_006062. FT VARIANT 808 808 C -> R (in TDH2A). FT {ECO:0000269|PubMed:12938097}. FT /FTId=VAR_021637. FT VARIANT 839 839 V -> I (in TDH2A). FT {ECO:0000269|PubMed:12490071}. FT /FTId=VAR_027235. FT VARIANT 846 846 R -> W (in dbSNP:rs28913014). FT /FTId=VAR_027236. FT VARIANT 847 847 V -> A (in dbSNP:rs1126799). FT {ECO:0000269|PubMed:12454013, FT ECO:0000269|PubMed:3453124, FT ECO:0000269|PubMed:3475693, FT ECO:0000269|Ref.6}. FT /FTId=VAR_027237. FT CONFLICT 70 70 P -> G (in Ref. 5; AAA61217). FT {ECO:0000305}. FT CONFLICT 354 354 A -> G (in Ref. 5 and 8). {ECO:0000305}. FT CONFLICT 371 371 A -> R (in Ref. 1; AAA61215/AAA61216). FT {ECO:0000305}. FT CONFLICT 381 381 I -> N (in Ref. 5 and 8). {ECO:0000305}. FT CONFLICT 574 574 D -> N (in Ref. 2; CAA68467). FT {ECO:0000305}. FT CONFLICT 732 732 W -> C (in Ref. 7; AAN11302). FT {ECO:0000305}. FT CONFLICT 748 748 V -> M (in Ref. 2 and 7). {ECO:0000305}. FT CONFLICT 816 816 N -> S (in Ref. 6; AAL74416). FT {ECO:0000305}. FT CONFLICT 872 872 R -> K (in Ref. 2 and 7). {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 //