ID   PERT_PIG                Reviewed;         926 AA.
AC   P09933;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   24-JAN-2024, entry version 173.
DE   RecName: Full=Thyroid peroxidase;
DE            Short=TPO;
DE            EC=1.11.1.8 {ECO:0000269|PubMed:12325367, ECO:0000269|PubMed:2996435, ECO:0000269|PubMed:7142155};
DE   Flags: Precursor;
GN   Name=TPO;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3654642; DOI=10.1016/s0021-9258(18)47875-1;
RA   Magnusson R.P., Gestautas J., Taurog A., Rapoport B.;
RT   "Molecular cloning of the structural gene for porcine thyroid peroxidase.";
RL   J. Biol. Chem. 262:13885-13888(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 595-926.
RX   PubMed=3780975; DOI=10.1016/0014-5793(86)81055-9;
RA   Magnusson R.P., Gestautas J., Seto P., Taurog A., Rapoport B.;
RT   "Isolation and characterization of a cDNA clone for porcine thyroid
RT   peroxidase.";
RL   FEBS Lett. 208:391-396(1986).
RN   [3]
RP   PROTEIN SEQUENCE OF 110-115; 267-274; 301-308 AND 340-351, AND
RP   GLYCOSYLATION AT ASN-129; ASN-277; ASN-307 AND ASN-342.
RX   PubMed=1497352; DOI=10.1016/0003-9861(92)90679-q;
RA   Rawitch A.B., Pollock G., Yang S.-X., Taurog A.;
RT   "Thyroid peroxidase glycosylation: the location and nature of the N-linked
RT   oligosaccharide units in porcine thyroid peroxidase.";
RL   Arch. Biochem. Biophys. 297:321-327(1992).
RN   [4]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=12325367; DOI=10.1016/s0021-9258(18)99388-9;
RA   Coval M.L., Taurog A.;
RT   "Purification and iodinating activity of hog thyroid peroxidase.";
RL   J. Biol. Chem. 242:5510-5523(1967).
RN   [5]
RP   CATALYTIC ACTIVITY, AND CHARACTERIZATION.
RX   PubMed=7142155; DOI=10.1016/s0021-9258(18)33462-8;
RA   Ohtaki S., Nakagawa H., Nakamura M., Yamazaki I.;
RT   "One- and two-electron oxidations of tyrosine, monoiodotyrosine, and
RT   diiodotyrosine catalyzed by hog thyroid peroxidase.";
RL   J. Biol. Chem. 257:13398-13403(1982).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION.
RX   PubMed=2996435; DOI=10.1016/0003-9861(85)90477-1;
RA   Virion A., Courtin F., Deme D., Michot J.L., Kaniewski J., Pommier J.;
RT   "Spectral characteristics and catalytic properties of thyroid peroxidase-
RT   H2O2 compounds in the iodination and coupling reactions.";
RL   Arch. Biochem. Biophys. 242:41-47(1985).
CC   -!- FUNCTION: Iodination and coupling of the hormonogenic tyrosines in
CC       thyroglobulin to yield the thyroid hormones T(3) and T(4).
CC       {ECO:0000269|PubMed:12325367, ECO:0000269|PubMed:2996435}.
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:0000269|PubMed:12325367, ECO:0000269|PubMed:2996435,
CC         ECO:0000269|PubMed:7142155};
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:0000269|PubMed:12325367, ECO:0000269|PubMed:2996435,
CC         ECO:0000269|PubMed:7142155};
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:0000269|PubMed:12325367, ECO:0000269|PubMed:2996435,
CC         ECO:0000269|PubMed:7142155};
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:0000269|PubMed:12325367, ECO:0000269|PubMed:2996435,
CC         ECO:0000269|PubMed:7142155};
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:0000269|PubMed:12325367, ECO:0000269|PubMed:2996435,
CC         ECO:0000269|PubMed:7142155};
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. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC   -!- PTM: Cleaved in its N-terminal part. {ECO:0000250}.
CC   -!- PTM: N-glycosylated; contains mannose and N-acetylglucosamine.
CC       {ECO:0000269|PubMed:1497352}.
CC   -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00298}.
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DR   EMBL; X04645; CAA28306.1; -; mRNA.
DR   PIR; A27416; OPPGIT.
DR   AlphaFoldDB; P09933; -.
DR   SMR; P09933; -.
DR   STRING; 9823.ENSSSCP00000074299; -.
DR   PeroxiBase; 3329; SscTPO.
DR   GlyCosmos; P09933; 4 sites, No reported glycans.
DR   iPTMnet; P09933; -.
DR   PaxDb; 9823-ENSSSCP00000025583; -.
DR   eggNOG; KOG2408; Eukaryota.
DR   InParanoid; P09933; -.
DR   BioCyc; MetaCyc:MONOMER-14809; -.
DR   BRENDA; 1.11.1.8; 6170.
DR   UniPathway; UPA00194; -.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unplaced.
DR   Proteomes; UP000694570; Unplaced.
DR   Proteomes; UP000694571; Unplaced.
DR   Proteomes; UP000694720; Unplaced.
DR   Proteomes; UP000694722; Unplaced.
DR   Proteomes; UP000694723; Unplaced.
DR   Proteomes; UP000694724; Unplaced.
DR   Proteomes; UP000694725; Unplaced.
DR   Proteomes; UP000694726; Unplaced.
DR   Proteomes; UP000694727; Unplaced.
DR   Proteomes; UP000694728; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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; IDA:UniProtKB.
DR   GO; GO:0004601; F:peroxidase activity; IBA:GO_Central.
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; IDA:UniProtKB.
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; 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; PF00084; Sushi; 1.
DR   PRINTS; PR00457; ANPEROXIDASE.
DR   SMART; SM00032; CCP; 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; PS50026; EGF_3; 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   Calcium; Direct protein sequencing; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Heme; Hydrogen peroxide; Iron; Membrane; Metal-binding;
KW   Oxidoreductase; Peroxidase; Reference proteome; Signal; Sushi;
KW   Thyroid hormones biosynthesis; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..14
FT                   /evidence="ECO:0000255"
FT   CHAIN           15..926
FT                   /note="Thyroid peroxidase"
FT                   /id="PRO_0000023664"
FT   TOPO_DOM        19..844
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        845..869
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        870..926
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          738..793
FT                   /note="Sushi"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT   DOMAIN          794..837
FT                   /note="EGF-like; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
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         398
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /note="covalent"
FT                   /evidence="ECO:0000250"
FT   BINDING         493
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            395
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:1497352"
FT   CARBOHYD        277
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:1497352"
FT   CARBOHYD        307
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:1497352"
FT   CARBOHYD        342
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:1497352"
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        596..653
FT                   /evidence="ECO:0000250"
FT   DISULFID        694..719
FT                   /evidence="ECO:0000250"
FT   DISULFID        740..780
FT                   /evidence="ECO:0000250"
FT   DISULFID        766..792
FT                   /evidence="ECO:0000250"
FT   DISULFID        798..812
FT                   /evidence="ECO:0000250"
FT   DISULFID        806..821
FT                   /evidence="ECO:0000250"
FT   DISULFID        823..836
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   926 AA;  100443 MW;  8549FF6F0F742C5E CRC64;
     MGARAVLGVT LAVACAGAFF ASILRRKDLL GGDTEASGVA GLVEASRLLV DEAIHTTMRR
     NLRKRGIFSP SQLLSFSKLP EPTSRTASRA AEIMETAVQE VKRRVCRRRD TDQLPTDVLS
     EELLSTIANL SGCLPHMLPP SCPHTCLANK YRLITGACNN RDHPRWGASN TALARWLPPA
     YEDGVTEPRG WNPHFLYNGL PLPPVREVTR QVIHVSNEAV TEDGQYSDLL MAWGQYIDHD
     IAFTPQSTSK AAFAGGADCQ LTCENRSPCF PIQLPTNASG AAGATCLPFY RSSAACGSGR
     QGALVGNLSW AAPRQQMNGL TSFLDASTVY GSSPAQEQRL RNWTSAEGLL RVNTRHRDAG
     RAFLPFAPPP APPACAPEPG TPAARAPCFL AGDSRASEVP GLTALHTLWL REHNRLAAAF
     KALNAHWSAD TVYQEARKVV GALHQIVTLR DYVPKILGAE AFGQHVGPYQ GYDPAVDPTV
     SNVFSTAAFR FGHATIHPLV RRLDARFQEH PGSHLPLRAA FFQPWRLLRE GGVDPVLRGL
     LARPAKLQVQ DQLMNEELTE RLFVLSNSGT LDLASINLQR GRDHGLPGYN EWREFCGLSR
     LETWADLSAA TANGRVADRI LGLYQHPDNI DVWLGGLAES FLPGARTGPL FACIIGKQMR
     ALRDGDRFWW ENPGVFTEAQ RRELSRHSMS RVICDNSGLS HVPLDAFRVG QWPQEFEPCA
     SIQGMDLGAW REAPPSGDAC GFPDPVEDGG FLLCEERGQR VLVFSCRHGF RLRGPAQITC
     TPRGWDSPPP LCKDINECED ETDPPCHASA RCKNTKGGVL CECSDPLVLG EDGRTCVDAG
     RLPRASVVSI ALGAVLVCGL AGLAWTVVCR WTHADARPLL PVGEGEGDGK SPSLPLPGCG
     NRRDVGAAPA LEVEQDLSCG SRGLCE
//