PERT_PIG
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 03-AUG-2022, entry version 166.
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;
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 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.ENSSSCP00000025583; -.
DR PeroxiBase; 3329; SscTPO.
DR iPTMnet; P09933; -.
DR PaxDb; P09933; -.
DR PRIDE; P09933; -.
DR eggNOG; KOG2408; Eukaryota.
DR InParanoid; P09933; -.
DR BioCyc; MetaCyc:MON-14809; -.
DR BRENDA; 1.11.1.8; 6170.
DR UniPathway; UPA00194; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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 Gene3D; 1.10.640.10; -; 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:SF60; PTHR11475:SF60; 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; SSF48113; SSF48113; 1.
DR SUPFAM; SSF57535; SSF57535; 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
