ID PERT_RAT Reviewed; 914 AA. AC P14650; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 24-JAN-2024, entry version 180. DE RecName: Full=Thyroid peroxidase; DE Short=TPO; DE EC=1.11.1.8 {ECO:0000250|UniProtKB:P09933}; DE Flags: Precursor; GN Name=Tpo; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2813071; DOI=10.1093/nar/17.20.8380; RA Derwahl M., Seto P., Rapoport B.; RT "Complete nucleotide sequence of the cDNA for thyroid peroxidase in FRTL5 RT rat thyroid cells."; RL Nucleic Acids Res. 17:8380-8380(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 145-914. RX PubMed=2691880; DOI=10.1210/mend-3-11-1681; RA Isozaki O., Kohn L.D., Kozak C.A., Kimura S.; RT "Thyroid peroxidase: rat cDNA sequence, chromosomal localization in mouse, RT and regulation of gene expression by comparison to thyroglobulin in rat RT FRTL-5 cells."; RL Mol. Endocrinol. 3:1681-1692(1989). 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. {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 -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00298}. 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; X17396; CAA35257.1; -; mRNA. DR EMBL; M31655; AAA42265.1; -; mRNA. DR PIR; S07047; S07047. DR AlphaFoldDB; P14650; -. DR SMR; P14650; -. DR STRING; 10116.ENSRNOP00000006526; -. DR PeroxiBase; 3973; RnoTPO. DR GlyCosmos; P14650; 5 sites, No reported glycans. DR GlyGen; P14650; 5 sites. DR PhosphoSitePlus; P14650; -. DR jPOST; P14650; -. DR PaxDb; 10116-ENSRNOP00000006526; -. DR UCSC; RGD:3900; rat. DR AGR; RGD:3900; -. DR RGD; 3900; Tpo. DR eggNOG; KOG2408; Eukaryota. DR InParanoid; P14650; -. DR PhylomeDB; P14650; -. DR Reactome; R-RNO-209968; Thyroxine biosynthesis. DR UniPathway; UPA00194; -. DR PRO; PR:P14650; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0009986; C:cell surface; IDA:RGD. 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; TAS:RGD. DR GO; GO:0004601; F:peroxidase activity; IBA:GO_Central. DR GO; GO:0071732; P:cellular response to nitric oxide; IEP:RGD. DR GO; GO:0035162; P:embryonic hemopoiesis; ISO:RGD. 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; IEP:RGD. DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro. DR GO; GO:0006590; P:thyroid hormone generation; TAS:RGD. 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. PE 2: Evidence at transcript level; KW Calcium; Disulfide bond; EGF-like domain; Glycoprotein; Heme; KW Hydrogen peroxide; Iron; Membrane; Metal-binding; Oxidoreductase; KW Peroxidase; Reference proteome; Signal; Sushi; KW Thyroid hormones biosynthesis; Transmembrane; Transmembrane helix. FT SIGNAL 1..31 FT /evidence="ECO:0000255" FT CHAIN 32..914 FT /note="Thyroid peroxidase" FT /id="PRO_0000023665" FT TOPO_DOM 32..834 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 835..859 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 860..914 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 728..783 FT /note="Sushi" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 784..827 FT /note="EGF-like; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 882..907 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 233 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 232 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /note="covalent" FT /evidence="ECO:0000250" FT BINDING 234 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 313 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 315 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 317 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 319 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT BINDING 387 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /note="covalent" FT /evidence="ECO:0000250" FT BINDING 482 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 384 FT /note="Transition state stabilizer" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" FT CARBOHYD 123 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 271 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 299 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 334 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 603 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 136..152 FT /evidence="ECO:0000250" FT DISULFID 253..263 FT /evidence="ECO:0000250" FT DISULFID 257..278 FT /evidence="ECO:0000250" FT DISULFID 586..643 FT /evidence="ECO:0000250" FT DISULFID 684..709 FT /evidence="ECO:0000250" FT DISULFID 730..770 FT /evidence="ECO:0000250" FT DISULFID 756..782 FT /evidence="ECO:0000250" FT DISULFID 788..802 FT /evidence="ECO:0000250" FT DISULFID 796..811 FT /evidence="ECO:0000250" FT DISULFID 813..826 FT /evidence="ECO:0000250" FT CONFLICT 194..195 FT /note="FP -> LG (in Ref. 2; AAA42265)" FT /evidence="ECO:0000305" FT CONFLICT 198 FT /note="P -> S (in Ref. 2; AAA42265)" FT /evidence="ECO:0000305" FT CONFLICT 228 FT /note="G -> A (in Ref. 2; AAA42265)" FT /evidence="ECO:0000305" FT CONFLICT 592..594 FT /note="DTG -> ETP (in Ref. 2; AAA42265)" FT /evidence="ECO:0000305" SQ SEQUENCE 914 AA; 101460 MW; B700B89439E85191 CRC64; MRTLGAMAVM LVVMGTAIFL PFLLRSRDIL GGKTMTSHVI SVVETSQLLV DNAVYNTMKR NLKKRGVLSP AQLLSFSKLP ESTSGAISRA AEIMETSIQV MKREQSQFST DALSADILAT IANLSGCLPF MLPPRCPDTC LANKYRPITG VCNNRDHPRW GASNTALARW LPPVYEDGFS QPRGWNPNFL YHGFPLPPVR EVTRHLIQVS NEAVTEDDQY SDFLPVWGQY IDHDIALTPQ STSTAAFWGG VDCQLTCENQ NPCFPIQLPS NSSRTTACLP FYRSSAACGT GDQGALFGNL SAANPRQQMN GLTSFLDAST VYGSSPGVEK QLRNWSSSAG LLRVNTLHLD SGRAYLPFAS AACAPEPGAP HANRTPCFLA GDGRASEVPA LAAVHTLWLR EHNRLATAFK AINTHWSANT AYQEARKVVG ALHQIITMRD YIPKILGPDA FRQYVGPYEG YNPTVNPTVS NVFSTAAFRF GHATVHPLVR RLNTDFQDHT ELPRLQLHDV FFRPWRLIQE GGLDPIVRGL LARPAKLQVQ EQLMNEELTE RLFVLSNVGT LDLASLNLQR GRDHGLPGYN EWREFCGLSR LDTGAELNKA IANRSMVNKI MELYKHADNI DVWLGGLAEK FLPGARTGPL FACIIGKQMK ALRDGDRFWW ENSHVFTDAQ RQELEKHSLP RVICDNTGLT RVPVDAFRIG KFPQDFESCE EIPSMDLRLW RETFPQDDKC VFPEKVDNGN FVHCEESGKL VLVYSCFHGY KLQGQEQVTC TQNGWDSEPP VCKDVNECAD LTHPPCHSSA KCKNTKGSFQ CVCTDPYMLG EDEKTCIDSG RLPRASWVSI ALGALLIGGL ASLSWTVICR WTHADKKSTL LITERVTMES GFRKSQESGI SPQKAEVQDA EQEPAYGSRV LLCE //