PERT_RAT
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 03-AUG-2022, entry version 175.
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;
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 -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00298}.
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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 GlyGen; P14650; 5 sites.
DR jPOST; P14650; -.
DR PaxDb; P14650; -.
DR PRIDE; P14650; -.
DR UCSC; RGD:3900; rat.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
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 Gene3D; 1.10.640.10; -; 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: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; SM00181; EGF; 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 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
