PERT_CANLF
ID PERT_CANLF Reviewed; 944 AA.
AC Q8HYB7; F1Q066;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 150.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thyroid;
RX PubMed=12564727; DOI=10.1892/0891-6640(2003)017<0050:chwgit>2.3.co;2;
RA Fyfe J.C., Kampschmidt K., Dang V., Poteet B.A., He Q., Lowrie C.,
RA Graham P.A., Fetro V.M.;
RT "Congenital hypothyroidism with goiter in toy fox terriers.";
RL J. Vet. Intern. Med. 17:50-57(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer;
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
RN [3]
RP SEQUENCE REVISION TO N-TERMINUS.
RA Dodgson S.E., Day R., Fyfe J.C.;
RL Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases.
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 -!- DISEASE: Note=Defects in TPO are the cause of congenital hypothyroidism
CC with goiter, a simple autosomal recessive trait observed in Toy Fox
CC Terriers (TFTs). Neonatal affected pups exhibited inactivity, abnormal
CC hair coat, stenotic ear canals, and delayed eye opening. Palpable
CC ventrolateral cervical swellings were evident by 1 week of age. Serum
CC thyroid hormone and thyroid-stimulating hormone concentrations were low
CC and high, respectively. Histologic examination of the cervical masses
CC disclosed cuboidal to columnar follicular epithelial cell hyperplasia
CC with widely varying follicular size, shape, and amount of colloid. Oral
CC thyroid hormone replacement therapy restored near-normal growth and
CC development. At 8 weeks of age, radioiodine uptake and perchlorate
CC discharge testing indicated an iodine organification defect.
CC Biochemical analysis of thyroid tissue from affected dogs demonstrated
CC enzymatic iodine oxidation deficiency and lack of sodium dodecyl
CC sulfate-resistant thyroglobulin dimers, suggesting thyroid peroxidase
CC deficiency.
CC -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00298}.
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DR EMBL; AY094504; AAM26737.2; -; mRNA.
DR EMBL; JH373195; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001003009.2; NM_001003009.2.
DR AlphaFoldDB; Q8HYB7; -.
DR SMR; Q8HYB7; -.
DR STRING; 9612.ENSCAFP00000004788; -.
DR PeroxiBase; 3334; CfaTPO.
DR PaxDb; Q8HYB7; -.
DR GeneID; 403521; -.
DR KEGG; cfa:403521; -.
DR CTD; 7173; -.
DR eggNOG; KOG2408; Eukaryota.
DR HOGENOM; CLU_006087_1_0_1; -.
DR InParanoid; Q8HYB7; -.
DR OMA; GPYEGYN; -.
DR OrthoDB; 276568at2759; -.
DR TreeFam; TF314316; -.
DR Reactome; R-CFA-209968; Thyroxine biosynthesis.
DR UniPathway; UPA00194; -.
DR Proteomes; UP000002254; Chromosome 17.
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: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; 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; IEA:UniProtKB-UniPathway.
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 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; 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..30
FT /evidence="ECO:0000255"
FT CHAIN 31..944
FT /note="Thyroid peroxidase"
FT /id="PRO_0000023661"
FT TOPO_DOM 31..858
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 859..879
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 880..944
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 748..804
FT /note="Sushi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 804..847
FT /note="EGF-like; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 895..944
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 927..944
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 251
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 250
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000250"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 330
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 332
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 334
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 336
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 408
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000250"
FT BINDING 503
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 405
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 351
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 623
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 154..170
FT /evidence="ECO:0000250"
FT DISULFID 271..281
FT /evidence="ECO:0000250"
FT DISULFID 275..295
FT /evidence="ECO:0000250"
FT DISULFID 606..663
FT /evidence="ECO:0000250"
FT DISULFID 704..729
FT /evidence="ECO:0000250"
FT DISULFID 750..790
FT /evidence="ECO:0000250"
FT DISULFID 776..802
FT /evidence="ECO:0000250"
FT DISULFID 808..822
FT /evidence="ECO:0000250"
FT DISULFID 816..831
FT /evidence="ECO:0000250"
FT DISULFID 833..846
FT /evidence="ECO:0000250"
FT CONFLICT 232
FT /note="V -> I (in Ref. 1; AAM26737)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="L -> F (in Ref. 1; AAM26737)"
FT /evidence="ECO:0000305"
FT CONFLICT 527
FT /note="G -> R (in Ref. 1; AAM26737)"
FT /evidence="ECO:0000305"
FT CONFLICT 533
FT /note="F -> FS (in Ref. 1; AAM26737)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 944 AA; 101406 MW; 95031FB3A3FEFBD1 CRC64;
MVGLVPAGSA WGGRALAVLG VTLLVALARG LLPFFLGGRD LLWGQSGEAS VLGVVEESRR
VVDGAIQHTV RRDLSKRGLP SPSQLLSFSK LPEPTSRAVS RAAEIMEASV QAVRTRVYGK
LGRSWPLTDT LPEAVLDTIA NASGCRPHML PPRCPDTCLA RKYRLITGAC NNRDHPRWGA
SNTALARWLP PAYEDGISEP RGWNPHVLYS GFPLPPVREV TRQVIRVPNE AVTEDDQYSD
LLTVWGQYID HDVAFTPQSA SGAAFGAGAD CQLTCENRSP CFPIQLPPDA SGPACLPFSR
SSAACGTGIQ GAFFGNLSSA NPRQQMNGLT SFLDASTVYG SSPALEKQLR NWTSAEGLLR
VNTRHWDAGR AHLPFMRPPA PLACVPEPGT RGTAGAPCFL AGDSRASEVP TLAALHTLWL
REHNRLASAL KALNAHWSAD TAYQEARKVV GALHQIITLR DYVPKVLGPE AFQQHVGPYE
GYDPTMDPTV SNVFSTAAFR LGHATVHPLV RRLDARFQEH PGLPPLGLQD AFFPWRLLKE
GGLDPLLRGL LASPAKLPVQ EQLMNEELTE RLFVLGSSGS LDLASINLQR GRDHGLPGYN
AWREFCGLGR LHTRAELRSA VANATLAGRI MDLYGHPDNI DVWLGGLAEP LLPRARTGPL
FACLIGRQMK ALRDGDRFWW ESSGVFTDEQ RRELARHSLS RVICDNTGLP SVPADAFQVS
RFPQDFEPCE NIPGLNLDVW REALPQGDAC GLPDSLDNGD VVLCGEAGRR VLVFSCRHGF
KLQGPEQVAC SPRGGAVRAP VCRDINECED ASHPPCHGSA RCRNTKGGFR CECTDPAVLG
EDGTTCVDSG RLPKASLVSI ALGIVLVVGL AGLTWTLVCR WAHAGRKASL SIAELGGRGA
PPPGRGAGQD GASGSLVPPL GPQGRTRAVD PTSSRSHVAQ GSPA
