GenomeNet

Database: UniProt
Entry: Q8HYB7
LinkDB: Q8HYB7
Original site: Q8HYB7 
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   10-APR-2019, entry version 137.
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;
OC   Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae;
OC   Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Thyroid;
RX   PubMed=12564727; DOI=10.1111/j.1939-1676.2003.tb01323.x;
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.,
RA   Mauceli E., Xie X., Breen M., Wayne R.K., Ostrander E.A.,
RA   Ponting C.P., Galibert F., Smith D.R., deJong P.J., Kirkness E.F.,
RA   Alvarez P., Biagi T., Brockman W., Butler J., Chin C.-W., Cook A.,
RA   Cuff J., Daly M.J., DeCaprio D., Gnerre S., Grabherr M., Kellis M.,
RA   Kleber M., Bardeleben C., Goodstadt L., Heger A., Hitte C., Kim L.,
RA   Koepfli K.-P., Parker H.G., Pollinger J.P., Searle S.M.J.,
RA   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.,
RA   Bachantsang P., Barry A., Bayul T., Benamara M., Berlin A.,
RA   Bessette D., Blitshteyn B., Bloom T., Blye J., Boguslavskiy L.,
RA   Bonnet C., Boukhgalter B., Brown A., Cahill P., Calixte N.,
RA   Camarata J., Cheshatsang Y., Chu J., Citroen M., Collymore A.,
RA   Cooke P., Dawoe T., Daza R., Decktor K., DeGray S., Dhargay N.,
RA   Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L., Duffey N.,
RA   Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA   Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K.,
RA   Foley C., Franke A., Friedrich D., Gage D., Garber M., Gearin G.,
RA   Giannoukos G., Goode T., Goyette A., Graham J., Grandbois E.,
RA   Gyaltsen K., Hafez N., Hagopian D., Hagos B., Hall J., Healy C.,
RA   Hegarty R., Honan T., Horn A., Houde N., Hughes L., Hunnicutt L.,
RA   Husby M., Jester B., Jones C., Kamat A., Kanga B., Kells C.,
RA   Khazanovich D., Kieu A.C., Kisner P., Kumar M., Lance K., Landers T.,
RA   Lara M., Lee W., Leger J.-P., Lennon N., Leuper L., LeVine S., Liu J.,
RA   Liu X., Lokyitsang Y., Lokyitsang T., Lui A., Macdonald J., Major J.,
RA   Marabella R., Maru K., Matthews C., McDonough S., Mehta T.,
RA   Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T., Miller K.,
RA   Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A., Naylor J.,
RA   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.,
RA   Osman S., Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F.,
RA   Priest M., Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C.,
RA   Rege F., Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S.,
RA   Sharpe T., Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J.,
RA   Smith C., Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S.,
RA   Stone C., Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S.,
RA   Thoulutsang D., Thoulutsang Y., Topham K., Topping I., Tsamla T.,
RA   Vassiliev H., Venkataraman V., Vo A., Wangchuk T., Wangdi T.,
RA   Weiand M., Wilkinson J., Wilson A., Yadav S., Yang S., Yang X.,
RA   Young G., Yu Q., Zainoun J., 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;
CC         EC=1.11.1.8; 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;
CC         Xref=Rhea:RHEA:48960, Rhea:RHEA-COMP:12275, Rhea:RHEA-
CC         COMP:12276, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:90870,
CC         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
CC         H2O; Xref=Rhea:RHEA:48964, Rhea:RHEA-COMP:12276, Rhea:RHEA-
CC         COMP:12277, Rhea:RHEA-COMP:12278, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:16240, ChEBI:CHEBI:90871, ChEBI:CHEBI:90872,
CC         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]-
CC         3-iodo-L-tyrosine + H2O2 = [thyroglobulin]-3,3',5-triiodo-L-
CC         thyronine + [thyroglobulin]-dehydroalanine + 2 H2O;
CC         Xref=Rhea:RHEA:48968, Rhea:RHEA-COMP:12275, Rhea:RHEA-
CC         COMP:12276, Rhea:RHEA-COMP:12278, Rhea:RHEA-COMP:12279,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:90870,
CC         ChEBI:CHEBI:90871, ChEBI:CHEBI:90873, ChEBI:CHEBI:90874;
CC         EC=1.11.1.8; 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
CC       per 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
CC       delivery of protein at the cell surface (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: Cleaved in its N-terminal part. {ECO:0000250}.
CC   -!- DISEASE: Note=Defects in TPO are the cause of congenital
CC       hypothyroidism with goiter, a simple autosomal recessive trait
CC       observed in Toy Fox Terriers (TFTs). Neonatal affected pups
CC       exhibited inactivity, abnormal hair coat, stenotic ear canals, and
CC       delayed eye opening. Palpable ventrolateral cervical swellings
CC       were evident by 1 week of age. Serum thyroid hormone and thyroid-
CC       stimulating hormone concentrations were low and high,
CC       respectively. Histologic examination of the cervical masses
CC       disclosed cuboidal to columnar follicular epithelial cell
CC       hyperplasia with widely varying follicular size, shape, and amount
CC       of colloid. Oral thyroid hormone replacement therapy restored
CC       near-normal growth and development. At 8 weeks of age, radioiodine
CC       uptake and perchlorate discharge testing indicated an iodine
CC       organification defect. Biochemical analysis of thyroid tissue from
CC       affected dogs demonstrated enzymatic iodine oxidation deficiency
CC       and lack of sodium dodecyl sulfate-resistant thyroglobulin dimers,
CC       suggesting thyroid peroxidase deficiency.
CC   -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00298}.
DR   EMBL; AY094504; AAM26737.2; -; mRNA.
DR   EMBL; JH373195; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001003009.2; NM_001003009.2.
DR   UniGene; Cfa.20; -.
DR   SMR; Q8HYB7; -.
DR   STRING; 9612.ENSCAFP00000004788; -.
DR   PeroxiBase; 3334; CfaTPO.
DR   PaxDb; Q8HYB7; -.
DR   PRIDE; Q8HYB7; -.
DR   Ensembl; ENSCAFT00000005172; ENSCAFP00000004788; ENSCAFG00000003217.
DR   GeneID; 403521; -.
DR   KEGG; cfa:403521; -.
DR   CTD; 7173; -.
DR   VGNC; VGNC:47746; TPO.
DR   eggNOG; KOG2408; Eukaryota.
DR   eggNOG; ENOG410XPZ3; LUCA.
DR   GeneTree; ENSGT00940000158104; -.
DR   HOGENOM; HOG000016084; -.
DR   HOVERGEN; HBG000071; -.
DR   InParanoid; Q8HYB7; -.
DR   KO; K00431; -.
DR   OMA; MVWGQYI; -.
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:0035162; P:embryonic hemopoiesis; IEA:Ensembl.
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; Complete proteome; 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     30       {ECO:0000255}.
FT   CHAIN        31    944       Thyroid peroxidase.
FT                                /FTId=PRO_0000023661.
FT   TOPO_DOM     31    858       Extracellular. {ECO:0000255}.
FT   TRANSMEM    859    879       Helical. {ECO:0000255}.
FT   TOPO_DOM    880    944       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN      748    804       Sushi. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00302}.
FT   DOMAIN      804    847       EGF-like; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   ACT_SITE    251    251       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   METAL       252    252       Calcium. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   METAL       330    330       Calcium. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   METAL       332    332       Calcium; via carbonyl oxygen.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00298}.
FT   METAL       334    334       Calcium. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   METAL       336    336       Calcium. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   METAL       503    503       Iron (heme axial ligand).
FT                                {ECO:0000255|PROSITE-ProRule:PRU00298}.
FT   BINDING     250    250       Heme (covalent; via 2 links).
FT                                {ECO:0000250}.
FT   BINDING     408    408       Heme (covalent; via 2 links).
FT                                {ECO:0000250}.
FT   SITE        405    405       Transition state stabilizer.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00298}.
FT   CARBOHYD    141    141       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    316    316       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    351    351       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    623    623       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    154    170       {ECO:0000250}.
FT   DISULFID    271    281       {ECO:0000250}.
FT   DISULFID    275    295       {ECO:0000250}.
FT   DISULFID    606    663       {ECO:0000250}.
FT   DISULFID    704    729       {ECO:0000250}.
FT   DISULFID    750    790       {ECO:0000250}.
FT   DISULFID    776    802       {ECO:0000250}.
FT   DISULFID    808    822       {ECO:0000250}.
FT   DISULFID    816    831       {ECO:0000250}.
FT   DISULFID    833    846       {ECO:0000250}.
FT   CONFLICT    232    232       V -> I (in Ref. 1; AAM26737).
FT                                {ECO:0000305}.
FT   CONFLICT    501    501       L -> F (in Ref. 1; AAM26737).
FT                                {ECO:0000305}.
FT   CONFLICT    527    527       G -> R (in Ref. 1; AAM26737).
FT                                {ECO:0000305}.
FT   CONFLICT    533    533       F -> FS (in Ref. 1; AAM26737).
FT                                {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
//
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