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Q8HYB7

- PERT_CANFA

UniProt

Q8HYB7 - PERT_CANFA

Protein

Thyroid peroxidase

Gene

TPO

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 2 (03 Oct 2012)
      Previous versions | rss
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    Functioni

    Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T3 and T4.

    Catalytic activityi

    2 iodide + H2O2 + 2 H+ = 2 iodine + 2 H2O.
    [Thyroglobulin]-L-tyrosine + iodide + H2O2 = [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O.
    [Thyroglobulin]-3-iodo-L-tyrosine + iodide + H2O2 = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O.
    2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-L-thyroxine + [thyroglobulin]-aminoacrylate + 2 H2O.
    [Thyroglobulin]-3-iodo-L-tyrosine + [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-3,5,3'-triiodo-L-thyronine + [thyroglobulin]-aminoacrylate + 2 H2O.

    Cofactori

    Binds 1 calcium ion per heterodimer.PROSITE-ProRule annotation
    Binds 1 heme B (iron-protoporphyrin IX) group covalently per heterodimer.PROSITE-ProRule annotation

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei250 – 2501Heme (covalent; via 2 links)By similarity
    Active sitei251 – 2511Proton acceptorPROSITE-ProRule annotation
    Metal bindingi252 – 2521CalciumPROSITE-ProRule annotation
    Metal bindingi330 – 3301CalciumPROSITE-ProRule annotation
    Metal bindingi332 – 3321Calcium; via carbonyl oxygenPROSITE-ProRule annotation
    Metal bindingi334 – 3341CalciumPROSITE-ProRule annotation
    Metal bindingi336 – 3361CalciumPROSITE-ProRule annotation
    Sitei405 – 4051Transition state stabilizerPROSITE-ProRule annotation
    Binding sitei408 – 4081Heme (covalent; via 2 links)By similarity
    Metal bindingi503 – 5031Iron (heme axial ligand)PROSITE-ProRule annotation

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. heme binding Source: InterPro
    3. iodide peroxidase activity Source: UniProtKB-EC

    GO - Biological processi

    1. embryonic hemopoiesis Source: Ensembl
    2. hormone biosynthetic process Source: UniProtKB-KW
    3. hydrogen peroxide catabolic process Source: UniProtKB-KW
    4. thyroid hormone generation Source: UniProtKB-UniPathway

    Keywords - Molecular functioni

    Oxidoreductase, Peroxidase

    Keywords - Biological processi

    Hydrogen peroxide, Thyroid hormones biosynthesis

    Keywords - Ligandi

    Calcium, Heme, Iron, Metal-binding

    Enzyme and pathway databases

    UniPathwayiUPA00194.

    Protein family/group databases

    PeroxiBasei3334. CfaTPO.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Thyroid peroxidase (EC:1.11.1.8)
    Short name:
    TPO
    Gene namesi
    Name:TPO
    OrganismiCanis familiaris (Dog) (Canis lupus familiaris)
    Taxonomic identifieri9615 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
    ProteomesiUP000002254: Chromosome 17

    Subcellular locationi

    Membrane By similarity; Single-pass type I membrane protein By similarity

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. mitochondrion Source: Ensembl

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Defects in TPO are the cause of congenital hypothyroidism with goiter, a simple autosomal recessive trait observed in Toy Fox Terriers (TFTs). Neonatal affected pups exhibited inactivity, abnormal hair coat, stenotic ear canals, and delayed eye opening. Palpable ventrolateral cervical swellings were evident by 1 week of age. Serum thyroid hormone and thyroid-stimulating hormone concentrations were low and high, respectively. Histologic examination of the cervical masses disclosed cuboidal to columnar follicular epithelial cell hyperplasia with widely varying follicular size, shape, and amount of colloid. Oral thyroid hormone replacement therapy restored near-normal growth and development. At 8 weeks of age, radioiodine uptake and perchlorate discharge testing indicated an iodine organification defect. Biochemical analysis of thyroid tissue from affected dogs demonstrated enzymatic iodine oxidation deficiency and lack of sodium dodecyl sulfate-resistant thyroglobulin dimers, suggesting thyroid peroxidase deficiency.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3030Sequence AnalysisAdd
    BLAST
    Chaini31 – 944914Thyroid peroxidasePRO_0000023661Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi141 – 1411N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi154 ↔ 170By similarity
    Disulfide bondi271 ↔ 281By similarity
    Disulfide bondi275 ↔ 295By similarity
    Glycosylationi316 – 3161N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi351 – 3511N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi606 ↔ 663By similarity
    Glycosylationi623 – 6231N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi704 ↔ 729By similarity
    Disulfide bondi750 ↔ 790By similarity
    Disulfide bondi776 ↔ 802By similarity
    Disulfide bondi808 ↔ 822By similarity
    Disulfide bondi816 ↔ 831By similarity
    Disulfide bondi833 ↔ 846By similarity

    Post-translational modificationi

    Heme is covalently bound through a H2O(2)-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface By similarity.By similarity
    Cleaved in its N-terminal part.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Interacts with DUOX1, DUOX2 and CYBA.By similarity

    Protein-protein interaction databases

    STRINGi9615.ENSCAFP00000004788.

    Structurei

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini31 – 858828ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini880 – 94465CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei859 – 87921HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini748 – 80457SushiPROSITE-ProRule annotationAdd
    BLAST
    Domaini804 – 84744EGF-like; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peroxidase family. XPO subfamily.PROSITE-ProRule annotation
    Contains 1 EGF-like domain.PROSITE-ProRule annotation
    Contains 1 Sushi (CCP/SCR) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Signal, Sushi, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG262194.
    GeneTreeiENSGT00550000074325.
    HOGENOMiHOG000016084.
    HOVERGENiHBG000071.
    InParanoidiQ8HYB7.
    KOiK00431.
    OMAiIMETSIQ.
    OrthoDBiEOG7D2FD6.
    TreeFamiTF314316.

    Family and domain databases

    Gene3Di1.10.640.10. 2 hits.
    InterProiIPR000742. EG-like_dom.
    IPR001881. EGF-like_Ca-bd_dom.
    IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
    IPR018097. EGF_Ca-bd_CS.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    IPR000436. Sushi_SCR_CCP.
    IPR029589. TPO.
    [Graphical view]
    PANTHERiPTHR11475:SF60. PTHR11475:SF60. 1 hit.
    PfamiPF03098. An_peroxidase. 1 hit.
    PF07645. EGF_CA. 1 hit.
    [Graphical view]
    PRINTSiPR00457. ANPEROXIDASE.
    SMARTiSM00032. CCP. 1 hit.
    SM00179. EGF_CA. 1 hit.
    [Graphical view]
    SUPFAMiSSF48113. SSF48113. 1 hit.
    SSF57535. SSF57535. 1 hit.
    PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS01187. EGF_CA. 1 hit.
    PS00435. PEROXIDASE_1. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    PS50923. SUSHI. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q8HYB7-1 [UniParc]FASTAAdd to Basket

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    MVGLVPAGSA WGGRALAVLG VTLLVALARG LLPFFLGGRD LLWGQSGEAS    50
    VLGVVEESRR VVDGAIQHTV RRDLSKRGLP SPSQLLSFSK LPEPTSRAVS 100
    RAAEIMEASV QAVRTRVYGK LGRSWPLTDT LPEAVLDTIA NASGCRPHML 150
    PPRCPDTCLA RKYRLITGAC NNRDHPRWGA SNTALARWLP PAYEDGISEP 200
    RGWNPHVLYS GFPLPPVREV TRQVIRVPNE AVTEDDQYSD LLTVWGQYID 250
    HDVAFTPQSA SGAAFGAGAD CQLTCENRSP CFPIQLPPDA SGPACLPFSR 300
    SSAACGTGIQ GAFFGNLSSA NPRQQMNGLT SFLDASTVYG SSPALEKQLR 350
    NWTSAEGLLR VNTRHWDAGR AHLPFMRPPA PLACVPEPGT RGTAGAPCFL 400
    AGDSRASEVP TLAALHTLWL REHNRLASAL KALNAHWSAD TAYQEARKVV 450
    GALHQIITLR DYVPKVLGPE AFQQHVGPYE GYDPTMDPTV SNVFSTAAFR 500
    LGHATVHPLV RRLDARFQEH PGLPPLGLQD AFFPWRLLKE GGLDPLLRGL 550
    LASPAKLPVQ EQLMNEELTE RLFVLGSSGS LDLASINLQR GRDHGLPGYN 600
    AWREFCGLGR LHTRAELRSA VANATLAGRI MDLYGHPDNI DVWLGGLAEP 650
    LLPRARTGPL FACLIGRQMK ALRDGDRFWW ESSGVFTDEQ RRELARHSLS 700
    RVICDNTGLP SVPADAFQVS RFPQDFEPCE NIPGLNLDVW REALPQGDAC 750
    GLPDSLDNGD VVLCGEAGRR VLVFSCRHGF KLQGPEQVAC SPRGGAVRAP 800
    VCRDINECED ASHPPCHGSA RCRNTKGGFR CECTDPAVLG EDGTTCVDSG 850
    RLPKASLVSI ALGIVLVVGL AGLTWTLVCR WAHAGRKASL SIAELGGRGA 900
    PPPGRGAGQD GASGSLVPPL GPQGRTRAVD PTSSRSHVAQ GSPA 944
    Length:944
    Mass (Da):101,406
    Last modified:October 3, 2012 - v2
    Checksum:i95031FB3A3FEFBD1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti232 – 2321V → I in AAM26737. (PubMed:12564727)Curated
    Sequence conflicti501 – 5011L → F in AAM26737. (PubMed:12564727)Curated
    Sequence conflicti527 – 5271G → R in AAM26737. (PubMed:12564727)Curated
    Sequence conflicti533 – 5331F → FS in AAM26737. (PubMed:12564727)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY094504 mRNA. Translation: AAM26737.2.
    JH373195 Genomic DNA. No translation available.
    RefSeqiNP_001003009.2. NM_001003009.2.
    UniGeneiCfa.20.

    Genome annotation databases

    EnsembliENSCAFT00000005172; ENSCAFP00000004788; ENSCAFG00000003217.
    GeneIDi403521.
    KEGGicfa:403521.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY094504 mRNA. Translation: AAM26737.2 .
    JH373195 Genomic DNA. No translation available.
    RefSeqi NP_001003009.2. NM_001003009.2.
    UniGenei Cfa.20.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9615.ENSCAFP00000004788.

    Protein family/group databases

    PeroxiBasei 3334. CfaTPO.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSCAFT00000005172 ; ENSCAFP00000004788 ; ENSCAFG00000003217 .
    GeneIDi 403521.
    KEGGi cfa:403521.

    Organism-specific databases

    CTDi 7173.

    Phylogenomic databases

    eggNOGi NOG262194.
    GeneTreei ENSGT00550000074325.
    HOGENOMi HOG000016084.
    HOVERGENi HBG000071.
    InParanoidi Q8HYB7.
    KOi K00431.
    OMAi IMETSIQ.
    OrthoDBi EOG7D2FD6.
    TreeFami TF314316.

    Enzyme and pathway databases

    UniPathwayi UPA00194 .

    Miscellaneous databases

    NextBioi 20817032.

    Family and domain databases

    Gene3Di 1.10.640.10. 2 hits.
    InterProi IPR000742. EG-like_dom.
    IPR001881. EGF-like_Ca-bd_dom.
    IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
    IPR018097. EGF_Ca-bd_CS.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    IPR000436. Sushi_SCR_CCP.
    IPR029589. TPO.
    [Graphical view ]
    PANTHERi PTHR11475:SF60. PTHR11475:SF60. 1 hit.
    Pfami PF03098. An_peroxidase. 1 hit.
    PF07645. EGF_CA. 1 hit.
    [Graphical view ]
    PRINTSi PR00457. ANPEROXIDASE.
    SMARTi SM00032. CCP. 1 hit.
    SM00179. EGF_CA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48113. SSF48113. 1 hit.
    SSF57535. SSF57535. 1 hit.
    PROSITEi PS00010. ASX_HYDROXYL. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS01187. EGF_CA. 1 hit.
    PS00435. PEROXIDASE_1. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    PS50923. SUSHI. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Thyroid.
    2. "Genome sequence, comparative analysis and haplotype structure of the domestic dog."
      Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B., Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E., Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F., Smith D.R.
      , deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W., Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S., Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A., Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P., Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A., Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P., Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P., Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B., Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A., Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M., Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S., Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L., Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S., Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C., Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G., Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N., Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A., Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A., Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M., Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L., LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A., Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S., Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T., Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A., Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N., Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S., Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M., Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F., Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T., Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C., Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C., Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D., Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H., Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J., Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J., Zembek L., Zimmer A., Lander E.S.
      Nature 438:803-819(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Boxer.
    3. Dodgson S.E., Day R., Fyfe J.C.
      Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION TO N-TERMINUS.

    Entry informationi

    Entry nameiPERT_CANFA
    AccessioniPrimary (citable) accession number: Q8HYB7
    Secondary accession number(s): F1Q066
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 23, 2003
    Last sequence update: October 3, 2012
    Last modified: October 1, 2014
    This is version 106 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3