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Protein

Thyroid peroxidase

Gene

TPO

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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

Protein has several cofactor binding sites:
  • Ca2+PROSITE-ProRule annotationNote: Binds 1 Ca2+ ion per heterodimer.PROSITE-ProRule annotation
  • heme bPROSITE-ProRule annotationNote: Binds 1 heme b (iron(II)-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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase, Peroxidase

Keywords - Biological processi

Hydrogen peroxide, Thyroid hormones biosynthesis

Keywords - Ligandi

Calcium, Heme, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_300986. Thyroxine biosynthesis.
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 Componenti: Chromosome 17

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini31 – 858828ExtracellularSequence AnalysisAdd
BLAST
Transmembranei859 – 87921HelicalSequence AnalysisAdd
BLAST
Topological domaini880 – 94465CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

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.

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_dom.
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

« Hide

        10         20         30         40         50
MVGLVPAGSA WGGRALAVLG VTLLVALARG LLPFFLGGRD LLWGQSGEAS
60 70 80 90 100
VLGVVEESRR VVDGAIQHTV RRDLSKRGLP SPSQLLSFSK LPEPTSRAVS
110 120 130 140 150
RAAEIMEASV QAVRTRVYGK LGRSWPLTDT LPEAVLDTIA NASGCRPHML
160 170 180 190 200
PPRCPDTCLA RKYRLITGAC NNRDHPRWGA SNTALARWLP PAYEDGISEP
210 220 230 240 250
RGWNPHVLYS GFPLPPVREV TRQVIRVPNE AVTEDDQYSD LLTVWGQYID
260 270 280 290 300
HDVAFTPQSA SGAAFGAGAD CQLTCENRSP CFPIQLPPDA SGPACLPFSR
310 320 330 340 350
SSAACGTGIQ GAFFGNLSSA NPRQQMNGLT SFLDASTVYG SSPALEKQLR
360 370 380 390 400
NWTSAEGLLR VNTRHWDAGR AHLPFMRPPA PLACVPEPGT RGTAGAPCFL
410 420 430 440 450
AGDSRASEVP TLAALHTLWL REHNRLASAL KALNAHWSAD TAYQEARKVV
460 470 480 490 500
GALHQIITLR DYVPKVLGPE AFQQHVGPYE GYDPTMDPTV SNVFSTAAFR
510 520 530 540 550
LGHATVHPLV RRLDARFQEH PGLPPLGLQD AFFPWRLLKE GGLDPLLRGL
560 570 580 590 600
LASPAKLPVQ EQLMNEELTE RLFVLGSSGS LDLASINLQR GRDHGLPGYN
610 620 630 640 650
AWREFCGLGR LHTRAELRSA VANATLAGRI MDLYGHPDNI DVWLGGLAEP
660 670 680 690 700
LLPRARTGPL FACLIGRQMK ALRDGDRFWW ESSGVFTDEQ RRELARHSLS
710 720 730 740 750
RVICDNTGLP SVPADAFQVS RFPQDFEPCE NIPGLNLDVW REALPQGDAC
760 770 780 790 800
GLPDSLDNGD VVLCGEAGRR VLVFSCRHGF KLQGPEQVAC SPRGGAVRAP
810 820 830 840 850
VCRDINECED ASHPPCHGSA RCRNTKGGFR CECTDPAVLG EDGTTCVDSG
860 870 880 890 900
RLPKASLVSI ALGIVLVVGL AGLTWTLVCR WAHAGRKASL SIAELGGRGA
910 920 930 940
PPPGRGAGQD GASGSLVPPL GPQGRTRAVD PTSSRSHVAQ GSPA
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
AY094504 mRNA. Translation: AAM26737.2.
JH373195 Genomic DNA. No translation available.
RefSeqiNP_001003009.2. NM_001003009.2.
UniGeneiCfa.20.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000004788.

Protein family/group databases

PeroxiBasei3334. CfaTPO.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7173.

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00194.
ReactomeiREACT_300986. Thyroxine biosynthesis.

Miscellaneous databases

NextBioi20817032.

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_dom.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: April 1, 2015
This is version 111 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.