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Q8HYB7 (PERT_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thyroid peroxidase

Short name=TPO
EC=1.11.1.8
Gene names
Name:TPO
OrganismCanis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis

Protein attributes

Sequence length944 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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

Catalytic activity

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.

Cofactor

Binds 1 calcium ion per heterodimer By similarity.

Binds 1 heme B (iron-protoporphyrin IX) group covalently per heterodimer By similarity.

Pathway

Hormone biosynthesis; thyroid hormone biosynthesis.

Subunit structure

Interacts with DUOX1, DUOX2 and CYBA By similarity.

Subcellular location

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

Post-translational modification

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.

Cleaved in its N-terminal part By similarity.

Involvement in disease

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.

Sequence similarities

Belongs to the peroxidase family. XPO subfamily.

Contains 1 EGF-like domain.

Contains 1 Sushi (CCP/SCR) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Potential
Chain31 – 944914Thyroid peroxidase
PRO_0000023661

Regions

Topological domain31 – 858828Extracellular Potential
Transmembrane859 – 87921Helical; Potential
Topological domain880 – 94465Cytoplasmic Potential
Domain748 – 80457Sushi
Domain804 – 84744EGF-like; calcium-binding Potential

Sites

Active site2511Proton acceptor By similarity
Metal binding2521Calcium By similarity
Metal binding3301Calcium By similarity
Metal binding3321Calcium; via carbonyl oxygen By similarity
Metal binding3341Calcium By similarity
Metal binding3361Calcium By similarity
Metal binding5031Iron (heme axial ligand) By similarity
Binding site2501Heme (covalent; via 2 links) By similarity
Binding site4081Heme (covalent; via 2 links) By similarity
Site4051Transition state stabilizer By similarity

Amino acid modifications

Glycosylation1411N-linked (GlcNAc...) Potential
Glycosylation3161N-linked (GlcNAc...) Potential
Glycosylation3511N-linked (GlcNAc...) Potential
Glycosylation6231N-linked (GlcNAc...) Potential
Disulfide bond154 ↔ 170 By similarity
Disulfide bond271 ↔ 281 By similarity
Disulfide bond275 ↔ 295 By similarity
Disulfide bond606 ↔ 663 By similarity
Disulfide bond704 ↔ 729 By similarity
Disulfide bond750 ↔ 790 By similarity
Disulfide bond776 ↔ 802 By similarity
Disulfide bond808 ↔ 822 By similarity
Disulfide bond816 ↔ 831 By similarity
Disulfide bond833 ↔ 846 By similarity

Experimental info

Sequence conflict2321V → I in AAM26737. Ref.1
Sequence conflict5011L → F in AAM26737. Ref.1
Sequence conflict5271G → R in AAM26737. Ref.1
Sequence conflict5331F → FS in AAM26737. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q8HYB7 [UniParc].

Last modified October 3, 2012. Version 2.
Checksum: 95031FB3A3FEFBD1

FASTA944101,406
        10         20         30         40         50         60 
MVGLVPAGSA WGGRALAVLG VTLLVALARG LLPFFLGGRD LLWGQSGEAS VLGVVEESRR 

        70         80         90        100        110        120 
VVDGAIQHTV RRDLSKRGLP SPSQLLSFSK LPEPTSRAVS RAAEIMEASV QAVRTRVYGK 

       130        140        150        160        170        180 
LGRSWPLTDT LPEAVLDTIA NASGCRPHML PPRCPDTCLA RKYRLITGAC NNRDHPRWGA 

       190        200        210        220        230        240 
SNTALARWLP PAYEDGISEP RGWNPHVLYS GFPLPPVREV TRQVIRVPNE AVTEDDQYSD 

       250        260        270        280        290        300 
LLTVWGQYID HDVAFTPQSA SGAAFGAGAD CQLTCENRSP CFPIQLPPDA SGPACLPFSR 

       310        320        330        340        350        360 
SSAACGTGIQ GAFFGNLSSA NPRQQMNGLT SFLDASTVYG SSPALEKQLR NWTSAEGLLR 

       370        380        390        400        410        420 
VNTRHWDAGR AHLPFMRPPA PLACVPEPGT RGTAGAPCFL AGDSRASEVP TLAALHTLWL 

       430        440        450        460        470        480 
REHNRLASAL KALNAHWSAD TAYQEARKVV GALHQIITLR DYVPKVLGPE AFQQHVGPYE 

       490        500        510        520        530        540 
GYDPTMDPTV SNVFSTAAFR LGHATVHPLV RRLDARFQEH PGLPPLGLQD AFFPWRLLKE 

       550        560        570        580        590        600 
GGLDPLLRGL LASPAKLPVQ EQLMNEELTE RLFVLGSSGS LDLASINLQR GRDHGLPGYN 

       610        620        630        640        650        660 
AWREFCGLGR LHTRAELRSA VANATLAGRI MDLYGHPDNI DVWLGGLAEP LLPRARTGPL 

       670        680        690        700        710        720 
FACLIGRQMK ALRDGDRFWW ESSGVFTDEQ RRELARHSLS RVICDNTGLP SVPADAFQVS 

       730        740        750        760        770        780 
RFPQDFEPCE NIPGLNLDVW REALPQGDAC GLPDSLDNGD VVLCGEAGRR VLVFSCRHGF 

       790        800        810        820        830        840 
KLQGPEQVAC SPRGGAVRAP VCRDINECED ASHPPCHGSA RCRNTKGGFR CECTDPAVLG 

       850        860        870        880        890        900 
EDGTTCVDSG RLPKASLVSI ALGIVLVVGL AGLTWTLVCR WAHAGRKASL SIAELGGRGA 

       910        920        930        940 
PPPGRGAGQD GASGSLVPPL GPQGRTRAVD PTSSRSHVAQ GSPA 

« Hide

References

« Hide 'large scale' references
[1]"Congenital hypothyroidism with goiter in toy fox terriers."
Fyfe J.C., Kampschmidt K., Dang V., Poteet B.A., He Q., Lowrie C., Graham P.A., Fetro V.M.
J. Vet. Intern. Med. 17:50-57(2003) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY094504 mRNA. Translation: AAM26737.2.
JH373195 Genomic DNA. No translation available.
RefSeqNP_001003009.2. NM_001003009.2.
UniGeneCfa.20.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9615.ENSCAFP00000004788.

Protein family/group databases

PeroxiBase3334. CfaTPO.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSCAFT00000005172; ENSCAFP00000004788; ENSCAFG00000003217.
GeneID403521.
KEGGcfa:403521.

Organism-specific databases

CTD7173.

Phylogenomic databases

eggNOGNOG262194.
GeneTreeENSGT00550000074325.
HOGENOMHOG000016084.
HOVERGENHBG000071.
InParanoidQ8HYB7.
KOK00431.
OMAIMETSIQ.
OrthoDBEOG7D2FD6.
TreeFamTF314316.

Enzyme and pathway databases

UniPathwayUPA00194.

Family and domain databases

Gene3D1.10.640.10. 2 hits.
InterProIPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR010255. Haem_peroxidase.
IPR002007. Haem_peroxidase_animal.
IPR019791. Haem_peroxidase_animal_subgr.
IPR000436. Sushi_SCR_CCP.
[Graphical view]
PfamPF03098. An_peroxidase. 1 hit.
PF07645. EGF_CA. 1 hit.
[Graphical view]
PRINTSPR00457. ANPEROXIDASE.
SMARTSM00032. CCP. 1 hit.
SM00179. EGF_CA. 1 hit.
[Graphical view]
SUPFAMSSF48113. SSF48113. 1 hit.
SSF57535. SSF57535. 1 hit.
PROSITEPS00010. 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]
ProtoNetSearch...

Other

NextBio20817032.

Entry information

Entry namePERT_CANFA
AccessionPrimary (citable) accession number: Q8HYB7
Secondary accession number(s): F1Q066
Entry history
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: October 3, 2012
Last modified: June 11, 2014
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways