Reviewed, UniProtKB/Swiss-Prot Q8HYB7 (PERT_CANFA)

Names and origin

Protein names

Recommended name:
    Thyroid peroxidase
      Short name=TPO
    EC=1.11.1.8

Gene names

Name:

TPO

Organism

Canis familiaris (Dog)

Taxonomic identifier

9615 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis

Protein attributes

Sequence length	933 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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.

Ontologies

Keywords
Biological process	Hydrogen peroxide Thyroid hormones biosynthesis
Cellular component	Membrane
Domain	EGF-like domain Signal Sushi Transmembrane
Ligand	Calcium Heme Iron Metal-binding
Molecular function	Oxidoreductase Peroxidase
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	hormone biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW hydrogen peroxide catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW heme binding Inferred from electronic annotation. Source: InterPro iodide peroxidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 933	915	Thyroid peroxidase		PRO_0000023661
Regions
	Topological domain	19 – 846	828	Extracellular Potential
	Transmembrane	847 – 867	21	Potential
	Topological domain	868 – 933	66	Cytoplasmic Potential
	Domain	737 – 792	56	Sushi
	Domain	793 – 836	44	EGF-like; calcium-binding Potential
Sites
	Active site	239	1	Proton acceptor By similarity
	Metal binding	240	1	Calcium By similarity
	Metal binding	318	1	Calcium By similarity
	Metal binding	320	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	322	1	Calcium By similarity
	Metal binding	324	1	Calcium By similarity
	Metal binding	491	1	Iron (heme axial ligand) By similarity
	Binding site	238	1	Heme (covalent; via 2 links) By similarity
	Binding site	396	1	Heme (covalent; via 2 links) By similarity
	Site	393	1	Transition state stabilizer By similarity
Amino acid modifications
	Glycosylation	129	1	N-linked (GlcNAc...) Potential
	Glycosylation	304	1	N-linked (GlcNAc...) Potential
	Glycosylation	339	1	N-linked (GlcNAc...) Potential
	Glycosylation	612	1	N-linked (GlcNAc...) Potential
	Disulfide bond	142 ↔ 158		By similarity
	Disulfide bond	259 ↔ 269		By similarity
	Disulfide bond	263 ↔ 283		By similarity
	Disulfide bond	595 ↔ 652		By similarity
	Disulfide bond	693 ↔ 718		By similarity
	Disulfide bond	739 ↔ 779		By similarity
	Disulfide bond	765 ↔ 791		By similarity
	Disulfide bond	797 ↔ 811		By similarity
	Disulfide bond	805 ↔ 820		By similarity
	Disulfide bond	822 ↔ 835		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q8HYB7-1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 30ABDDD87FE70587	FASTA	933	100,461
	10 20 30 40 50 60 MGALAVLGVT LLVALARGLL PFFLGGRDLL WGQSGEASVL GVVEESRRVV DGAIQHTVRR 70 80 90 100 110 120 DLSKRGLPSP SQLLSFSKLP EPTSRAVSRA AEIMEASVQA VRTRVYGKLG RSWPLTDTLP 130 140 150 160 170 180 EAVLDTIANA SGCRPHMLPP RCPDTCLARK YRLITGACNN RDHPRWGASN TALARWLPPA 190 200 210 220 230 240 YEDGISEPRG WNPHVLYSGF PLPPVREVTR QVIRVPNEAV TEDDQYSDLL TVWGQYIDHD 250 260 270 280 290 300 VAFTPQSASG AAFGAGADCQ LTCENRSPCF PIQLPPDASG PACLPFSRSS AACGTGIQGA 310 320 330 340 350 360 FFGNLSSANP RQQMNGLTSF LDASTVYGSS PALEKQLRNW TSAEGLLRVN TRHWDAGRAH 370 380 390 400 410 420 LPFMRPPAPL ACVPEPGTRG TAGAPCFLAG DSRASEVPTL AALHTLWLRE HNRLASALKA 430 440 450 460 470 480 LNAHWSADTA YQEARKVVGA LHQIITLRDY VPKVLGPEAF QQHVGPYEGY DPTMDPTVSN 490 500 510 520 530 540 VFSTAAFRFG HATVHPLVRR LDARFQEHPG LPPLRLQDAF FSPWRLLKEG GLDPLLRGLL 550 560 570 580 590 600 ASPAKLPVQE QLMNEELTER LFVLGSSGSL DLGSINLQRG RDHGLPGYNA WREFCGLGRL 610 620 630 640 650 660 HTRAELRSAV ANATLAGRIM DLYGHPDNID VWLGGLAEPL LPRARTGPLF ACLIGRQMKA 670 680 690 700 710 720 LRDGDRFWWE SSGVFTDEQR RELARHSLSR VICDNTGLPS VPADAFQVSR FPQDFEPCEN 730 740 750 760 770 780 IPGLNLDVWR EALPQGDACG LPDSLDNGDV VLCGEAGRRV LVFSCRHGFK LQGPEQVACS 790 800 810 820 830 840 PRGGAVRAPV CRDINECEDA SHPPCHGSAR CRNTKGGFRC ECTDPAVLGE DGTTCVDSGR 850 860 870 880 890 900 LPKASLVSIA LGIVLVVGLA GLTWTLVCRW AHAGRKASLS IAELGGRGAP PPGRGAGQDG 910 920 930 ASGSLVPPLG PQGRTRAVDP TSSRSHVAQG SPA

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: 12564727] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Thyroid.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY094504 mRNA. Translation: AAM26737.1.
RefSeq	NP_001003009.1.
UniGene	Cfa.20
3D structure databases
HSSP	HSSP built from PDB template 1D5L based on UniProtKB P05164.
ModBase	Search...
Protein family/group databases
PeroxiBase	3334. CfaTPO.
Genome annotation databases
Ensembl	ENSCAFG00000003217. Canis familiaris. [Contig view]
GeneID	403521.
KEGG	cfa:403521.
Phylogenomic databases
HOVERGEN	Q8HYB7.
Enzyme and pathway databases
BRENDA	1.11.1.8. 463.
Family and domain databases
InterPro	IPR013032. EGF-like_reg_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_CS. IPR000742. EGF_3. IPR001881. EGF_Ca_bd. IPR013091. EGF_Ca_bd_2. IPR018097. EGF_Ca_bd_CS. IPR002007. Haem_peroxidase_animal. IPR019791. Haem_peroxidase_animal_sg. IPR019794. Peroxidases_AS. IPR019793. Peroxidases_heam-ligand_BS. IPR000436. Sushi_SCR_CCP. [Graphical view]
Gene3D	G3DSA:1.10.640.10. Haem_peroxidase_animal. 1 hit.
Pfam	PF03098. An_peroxidase. 1 hit. PF07645. EGF_CA. 1 hit. [Graphical view]
PRINTS	PR00457. ANPEROXIDASE.
SMART	SM00032. CCP. 1 hit. SM00179. EGF_CA. 1 hit. [Graphical view]
PROSITE	PS00010. ASX_HYDROXYL. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. False negative. PS50026. EGF_3. 1 hit. PS01187. EGF_CA. 1 hit. PS00435. PEROXIDASE_1. 1 hit. PS00436. PEROXIDASE_2. False negative. PS50292. PEROXIDASE_3. 1 hit. PS50923. SUSHI. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PERT_CANFA

Accession

Primary (citable) accession number: Q8HYB7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 23, 2003
Last sequence update:	March 1, 2003
Last modified:	June 16, 2009
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)