Q8HYB7 (PERT_CANFA) Reviewed, UniProtKB/Swiss-Prot

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) (Canis lupus familiaris) [Reference proteome]

Taxonomic identifier

9615 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › Canis lupus

Protein attributes

Sequence length	944 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. [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.

Ontologies

Keywords
Biological process	Hydrogen peroxide Thyroid hormones biosynthesis
Cellular component	Membrane
Domain	EGF-like domain Signal Sushi Transmembrane Transmembrane helix
Ligand	Calcium Heme Iron Metal-binding
Molecular function	Oxidoreductase Peroxidase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
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 thyroid hormone generation Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro 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 – 30	30	Potential
	Chain	31 – 944	914	Thyroid peroxidase		PRO_0000023661
Regions
	Topological domain	31 – 858	828	Extracellular Potential
	Transmembrane	859 – 879	21	Helical; Potential
	Topological domain	880 – 944	65	Cytoplasmic Potential
	Domain	748 – 804	57	Sushi
	Domain	804 – 847	44	EGF-like; calcium-binding Potential
Sites
	Active site	251	1	Proton acceptor By similarity
	Metal binding	252	1	Calcium By similarity
	Metal binding	330	1	Calcium By similarity
	Metal binding	332	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	334	1	Calcium By similarity
	Metal binding	336	1	Calcium By similarity
	Metal binding	503	1	Iron (heme axial ligand) By similarity
	Binding site	250	1	Heme (covalent; via 2 links) By similarity
	Binding site	408	1	Heme (covalent; via 2 links) By similarity
	Site	405	1	Transition state stabilizer By similarity
Amino acid modifications
	Glycosylation	141	1	N-linked (GlcNAc...) Potential
	Glycosylation	316	1	N-linked (GlcNAc...) Potential
	Glycosylation	351	1	N-linked (GlcNAc...) Potential
	Glycosylation	623	1	N-linked (GlcNAc...) Potential
	Disulfide bond	154 ↔ 170		By similarity
	Disulfide bond	271 ↔ 281		By similarity
	Disulfide bond	275 ↔ 295		By similarity
	Disulfide bond	606 ↔ 663		By similarity
	Disulfide bond	704 ↔ 729		By similarity
	Disulfide bond	750 ↔ 790		By similarity
	Disulfide bond	776 ↔ 802		By similarity
	Disulfide bond	808 ↔ 822		By similarity
	Disulfide bond	816 ↔ 831		By similarity
	Disulfide bond	833 ↔ 846		By similarity
Experimental info
	Sequence conflict	232	1	V → I in AAM26737. Ref.1
	Sequence conflict	501	1	L → F in AAM26737. Ref.1
	Sequence conflict	527	1	G → R in AAM26737. Ref.1
	Sequence conflict	533	1	F → FS in AAM26737. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8HYB7 [UniParc]. Last modified October 3, 2012. Version 2. Checksum: 95031FB3A3FEFBD1	FASTA	944	101,406
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
RefSeq	NP_001003009.2. NM_001003009.2.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	9615.ENSCAFP00000004788.
Protein family/group databases
PeroxiBase	3334. CfaTPO.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSCAFT00000005172; ENSCAFP00000004788; ENSCAFG00000003217.
GeneID	403521.
KEGG	cfa:403521.
Organism-specific databases
CTD	7173.
Phylogenomic databases
eggNOG	NOG262194.
GeneTree	ENSGT00550000074325.
HOGENOM	HOG000016084.
HOVERGEN	HBG000071.
InParanoid	Q8HYB7.
KO	K00431.
OMA	IMETSIQ.
OrthoDB	EOG415GD3.
Enzyme and pathway databases
UniPathway	UPA00194.
Family and domain databases
Gene3D	1.10.640.10. 2 hits.
InterPro	IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. 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]
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]
SUPFAM	SSF57535. Complement_control_module. 1 hit. SSF48113. Peroxidase_super. 1 hit.
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...
Other
NextBio	20817032.

Entry information

Entry name

PERT_CANFA

Accession

Primary (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:	April 3, 2013
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program