Thyroid peroxidase

Short name=TPO
EC=1.11.1.8
Gene names
Name: TPO
Organism Homo sapiens (Human) [Reference proteome]
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 protein 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. Ref.10
Subcellular location
Membrane; Single-pass type I membrane protein.
Isoform 3: Cell surface.
Post-translational modification
Glycosylated.
Heme is covalently bound through a H2O(2)-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface.
Cleaved in its N-terminal part.
Involvement in disease
An alternative splicing in the thyroperoxidase mRNA can cause Graves' disease. Ref.9
Thyroid dyshormonogenesis 2A (TDH2A) [MIM:274500]: A disorder due to defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26
Sequence similarities
Belongs to the peroxidase family. XPO subfamily.
Contains 1 EGF-like domain.
Contains 1 Sushi (CCP/SCR) domain.