thyroid peroxidase

Function: - iodination & coupling of the hormonogenic Tyr in thyroglobulin to yield the thyroid hormones T3 & T4 - catalyzes both Tyr iodination & coupling of iodotyrosyl residues to form T4 - interacts with DUOX1, DUOX2 & CYBA - hormone biosynthesis; thyroid hormone biosynthesis 2 iodide + H₂O2 + 2 H⁺ 2 iodine + 2 H₂O Cofactor: - binds 1 Ca⁺² per heterodimer (putative) - binds 1 heme B (iron-protoporphyrin IX) group covalently per heterodimer (putative) Structure: - glycosylated - belongs to the peroxidase family. XPO subfamily - contains 1 EGF-like domain - contains 1 Sushi (CCP/SCR) domain - heme is covalently bound through a H₂O2-dependent autocatalytic process; heme insertion is important for the delivery of protein at the cell surface cleaved in its N-terminal part Compartment: - membrane - present on the luminal surface of microvilli of thyroid epithelial cells Alternative splicing: - named isoforms=8 - additional isoforms seem to exist Expression: - thyroid epithelial cells Pathology: - an alternative splicing in the thyroperoxidase mRNA can cause Graves' disease - defects in TPO are the cause of total iodide organification defect

Specific

thyroid peroxidase-1 thyroid peroxidase-2

General

glycoprotein membrane protein peroxidase

Properties

SIZE: entity length = 933 aa MW = 103 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-14} N-glycosylation site {N129} cysteine residue {C142} MODIFICATION: cysteine residue {C158} cysteine residue {C158} MODIFICATION: cysteine residue {C142} heme-binding site [238-238] histidine residue {H239} Ca+2-binding site SITE: 240-240 cysteine residue {C259} MODIFICATION: cysteine residue {C269} cysteine residue {C263} MODIFICATION: cysteine residue {C286} cysteine residue {C269} MODIFICATION: cysteine residue {C259} cysteine residue {C286} MODIFICATION: cysteine residue {C263} N-glycosylation site {N307} Ca+2-binding site SITE: 321-321 Ca+2-binding site SITE: 323-323 Ca+2-binding site SITE: 325-325 Ca+2-binding site SITE: 327-327 N-glycosylation site {N342} Transition state stabilizer {396-396} heme-binding site [399-399] Iron [Fe]-binding site SITE: 494-494 N-glycosylation site {N569} cysteine residue {C598} MODIFICATION: cysteine residue {C655} cysteine residue {C655} MODIFICATION: cysteine residue {C598} cysteine residue {C696} MODIFICATION: cysteine residue {C721} cysteine residue {C721} MODIFICATION: cysteine residue {C696} Sushi domain {740-795} EGF domain {796-839} MOTIF: cysteine residue {C800} MODIFICATION: cysteine residue {C814} cysteine residue {C808} MODIFICATION: cysteine residue {C823} cysteine residue {C814} MODIFICATION: cysteine residue {C800} cysteine residue {C823} MODIFICATION: cysteine residue {C808} cysteine residue {C825} MODIFICATION: cysteine residue {C838} cysteine residue {C838} MODIFICATION: cysteine residue {C825} transmembrane domain {847-871}

Database Correlations

OMIM correlations UniProt P07202 PFAM correlations KEGG correlations ENZYME 1.11.1.8