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Hydrogen peroxide is the final electron acceptor for the biosynthesis of thyroid hormone catalyzed by thyroperoxidase at the apical surface of thyrocytes. Pig and human thyroid plasma membrane contain a Ca2+-dependent NAD(P)H oxidase that generates H2O2 by transferring electrons from NAD(P)H to molecular oxygen. We purified from pig thyroid plasma membrane a flavoprotein which constitutes the main, if not the sole, component of the thyroid NAD(P)H oxidase. Microsequences permitted the cloning of porcine and human full-length cDNAs encoding, respectively, 1207- and 1210-amino acid proteins with a predicted molecular mass of 138 kDa (p138Tox). Human and porcine p138Tox have 86.7% identity. The strongest similarity was to a predicted polypeptide encoded by a CaenorhabditiscDNA and with rbohA, a protein involved in theArabidopsis NADPH oxidase. p138Tox shows also similarity to the p65Mox and to the gp91Phox in their C-terminal region and have consensus sequences for FAD- and NADPH-binding sites. Compared with gp91Phox, p138Tox shows an extended N-terminal containing two EF-hand motifs that may account for its calcium-dependent activity, whereas three of four sequences implicated in the interaction of gp91Phox with the p47Phox cytosolic factor are absent in p138Tox. The expression of porcine p138Tox mRNA analyzed by Northern blot is specific of thyroid tissue and induced by cyclic AMP showing that p138Tox is a differentiation marker of thyrocytes. The gene of human p138Tox has been localized on chromosome 15q15. |
