Journal of Biological Chemistry
Volume 279, Issue 46, 12 November 2004, Pages 48159-48167
Journal home page for Journal of Biological Chemistry

Enzyme Catalysis and Regulation
Monooxygenase X, a Member of the Copper-dependent Monooxygenase Family Localized to the Endoplasmic Reticulum*

https://doi.org/10.1074/jbc.M407486200Get rights and content
Under a Creative Commons license
open access

Based on sequence comparisons, MOX (monooxygenase X), is a member of the copper monooxygenase family that includes dopamine β-monooxygenase (DBM) and peptidylglycine α-hydroxylating monooxygenase (PHM). MOX has all of the residues expected to be critical for copper binding, and its cysteine residues can yield the intramolecular disulfide bond pattern observed in DBM. Although DBM and PHM function within the lumen of the secretory pathway, the published sequence for human MOX lacks a signal sequence, suggesting that it does not enter this compartment. We identified an upstream exon that encodes the signal sequence of human MOX. A retained intron yields minor amounts of transcript encoding MOX without a signal sequence. MOX transcripts are widely expressed, with the highest levels in the salivary gland and ovary and moderate levels in brain, pituitary, and heart. Despite the presence of a signal sequence, exogenous MOX is not secreted, and it localizes throughout the endoplasmic reticulum in both endocrine or nonendocrine cells. Neither appending green fluorescent protein to its C terminus nor deleting the hydrophobic domain near its C terminus facilitates secretion of MOX. MOX is N-glycosylated, is tightly membrane-associated, and forms oligomers that are not disulfide-linked. Based on its sequence and localization, MOX is predicted to hydroxylate a hydrophobic substrate in the endoplasmic reticulum.

Cited by (0)

*

This work was supported by National Institutes of Health Grant DK-32949. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.