Identification of zyklopen, a new member of the vertebrate multicopper ferroxidase family, and characterization in rodents and human cells

Huijun Chen, Zouhair K Attieh, Basharut A Syed, Yien-Ming Kuo, Valerie Stevens, Brie K Fuqua, Henriette S Andersen, Claire E Naylor, Robert W Evans, Lorraine Gambling, Ruth Danzeisen, Mhenia Bacouri-Haidar, Julnar Usta, Chris D Vulpe, Harry J McArdle

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We previously detected a membrane-bound, copper-containing oxidase that may be involved in iron efflux in BeWo cells, a human placental cell line. We have now identified a gene encoding a predicted multicopper ferroxidase (MCF) with a putative C-terminal membrane-spanning sequence and high sequence identity to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate MCF. Molecular modeling revealed conservation of all type I, II, and III copper-binding sites as well as a putative iron-binding site. Protein expression was observed in multiple diverse mouse tissues, including placenta and mammary gland, and the expression pattern was distinct from that of Cp and Heph. The protein possessed ferroxidase activity, and protein levels decreased in cellular copper deficiency. Knockdown with small interfering RNA in BeWo cells indicates that this gene represents the previously detected oxidase. We propose calling this new member of the MCF family "zyklopen."
Original languageEnglish
Pages (from-to)1728-1735
Number of pages8
JournalThe Journal of Nutrition
Issue number10
Early online date4 Aug 2010
Publication statusPublished - 1 Oct 2010


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