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

doi:10.3945/jn.109.117531

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

J Nutr. 2010 Oct;140(10):1728-35. doi: 10.3945/jn.109.117531. Epub 2010 Aug 4.

Authors

Huijun Chen¹, 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

Affiliation

¹ Department of Nutritional Science and Toxicology, University of California, Berkeley, CA 94720, USA.

Abstract

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."

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amino Acid Sequence
Animals
Base Sequence
Binding Sites
Caco-2 Cells
Cell Line
Cell Line, Tumor
Ceruloplasmin / analysis
Ceruloplasmin / chemistry*
Ceruloplasmin / genetics*
Copper / analysis*
Copper / metabolism
Female
Gene Expression
Humans
Iron / metabolism
Mammary Glands, Animal / enzymology
Membrane Proteins / chemistry
Membrane Proteins / genetics
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Models, Molecular
Organ Specificity
Oxidoreductases Acting on CH-NH Group Donors / metabolism
Peptide Fragments / chemistry
Placenta / enzymology
Pregnancy
RNA, Small Interfering / pharmacology
Rats
Sequence Homology

Substances

HEPH protein, human
Heph protein, mouse
Heph, protein, rat
Membrane Proteins
Peptide Fragments
RNA, Small Interfering
Copper
Iron
Ceruloplasmin
4-phenylenediamine oxidase
Oxidoreductases Acting on CH-NH Group Donors

Abstract

Publication types

MeSH terms

Substances

Grants and funding