Open Access Research article

A subset of the diverse COG0523 family of putative metal chaperones is linked to zinc homeostasis in all kingdoms of life

Crysten E Haas1, Dmitry A Rodionov23, Janette Kropat4, Davin Malasarn4, Sabeeha S Merchant4 and Valérie de Crécy-Lagard1*

Author Affiliations

1 Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA

2 Burnham Institute for Medical Research, La Jolla, CA, USA

3 Institute for Information Transmission Problems (the Kharkevich Institute), RAS, Moscow, Russia

4 Department of Chemistry and Biochemistry and Institute for Genomics and Proteomics, University of California at Los Angeles, Los Angeles, CA, USA

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BMC Genomics 2009, 10:470  doi:10.1186/1471-2164-10-470

Published: 12 October 2009



COG0523 proteins are, like the nickel chaperones of the UreG family, part of the G3E family of GTPases linking them to metallocenter biosynthesis. Even though the first COG0523-encoding gene, cobW, was identified almost 20 years ago, little is known concerning the function of other members belonging to this ubiquitous family.


Based on a combination of comparative genomics, literature and phylogenetic analyses and experimental validations, the COG0523 family can be separated into at least fifteen subgroups. The CobW subgroup involved in cobalamin synthesis represents only one small sub-fraction of the family. Another, larger subgroup, is suggested to play a predominant role in the response to zinc limitation based on the presence of the corresponding COG0523-encoding genes downstream from putative Zur binding sites in many bacterial genomes. Zur binding sites in these genomes are also associated with candidate zinc-independent paralogs of zinc-dependent enzymes. Finally, the potential role of COG0523 in zinc homeostasis is not limited to Bacteria. We have predicted a link between COG0523 and regulation by zinc in Archaea and show that two COG0523 genes are induced upon zinc depletion in a eukaryotic reference organism, Chlamydomonas reinhardtii.


This work lays the foundation for the pursuit by experimental methods of the specific role of COG0523 members in metal trafficking. Based on phylogeny and comparative genomics, both the metal specificity and the protein target(s) might vary from one COG0523 subgroup to another. Additionally, Zur-dependent expression of COG0523 and putative paralogs of zinc-dependent proteins may represent a mechanism for hierarchal zinc distribution and zinc sparing in the face of inadequate zinc nutrition.