Bacterial gene regulators with transition metal cofactors

Criteria for inclusion in this database:

Cases where a metal ion functions exclusively as an inducer or co-repressor (for example nickel binding to NikR) are excluded

Only proteins that regulate gene expression are included. So, proteins that are components of other types of signaling pathway (for example chemotaxis or dcGMP signaling) are, for the time being, excluded

Gene regulation can be either direct (by DNA binding proteins) or indirect (by histidine kinases, proteins that interact with histidine kinases, anti-repressors and anti-sigma factors)

Some biochemical or physiological support for the presence of a metal cofactor is required, so there are no inferences based solely on sequence information

Abbreviations. HK: histidine kinase; R-HK: regulator of a histidine kinase; AR: anti-repressor; AS: anti-sigma factor

Acknowledgements: I am grateful to Mark Buttner, Chris den Hengst, Ray Dixon and Matt Hutchings for helping to ensure the completeness of this database. Any errors or omissions remain the responsibility of the author. If you have additions or corrections to make please e-mail me. Support of the NSF (award MCB-0702858) is gratefully acknowledged.

© Stephen Spiro, 2010

Protein	Cofactor	Primary Signal	Secondary signals	Comments	References	Links
FNR	[4Fe-4S]	Oxygen	NO		Khoroshilova et al. (1995) Cruz-Ramos et al. (2002)	Uniprot
NreB (HK)	[4Fe-4S]	Oxygen			Kamps et al. (2004)	Uniprot
ArnR	[Fe-S]	Oxygen			Nishimura et al. (2008)
IscR	[2Fe-2S]	Iron depletion?	Oxygen, NO, hydrogen peroxide		Zheng et al. (2001) Schwartz et al. (2001) Outten et al. (2004) Giel et al. (2006) Hyduke et al. (2007)	Uniprot Pfam
SoxR	[2Fe-2S]	Superoxide or guanine radicals?	NO, singlet oxygen, hydrogen peroxide		Hidalgo & Demple (1994) Ding & Demple (2000) Agnez-Lima et al. (2001) Zheng et al. (2001) Lee et al. (2009)	Uniprot PDB PDB
NsrR	[Fe-S]	NO			Bodenmiller & Spiro (2006) Nakano et al. (2006)	Uniprot Pfam
SufR	[4Fe-4S]	?			Shen at al. (2007)	Uniprot
PqrR	[Fe-S]	Superoxide			Rungrassamee et al. (2009)
RsmA (AS)	[2Fe-2S]	?			Gaskell et al. (2007)
FixL (HK)	Heme	Oxygen			Gilles-Gonzalez et al. (1991) Rodgers & Lukat-Rodgers (2005)	Uniprot
AppA (AR)	Heme	Oxygen			Moskvin et al. (2007)	Uniprot
DosS/DosT (HK)	Heme	Oxygen		NO binds to DosS/DosT, preventing oxygen from binding and so mimicking anoxia	Sousa et al. (2007) Kumar et al. (2007)	Uniprot
CooA	Heme	CO			Lanzilotta et al. (2000) Roberts et al. (2005) Borjigin et al. (2007)	Uniprot
RcoM	Heme	CO	NO?		Kerby et al. (2008)
DNR	Heme	NO			Giardina et al. (2008)	Uniprot
H-NOX (R-HK)	Heme	Oxygen and NO		The H-NOX family contains some members that bind oxygen and some that bind NO	Boon & Marletta (2005) Boon et al. (2006) Price et al. (2007)
PerR (CatR)	Iron, zinc	Peroxide	NO	PerR contains a structural zinc, and a second site that can be occupied by Fe or Mn. The Fe protein is a peroxide sensor, the zinc site is sensitive to severe oxidative stress	Lee & Helmann (2006a) Lee & Helmann (2006b)	Uniprot PDB
Fur	Iron, zinc	Iron	NO, peroxide	Fur is an iron sensor; Fe functions both as a co-repressor and as a cofactor that can be modified by NO. A structural zinc site is sensitive to severe oxidative stress	D’Autreaux et al. (2002) Mukhopadhyay et al. (2004) D’Autreaux et al. (2007)	Uniprot PDB
NorR	Iron	NO			D’Autreaux et al. (2005) Klink et al. (2007) Tucker et al. (2008)	Uniprot
ChrR (AS)	Zinc	Singlet oxygen			Anthony et al. (2005) Campbell et al. (2007)	Uniprot PDB
NmlR	Zinc	NO/nitrosative stress		Zinc is required for NmlR activity in vivo; zinc binding to the protein has not been shown directly	Kidd et al. (2005)
RsrA (AS)	Zinc	Thiol oxidation			Li et al. (2003) Zdanowski et al. (2006)	Uniprot
Ada	Zinc	Thiol methylation			He et al. (2005)	Uniprot
NrdR	Zinc	ATP/dATP		Zinc site is structural	Grinberg et al. (2006)
HoxBC (R-HK)	Nickel, iron	Hydrogen			Gebler et al. (2007)	Uniprot