The CAP family of proteins
Structurally CAP is related to the E. coli transcription factor FNR [Journal of Molecular Biology]. FNR (Fumarate-Nitrate Reduction) is a global regulator acting upon the availability of oxygen in the environment [JBC] [PNAS]. The FNR regulon was characterized by microarray studies [JBC]. In vivo regulation by FNR was shown to involve cycling of FNR between active and inactive states [Microbiology]. Studies of transcriptional regulation by FNR using artificial FNR-dependent promoters [JB] and mutagenesis [JB] have uncovered some differences between FNR and CAP.
The third member in the E. coli family of proteins affiliated to CAP is YeiL, the product of the yeiL gene [Microbiology].
The CAP/FNR family has expanded to a superfamily of versatile transcriptional regulators [Medline]. Interestingly E. coli FNR was shown to respond not only to oxygen but also to nitric oxyde (NO) [The EMBO Journal], and accumulation of NO may inactivate FNR in mutant strains lacking the NO-detoxifying flavohaemoglobin Hmp [JBC]. In Paracoccus denitrificans NNR (the nitrite reductase and nitric oxide reductase regulator, a member of the CAP/FNR family) also senses both oxygen and NO [Microbiology]. In Salmonella enterica serovar Typhimurium FNR (OxrA) plays a major role in virulence [JB].
Cyclic nucleotide-binding domains homologous to CAP cAMP-binding domain are present in regulatory subunits of cAMP-dependent protein kinases [PNAS] as well as cyclic nucleotide-gated (CNG) ion channels. CNG channels are opened upon binding of cyclic nucleotides, especially cAMP or cGMP [Physiological Reviews]. A fusion between the cyclic nucleotide-binding domain of the bovine retinal rod channel (alpha subunit) and the DNA-binding domain of CAP was shown to be functional [Biochemistry].
Proteins bearing a CAP like cAMP-binding domain are members of COG0664 [COG database]. Additional eukaryotic members of COG0664 are from Drosophila melanogaster (fruit fly) and Caenorhabditis elegans (soil nematode).
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