The CAP family of proteins

Structurally CAP (also called CRP, the Cyclic AMP Receptor Protein) is related to the Escherichia coli transcription factor FNR (Shaw DJ, 1983) FNR at UniProtKB.  FNR (Fumarate-Nitrate Reduction) is a global regulator acting upon the availability of oxygen in the environment (Crack J, 2004; Crack JC, 2007).  The FNR regulon was characterized by microarray studies (Constantinidou C, 2006).  In vivo regulation by FNR was shown to involve cycling of FNR between active and inactive states (Dibden DP, 2005).  Studies of transcriptional regulation by FNR using artificial FNR-dependent promoters (Barnard AM, 2003) and mutagenesis (Weber KD, 2005) 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 (Anjum MF, 2000).

The CAP/FNR family has expanded to a superfamily of versatile transcriptional regulators (Green J, 2001).  E. coli FNR was shown to respond not only to  oxygen but also to nitric oxyde (NO) (Cruz‐Ramos H, 2002), and accumulation of NO inactivated FNR in mutant strains lacking the NO-detoxifying flavohaemoglobin Hmp (Corker H, 2003).  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 (Lee YY, 2006).  In Salmonella enterica serovar Typhimurium FNR (OxrA) plays a major role in virulence (Fink RC, 2007).

As regards cyclic nucleotide-binding domains homologous to CAP cAMP-binding domain, they are present in regulatory subunits of cAMP-dependent protein kinases (Weber IT, 1982) as well as cyclic nucleotide-gated (CNG) ion channels.  CNG channels are opened upon binding of cyclic nucleotides, especially cAMP or cGMP (Kaupp UB, 2002).  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 (Scott SP, 2001).

Proteins bearing a CAP like cAMP-binding domain are members of COG0664.  Additional eukaryotic members of COG0664 are from Drosophila melanogaster (fruit fly) and Caenorhabditis elegans (soil nematode).