PROSITE documentation PDOC00691
Cyclic nucleotide-binding domain signatures and profile


Proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues [1,2,3]. The best studied of these proteins is the prokaryotic catabolite gene activator (also known as the cAMP receptor protein) (gene crp) where such a domain is known to be composed of three α-helices and a distinctive eight-stranded, antiparallel β-barrel structure. Such a domain is known to exist in the following proteins:

  • Prokaryotic catabolite gene activator protein (CAP).
  • cAMP- and cGMP-dependent protein kinases (cAPK and cGPK). Both types of kinases contains two tandem copies of the cyclic nucleotide-binding domain. The cAPK's are composed of two different subunits: a catalytic chain and a regulatory chain which contains both copies of the domain. The cGPK's are single chain enzymes that include the two copies of the domain in their N- terminal section. The nucleotide specificity of cAPK and cGPK is due to an amino acid in the conserved region of β-barrel 7: a threonine that is invariant in cGPK is an alanine in most cAPK.
  • Vertebrate cyclic nucleotide-gated ion-channels. Two such cations channels have been fully characterized. One is found in rod cells where it plays a role in visual signal transduction. It specifically binds to cGMP leading to an opening of the channel and thereby causing a depolarization of rod photoreceptors. In olfactory epithelium a similar, cAMP-binding, channel plays a role in odorant signal transduction.

There are six invariant amino acids in this domain, three of which are glycine residues that are thought to be essential for maintenance of the structural integrity of the β-barrel. We developed two signature patterns for this domain. The first pattern is located within β-barrels 2 and 3 and contains the first two conserved Gly. The second pattern is located within β-barrels 6 and 7 and contains the third conserved Gly as well as the three other invariant residues.

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

CNMP_BINDING_3, PS50042; cAMP/cGMP binding motif profile  (MATRIX)

CNMP_BINDING_1, PS00888; Cyclic nucleotide-binding domain signature 1  (PATTERN)

CNMP_BINDING_2, PS00889; Cyclic nucleotide-binding domain signature 2  (PATTERN)


1AuthorsWeber I.T. Shabb J.B. Corbin J.D.
TitlePredicted structures of the cGMP binding domains of the cGMP-dependent protein kinase: a key alanine/threonine difference in evolutionary divergence of cAMP and cGMP binding sites.
SourceBiochemistry 28:6122-6127(1989).
PubMed ID2550070

2AuthorsKaupp U.B.
TitleThe cyclic nucleotide-gated channels of vertebrate photoreceptors and olfactory epithelium.
SourceTrends Neurosci. 14:150-157(1991).
PubMed ID1710853

3AuthorsShabb J.B. Corbin J.D.
TitleCyclic nucleotide-binding domains in proteins having diverse functions.
SourceJ. Biol. Chem. 267:5723-5726(1992).
PubMed ID1313416

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