{PDOC00691}
{PS00888; CNMP_BINDING_1}
{PS00889; CNMP_BINDING_2}
{PS50042; CNMP_BINDING_3}
{BEGIN}
***********************************************************
* Cyclic nucleotide-binding domain signatures and profile *
***********************************************************

Proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain
of about  120  residues  [1-3].  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
alpha-helices and  a    distinctive   eight-stranded, antiparallel beta-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 beta-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 beta-barrel. We developed  two  signature patterns for  this
domain.  The first pattern is located within beta-barrels 2 and 3 and contains
the  first two  conserved  Gly. The second  pattern  is  located  within beta-
barrels 6  and  7  and  contains  the third conserved Gly as well as the three
other invariant residues.

-Consensus pattern: [LIVM]-[VIC]-x-{H}-G-[DENQTA]-x-[GAC]-{L}-x-[LIVMFY](4)-
                    x(2)-G
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Consensus pattern: [LIVMF]-G-E-x-[GAS]-[LIVM]-x(5,11)-R-[STAQ]-A-x-[LIVMA]-x-
                    [STACV]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 1.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: 3.

-Last update: December 2004 / Pattern and text revised.

[ 1] Weber I.T., Shabb J.B., Corbin J.D.
     "Predicted 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."
     Biochemistry 28:6122-6127(1989).
     PubMed=2550070
[ 2] Kaupp U.B.
     "The cyclic nucleotide-gated channels of vertebrate photoreceptors and
     olfactory epithelium."
     Trends Neurosci. 14:150-157(1991).
     PubMed=1710853
[ 3] Shabb J.B., Corbin J.D.
     "Cyclic nucleotide-binding domains in proteins having diverse
     functions."
     J. Biol. Chem. 267:5723-5726(1992).
     PubMed=1313416

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}