RGD Reference Report - AKAP18 contains a phosphoesterase domain that binds AMP. - Rat Genome Database

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AKAP18 contains a phosphoesterase domain that binds AMP.

Authors: Gold, MG  Smith, FD  Scott, JD  Barford, D 
Citation: Gold MG, etal., J Mol Biol. 2008 Feb 1;375(5):1329-43. Epub 2007 Nov 22.
RGD ID: 2312620
Pubmed: PMID:18082768   (View Abstract at PubMed)
PMCID: PMC3188456   (View Article at PubMed Central)
DOI: DOI:10.1016/j.jmb.2007.11.037   (Journal Full-text)

Protein kinase A anchoring proteins (AKAPs), defined by their capacity to target the cAMP-dependent protein kinase to distinct subcellular locations, function as molecular scaffolds mediating the assembly of multicomponent complexes to integrate and organise multiple signalling events. Despite their central importance in regulating cellular processes, little is known regarding their diverse structures and molecular mechanisms. Here, using bioinformatics and X-ray crystallography, we define a central domain of AKAP18 delta (AKAP18(CD)) as a member of the 2H phosphoesterase family. The domain features two conserved His-x-Thr motifs positioned at the base of a groove located between two lobes related by pseudo 2-fold symmetry. Nucleotide co-crystallisation screening revealed that this groove binds specifically to adenosine 5'-monophosphate (5'AMP) and cytosine 5'-monophosphate (5'CMP), with the affinity constant for AMP in the physiological concentration range. This is the first example of an AKAP capable of binding a small molecule. Our data generate two functional hypotheses for the AKAP18 central domain. It may act as a phosphoesterase, although we did not identify a substrate, or as an AMP sensor with the potential to couple intracellular AMP levels to PKA signalling events.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
AMP binding  IDA 2312620 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akap7  (A-kinase anchoring protein 7)


Additional Information