SMART: RIIa domain annotation

RIIa RIIalpha, Regulatory subunit portion of type II PKA R-subunit

SMART accession number:	SM00394
Description:	RIIalpha, Regulatory subunit portion of type II PKA R-subunit. Contains dimerisation interface and binding site for A-kinase-anchoring proteins (AKAPs).
Interpro abstract (IPR003117):	Protein kinases are a group of enzymes that possess a catalytic subunit which transfers the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. The enzymes fall into two broad classes, characterised with respect to substrate specificity: serine/threonine specific and tyrosine specific (PUBMED:3291115). Protein kinase function has been evolutionarily conserved from Escherichia coli to Homo sapiens. Protein kinases play a role in a mulititude of cellular processes, including division, proliferation, apoptosis, and differentiation (PUBMED:12368087). Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved (PUBMED:15078142), leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases (PUBMED:15320712). In the absence of cAMP, Protein Kinase A (PKA) exists as an equimolar tetramer of regulatory (R) and catalytic (C) subunits (PUBMED:11734894). In addition to its role as an inhibitor of the C subunit, the R subunit anchors the holoenzyme to specific intracellular locations and prevents the C subunit from entering the nucleus. All R subunits have a conserved domain structure consisting of the N-terminal dimerization domain, inhibitory region, cAMP-binding domain A and cAMP-binding domain B. R subunits interact with C subunits primarily through the inhibitory site. The cAMP-binding domains show extensive sequence similarity and bind cAMP cooperatively. Two types of regulatory (R) subunits exist - types I and I - which differ in molecular weight, sequence, autophosphorylation cabaility, cellular location and tissue distribution. Types I and II were further sub-divided into alpha and beta subtypes, based mainly on sequence similarity. This entry represents types I-alpha, I-beta, II-alpha and II-beta regulatory subunits of PKA proteins. These subunits contain the dimerisation interface and binding site for A-kinase-anchoring proteins (AKAPs).
GO process:	signal transduction (GO:0007165)
GO function:	cAMP-dependent protein kinase regulator activity (GO:0008603)
Family alignment:	View or

There are 156 RIIa domains in 154 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
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Go to specific node: Anopheles gambiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
Cellular role (predicted cellular role)
Cellular role: signalling
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Newlon MG et al.
- The molecular basis for protein kinase A anchoring revealed by solution NMR.
- Nat Struct Biol. 1999; 6: 222-7
- Display abstract
- Compartmentalization of signal transduction enzymes into signaling complexes is an important mechanism to ensure the specificity of intracellular events. Formation of these complexes is mediated by specialized protein motifs that participate in protein-protein interactions. The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) is localized through interaction of the regulatory (R) subunit dimer with A-kinase-anchoring proteins (AKAPs). We now report the solution structure of the type II PKA R-subunit fragment RIIalpha(1-44), which encompasses both the AKAP-binding and dimerization interfaces. This structure incorporates an X-type four-helix bundle dimerization motif with an extended hydrophobic face that is necessary for high-affinity AKAP binding. NMR data on the complex between RIIalpha(1-44) and an AKAP fragment reveals extensive contacts between the two proteins. Interestingly, this same dimerization motif is present in other signaling molecules, the S100 family. Therefore, the X-type four-helix bundle may represent a conserved fold for protein-protein interactions in signal transduction.
- Rubin CS
- A kinase anchor proteins and the intracellular targeting of signals carried by cyclic AMP.
- Biochim Biophys Acta. 1994; 1224: 467-79
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

Links (links to other resources describing this domain)
INTERPRO IPR003117

PDB code	Main view	Title
1l6e		Solution structure of the docking and dimerization domain of protein kinase a ii-alpha (riialpha d/d). alternatively called the n-terminal dimerization domain of the regulatory subunit of protein kinase a.
1r2a		The molecular basis for protein kinase a anchoring revealed by solution nmr
2drn		Docking and dimerization domain (d/d) of the type ii-alpha regulatory subunity of protein kinase a (pka) in complex with a peptide from an a-kinase anchoring protein
2ezw		Solution structure of the docking and dimerization domain of the type i alpha regulatory subunit of protein kinase a (rialpha d/d)
2h9r		Docking and dimerization domain (d/d) of the regulatory subunit of the type ii-alpha camp-dependent protein kinase a associated with a peptide derived from an a-kinase anchoring protein (akap)
2hwn		Crystal structure of rii alpha dimerization/docking domain of pka bound to the d-akap2 peptide
2izx		Molecular basis of akap specificity for pka regulatory subunits
2izy		Molecular basis of akap specificity for pka regulatory subunits

RIIa

3D Structures of RIIa domains in PDB