IUBMB Enzyme Nomenclature


Accepted name: cAMP-dependent protein kinase

Reaction: ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate

Glossary: 3',5'-cyclic-AMP = cAMP

Other name(s): PKA; protein kinase A; PKA catalytic (C) subunit; A kinase; ATP:protein phosphotransferase (cAMP-dependent)

Systematic name: ATP:protein Ser/Thr-phosphotransferase (3',5'-cAMP-dependent)

Comments: This eukaryotic enzyme recognizes the sequence -Arg-Arg-X-Ser*/Thr*-Hpo, where * indicates the phosphorylated residue and Hpo indicates a hydrophobic residue.The inactive holoenzyme is a heterotetramer composed of two regulatory (R) subunits and two catalytic (C) subunits. Each R subunit occludes the active site of a C subunit and contains two binding sites for 3',5'-cyclic-AMP (cAMP). Binding of cAMP activates the enzyme by causing conformational changes that release two free monomeric C subunits from a dimer of the R subunits, i.e. R2C2 + 4 cAMP = R2(cAMP)4 + 2 C. Activity requires phosphorylation of a conserved Thr in the activation loop (T-loop) sequence (Thr198 in human Cα; Thr224 in budding yeast Tpk2), installed by auto-phosphorylation or by the 3-phosphoinositide-dependent protein kinase-1 (PDPK1). Certain R2C2 combinations can be localized to particular subcellular regions by their association with diverse species of 'A Kinase-Anchoring Proteins' (AKAPs). The enzyme has been characterized from many organisms. Humans have three C units (Cα, Cβ, and Cγ) encoded by the paralogous genes PRKACA, PRKACB and PRKACG, respectively, and four R subunits (R1α, RIβ, RIIα and RIIβ), encoded by PKRAR1A, PKRAR1B, PKRAR2A and PKRAR2B, respectively. Yeast (Saccharomyces cerevisiae) has three C subunits (Tpk1, Tpk2, and Tpk3) encoded by the paralogous genes TPK1, TPK2 and TPK3, respectively, and a single R subunit (Bcy1) encoded by the BCY1 gene. Some validated substrates of the enzyme include cAMP-response element-binding protein (CREB), phosphorylase kinase α subunit (PHKA), and tyrosine 3-monooxygenase (TH) in mammals; Adr1, Whi3, Nej1, and Pyk1 in yeast.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 142008-29-5


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3. Smith, F.D., Samelson, B.K. and Scott, J.D. Discovery of cellular substrates for protein kinase A using a peptide array screening protocol. Biochem. J. 438 (2011) 103-110. [PMID: 21644927]

4. Broach, J.R. Nutritional control of growth and development in yeast. Genetics 192 (2012) 73-105. [PMID: 22964838]

5. Embogama, D.M. and Pflum, M.K. K-BILDS: A kinase substrate discovery tool. Chembiochem 18 (2017) 136-141. [PMID: 27860220]

6. Taylor, S.S., Wu, J., Bruystens, J.GH., Del Rio, J.C., Lu, T.W., Kornev, A.P. and Ten Eyck, L.F. From structure to the dynamic regulation of a molecular switch: A journey over 3 decades. J. Biol. Chem. 296 (2021) 100746. [PMID: 33957122]

7. Ramms, D.J., Raimondi, F., Arang, N., Herberg, F.W., Taylor, S.S. and Gutkind, J.S. Galphas-protein kinase A (PKA) pathway signalopathies: The emerging genetic landscape and therapeutic potential of human diseases driven by aberrant Galphas-PKA signaling. Pharmacol Rev 73 (2021) 155-197. [PMID: 34663687]

[EC created 2005 (EC part-incorporated 2005), modified 2022]

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