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EC 2.7.11.11 Details

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EC number

2.7.11.11

Accepted name

cAMP-dependent protein kinase

Reaction

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

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)

CAS registry number

142008-29-5

Comment

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.

History

created 2005 (EC 2.7.1.37 part-incorporated 2005), modified 2022

EC Tree

1 Oxidoreductases

1.1 Acting on the CH-OH group of donors

1.2 Acting on the aldehyde or oxo group of donors

1.3 Acting on the CH-CH group of donors

1.4 Acting on the CH-NH₂ group of donors

1.5 Acting on the CH-NH group of donors

1.6 Acting on NADH or NADPH

1.7 Acting on other nitrogenous compounds as donors

1.8 Acting on a sulfur group of donors

1.9 Acting on a heme group of donors

1.10 Acting on diphenols and related substances as donors

1.11 Acting on a peroxide as acceptor

1.11.1 Peroxidases

1.11.2 Peroxygenases

1.12 Acting on hydrogen as donor

1.12.1 With NAD⁺ or NADP⁺ as acceptor

1.12.2 With a cytochrome as acceptor

1.12.5 With a quinone or similar compound as acceptor

1.12.7 With an iron-sulfur protein as acceptor

1.12.98 With other, known, physiological acceptors

1.12.99 With unknown physiological acceptors

1.13 Acting on single donors with incorporation of molecular oxygen (oxygenases)

1.14 Acting on paired donors, with incorporation or reduction of molecular oxygen

1.15 Acting on superoxide as acceptor

1.16 Oxidizing metal ions

1.17 Acting on CH or CH₂ groups

1.18 Acting on iron-sulfur proteins as donors

1.19 Acting on reduced flavodoxin as donor

1.20 Acting on phosphorus or arsenic in donors

1.21 Catalysing the reaction X-H + Y-H = X-Y

1.21.1 With NAD⁺ or NADP⁺ as acceptor

1.21.3 With oxygen as acceptor

1.21.4 With a disulfide as acceptor

1.21.98 With other, known, physiological acceptors

1.21.99 With unknown physiological acceptors

1.22 Acting on halogen in donors

1.23 Reducing C-O-C group as acceptor

1.97 Other oxidoreductases

1.98 Enzymes using H₂ as reductant (deleted subclass)

1.99 Other enzymes using O₂ as oxidant (deleted subclass)

2.1 Transferring one-carbon groups

2.2 Transferring aldehyde or ketonic groups

2.3 Acyltransferases

2.4 Glycosyltransferases

2.5 Transferring alkyl or aryl groups, other than methyl groups

2.6 Transferring nitrogenous groups

2.7 Transferring phosphorus-containing groups

2.7.1 Phosphotransferases with an alcohol group as acceptor

2.7.2 Phosphotransferases with a carboxy group as acceptor

2.7.3 Phosphotransferases with a nitrogenous group as acceptor

2.7.4 Phosphotransferases with a phosphate group as acceptor

2.7.5 Phosphotransferases with regeneration of donors, apparently catalysing intramolecular transfers (deleted sub-subclass)

2.7.6 Diphosphotransferases

2.7.7 Nucleotidyltransferases

2.7.8 Transferases for other substituted phosphate groups

2.7.9 Phosphotransferases with paired acceptors

2.7.10 Protein-tyrosine kinases

2.7.11 Protein-serine/threonine kinases

2.7.11.1 non-specific serine/threonine protein kinase

2.7.11.2 [pyruvate dehydrogenase (acetyl-transferring)] kinase

2.7.11.3 dephospho-[reductase kinase] kinase

2.7.11.4 [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase

2.7.11.5 [isocitrate dehydrogenase (NADP⁺)] kinase

2.7.11.6 [tyrosine 3-monooxygenase] kinase

2.7.11.7 myosin-heavy-chain kinase

2.7.11.8 Fas-activated serine/threonine kinase

2.7.11.9 Goodpasture-antigen-binding protein kinase

2.7.11.10 IκB kinase

2.7.11.11 cAMP-dependent protein kinase

2.7.11.12 cGMP-dependent protein kinase

2.7.11.13 protein kinase C

2.7.11.14 rhodopsin kinase

2.7.11.15 β-adrenergic-receptor kinase

2.7.11.16 G-protein-coupled receptor kinase

2.7.11.17 Ca²⁺/calmodulin-dependent protein kinase

2.7.11.18 myosin-light-chain kinase

2.7.11.19 phosphorylase kinase

2.7.11.20 elongation factor 2 kinase

2.7.11.21 polo kinase

2.7.11.22 cyclin-dependent kinase

2.7.11.23 [RNA-polymerase]-subunit kinase

2.7.11.24 mitogen-activated protein kinase

2.7.11.25 mitogen-activated protein kinase kinase kinase

2.7.11.26 tau-protein kinase

2.7.11.27 [acetyl-CoA carboxylase] kinase

2.7.11.28 tropomyosin kinase

2.7.11.29 low-density-lipoprotein receptor kinase

2.7.11.30 receptor protein serine/threonine kinase

2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase

2.7.11.32 [pyruvate, phosphate dikinase] kinase

2.7.11.33 [pyruvate, water dikinase] kinase

2.7.11.34 NEK6-subfamily protein kinase

2.7.12 Dual-specificity kinases (those acting on Ser/Thr and Tyr residues)

2.7.13 Protein-histidine kinases

2.7.14 Protein-arginine kinases

2.7.99 Other protein kinases

2.8 Transferring sulfur-containing groups

2.9 Transferring selenium-containing groups

2.10 Transferring molybdenum- or tungsten-containing groups

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Release 2023.1 (January 2023)