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ENZYME

ENZYME entry: EC 2.7.11.11

Accepted Name
cAMP-dependent protein kinase
Alternative Name(s)
PKA
PKA C
protein kinase A
Reaction catalysed
  • ATP + L-seryl-[protein] <=> ADP + H(+) + O-phospho-L-seryl-[protein]
  • ATP + L-threonyl-[protein] <=> ADP + H(+) + O-phospho-L-threonyl-[protein]
Comment(s)
  • 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 (Thr(198) in human Calpha; Thr(224) 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 (Calpha, Cbeta, and Cgamma) encoded by the paralogous genes PRKACA, PRKACB and PRKACG, respectively, and four R subunits (R1alpha, RIbeta, RIIalpha and RIIbeta), 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 alpha subunit (PHKA), and tyrosine 3-monooxygenase (TH) in mammals; Adr1, Whi3, Nej1, and Pyk1 in yeast.
  • Formerly EC 2.7.1.37.
Cross-references
BRENDA2.7.11.11
EC2PDB2.7.11.11
ExplorEnz2.7.11.11
PRIAM enzyme-specific profiles2.7.11.11
KEGG Ligand Database for Enzyme Nomenclature2.7.11.11
IUBMB Enzyme Nomenclature2.7.11.11
IntEnz2.7.11.11
MEDLINEFind literature relating to 2.7.11.11
MetaCyc2.7.11.11
Rhea expert-curated reactions2.7.11.11
UniProtKB/Swiss-Prot
P06244, KAPA_YEASTP40376, KAPB_SCHPOP06245, KAPB_YEAST
A8XW88, KAPC1_CAEBRP21137, KAPC1_CAEELP12370, KAPC1_DROME
A8XJQ6, KAPC2_CAEBRQ7JP68, KAPC2_CAEELP00517, KAPCA_BOVIN
Q8MJ44, KAPCA_CANLFP25321, KAPCA_CRIGRP17612, KAPCA_HUMAN
P05132, KAPCA_MOUSEP36887, KAPCA_PIGP27791, KAPCA_RAT
Q9MZD9, KAPCA_SHEEPP05131, KAPCB_BOVINP68180, KAPCB_CRIGR
P22694, KAPCB_HUMANP68181, KAPCB_MOUSEP05383, KAPCB_PIG
P68182, KAPCB_RATP22612, KAPCG_HUMANO62846, KAPCG_MACMU
P49673, KAPC_ASCSUP34099, KAPC_DICDIQ8SRK8, KAPC_ENCCU
P05986, KAPC_YEAST

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