| Accepted Name |
|---|
| cAMP-dependent protein kinase
|
| Alternative Name(s) |
|---|
| PKA |
| PKA C |
| protein kinase A |
| Reaction catalysed |
|---|
- L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)
- L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)
|
| 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 |
|---|
| Rhea expert-curated reactions | 2.7.11.11 |
| ExplorEnz | 2.7.11.11 |
| IUBMB Enzyme Nomenclature | 2.7.11.11 |
| UniProtKB/Swiss-Prot |
| P06244, KAPA_YEAST | G1X456, KAPB_ARTOA | P40376, KAPB_SCHPO |
| P06245, KAPB_YEAST | A8XW88, KAPC1_CAEBR | P21137, KAPC1_CAEEL |
| P12370, KAPC1_DROME | A8XJQ6, KAPC2_CAEBR | Q7JP68, KAPC2_CAEEL |
| P00517, KAPCA_BOVIN | Q8MJ44, KAPCA_CANLF | P25321, KAPCA_CRIGR |
| P17612, KAPCA_HUMAN | P05132, KAPCA_MOUSE | P36887, KAPCA_PIG |
| P27791, KAPCA_RAT | Q9MZD9, KAPCA_SHEEP | P05131, KAPCB_BOVIN |
| P68180, KAPCB_CRIGR | P22694, KAPCB_HUMAN | P68181, KAPCB_MOUSE |
| P05383, KAPCB_PIG | P68182, KAPCB_RAT | P22612, KAPCG_HUMAN |
| O62846, KAPCG_MACMU | P49673, KAPC_ASCSU | P34099, KAPC_DICDI |
| Q8SRK8, KAPC_ENCCU | P05986, KAPC_YEAST |
|
| BRENDA | 2.7.11.11 |
| MetaCyc | 2.7.11.11 |
| KEGG Ligand Database for Enzyme Nomenclature | 2.7.11.11 |
| EC2PDB | 2.7.11.11 |
| MEDLINE | Find literature relating to 2.7.11.11 |
