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Information on EC 2.7.11.11 - cAMP-dependent protein kinase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P06244

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IUBMB 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 Calpha; 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 (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.
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Saccharomyces cerevisiae
UNIPROT: P06244
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Word Map
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
camp-dependent protein kinase, a kinase, cyclic amp-dependent protein kinase, camp-pka, camp/protein kinase a, capk, prkaca, camp dependent protein kinase, camp-dependent pka, cyclic amp-dependent protein kinase a, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cAMP-dependent protein kinase type 1
-
A kinase
-
-
-
-
ATP:protein phosphotransferase (cAMP-dependent)
-
-
-
-
cAMP-dependent protein kinase
-
-
-
-
cAMP-dependent protein kinase type 2
-
cAMP-dependent protein kinase type 3
-
cyclic AMP-protein kinase A
-
-
PK-25
-
-
-
-
PKA C-alpha
-
-
-
-
PKA C-beta
-
-
-
-
PKA C-gamma
-
-
-
-
PKA catalytic (C) subunit
-
-
-
-
protein kinase A
Ras/cAMP-dependent protein kinase
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
show the reaction diagram
conserved residues K336 and H338 are important for catalytic activity, R324 is important in substrate binding
-
SYSTEMATIC NAME
IUBMB Comments
ATP:protein Ser/Thr-phosphotransferase (3',5'-cAMP-dependent)
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 Calpha; 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 (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.
CAS REGISTRY NUMBER
COMMENTARY hide
142008-29-5
-
142008-29-5
cAMP-dependent protein kinase
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + phosphorylated protein
show the reaction diagram
-
-
-
-
?
ATP + autophagy-related protein kinase Atg1
ADP + phosphorylated autophagy-related protein kinase Atg1
show the reaction diagram
ATP + Dot6
ADP + phosphorylated Dot6
show the reaction diagram
ATP + [Whi3 cell cycle regulator protein]
ADP + [Whi3 cell cycle regulator phosphoprotein]
show the reaction diagram
additional information
?
-
-
potential substrate identification by an evolutionary proteomics approach, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + phosphorylated protein
show the reaction diagram
-
-
-
-
?
ATP + autophagy-related protein kinase Atg1
ADP + phosphorylated autophagy-related protein kinase Atg1
show the reaction diagram
-
initiating the degradative pathway, PKA regulates the association of Atg1 with the preautophagosomal structure PAS, overview
-
-
?
ATP + Dot6
ADP + phosphorylated Dot6
show the reaction diagram
-
a protein implicated in telomere function
-
-
?
ATP + [Whi3 cell cycle regulator protein]
ADP + [Whi3 cell cycle regulator phosphoprotein]
show the reaction diagram
-
phosphorylation of Ser568 leads to inhibition of Whi3
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
GTPase activating proteins negatively regulate Ras in nutrient-poor conditions, downregulation of Ras lowers cAMP levels leading to reduced activity of protein kinase A
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Ras-2 protein
-
-
-
sucrose
-
direct inducer of cAMP-PKA signaling
additional information
-
Ras stimulates adenylate cyclase leading to increasing cAMP levels and in turn increased activity of protein kinase A
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
PKA associates with substrates with a relatively low affinity
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
54 S subunit of the yeast mitochondrial ribosome
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
enzyme activity decreases invertase levels in cells growing in lactate, and increased them during growth in lactate + 0.1% (w/v) D-glucose
physiological function
-
phosphorylation of Whi3 by PKA leads to its decreased interaction with CLN3 G1 cyclin mRNA and is required for the promotion of G1/S progression, phosphorylation state of Ser568 in Whi3 affects G1/S transition by modulating CLN2 transcription. PKA causes a decrease in cell size by downregulating Whi3 function. Implication of PKA-mediated modulation of Whi3 in multiple cellular events
additional information
-
the phosphomimetic S568D mutation of Whi3 prevents the developmental fate switch to sporulation or invasive growth
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K336A/H338A
-
i.e. Tpk1K336A/H338A, site-directed mutagenesis, a catalytically inactive PKA variant, that exhibits a stable binding to the substrate
R324A
-
i.e. Tpk1R324A, site-directed mutagenesis, a catalytically inactive PKA variant, that exhibits a stable binding to the substrate with increased affinity through a conformational change
additional information
-
TPK1 overexpression resulted in a severe growth defect
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged enzyme and GST-tagged Whi3 protein from Saccharomyces cerevisiae by glutathione affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-overexpression of GST-tagged enzyme with GST-tagged Whi3 protein in Saccharomyces cerevisiae
-
expression of HA-tagged PKA-Atg1345-559 fusion protein in Saccharomyces cerevisiae
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Fearon, K.; Mason, T.L.
Structure and function of MRP20 and MRP49, the nuclear genes for two proteins of the 54 S subunit of the yeast mitochondrial ribosome
J. Biol. Chem.
267
5162-5170
1992
Saccharomyces cerevisiae (P05986)
Manually annotated by BRENDA team
Toda, T.; Cameron, S.; Sass, P.; Zoller, M.; Wigler, M.
Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase
Cell
50
277-287
1987
Saccharomyces cerevisiae (P05986), Saccharomyces cerevisiae (P06244), Saccharomyces cerevisiae (P06245), Saccharomyces cerevisiae
Manually annotated by BRENDA team
Vandenbol, M.; Bolle, P.A.; Dion, C.; Portetelle, D.; Hilger, F.
Sequencing and analysis of a 20.5 kb DNA segment located on the left arm of yeast chromosome XI
Yeast
10
S25-33
1994
Saccharomyces cerevisiae (P05986)
-
Manually annotated by BRENDA team
Cannon, J.F.; Tatchell, K.
Characterization of Saccharomyces cerevisiae genes encoding subunits of cyclic AMP-dependent protein kinase
Mol. Cell. Biol.
7
2653-2663
1987
Saccharomyces cerevisiae (P06244), Saccharomyces cerevisiae
Manually annotated by BRENDA team
Lisziewicz, J.; Godany, A.; Forster, H.H.; Kuntzel, H.
Isolation and nucleotide sequence of a Saccharomyces cerevisiae protein kinase gene suppressing the cell cycle start mutation cdc25
J. Biol. Chem.
262
2549-2553
1987
Saccharomyces cerevisiae (P06244), Saccharomyces cerevisiae
Manually annotated by BRENDA team
Ohno, S.; Aoshima, M.; Matsumoto, S.; Yahara, I.; Suzuki, K.
A yeast gene coding for a putative protein kinase homologous to cdc25 suppressing protein kinase
FEBS Lett.
222
279-285
1987
Saccharomyces cerevisiae (P06245), Saccharomyces cerevisiae
Manually annotated by BRENDA team
Bussey, H.; Storms, R.K.; Ahmed, A.; Albermann, K.; et al.
The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI
Nature
387
103-105
1997
Saccharomyces cerevisiae (P06245)
Manually annotated by BRENDA team
Budovskaya, Y.V.; Stephan, J.S.; Deminoff, S.J.; Herman, P.K.
An evolutionary proteomics approach identifies substrates of the cAMP-dependent protein kinase
Proc. Natl. Acad. Sci. USA
102
13933-13938
2005
Saccharomyces cerevisiae, Saccharomyces cerevisiae Y258
Manually annotated by BRENDA team
Deminoff, S.J.; Howard, S.C.; Hester, A.; Warner, S.; Herman, P.K.
Using substrate-binding variants of the cAMP-dependent protein kinase to identify novel targets and a kinase domain important for substrate interactions in Saccharomyces cerevisiae
Genetics
173
1909-1917
2006
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Van de Velde, S.; Thevelein, J.M.
Cyclic AMP-protein kinase A and Snf1 signaling mechanisms underlie the superior potency of sucrose for induction of filamentation in Saccharomyces cerevisiae
Eukaryot. Cell
7
286-293
2008
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Bond, S.; Forgac, M.
The Ras/cAMP/protein kinase A pathway regulates glucose-dependent assembly of the V-ATPase in yeast
J. Biol. Chem.
283
36513-36521
2008
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Mizunuma, M.; Tsubakiyama, R.; Ogawa, T.; Shitamukai, A.; Kobayashi, Y.; Inai, T.; Kume, K.; Hirata, D.
Ras/cAMP-dependent protein kinase (PKA) regulates multiple aspects of cellular events by phosphorylating the Whi3 cell cycle regulator in budding yeast
J. Biol. Chem.
288
10558-10566
2013
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Gancedo, J.M.; Flores, C.L.; Gancedo, C.
The repressor Rgt1 and the cAMP-dependent protein kinases control the expression of the SUC2 gene in Saccharomyces cerevisiae
Biochim. Biophys. Acta
1850
1362-1367
2015
Saccharomyces cerevisiae, Saccharomyces cerevisiae W303-1A
Manually annotated by BRENDA team