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Information on EC 2.7.11.11 - cAMP-dependent protein kinase and Organism(s) Cricetulus griseus and UniProt Accession P25321

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EC Tree
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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Cricetulus griseus
UNIPROT: P25321
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The taxonomic range for the selected organisms is: Cricetulus griseus
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Reaction Schemes
hide
ATP
+
a [protein]-(L-serine/L-threonine)
=
ADP
+
a [protein]-(L-serine/L-threonine) phosphate
+
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, alpha-catalytic subunit
-
PKAc
catalytic subunit of cAMP-dependent protein kinase
A kinase
-
-
-
-
ATP:protein phosphotransferase (cAMP-dependent)
-
-
-
-
cAMP-dependent protein kinase
-
-
-
-
cAMP-dependent protein kinase, beta-catalytic subunit
-
PK-25
-
-
-
-
PKA C-alpha
-
-
-
-
PKA C-beta
-
-
-
-
PKA C-gamma
-
-
-
-
PKA catalytic (C) subunit
-
-
-
-
protein kinase A
-
-
-
-
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 + a phosphoprotein
show the reaction diagram
-
-
-
?
ATP + Kemptide
ADP + phosphorylated Kemptide
show the reaction diagram
-
activity of catalytic PKA subunit
-
-
?
additional information
?
-
-
the enzyme performs autophosphorylation at Ser10, Ser139, Thr197, and Ser338
-
-
?
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 + a phosphoprotein
show the reaction diagram
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
IAAGRTGRRQAIHDILVAA
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cAMP
-
dependent on
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at room temperature
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
KAPCA_CRIGR
351
0
40620
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
structure of catalytic subunit C with ATP binding cleft and activation loop, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
autophosphorylation at Ser10, Ser139, Thr197, and Ser338
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 16-23% (v/v) methanol
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
S10A/S139D/S338D
-
site-directed mutagenesis, mutant shows activity and properties similar to the wild-type enzyme
S10A/S139D/T197D/S338D
-
site-directed mutagenesis, mutant shows reduced expression level in Escherichia coli and impaired folding
S10A/S139D/T197E/S338D
-
site-directed mutagenesis, mutant shows reduced expression level in Escherichia coli and impaired folding
additional information
-
removal of residues S10, S139, and S338 plus Akt/PKB-like mutations of the ATP binding site render PKA to a Akt/PKB similar enzyme, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
HisTrap column chromatography and Mono S column chromatography
recombinant wild-type and mutant PKAs from Escherichia coli strain BL21(DE3)
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
expression of wild-type and mutant PKAs in Escherichia coli strain BL21(DE3)
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
-
recombinant PKA can be mutated to resemble Akt/PKB, which cannot be easily recombinantly expressed, mutant PKA can be used as surrogate enzyme for Akt/PKB in drug design
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Howard, P.; Day, K.H.; Kim, K.E.; Richardson, J.; Thomas, J.; Abraham, I.; Fleischmann, R.D.; Gottesman, M.M.; Maurer, R.A.
Decreased catalytic subunit mRNA levels and altered catalytic subunit mRNA structure in a cAMP-resistant Chinese hamster ovary cell line
J. Biol. Chem.
266
10189-10195
1991
Cricetulus griseus (P25321), Cricetulus griseus (P68180), Cricetulus griseus, Mus musculus (P68181)
Manually annotated by BRENDA team
Langer, T.; Sreeramulu, S.; Vogtherr, M.; Elshorst, B.; Betz, M.; Schieborr, U.; Saxena, K.; Schwalbe, H.
Folding and activity of cAMP-dependent protein kinase mutants
FEBS Lett.
579
4049-4054
2005
Cricetulus griseus
Manually annotated by BRENDA team
Kudlinzki, D.; Linhard, V.L.; Saxena, K.; Sreeramulu, S.; Gande, S.; Schieborr, U.; Dreyer, M.; Schwalbe, H.
High-resolution crystal structure of cAMP-dependent protein kinase from Cricetulus griseus
Acta Crystallogr. Sect. F
71
1088-1093
2015
Cricetulus griseus (P25321), Cricetulus griseus
Manually annotated by BRENDA team