Information on EC 2.7.11.11 - cAMP-dependent protein kinase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
2.7.11.11
-
RECOMMENDED NAME
GeneOntology No.
cAMP-dependent protein kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
-
-
-
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
catalytic site structure, Asp166 is the catalytic base invariant in all kinases, activation mechanism, overview
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated at Thr197, phosphorylation leads to enzyme inhibition, activation mechanism, overview
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
random kinetic mechanism, active site structure with key residues E91, K72, N171, K168, the general base catalyst D166, and essential catalytic D184, overview, reaction mechanism
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
the substrate binds to the regulatory subunit which is released from the catalytic subunit for enzyme activity, mechanism and structure-function relationship
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
catalytic mechanism
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
active site residues and structure, mechanism of ligand binding and ligand-induced conformational changes
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
catalytic mechanism, active site structure, Tyr204 is required and involved in the hydrophobic network, substrate-induced interaction of Tyr204 and Asp166, overview
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
substrate binding site structure involving E230, the electrostatic surface is important for substrate binding and catalysis, and also for the mechanism of closing the active site cleft of subunit C, conformation and mechanism, overview, the catalytic loop consists of residues Arg165-Asn171
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
activation mechanism
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
conserved residues K336 and H338 are important for catalytic activity, R324 is important in substrate binding
-
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
phosphoryltransfer mechanism, substrate-binding site structure, the phosphorylated Thr197 in the catalytic subunit of cAMP-dependent protein is essential for activity, overview
-
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (cAMP-dependent)
cAMP is required to activate this enzyme. The inactive holoenzyme of cAMP-dependent protein kinase is a tetramer composed of two regulatory (R) and two catalytic (C) subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP molecules and two free monomeric catalytic subunits [i.e. R2C2 + 4 cAMP = R2(cAMP)4 + 2 C].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
cAMP dependent protein kinase
-
-
cAMP dependent protein kinase
-
-
cAMP-dependent protein kinase
-
-
-
-
cAMP-dependent protein kinase
-
-
cAMP-dependent protein kinase
-
-
cAMP-dependent protein kinase
-
-
cAMP-dependent protein kinase
O00843
-
cAMP-dependent protein kinase A
-
-
cAMP-dependent protein kinase A
-
-
cAMP-dependent protein kinase A
-
-
cAMP-dependent protein kinase A
-
-
cAMP-dependent protein kinase A
-
-
cAMP-dependent protein kinase catalytic subunit
P49673
-
cAMP-dependent protein kinase catalytic subunit
P21137
-
cAMP-dependent protein kinase catalytic subunit
P34099
-
cAMP-dependent protein kinase catalytic subunit
P12370
-
cAMP-dependent protein kinase catalytic subunit
P40376
-
cAMP-dependent protein kinase catalytic subunit (C-subunit)
-
-
cAMP-dependent protein kinase type 1
P06244
-
cAMP-dependent protein kinase type 2
P06245
-
cAMP-dependent protein kinase type 3
P05986
-
cAMP-dependent protein kinase type I
-
-
cAMP-dependent protein kinase, alpha-catalytic subunit
P00517
-
cAMP-dependent protein kinase, alpha-catalytic subunit
P25321
-
cAMP-dependent protein kinase, alpha-catalytic subunit
P17612
-
cAMP-dependent protein kinase, alpha-catalytic subunit
P05132
-
cAMP-dependent protein kinase, alpha-catalytic subunit
P27791
-
cAMP-dependent protein kinase, beta-1 catalytic subunit
P05131
-
cAMP-dependent protein kinase, beta-2-catalytic subunit
P05131
-
cAMP-dependent protein kinase, beta-catalytic subunit
P68180
-
cAMP-dependent protein kinase, beta-catalytic subunit
P22694
-
cAMP-dependent protein kinase, beta-catalytic subunit
P68181
-
cAMP-dependent protein kinase, gamma-catalytic subunit
P22612
-
cAMP-PKA
-
-
cAMP/protein kinase A
-
-
cAMP/protein kinase A
-
-
cAMP/protein kinase A
-
-
cAPK
-
-
Cgs1p
P40376
regulatory PKA subunit
cPKA
-
catalytic subunit of cAMP-dependent protein kinase
cyclic AMP dependent protein kinase
-
-
cyclic AMP dependent protein kinase
Komagataella pastoris JC100
-
-
-
cyclic AMP-dependent kinase
-
-
cyclic AMP-dependent protein kinase
-
-
cyclic AMP-dependent protein kinase
Q7K6A0, Q7KQK0
-
cyclic AMP-dependent protein kinase
P40376
-
cyclic AMP-dependent protein kinase
-
-
cyclic AMP-dependent protein kinase A
-
-
cyclic AMP-protein kinase A
-
-
pFC-PKA
-
catalytic subunit of PKA
PK-25
-
-
-
-
PKA
Komagataella pastoris JC100
-
-
-
PKA
Mus musculus FVB/N
-
-
-
PKA
Q7K6A0, Q7KQK0
-
PKA
Saccharomyces cerevisiae Y258
-
-
-
PKA
C3W7W0, F2XG10
-
PKA
-
-
PKA C-alpha
-
-
-
-
PKA C-beta
-
-
-
-
PKA C-gamma
-
-
-
-
PKA Calpha
-
-
PKA RIalpha
-
regulatory subunit I alpha of PKA
PKA type I
-
isoform
PKA type II
-
-
PKA type II
-
isoform
Pka1p
P40376
catalytic PKA subunit
PKAc
-
catalytic subunit of protein kinase A
PKAII
Q6ZXJ1
-
protein kinase A
-
-
protein kinase A
-
-
protein kinase A
-
-
protein kinase A
-
-
protein kinase A
-
-
protein kinase A
-
-
protein kinase A
Komagataella pastoris JC100
-
-
-
protein kinase A
-
-
protein kinase A
Q7K6A0, Q7KQK0
-
protein kinase A
-
-
protein kinase A
-
-
protein kinase A
-
-
protein kinase A Calpha
-
subunit
protein kinase A Cbeta
-
subunit
protein kinase A type II
Q6ZXJ1
-
protein kinase A type II
-
-
protein kinase-A
-
-
Ras/cAMP-dependent protein kinase
-
-
type I PKA
-
-
type I PKA
-
-
type I protein kinase A
-
-
type I protein kinase A
-
-
type II PKA
-
-
type II protein kinase A
-
-
type IIbeta cyclic AMP-dependent protein kinase
-
-
cyclic AMP-protein kinase A
-
-
additional information
-
see also EC 2.7.11.26
additional information
-
see also EC 2.7.11.1 and EC 2.7.11.26
CAS REGISTRY NUMBER
COMMENTARY
142008-29-5
-, cAMP-dependent protein kinase
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
male ticks, three isozymes
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
bovine catalytic subunit C and human regulatory subunits RI and RII
-
-
Manually annotated by BRENDA team
female
-
-
Manually annotated by BRENDA team
genes kin-1 and F47F2.1b encode two PK-A-like catalytic subunits
-
-
Manually annotated by BRENDA team
genes kin-1 and F47F2.1b encode two PK-A-like catalytic subunits
-
-
Manually annotated by BRENDA team
single genes encode the catalytic (C) subunit (kin-1), the regulatory (R) subunit (kin-2) and an A-kinase anchor protein (AKAP)
-
-
Manually annotated by BRENDA team
catfish, female
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
2 isozymes PKAI and PKAII
-
-
Manually annotated by BRENDA team
bovine catalytic subunit C and human regulatory subunits RI and RII
-
-
Manually annotated by BRENDA team
strain JC100
-
-
Manually annotated by BRENDA team
Komagataella pastoris JC100
strain JC100
-
-
Manually annotated by BRENDA team
2 types of PKA
-
-
Manually annotated by BRENDA team
C57/BL6 mice
-
-
Manually annotated by BRENDA team
FVB/N mice
-
-
Manually annotated by BRENDA team
pregnant female and male NMRI mice
-
-
Manually annotated by BRENDA team
Mus musculus FVB/N
FVB/N mice
-
-
Manually annotated by BRENDA team
bivalve mollusk, mussel
-
-
Manually annotated by BRENDA team
bivalve mollusk, sea mussel, 2 isozymes PKAmyt1 and PKAmyt2
-
-
Manually annotated by BRENDA team
two isozymes PKAmyt1 and PKAmyt2
-
-
Manually annotated by BRENDA team
New Zealand white rabbits
-
-
Manually annotated by BRENDA team
New Zealand White rabbits, constitutive PKA
-
-
Manually annotated by BRENDA team
catalytic subunit
Q7K6A0
UniProt
Manually annotated by BRENDA team
regulatory subunit
UniProt
Manually annotated by BRENDA team
male Harlan Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
several strains, overview
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae Y258
strain Y258
-
-
Manually annotated by BRENDA team
catalytic PKA subunit Pka1p
SwissProt
Manually annotated by BRENDA team
mature female frogs
-
-
Manually annotated by BRENDA team
catalytic subunit, gene TPK1; strains PO1a and AC11, genes TPK1 and RKA1 encoding catalytic and regulatory subunits
UniProt
Manually annotated by BRENDA team
regulatory subunit, gene RKA1; strains PO1a and AC11, genes TPK1 and RKA1 encoding catalytic and regulatory subunits
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
protein kinase A Calpha and Cbeta ablation both results in a 50% reduction in PKA-specific kinase activity and the level of PKA type I but not PKA type II, PKA subunit Calpha but not Cbeta ablation augments expression of the activation marker CD69 on lymphocytes
malfunction
-
combined inhibition of the androgen receptor and the regulatory subunit I alpha of PKA with small interference RNAs significantly increases the growth-inhibitory and proapoptotic effects of androgen receptor knockdown. Downregulating PKA RIalpha is sufficient to inhibit PKA signaling and also impairs androgen receptor expression and activation. Depletion of PKA RIalpha also potentiates the antiproliferative effect of the antiandrogen bicalutamide in androgen-sensitive LNCaP cells
malfunction
-
inhibition of PKA reduces accuracy in the 5-choice serial reaction time task and causes substantial increases in locomotor activity without affecting motivation or the capacity to emit operant responses at high rates, PKA inhibition within the medial prefrontal cortex of rats produces inattention and hyperactivity
malfunction
-
enzyme-deficient cells show a higher glutathione reductase expression level and are less sensitive to cell killing and generation of malondialdehyde than are wild-type cells incubated with H2O2
malfunction
-
catalytic subunit of cAMP-dependent protein kinase A silencing results in reduced conidiation and conidium morphogenesis
malfunction
Q7K6A0, Q7KQK0
downregulation of gene pfpkac mRNA using gene silencing leads to morphological changes in schizont stages and cell cycle arrest, and is also associated with a compensatory decrease in pfpkar mRNA levels, suggesting a transcriptional self-regulation of the PfPKA signalling network; downregulation of gene pfpkac mRNA using gene silencing leads to morphological changes in schizont stages and cell cycle arrest, and is also associated with a compensatory decrease in pfpkar mRNA levels, suggesting a transcriptional self-regulation of the PfPKA signalling network
malfunction
-
inhibition of PKA with KT5720 abolishes lactic-acid- or contraction-induced ATP release from muscle
malfunction
Rattus norvegicus Sprague-Dawley
-
inhibition of PKA with KT5720 abolishes lactic-acid- or contraction-induced ATP release from muscle
-
metabolism
-
CREB phosphorylation, by PKA and/or CaMKs, activates at nuclear and mitochondrial level a transcriptional regulatory cascade which promotes the concerted expression of nuclear and mitochondrial encoded subunits of complex I and other respiratory chain proteins. The post-translational cAMP/PKA stimulation of the catalytic activity of complex I, is evidently associated with stimulation of protein biosynthesis, which characterizes the G1 phase of the cell cycle, in which fibroblasts are re-introduced from the G0 phase by serum supplementation
metabolism
-
the catalytic subunit of cAMP-dependent protein kinase is a major target of cAMP signaling, and its regulation is of fundamental importance to biological processes
metabolism
Q7K6A0, Q7KQK0
the cAMP/PfPKA signalling pathway is essential for parasite growth and survival, mechanism and regulation, model of cAMP/PKA signalling pathway in Plasmodium falciparum, and of signalling events including PfPKA catalytic subunit during the Plasmodium falciparum life cycle, overview. The cAMP pathway regulates sporozoite motility and hepatic cell invasion by Plasmodium falciparum sporozoites. Putative role for PfPKA in the induction of gametocytogenesis, in erythrocyte invasion by merozoites, and in the regulation of mitochondrial protein traffic. Highly complex relationship between cAMP/PfPKA and calcium pathways in the asexual life cycle, with a key role of PfPKA in anion transport across the erythrocyte membrane, overview; the cAMP/PfPKA signalling pathway is essential for parasite growth and survival, mechanism and regulation, model of cAMP/PKA signalling pathway in Plasmodium falciparum, and of signalling events including PfPKA catalytic subunit during the Plasmodium falciparum life cycle, overview. The cAMP pathway regulates sporozoite motility and hepatic cell invasion by Plasmodium falciparum sporozoites. Putative role for PfPKA in the induction of gametocytogenesis, in erythrocyte invasion by merozoites, and in the regulation of mitochondrial protein traffic. Highly complex relationship between cAMP/PfPKA and calcium pathways in the asexual life cycle, with a key role of PfPKA in anion transport across the erythrocyte membrane, overview
metabolism
-
the cAMP/PKA pathway is involved in the signal transduction pathway for cystic fibrosis transmembrane conductance regulator-regulated ATP release from muscle
physiological function
-
protein kinase A Calpha is required for normal immune cell reactivity
physiological function
-
PKA activates phosphodiesterase-4 and increases the sensitivity of phosphodiesterase-4 to inhibition by rolipram
physiological function
-
PKAmyt2 isozyme might mediate the effects of cAMP on the ciliary beat frequency
physiological function
-
PKA catalyzed phosphorylation of beta-catenin at Ser552 and Ser675 results in stabilization of the protein and activation of its transcriptional activity. beta-Catenin is required for the glucose-dependent increase in cyclin D1 expression in INS-1E beta-cells
physiological function
-
the cAMP-dependent protein kinase regulates post-translational processing and expression of complex I subunits in mammalian cells, it promotes the activity of complex I and lowers reactive oxygen species level in mammalian cell cultures, overview. cAMP-dependent phosphorylation of the NDUFS4 subunit of the complex promotes the import in mitochondria of this nuclear encoded protein
physiological function
-
the cAMP-dependent protein kinase, PKA, and the transcription factor CREB play a critical role in the biosynthesis of complex I subunits, and PKA also regulates post-translational processing and expression of complex I subunits in mammalian cells, it promotes the activity of complex I and lowers reactive oxygen species level in mammalian cell cultures, overview. cAMP-dependent phosphorylation of the NDUFS4 subunit of the complex promotes the import in mitochondria of this nuclear encoded protein
physiological function
-
the cAMP-dependent protein kinase regulates post-translational processing and expression of complex I subunits in mammalian cells, it promotes the activity of complex I and lowers reactive oxygen species level in mammalian cell cultures, overview. cAMP-dependent phosphorylation of the NDUFS4 subunit of the complex promotes the import in mitochondria of this nuclear encoded protein
physiological function
-
PKA activity at the mitochondria is associated with the regulation of apoptosis, mitochondrial respiration, and ATP synthesis. Mitochondrial cAMP-dependent protein kinase is regulted by the protease calpain. Upon exposure of bovine heart mitochondria to digitonin, Ca2+, and a variety of electron transport chain inhibitors, the regulatory subunits of the PKA holoenzyme are digested by calpain, releasing active catalytic subunits. The proteolysis can be attenuated by calpain inhibitor I
physiological function
-
the catalytic subunit of cAMP-dependent protein kinase A contributes to conidiation and and is required for early invasion in the phytopathogenic fungus. It is an important regulator of pathogenesis and disease severity during fungus-host interactions. The catalytic subunit is essential for melanin biosynthesis
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
physiological function
Q7K6A0, Q7KQK0
Plasmodium falciparum cAMP-dependent protein kinase plays an important role in the parasite's life cycle. The parasites appear to have tightly controlled mechanisms for selfregulating PfPKA levels to maintain appropriate PKA signalling; Plasmodium falciparum cAMP-dependent protein kinase plays an important role in the parasite's life cycle. The parasites appear to have tightly controlled mechanisms for selfregulating PfPKA levels to maintain appropriate PKA signalling
physiological function
-
PKA plays an important role in the growth of tachyzoites
physiological function
-
cAMP and PKA are involved in the activation of cystic fibrosis transmembrane conductance regulator, CFTR, during muscle contractions or acidosis. CFTR is involved in the release of ATP from the contracting skeletal muscle in vivo, role of intracellular cAMP in stimulating the increase in extracellular ATP at low pH
physiological function
Rattus norvegicus Sprague-Dawley
-
cAMP and PKA are involved in the activation of cystic fibrosis transmembrane conductance regulator, CFTR, during muscle contractions or acidosis. CFTR is involved in the release of ATP from the contracting skeletal muscle in vivo, role of intracellular cAMP in stimulating the increase in extracellular ATP at low pH
-
metabolism
Rattus norvegicus Sprague-Dawley
-
the cAMP/PKA pathway is involved in the signal transduction pathway for cystic fibrosis transmembrane conductance regulator-regulated ATP release from muscle
-
additional information
-
mitochondrial cAMP-dependent protein kinase is activatable in a cAMP-independent fashion. Signals, originating from cAMP-independent sources, elicit enhanced mitochondrial PKA activity, overview
additional information
-
analysis of proteomic differences between wild-type and enzyme-deficient S-49 cells, overview. Identification of cAMP/PKA-regulated protein expressions
additional information
-
NDUFS4 mutations result in defective assembly of complex I with severe effects on the respiratory chain, mouse model NDUFS4 point mutations and phenotypes, overview
additional information
-
several conformationally disordered regions in free RIalpha become structured upon cAMP binding, including the interdomain alphaC:A and alphaC':A helices that connect cyclic nucleotide binding domains A and B and are primary recognition sites for the C subunit, unidirectional allosteric communication between the sites, Trp262, which lines the cyclic nucleotide binding A site but resides in the sequence of domain B, is an important structural determinant for intersite communication, overview
additional information
-
the phosphomimetic S568D mutation of Whi3 prevents the developmental fate switch to sporulation or invasive growth
additional information
Q7K6A0, Q7KQK0
PKA has two regulatory subunits, which bind to and inhibit two catalytic subunits, domain organization and structure comparison with mammalian/human enzymes, overview. Sequence E221-C226-P227-P228-F229-Y23 and residue E161 of the PfPKA catalytic subunit are involved in substrate recognition, residues K63, D211, D157, N162, and E199 are required for catalysis; PKA has two regulatory subunits, which bind to and inhibit two catalytic subunits, domain organization and structure comparison with mammalian/human enzymes, overview. Sequence E221-C226-P227-P228-F229-Y23 and residue E161 of the PfPKA catalytic subunit are involved in substrate recognition, residues K63, D211, D157, N162, and E199 are required for catalysis
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 5HT7 receptor
ADP + phosphorylated 5HT7 receptor
show the reaction diagram
-
recombinant rat 5HT7 receptor reconstituted in frog oocytes, overview
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
-
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
-
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
regulation by reversible phosphorylation, overview
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
regulation of the enzyme involves reversible phosphorylation at the activation loop, and associative or dissociative mechanisms
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
the enzyme is a key player in cellular responses to the second messenger cAMP, phosphorylates nuclear proteins important for gene replication
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
the enzyme phosphorylates the peptide substrate LRRASLG
-
-
?
ATP + A-kinase anchor protein
ADP + phosphorylated A-kinase anchor protein
show the reaction diagram
-
phosphorylation at Ser1928, i.e. AKAP, phosphorylation at Ser1928, the rat enzyme is active with different AKAP substrate variants from different sources, overview
-
-
?
ATP + actin
ADP + phosphorylated actin
show the reaction diagram
-
-
-
-
?
ATP + actin
ADP + phosphorylated actin
show the reaction diagram
-
low activity
-
-
?
ATP + actin
ADP + phosphorylated actin
show the reaction diagram
-
sperm protein substrate
-
-
?
ATP + adenylate kinase 1
ADP + phosphorylated adenylate kinase 1
show the reaction diagram
-
-, sperm protein substrate
-
-
?
ATP + adenylate kinase 5
ADP + phosphorylated adenylate kinase 5
show the reaction diagram
-
-, sperm protein substrate
-
-
?
ATP + aquaporin
ADP + phosphorylated aquaporin
show the reaction diagram
-
-
-
-
?
ATP + ATPase
ADP + phosphorylated ATPase
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, phosphorylation at Ser508 and Ser515
-
-
?
ATP + autophagy-related protein kinase Atg1
ADP + phosphorylated autophagy-related protein kinase Atg1
show the reaction diagram
Saccharomyces cerevisiae Y258
-
initiating the degradative pathway, PKA regulates the association of Atg1 with the preautophagosomal structure PAS, overview, phosphorylation at Ser508 and Ser515
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
PKA phosphorylation mediates beta-1 adrenergic receptor endocytosis via the caveolae pathway, mouse wild-type receptor, cytosolic phosphorylation domain near the transmembrane domains of the substrate, overview
-
-
?
ATP + beta-catenin
ADP + phosphorylated beta-cateniin
show the reaction diagram
-
-, phosphorylation on Ser552 and Ser675
-
-
?
ATP + beta1-adrenergic receptor
ADP + phosphorylated beta1-adrenergic receptor
show the reaction diagram
-
recombinant beta1-adrenergic receptor expressed in HEK-293 cell membranes, phosphorylation at Ser312 is essential for activation of endocytic recycling of the agonist-internalized beta1-adrenergic receptor, beta1-AR mutant S312A is not recycled, overview, phosphorylation at Ser312 in the third intracellular loop of the receptor protein by the PKA catalytic subunit
-
-
?
ATP + BKCa channel ZERO
ADP + phosphorylated BKCa channel ZERO
show the reaction diagram
-
recombinant murine HA-tagged tetrameric protein expressed in HEK-293 cells, activity with wild-type and mutant Y334V channel tetramers, but no activity with S899A mutant, phosphorylation at Ser899 activates the channels, overview, recombinant murine HA-tagged tetrameric protein expressed in HEK-293 cells, activity with wild-type and mutant Y334V channel tetramers, but no activity with S899A mutant, phosphorylation at Ser899, overview
-
-
?
ATP + BKCa channel ZERO
ADP + phosphorylated BKCa channel ZERO
show the reaction diagram
-
recombinant murine HA-tagged tetrameric protein expressed in HEK-293 cells, phosphorylation at Ser899 activates the channel
-
-
?
ATP + cAMP response element binding protein
ADP + cAMP response element binding protein
show the reaction diagram
-
-
-
-
?
ATP + cAMP response element binding protein
ADP + phosphorylated cAMP response element binding protein
show the reaction diagram
-
the transcription factor cAMP response element binding protein is directly activated by PKA
-
-
?
ATP + cAMP-response element-binding protein
ADP + phosphorylated cAMP-response element-binding protein
show the reaction diagram
-
-
-
-
?
ATP + cAMP-responsive element binding protein
ADP + phosphorylated cAMP-responsive element binding protein
show the reaction diagram
-
i.e. CREB, the enzyme as well as GABAB receptors are involved in induction of cAMP-responsive element binding protein phosphorylation in hippocampus by gamma-hydroxybutyrate, overview
-
-
?
ATP + cAMP-responsive element-binding protein
ADP + phosphorylated cAMP-responsive element-binding protein
show the reaction diagram
-
-
-
-
?
ATP + carboxyl-terminal binding protein 1
ADP + phosphorylated carboxyl-terminal binding protein 1
show the reaction diagram
-
-
-
-
?
ATP + casein
ADP + phosphorylated casein
show the reaction diagram
Komagataella pastoris, Komagataella pastoris JC100
-
enzyme activity is preferably activated by cAMP, 25% lower activity with cGMP
-
-
?
ATP + catchin
ADP + phosphorylated catchin
show the reaction diagram
-
low activity
-
-
?
ATP + Cav1.2
ADP + phosphorylated Cav1.2
show the reaction diagram
-
in anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons plays a critical role involving phosphorylation by the enzyme, PKA increases the activity of the L-type Ca2+ channel Cav1.2 in response to beta-adrenergic stimulation in heart and brain, an L-type calcium channel Cav1.2
-
-
?
ATP + Cav3.2 T-type Ca2+ channel
ADP + phosphorylated Cav3.2 T-type Ca2+ channel
show the reaction diagram
-
recombinant human Ca2+ channel reconstituted in frog oocytes, overview
-
-
?
ATP + cellular nucleic acid binding protein
ADP + phosphorylated cellular nucleic acid binding protein
show the reaction diagram
-
CNBP performs a fine tune expression regulation of a group of target including c-myc, during vertebrate embryogenesis, different phosphorylation patterns at different development al stages, overview, i.e. CNBP, a zinc finger protein, phosphorylation at multiple sites, putative phosphorylation sites are residues Ser4, Thr56, Ser70, and Ser158, substrate is recombinant GST- or His6-tagged CNBP
-
-
?
ATP + ChChd3
ADP + phosphorylated ChChd3
show the reaction diagram
-
an endogenous mitochondrial protein
-
-
?
ATP + class III phosphatidylinositol 3-phosphate kinase
ADP + phosphorylated class III phosphatidylinositol 3-phosphate kinase
show the reaction diagram
-
-
-
-
?
ATP + claudin-3
ADP + phosphorylated claudin-3
show the reaction diagram
-
high activity in ovarian cancer cells with recombinantly overexpressed claudin-3, phosphorylation of claudin-3 affecting the barrier function with extracellular Ca2+, overview, recombinant GST-fusion claudin-3 expressed in Escherichia coli, phosphorylation at Thr192, activity of catalytic PKA subunit
-
-
?
ATP + claudin-3 S199A
ADP + phosphorylated claudin-3 S199A
show the reaction diagram
-
recombinant GST-fusion claudin-3 mutant S199A expressed in Escherichia coli, phosphorylation at Thr192, activity of catalytic PKA subunit is lower compared to wild-type claudin-3
-
-
?
ATP + CRE-binding protein
ADP + CRE-binding phosphoprotein
show the reaction diagram
-
i.e. CREB, a transcription factor, activition by type I PKA
-
-
?
ATP + creatine kinase
ADP + phosphorylated creatine kinase
show the reaction diagram
-
-, sperm protein substrate
-
-
?
ATP + CREB protein
ADP + CREB phosphoprotein
show the reaction diagram
-
-
-
-
?
ATP + CREB protein
ADP + CREB phosphoprotein
show the reaction diagram
-
in brain synapses
-
-
?
ATP + CREB-binding protein
ADP + CREB-binding phosphoprotein
show the reaction diagram
-
i.e. CBP, activition by type II PKA
-
-
?
ATP + DNA excision repair protein
ADP + phosphorylated DNA excision repair protein
show the reaction diagram
-
-
-
-
?
ATP + Dot6
ADP + phosphorylated Dot6
show the reaction diagram
-
a protein implicated in telomere function, a protein implicated in telomere function, substrate of Tpk1
-
-
?
ATP + EPS8 protein
ADP + EPS8 phosphoprotein
show the reaction diagram
-
-, sperm protein substrate
-
-
?
ATP + extracellular signal-regulated kinase
ADP + phosphorylated extracellular signal-regulated kinase
show the reaction diagram
-
-
-
-
?
ATP + ezrin
ADP + phosphoezrin
show the reaction diagram
-
recombinant GST-tagged wild-type ezrin transiently expressed in primary gastric parietal cells from stomach, recombinant mutant S66A and S66D ezrin proteins are no substrates, phosphorylation of ezrin leads to activation of parietal cells required for dilation of apical vacuolar membrane and histamine-stimulated acid secretion in gastric mucosa, overview, phosphorylation at Ser66, catalytic subunit of PKA
-
-
?
ATP + fat body triglyceride lipase
ADP + phosphorylated fat body triglyceride lipase
show the reaction diagram
-
protein substrate is phosphorylated at Ser563, but not activated by the enzyme, Ser563 is the regulatory site of the enzyme substrate
-
-
?
ATP + G protein-coupled receptor GRK1
ADP + phosphorylated G protein-coupled receptor GRK1
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor GRK1
ADP + phosphorylated G protein-coupled receptor GRK1
show the reaction diagram
-
recombinant FLAG-tagged GRK1 expressed in HEK-293 cells, enzymatic inactivation of the receptor activity inhibiting rhodopsin phosphorylation, phosphorylation at Ser21, enzymatic inactivation of the receptor activity inhibiting rhodopsin phosphorylation, no activity with GRK1 mutant S21A
-
-
?
ATP + G protein-coupled receptor GRK1
ADP + phosphorylated G protein-coupled receptor GRK1
show the reaction diagram
-
recombinant FLAG-tagged GRK1, phosphorylation at Ser21
-
-
?
ATP + G protein-coupled receptor GRK7
ADP + phosphorylated G protein-coupled receptor GRK7
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor GRK7
ADP + phosphorylated G protein-coupled receptor GRK7
show the reaction diagram
-
recombinant FLAG-tagged GRK1 expressed in HEK-293 cells, enzymatic inactivation of the receptor activity inhibiting rhodopsin phosphorylation, phosphorylation at Ser23 and Ser36, enzymatic inactivation of the receptor activity inhibiting rhodopsin phosphorylation, no activity with GRK1 mutants S23A/S36A and S23E/S36E
-
-
?
ATP + G protein-coupled receptor GRK7
ADP + phosphorylated G protein-coupled receptor GRK7
show the reaction diagram
-
recombinant FLAG-tagged GRK7, phosphorylation at Ser23 and Ser36
-
-
?
ATP + glycogen synthase kinase 3beta
ADP + phosphorylated glycogen synthase kinase 3beta
show the reaction diagram
-
phosphorylation of glycogen synthase kinase 3beta is carried out by the PKA type II isoform
-
-
?
ATP + hemagglutin-tagged PKI peptide
ADP + phosphorylated hemagglutin-tagged PKI peptide
show the reaction diagram
-
-
-
-
?
ATP + hexokinase
ADP + phosphorylated hexokinase
show the reaction diagram
-
-
-
-
?
ATP + histone
ADP + phosphorylated histone
show the reaction diagram
-
-
-
-
?
ATP + histone
ADP + phosphorylated histone
show the reaction diagram
-
-
-
-
?
ATP + histone 3s
ADP + phosphorylated histone 3s
show the reaction diagram
-
activity of the catalytic subunit Cgamma
-
-
?
ATP + histone deacetylase 8
ADP + phosphorylated histone deacetylase 8
show the reaction diagram
-
FLAG-tagged class 1 histone deacetylase HDAC8 expressed in HeLa cells via adenovirus infection, phosphorylation at Ser39 reduces the enzyme activity of HDAC8, hyperphosphorylation inhibits the enzyme, class 1 histone deacetylase HDAC8, recombinantly expressed FLAG-tagged GST-fusion substrate protein, Ser39 is the major phosphorylation site, low activity with HDAC8 mutant S39A
-
-
?
ATP + histone H2A
ADP + phosphorylated histone H2A
show the reaction diagram
Komagataella pastoris, Komagataella pastoris JC100
-
enzyme activity is preferably activated by cAMP, 40% lower activity with cGMP
-
-
?
ATP + histone H3S
ADP + phosphorylated histone H3S
show the reaction diagram
Komagataella pastoris, Komagataella pastoris JC100
-
enzyme activity is preferably activated by cAMP, 60% lower activity with cGMP
-
-
?
ATP + histone IIIS
ADP + phosphorylated histone IIIS
show the reaction diagram
-
activity of the catalytic subunit Cgamma
-
-
?
ATP + inositol 1,4,5-trisphosphate receptor-I
ADP + phosphorylated inositol 1,4,5-trisphosphate receptor-I
show the reaction diagram
-
isolated catalytic subunit of PKA, selective phosphorylation at Ser1589 and Ser1755
-
-
?
ATP + IP3R-2
ADP + phosphorylated IP3R-2
show the reaction diagram
-
-, phosphoregulation of the inositol 1,4,5-trisphosphate receptor subtype 2, PKA enhances inositol 1,4,5-trisphosphate-induced Ca2+ release in AR4-2J cells, regulation, overview
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
-
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
-
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
-
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
-
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
-
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
-
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
activity of the catalytic subunit C
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
activity of the catalytic subunit Calpha
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
catalytic subunit C
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
enzyme activity is preferably activated by cAMP, 80% lower activity with cGMP
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
LRRASLG peptide substrate
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
LRRASLG peptide substrate, activity of the catalytic subunit C
-
-
?
ATP + Kemptide
ADP + Kemptide phosphate
show the reaction diagram
-
PKA-derived substrate, activity of the catalytic subunit Cgamma
-
-
?
ATP + kemptide
ADP + phospho-kemptide
show the reaction diagram
-
-
-
-
?
ATP + kemptide
ADP + phospho-kemptide
show the reaction diagram
-
-
-
-
?
ATP + kemptide
ADP + phospho-kemptide
show the reaction diagram
-
-
-
-
?
ATP + kemptide
ADP + phospho-kemptide
show the reaction diagram
-
-
-
-
?
ATP + Kemptide
ADP + phosphorylated Kemptide
show the reaction diagram
-
-
-
-
?
ATP + Kemptide
ADP + phosphorylated Kemptide
show the reaction diagram
-
-
-
-
?
ATP + Kemptide
ADP + phosphorylated Kemptide
show the reaction diagram
-
activity of catalytic PKA subunit
-
-
?
ATP + Kemptide
ADP + phosphorylated Kemptide
show the reaction diagram
-
activity of catalytic PKA subunit
-
-
?
ATP + Kemptide
ADP + phosphorylated Kemptide
show the reaction diagram
-
LRRASLG peptides substrate
LRRA-phosphoserine-LG
-
?
ATP + Kemptide
ADP + phosphorylated Kemptide
show the reaction diagram
-
peptide substrate, activity of catalytic PKA subunit
-
-
?
ATP + L-pyruvate kinase
ADP + phosphorylated L-pyruvate kinase
show the reaction diagram
-
recombinant rat protein substrate expressed in Escherichia coli, phosphorylation at Ser12, activity of catalytic PKA subunit
-
-
?
ATP + lactate dehydrogenase subunit A mRNA
ADP + 3'-UTR phosphorylated lactate dehydrogenase subunit A mRNA
show the reaction diagram
-
-, the enzyme stabilizes lactate dehydrogenase LDH-A mRNA and increases intracellular LDH-A mRNA levels by phosphorylation of a cAMP-stabilizing region CSR on the 3'-untranslated region of the LDH-A mRNA, regulation, mechanism
-
-
?
ATP + Leu-Arg-Arg-Ala-Ser-Leu-Gly
ADP + Leu-Arg-Arg-Ala-phospho-Ser-Leu-Gly
show the reaction diagram
-
commercial artificial heptapeptide substrate kemptide
-
-
?
ATP + Leu-Arg-Arg-Ala-Ser-Leu-Gly
ADP + Leu-Arg-Arg-Ala-phospho-Ser-Leu-Gly
show the reaction diagram
-
commercial artificial heptapeptide substrate kemptide
-
-
?
ATP + low-density lipoprotein-related protein
ADP + phosphorylated low-density lipoprotein-related protein
show the reaction diagram
-
-
-
-
?
ATP + LRRASLG
ADP + LRRA-phosphoserine-LG
show the reaction diagram
-
i.e. Kemptide
-
-
?
ATP + LRRASLG
ADP + LRRA-phosphoserine-LG
show the reaction diagram
-
i.e. Kemptide, recombinant PKA catalytic subunit
-
-
?
ATP + maltose binding protein
ADP + phosphorylated maltose binding protein
show the reaction diagram
-
enzyme activity is preferably activated by cAMP, 35% lower activity with cGMP
-
-
?
ATP + merlin
ADP + phosphorylated merlin
show the reaction diagram
-
recombinant human substrate protein expressed in HEK-293 cells, activity of the catalytic subunit C, phosphorylation at Ser518 induces N-terminal binding of merlin to ezrin, a membrane/cytoskeleton linker protein, activity of the catalytic subunit C, phosphorylation at the N- and the C-terminus, e.g. at Ser518
-
-
?
ATP + mitogen-activated protein kinase phosphatase-1
ADP + phosphorylated mitogen-activated protein kinase phosphatase-1
show the reaction diagram
-
the enzyme enhances steroid hydroxylase CYP17 transcription via mitogen-activated protein kinase phosphatase-1 MKP-1 activation in H295R adrenocortical cells, i.e. MKP-1
-
-
?
ATP + myocyte enhancer factor 2D
ADP + phosphorylated myocyte enhancer factor 2D
show the reaction diagram
-
myocyte enhancer factor 2D serine 121 and serine 190 are targeted by PKA
-
-
?
ATP + N-(8-([4-[3-(ethoxycarbonyl)-6,8,8-trimethyl-2-oxo-7,8-dihydro-2H-pyrano[3,2-g]quinolin-9(6H)-yl]butanoyl]amino)octanoyl)-GRTGRRFSYP-amide
ADP + N-(8-([4-[3-(ethoxycarbonyl)-6,8,8-trimethyl-2-oxo-7,8-dihydro-2H-pyrano[3,2-g]quinolin-9(6H)-yl]butanoyl]amino)octanoyl)-GRTGRRFpSYP-amide
show the reaction diagram
-
-
-
-
?
ATP + N-(8-([[7-(diethylamino)-2-oxo-2H-chromen-3-yl]carbonyl]amino)octanoyl)-GRTGRRFSYP-amide
ADP + N-(8-([[7-(diethylamino)-2-oxo-2H-chromen-3-yl]carbonyl]amino)octanoyl)-GRTGRRFpSYP-amide
show the reaction diagram
-
-
-
-
?
ATP + N-(8-[[(11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-10-yl)carbonyl]amino]octanoyl)-GRTGRRFSYP-amide
ADP + N-(8-[[(11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-10-yl)carbonyl]amino]octanoyl)-GRTGRRFpSYP-amide
show the reaction diagram
-
-
-
-
?
ATP + Nav1.4 T-type Na+ channel
ADP + phosphorylated Nav1.4 T-type Na+ channel
show the reaction diagram
-
recombinant rat Na+ channel reconstituted in frog oocytes, overview
-
-
?
ATP + NDUFS-4 protein
ADP + phosphorylated NDUFS-4 protein
show the reaction diagram
-
-
-
-
?
ATP + NDUFS4 subunit of complex I
ADP + phosphorylated NDUFS4 subunit of complex I
show the reaction diagram
-
complex I is the NADH-ubiquinone oxidoreductase, E.C 1.6.5.3
-
-
?
ATP + NF-kappaB p65
ADP + phoshorylated NF-kappaB p65
show the reaction diagram
-
phosphorylation by the catalytic subunit of PKA
-
-
?
ATP + p270 protein
ADP + phosphorylated p270 protein
show the reaction diagram
-
-
-
-
?
ATP + paramyosin
ADP + phosphorylated paramyosin
show the reaction diagram
-
low activity
-
-
?
ATP + PDE11A protein
ADP + PDE11A phosphoprotein
show the reaction diagram
-
-, sperm protein substrate
-
-
?
ATP + PDE5A protein
ADP + PDE5A phosphoprotein
show the reaction diagram
-
-, sperm protein substrate
-
-
?
ATP + phosphatase inhibitor PKI
ADP + phosphorylated phosphatase inhibitor PKI
show the reaction diagram
Q6ZXJ1
-
-
-
?
ATP + phosphatidylinositol 3-kinase
ADP + phosphorylated phosphatidylinositol 3-kinase
show the reaction diagram
-
-
-
-
?
ATP + phosphodiesterase-4
ADP + phosphorylated phosphodiesterase-4
show the reaction diagram
-
-
-
-
?
ATP + phosvitin
ADP + phosphorylated phosvitin
show the reaction diagram
-
enzyme activity is preferably activated by cAMP, 33% lower activity with cGMP
-
-
?
ATP + PKA regulatory subunit IIalpha
ADP + phosphorylated PKA regulatory subunit IIalpha
show the reaction diagram
-
-
-
-
?
ATP + PLARTLSVAGLPGKK
ADP + PLARTL-phosphoserine-VAGLPGKK
show the reaction diagram
-
syntide 2-derived peptide substrate
-
-
?
ATP + protamine sulfate
ADP + phosphoprotamine sulfate
show the reaction diagram
-
enzyme activity is about equally activated by cAMP and cGMP, and derivatives of cAMP
-
-
?
ATP + protein tyrosine phosphatase
ADP + phosphorylated protein tyrosine phosphatase
show the reaction diagram
-
i.e. PTP, contains a PEST motif
-
-
?
ATP + pyruvate kinase
ADP + phosphorylated pyruvate kinase
show the reaction diagram
-
enzyme activity is about equally activated by cAMP and cGMP
-
-
?
ATP + RFARKGSLREKNV
ADP + RFARKG-phosphoserine-LREKNV
show the reaction diagram
-
protein kinase C-derived peptide, activity of the catalytic subunit Calpha
-
-
?
ATP + RFARKGSLREKNV
ADP + RFARKG-phosphoserine-LREKNV
show the reaction diagram
-
protein kinase C-derived peptide, activity of the catalytic subunit Cgamma
-
-
?
ATP + RFARKGSLRQKNV
ADP + RFARKG-phosphoserine-LRQKNV
show the reaction diagram
-
PKC-derived peptide substrate
-
-
?
ATP + RGS protein
ADP + RGS protein phosphate
show the reaction diagram
-
recombinant HA-tagged substrate expressed in B35 cells, phosphorylation of RGS14 by PKA potentiates its activity toward Galphai-GDP, i.e. regulator of G protein signaling protein, recombinant His-tagged substrate R14-RSG residues 1-205 and 299-544, phosphorylation of wild-type R14-RSG at Ser258 and Thr494
-
-
?
ATP + ribosomal protein S6
ADP + phosphorylated ribosomal protein S6
show the reaction diagram
Komagataella pastoris, Komagataella pastoris JC100
-
substrate from purified Saccharomyces cerevisiae ribosomes, enzyme activity is preferably activated by cAMP, lower activity with cGMP
-
-
?
ATP + ribosomal S6 protein
ADP + phosphorylated ribosomal S6 protein
show the reaction diagram
-
-
-
-
?
ATP + RKRSRAE
ADP + RKR-phosphoserine-RAE
show the reaction diagram
-
cGPK-1-derived peptide, activity of the catalytic subunit Calpha
-
-
?
ATP + RKRSRAE
ADP + RKR-phosphoserine-RAE
show the reaction diagram
-
cGPK-1-derived peptide, activity of the catalytic subunit Cgamma
-
-
?
ATP + RKRSRKE
ADP + RKR-phosphoserine-RKE
show the reaction diagram
-
cGPK-2-derived peptide, activity of the catalytic subunit Calpha
-
-
?
ATP + RKRSRKE
ADP + RKR-phosphoserine-RKE
show the reaction diagram
-
cGPK-2-derived peptide, activity of the catalytic subunit Cgamma
-
-
?
ATP + RRASVA
ADP + RRA-phosphoserine-VA
show the reaction diagram
-
pyruvate kinase-derived peptide substrate comprising the phosphorylation site around Ser12 of the protein, activity of catalytic PKA subunit
-
-
?
ATP + RRLSSLRA
ADP + RRL-phosphoserine-phosphoserine-LRA
show the reaction diagram
-
S6 kinase-derived peptide, activity of the catalytic subunit Calpha
-
-
?
ATP + RRLSSLRA
ADP + RRL-phosphoserine-phosphoserine-LRA
show the reaction diagram
-
S6 kinase-derived peptide, activity of the catalytic subunit Cgamma
-
-
?
ATP + ryanodine receptor
ADP + phosphorylated ryanodine receptor
show the reaction diagram
-
-
-
-
?
ATP + small heat shock protein HSP22
ADP + phosphorylated small heat shock protein HSP22
show the reaction diagram
-
-
-
-
?
ATP + small heat shock-related protein HSP20
ADP + phosphorylated small heat shock-related protein HSP20
show the reaction diagram
-
-
-
-
?
ATP + SP20
ADP + SP20 phosphate
show the reaction diagram
-
substrate peptide, the C subunit SP20-binding residues are E203, F129, E170, E230, D166, and K168
-
-
?
ATP + SP20 peptide
ADP + phosphorylated SP20 peptide
show the reaction diagram
-
-
-
-
?
ATP + syntaphilin
ADP + syntaphilin phosphate
show the reaction diagram
-
-
-
-
?
ATP + tomosyn
ADP + tomosyn phosphate
show the reaction diagram
-
-
-
-
?
ATP + twitchin
ADP + phosphorylated twitchin
show the reaction diagram
-
-, a high molecular mass protein associated with thick filaments, high activity
-
-
?
ATP + type III inositol 1,4,5-trisphosphate receptor
ADP + phosphorylated type III inositol 1,4,5-trisphosphate receptor
show the reaction diagram
-
i.e. IP3 receptor, recombinantly expressed in HEK cells, forms tetrameric Ca2+ channels in the endoplasmic reticulum, phosphorylation sites are Ser916, Ser934, and Ser1832, Ser934 is the most susceptible site
-
-
?
ATP + tyrosine hydroxylase
ADP + phosphorylated tyrosine hydroxylase
show the reaction diagram
-
-, enzyme is involved in the signal transduction regulatory mechanism in the triiodothyronine T3-activation of forebrain tyrosine hydroxylase
-
-
?
ATP + tyrosine hydroxylase
ADP + phosphorylated tyrosine hydroxylase
show the reaction diagram
-
4 isoforms of the human enzyme as substrate, phosphorylation at Ser40 of the regulatory subunit of the substrate results in release of bound inhibiting catecholamines, e.g. dopamine and dihydroxyphenylalanine, from the tyrosine hydroxylase
-
-
?
ATP + tyrosine hydroxylase
ADP + phosphorylated tyrosine hydroxylase
show the reaction diagram
-
activity of catalytic PKA subunit
-
-
?
ATP + ubiquinol-cytochrome c reductase complex core protein 2
ADP + ubiquinol-cytochrome c reductase complex core phosphoprotein 2
show the reaction diagram
-
-, sperm protein substrate
-
-
?
ATP + VASP
ADP + phosphorylated VASP
show the reaction diagram
-
i.e. vasodilator-stimulated phosphoprotein
-
-
?
ATP + [cystic fibrosis transmembrane conductance regulator protein]
ADP + [cystic fibrosis transmembrane conductance regulator phosphoprotein]
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
-
abnormal hyperphosphorylation of tau by PKA is associated with Alzheimer's disease and other tauopathies leading to neuronal degeneration, phosphorylation by PKA at Ser214, PKA catalyzes the reaction of EC 2.7.11.26 in brain
-
-
?
N6-benzyl-ATP + ChChd3
N6-benzyl-ADP + phosphorylated ChChd3
show the reaction diagram
-
cofactor of mutant M120G, poor activity with the wild-type catalytic subunit
-
-
?
N6-phenethyl-ATP + ChChd3
N6-phenethyl-ADP + phosphorylated ChChd3
show the reaction diagram
-
cofactor of mutant M120G, poor activity with the wild-type catalytic subunit
-
-
?
ATP + [Whi3 cell cycle regulator protein]
ADP + [Whi3 cell cycle regulator phosphoprotein]
show the reaction diagram
-
phosphorylation of Ser568 leads to inhibition of Whi3, phosphorylation of Ser568
-
-
?
additional information
?
-
-
substrate specificity, overview
-
-
-
additional information
?
-
P34099
enzyme plays an essential role during differentiation and fruit morphogenesis in Dictyostelium discoideum
-
-
-
additional information
?
-
P17612
the enzyme plays a central role in the control of mammalian sperm capacitation and motility
-
-
-
additional information
?
-
-
activated PKA catalytic subunit C with cAMP or 8-bromo-cAMP, stimulated by beta1-adrenoreceptor activity, inhibits store-operated channel current activity in vascular tissue
-
-
-
additional information
?
-
-
cAMP concentration and PKA activity are increased and important in exocytotic acrosome reaction taking place in fertilization when sperm contacts the egg jelly layer EJ, EJ component fucose sulfate polymer triggers sperm PKA activation
-
-
-
additional information
?
-
-
cAMP-dependent activation of BKCa channels in pulmonary arterial smooth muscle is not catalyzed by PKA but by cGMP-dependent protein kinase PKG, thus PKA is not involved in cAMP-induced signaling in pulmonary vasodilation
-
-
-
additional information
?
-
-
enzyme regulation, overview
-
-
-
additional information
?
-
-
induced by the pituitary follicle-stimulating hormone FSH PKA also catalyzes the dephosphorylation of residues T421 and S424 of the autoinhibitory domain of p70S6K, resulting in activation of p70S6K important for differentiation of Sertoli cells in male reproduction, regulation overview
-
-
-
additional information
?
-
-
inositol 1,4,5-trisphosphate receptor-I is no substrate of PKA in vivo
-
-
-
additional information
?
-
-
merlin acts as an PKA-anchoring protein being linked to the cAMP/PKA signaling pathway
-
-
-
additional information
?
-
-
no activity with claudin-4
-
-
-
additional information
?
-
-
oestrogen-dependent increase in cAMP increases Ca2+-dependent exocytosis through protein kinase A-dependent pathway and through alternative cAMP-guanine nucleotide exchange factor GEF/Epac-dependent pathway in secretory cells
-
-
-
additional information
?
-
-
PKA regulatory and catalytic subunits are bound in the CSR complex including the protein kinase A anchoring protein AKAP 95 and several CSR-binding proteins, the complex acts in stabilizing the LDH-A mRNA, overview
-
-
-
additional information
?
-
-
PKA type I regulates ethanol-induced cAMP response element-mediated gene expression via activation of CREB-binding protein and inhibition of MAPK, regulation overview
-
-
-
additional information
?
-
-
PKA works coordinatedly with GSK3beta, EC 2.7.11.1, on tau phosphorylation
-
-
-
additional information
?
-
-
regulation of GRK1 and GRK7 by cAMP level during light and dark phases
-
-
-
additional information
?
-
-
tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain, inhibition of tau hyperphosphorylation inhibits an associated loss in spatial memory
-
-
-
additional information
?
-
-
the enzyme activates NS1619-induced flavoprotein oxidation modulating mitochondrial Ca2+-activated K+ channels, mechanism of the cardioprotective effect and modulation by PKA, overview
-
-
-
additional information
?
-
-
the enzyme interacts with the neuron cortex membrane protein gravin via Ca2+-independent binding to the regulatory RII enzyme subunit, gravin provides a platform to localize kinases, besides PKA also PKCalpha and PKCbetaII, in an isozyme-specific and activation-dependent manner at specific sites in neurons, gravin is strongly upregulated in cells during differentiation, overview
-
-
-
additional information
?
-
-
the enzyme is not required for adenosine-induced dilation of intracerebral arterioles and regulation of cerebral blood flow
-
-
-
additional information
?
-
-
the enzyme plays a central role in the adipokinetic signaling controling the mobilization of stored lipids in the fat body
-
-
-
additional information
?
-
-
the enzyme plays a paradoxical role in cell motility facilitating and inhibiting actin cytoskeletal dynamics and cell migration, overview, the enzyme is regulated in a subcellular space during cell migration, regulatory subunits RII are enriched in protrusive cellular structures and pseudopodia formed during chemotaxis, anchoring of PKA inhibits pseudopod formation and cell migration, regulation of the process overview
-
-
-
additional information
?
-
-
the enzyme regulates the G2/M transition in oocytes of Xenopus laevis, it also blocks progesterone-induced germinal vesicle envelope breakdown GVBD, Cdc-25-dependent dephosphorylation of Tyr15 in Cdc2, and synthesis of MEKK Mos
-
-
-
additional information
?
-
-
cAMP binds to the helical subunit C binding regions relayed by the highly dynamic switch of the C-helix of subunit RIalpha, which is linked to cAMP by a salt bridge essential for activation
-
-
-
additional information
?
-
-
no activity with claudin-4, poor activity with claudin-3 mutant T192A
-
-
-
additional information
?
-
-
PKA catalyzes tau phosphorylation in brain, but phosphorylation of other proteins, EC 2.7.11.11, in different tissues
-
-
-
additional information
?
-
-
poor activity on free amino acids, consensus sequence of PKA is R-RXS/T hyd
-
-
-
additional information
?
-
-
potential substrate identification by an evolutionary proteomics approach, overview
-
-
-
additional information
?
-
-
recognition motif and phosphorylation sequences, substrate binding structure, peptide binding in an extended conformation, N-terminal and C-terminal extensions bind pseudosubstrates
-
-
-
additional information
?
-
-
sperm protein substrate identification using peptide analysis via tandem mass spectrometry
-
-
-
additional information
?
-
-
substrate specificity profile utilizing L-pyruvate kinase mutants and pyruvate kinase-derived peptide substrate mutants, mutated to different amino acids at positions 9,10, and 13, as protein substrates, overview
-
-
-
additional information
?
-
-
substrate specificity, no activity with peptides derived from Thr-kinase or Tyr-kinase, overview
-
-
-
additional information
?
-
-
substrates have differential effects on type I and type II PKA holoenzyme dissociation, the isolated catalytic subunit is catalytically active
-
-
-
additional information
?
-
-
the enzyme autophosphorylates at Ser10, Thr197, and Ser338 of PKA Calpha, substrate-induced conformational changes
-
-
-
additional information
?
-
-
the enzyme performs autophosphorylation at K72, S338, and T197
-
-
-
additional information
?
-
-
the enzyme performs autophosphorylation at Ser10, Ser139, Thr197, and Ser338
-
-
-
additional information
?
-
-
the enzyme performs autophosphorylation, substrate specificity depends on activating agents cAMP or cGMP, overview
-
-
-
additional information
?
-
-
cystic fibrosis results from mutations in the cystic fibrosis conductance regulator protein, CFTR, a cAMP/protein kinase A, PKA, and ATP-regulated Cl- channel, the formation of the cAMP/protein kinase A-dependent annexin 2 S100A10 complex with cystic fibrosis conductance regulator protein, CFTR, regulates CFTR channel function, overview, PKA regulates anx 2 and S100A10 cellular distribution in HNE cells, modulation of PKA activity alters localization and distribution of anx 2S100A10 in HNE cells, overview
-
-
-
additional information
?
-
-
inhibition of caspase-dependent spontaneous apoptosis via a cAMP-protein kinase A dependent pathway in neutrophils from sickle cell disease patients, overview
-
-
-
additional information
?
-
-
PKA plays a crucial role in the release of the catch state of molluskan muscles, mechanism, overview
-
-
-
additional information
?
-
-
redox regulation of cAMP-dependent protein kinase signaling: kinase versus phosphatase inactivation, in HeLa cells PKA activity follows a biphasic response to thiol oxidation, overview
-
-
-
additional information
?
-
-
the enzyme is involved in cyclic nucleotide signaling, overview, individually phosphorylated PKA-R isozymes are differentially targeted to distinct cellular compartments by AKAP-isozymes, providing a multifaceted platform for the kinase
-
-
-
additional information
?
-
-
the enzyme plays a central role in regulation of diverse aspects of cellular activity, especially in the controlling of maturation of spermatids
-
-
-
additional information
?
-
-
no activity with myosin heavy chain and tropomyosin
-
-
-
additional information
?
-
-
phosphorylated residue pThr197 not only facilitates the phosphoryl transfer reaction by stabilizing the transition state through electrostatic interactions but also strongly affects its essential protein dynamics as well as the active site conformation, overview, free energy difference is,1.4 kcal/mol, it is necessary that Asp166 is available as the catalytic base to accept the hydroxyl proton in the late stages of the phosphoryl transfer
-
-
-
additional information
?
-
-
the catalytic subunit has a cluster of nonconserved acidic residues, Glu127, Glu170, Glu203, Glu230, and Asp241, that are crucial for substrate recognition and binding
-
-
-
additional information
?
-
-
the localization of the structural region of the reconstituted channel protein substrates contribute to PKA-mediated stimulation
-
-
-
additional information
?
-
-
the regulatory subunit of PKA inhibits its kinase activity by shielding the catalytic subunit from physiological substrates, Asp170 not only plays a pivotal role in controlling the local conformation of the phosphate binding cassette, where cAMP docks, but also significantly affects the long-range cAMP-dependent interaction network that extends from the phosphate binding cassette to the three major sites of C-recognition
-
-
-
additional information
?
-
-
cAMP elevation in the Schwann cell is sufficient to induce E-cadherin expression accompanied by suppression of N-cadherin expression
-
-
-
additional information
?
-
-
cAMP-dependent neurite outgrowth is mediated by PKA
-
-
-
additional information
?
-
-
cAMP-dependent PKA induces type I tumor necrosis factor receptor exosome-like vesicle release via anchoring of PKA regulatory subunit RIIbeta to A kinase-anchoring protein domains B and C of the guanine nucleotide exchange protein BIG2
-
-
-
additional information
?
-
-
elevated PKA activity results in activation of stress-associated proteins and of enzymes involved in protein biosynthesis and glucose catabolism, in contrast, proteins which are involved in nucleotide and amino acid biosynthesis are downregulated
-
-
-
additional information
?
-
-
exchange protein activated by cAMP acts synergistically with PKA in cAMP-mediated mitogenesis
-
-
-
additional information
?
-
-
signaling by cAMP-dependent protein kinase plays an important role in the regulation of mammalian sperm motility
-
-
-
additional information
?
-
-
autophosphorylation of the PKA type II regulatory subunit (RII) can alter its affinity for protein kinase A-anchoring proteins and the catalytic subunit of PKA, RII phosphorylation regulates PKA-dependent substrate phosphorylation and may have significant implications for modulation of cardiac function
-
-
-
additional information
?
-
-
complex I subunit ESSS is not phosphorylated by PKA
-
-
-
additional information
?
-
-
Ets2 is not a substrate for PKA
-
-
-
additional information
?
-
-
localized PKA activity is required for fusion of mononucleated myoblasts and plays a pivotal role in the early steps of myogenic cell fusion
-
-
-
additional information
?
-
-
the activation of protein kinase A is required for TIP39-mediated nociception
-
-
-
additional information
?
-
Q7K6A0, Q7KQK0
the PKA catalytic subunit a serine/threonine kinase, that can phosphorylate many substrates, such as additional protein kinases and transcription factors
-
-
-
additional information
?
-
-
development of kinase activity sensor fluorogenic substrates, upon phosphorylation the peptide interacts with a phosphoserine-binding protein 14-3-3 domain, displacing the quencher, and resulting in a burst of fluorescence, overview
-
-
-
additional information
?
-
Mus musculus FVB/N
-
the enzyme is involved in cyclic nucleotide signaling, overview, individually phosphorylated PKA-R isozymes are differentially targeted to distinct cellular compartments by AKAP-isozymes, providing a multifaceted platform for the kinase
-
-
-
additional information
?
-
Saccharomyces cerevisiae Y258
-
potential substrate identification by an evolutionary proteomics approach, overview
-
-
-
additional information
?
-
Komagataella pastoris JC100
-
the enzyme performs autophosphorylation, substrate specificity depends on activating agents cAMP or cGMP, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
regulation by reversible phosphorylation, overview
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
regulation of the enzyme involves reversible phosphorylation at the activation loop, and associative or dissociative mechanisms
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
the enzyme is a key player in cellular responses to the second messenger cAMP
-
-
?
ATP + A-kinase anchor protein
ADP + phosphorylated A-kinase anchor protein
show the reaction diagram
-
phosphorylation at Ser1928
-
-
?
ATP + actin
ADP + phosphorylated actin
show the reaction diagram
-
low activity
-
-
?
ATP + actin
ADP + phosphorylated actin
show the reaction diagram
-
sperm protein substrate
-
-
?
ATP + adenylate kinase 1
ADP + phosphorylated adenylate kinase 1
show the reaction diagram
-
sperm protein substrate
-
-
?
ATP + adenylate kinase 5
ADP + phosphorylated adenylate kinase 5
show the reaction diagram
-
sperm protein substrate
-
-
?
ATP + autophagy-related protein kinase Atg1
ADP + phosphorylated autophagy-related protein kinase Atg1
show the reaction diagram
Saccharomyces cerevisiae, Saccharomyces cerevisiae Y258
-
initiating the degradative pathway, PKA regulates the association of Atg1 with the preautophagosomal structure PAS, overview
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
PKA phosphorylation mediates beta-1 adrenergic receptor endocytosis via the caveolae pathway
-
-
?
ATP + beta-catenin
ADP + phosphorylated beta-cateniin
show the reaction diagram
-
-
-
-
?
ATP + beta1-adrenergic receptor
ADP + phosphorylated beta1-adrenergic receptor
show the reaction diagram
-
recombinant beta1-adrenergic receptor expressed in HEK-293 cell membranes, phosphorylation at Ser312 is essential for activation of endocytic recycling of the agonist-internalized beta1-adrenergic receptor, beta1-AR mutant S312A is not recycled, overview
-
-
?
ATP + BKCa channel ZERO
ADP + phosphorylated BKCa channel ZERO
show the reaction diagram
-
recombinant murine HA-tagged tetrameric protein expressed in HEK-293 cells, activity with wild-type and mutant Y334V channel tetramers, but no activity with S899A mutant, phosphorylation at Ser899 activates the channels, overview
-
-
?
ATP + cAMP-responsive element binding protein
ADP + phosphorylated cAMP-responsive element binding protein
show the reaction diagram
-
the enzyme as well as GABAB receptors are involved in induction of cAMP-responsive element binding protein phosphorylation in hippocampus by gamma-hydroxybutyrate, overview
-
-
?
ATP + catchin
ADP + phosphorylated catchin
show the reaction diagram
-
low activity
-
-
?
ATP + Cav1.2
ADP + phosphorylated Cav1.2
show the reaction diagram
-
in anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons plays a critical role involving phosphorylation by the enzyme, PKA increases the activity of the L-type Ca2+ channel Cav1.2 in response to beta-adrenergic stimulation in heart and brain
-
-
?
ATP + cellular nucleic acid binding protein
ADP + phosphorylated cellular nucleic acid binding protein
show the reaction diagram
-
CNBP performs a fine tune expression regulation of a group of target including c-myc, during vertebrate embryogenesis, different phosphorylation patterns at different development al stages, overview
-
-
?
ATP + claudin-3
ADP + phosphorylated claudin-3
show the reaction diagram
-
high activity in ovarian cancer cells with recombinantly overexpressed claudin-3, phosphorylation of claudin-3 affecting the barrier function with extracellular Ca2+, overview
-
-
?
ATP + CRE-binding protein
ADP + CRE-binding phosphoprotein
show the reaction diagram
-
i.e. CREB, a transcription factor, activition by type I PKA
-
-
?
ATP + creatine kinase
ADP + phosphorylated creatine kinase
show the reaction diagram
-
sperm protein substrate
-
-
?
ATP + CREB protein
ADP + CREB phosphoprotein
show the reaction diagram
-
-
-
-
?
ATP + CREB protein
ADP + CREB phosphoprotein
show the reaction diagram
-
in brain synapses
-
-
?
ATP + CREB-binding protein
ADP + CREB-binding phosphoprotein
show the reaction diagram
-
i.e. CBP, activition by type II PKA
-
-
?
ATP + Dot6
ADP + phosphorylated Dot6
show the reaction diagram
-
a protein implicated in telomere function
-
-
?
ATP + EPS8 protein
ADP + EPS8 phosphoprotein
show the reaction diagram
-
sperm protein substrate
-
-
?
ATP + ezrin
ADP + phosphoezrin
show the reaction diagram
-
recombinant GST-tagged wild-type ezrin transiently expressed in primary gastric parietal cells from stomach, recombinant mutant S66A and S66D ezrin proteins are no substrates, phosphorylation of ezrin leads to activation of parietal cells required for dilation of apical vacuolar membrane and histamine-stimulated acid secretion in gastric mucosa, overview
-
-
?
ATP + G protein-coupled receptor GRK1
ADP + phosphorylated G protein-coupled receptor GRK1
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor GRK1
ADP + phosphorylated G protein-coupled receptor GRK1
show the reaction diagram
-
recombinant FLAG-tagged GRK1 expressed in HEK-293 cells, enzymatic inactivation of the receptor activity inhibiting rhodopsin phosphorylation
-
-
?
ATP + G protein-coupled receptor GRK7
ADP + phosphorylated G protein-coupled receptor GRK7
show the reaction diagram
-
-
-
-
?
ATP + G protein-coupled receptor GRK7
ADP + phosphorylated G protein-coupled receptor GRK7
show the reaction diagram
-
recombinant FLAG-tagged GRK1 expressed in HEK-293 cells, enzymatic inactivation of the receptor activity inhibiting rhodopsin phosphorylation
-
-
?
ATP + histone deacetylase 8
ADP + phosphorylated histone deacetylase 8
show the reaction diagram
-
FLAG-tagged class 1 histone deacetylase HDAC8 expressed in HeLa cells via adenovirus infection, phosphorylation at Ser39 reduces the enzyme activity of HDAC8, hyperphosphorylation inhibits the enzyme
-
-
?
ATP + IP3R-2
ADP + phosphorylated IP3R-2
show the reaction diagram
-
phosphoregulation of the inositol 1,4,5-trisphosphate receptor subtype 2, PKA enhances inositol 1,4,5-trisphosphate-induced Ca2+ release in AR4-2J cells, regulation, overview
-
-
?
ATP + lactate dehydrogenase subunit A mRNA
ADP + 3'-UTR phosphorylated lactate dehydrogenase subunit A mRNA
show the reaction diagram
-
the enzyme stabilizes lactate dehydrogenase LDH-A mRNA and increases intracellular LDH-A mRNA levels by phosphorylation of a cAMP-stabilizing region CSR on the 3'-untranslated region of the LDH-A mRNA, regulation, mechanism
-
-
?
ATP + merlin
ADP + phosphorylated merlin
show the reaction diagram
-
recombinant human substrate protein expressed in HEK-293 cells, activity of the catalytic subunit C, phosphorylation at Ser518 induces N-terminal binding of merlin to ezrin
-
-
?
ATP + mitogen-activated protein kinase phosphatase-1
ADP + phosphorylated mitogen-activated protein kinase phosphatase-1
show the reaction diagram
-
the enzyme enhances steroid hydroxylase CYP17 transcription via mitogen-activated protein kinase phosphatase-1 MKP-1 activation in H295R adrenocortical cells
-
-
?
ATP + NDUFS4 subunit of complex I
ADP + phosphorylated NDUFS4 subunit of complex I
show the reaction diagram
-
complex I is the NADH-ubiquinone oxidoreductase, E.C 1.6.5.3
-
-
?
ATP + paramyosin
ADP + phosphorylated paramyosin
show the reaction diagram
-
low activity
-
-
?
ATP + PDE11A protein
ADP + PDE11A phosphoprotein
show the reaction diagram
-
sperm protein substrate
-
-
?
ATP + PDE5A protein
ADP + PDE5A phosphoprotein
show the reaction diagram
-
sperm protein substrate
-
-
?
ATP + RGS protein
ADP + RGS protein phosphate
show the reaction diagram
-
recombinant HA-tagged substrate expressed in B35 cells, phosphorylation of RGS14 by PKA potentiates its activity toward Galphai-GDP
-
-
?
ATP + ribosomal S6 protein
ADP + phosphorylated ribosomal S6 protein
show the reaction diagram
-
-
-
-
?
ATP + twitchin
ADP + phosphorylated twitchin
show the reaction diagram
-
-
-
-
?
ATP + type III inositol 1,4,5-trisphosphate receptor
ADP + phosphorylated type III inositol 1,4,5-trisphosphate receptor
show the reaction diagram
-
i.e. IP3 receptor, recombinantly expressed in HEK cells, forms tetrameric Ca2+ channels in the endoplasmic reticulum
-
-
?
ATP + tyrosine hydroxylase
ADP + phosphorylated tyrosine hydroxylase
show the reaction diagram
-
enzyme is involved in the signal transduction regulatory mechanism in the triiodothyronine T3-activation of forebrain tyrosine hydroxylase
-
-
?
ATP + ubiquinol-cytochrome c reductase complex core protein 2
ADP + ubiquinol-cytochrome c reductase complex core phosphoprotein 2
show the reaction diagram
-
sperm protein substrate
-
-
?
ATP + [cystic fibrosis transmembrane conductance regulator protein]
ADP + [cystic fibrosis transmembrane conductance regulator phosphoprotein]
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
-
abnormal hyperphosphorylation of tau by PKA is associated with Alzheimer's disease and other tauopathies leading to neuronal degeneration
-
-
?
ATP + [Whi3 cell cycle regulator protein]
ADP + [Whi3 cell cycle regulator phosphoprotein]
show the reaction diagram
-
phosphorylation of Ser568 leads to inhibition of Whi3
-
-
?
additional information
?
-
P34099
enzyme plays an essential role during differentiation and fruit morphogenesis in Dictyostelium discoideum
-
-
-
additional information
?
-
P17612
the enzyme plays a central role in the control of mammalian sperm capacitation and motility
-
-
-
additional information
?
-
-
activated PKA catalytic subunit C with cAMP or 8-bromo-cAMP, stimulated by beta1-adrenoreceptor activity, inhibits store-operated channel current activity in vascular tissue
-
-
-
additional information
?
-
-
cAMP concentration and PKA activity are increased and important in exocytotic acrosome reaction taking place in fertilization when sperm contacts the egg jelly layer EJ, EJ component fucose sulfate polymer triggers sperm PKA activation
-
-
-
additional information
?
-
-
cAMP-dependent activation of BKCa channels in pulmonary arterial smooth muscle is not catalyzed by PKA but by cGMP-dependent protein kinase PKG, thus PKA is not involved in cAMP-induced signaling in pulmonary vasodilation
-
-
-
additional information
?
-
-
enzyme regulation, overview
-
-
-
additional information
?
-
-
induced by the pituitary follicle-stimulating hormone FSH PKA also catalyzes the dephosphorylation of residues T421 and S424 of the autoinhibitory domain of p70S6K, resulting in activation of p70S6K important for differentiation of Sertoli cells in male reproduction, regulation overview
-
-
-
additional information
?
-
-
inositol 1,4,5-trisphosphate receptor-I is no substrate of PKA in vivo
-
-
-
additional information
?
-
-
merlin acts as an PKA-anchoring protein being linked to the cAMP/PKA signaling pathway
-
-
-
additional information
?
-
-
no activity with claudin-4
-
-
-
additional information
?
-
-
oestrogen-dependent increase in cAMP increases Ca2+-dependent exocytosis through protein kinase A-dependent pathway and through alternative cAMP-guanine nucleotide exchange factor GEF/Epac-dependent pathway in secretory cells
-
-
-
additional information
?
-
-
PKA regulatory and catalytic subunits are bound in the CSR complex including the protein kinase A anchoring protein AKAP 95 and several CSR-binding proteins, the complex acts in stabilizing the LDH-A mRNA, overview
-
-
-
additional information
?
-
-
PKA type I regulates ethanol-induced cAMP response element-mediated gene expression via activation of CREB-binding protein and inhibition of MAPK, regulation overview
-
-
-
additional information
?
-
-
PKA works coordinatedly with GSK3beta, EC 2.7.11.1, on tau phosphorylation
-
-
-
additional information
?
-
-
regulation of GRK1 and GRK7 by cAMP level during light and dark phases
-
-
-
additional information
?
-
-
tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain, inhibition of tau hyperphosphorylation inhibits an associated loss in spatial memory
-
-
-
additional information
?
-
-
the enzyme activates NS1619-induced flavoprotein oxidation modulating mitochondrial Ca2+-activated K+ channels, mechanism of the cardioprotective effect and modulation by PKA, overview
-
-
-
additional information
?
-
-
the enzyme interacts with the neuron cortex membrane protein gravin via Ca2+-independent binding to the regulatory RII enzyme subunit, gravin provides a platform to localize kinases, besides PKA also PKCalpha and PKCbetaII, in an isozyme-specific and activation-dependent manner at specific sites in neurons, gravin is strongly upregulated in cells during differentiation, overview
-
-
-
additional information
?
-
-
the enzyme is not required for adenosine-induced dilation of intracerebral arterioles and regulation of cerebral blood flow
-
-
-
additional information
?
-
-
the enzyme plays a central role in the adipokinetic signaling controling the mobilization of stored lipids in the fat body
-
-
-
additional information
?
-
-
the enzyme plays a paradoxical role in cell motility facilitating and inhibiting actin cytoskeletal dynamics and cell migration, overview, the enzyme is regulated in a subcellular space during cell migration, regulatory subunits RII are enriched in protrusive cellular structures and pseudopodia formed during chemotaxis, anchoring of PKA inhibits pseudopod formation and cell migration, regulation of the process overview
-
-
-
additional information
?
-
-
the enzyme regulates the G2/M transition in oocytes of Xenopus laevis, it also blocks progesterone-induced germinal vesicle envelope breakdown GVBD, Cdc-25-dependent dephosphorylation of Tyr15 in Cdc2, and synthesis of MEKK Mos
-
-
-
additional information
?
-
-
cystic fibrosis results from mutations in the cystic fibrosis conductance regulator protein, CFTR, a cAMP/protein kinase A, PKA, and ATP-regulated Cl- channel, the formation of the cAMP/protein kinase A-dependent annexin 2 S100A10 complex with cystic fibrosis conductance regulator protein, CFTR, regulates CFTR channel function, overview, PKA regulates anx 2 and S100A10 cellular distribution in HNE cells, modulation of PKA activity alters localization and distribution of anx 2S100A10 in HNE cells, overview
-
-
-
additional information
?
-
-
inhibition of caspase-dependent spontaneous apoptosis via a cAMP-protein kinase A dependent pathway in neutrophils from sickle cell disease patients, overview
-
-
-
additional information
?
-
-
PKA plays a crucial role in the release of the catch state of molluskan muscles, mechanism, overview
-
-
-
additional information
?
-
-
redox regulation of cAMP-dependent protein kinase signaling: kinase versus phosphatase inactivation, in HeLa cells PKA activity follows a biphasic response to thiol oxidation, overview
-
-
-
additional information
?
-
-
the enzyme is involved in cyclic nucleotide signaling, overview, individually phosphorylated PKA-R isozymes are differentially targeted to distinct cellular compartments by AKAP-isozymes, providing a multifaceted platform for the kinase
-
-
-
additional information
?
-
-
the enzyme plays a central role in regulation of diverse aspects of cellular activity, especially in the controlling of maturation of spermatids
-
-
-
additional information
?
-
-
cAMP elevation in the Schwann cell is sufficient to induce E-cadherin expression accompanied by suppression of N-cadherin expression
-
-
-
additional information
?
-
-
cAMP-dependent neurite outgrowth is mediated by PKA
-
-
-
additional information
?
-
-
cAMP-dependent PKA induces type I tumor necrosis factor receptor exosome-like vesicle release via anchoring of PKA regulatory subunit RIIbeta to A kinase-anchoring protein domains B and C of the guanine nucleotide exchange protein BIG2
-
-
-
additional information
?
-
-
elevated PKA activity results in activation of stress-associated proteins and of enzymes involved in protein biosynthesis and glucose catabolism, in contrast, proteins which are involved in nucleotide and amino acid biosynthesis are downregulated
-
-
-
additional information
?
-
-
exchange protein activated by cAMP acts synergistically with PKA in cAMP-mediated mitogenesis
-
-
-
additional information
?
-
-
signaling by cAMP-dependent protein kinase plays an important role in the regulation of mammalian sperm motility
-
-
-
additional information
?
-
Q7K6A0, Q7KQK0
the PKA catalytic subunit a serine/threonine kinase, that can phosphorylate many substrates, such as additional protein kinases and transcription factors
-
-
-
additional information
?
-
Mus musculus FVB/N
-
the enzyme is involved in cyclic nucleotide signaling, overview, individually phosphorylated PKA-R isozymes are differentially targeted to distinct cellular compartments by AKAP-isozymes, providing a multifaceted platform for the kinase
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ATP
-
binding site structure: spans both lobes, the N-terminal beta-sheet and C-terminal alpha-helix of the core scaffold, binding of ATP and release of ADP in the open enzyme conformation, residues Asp184, Lys72, and Asp166 are involved, schematic overview
ATP
-
the binding site is a deep pocket lined by hydrophobic residues, enzyme affinity for ATP is increased 2fold by phosphorylation of the activation loop at Thr197, ATP competes with the phosphorylated activation loop, that acts as an autoinhibitory substrate
ATP
-
dependent on, the binding site is a deep pocket lined by hydrophobic residues, enzyme affinity for ATP is increased 2fold by phosphorylation of the activation loop at THr197, ATP competes with the phosphorylated activation loop, that acts as an autoinhibitory substrate
ATP
-
binds between two lobes, directing the gamma-phosphate outwards while the adenine ring lies deep in the cleft between the lobes
ATP
-
binding mechanism
ATP
-
optimal at 0.0025 mM, binding involves phosphorylation of Thr197
ATP
-
as MgATP2-
ATP
-
as MgATP2-, binding site structure
ATP
-
binding pocket and small lobe structure, binding involves D166, N171, D184, and K72
ATP
-
preferred cofactor of the wild-type catalytic subunit
ATP
-
PKA-Mg2+-ATP-substrate complex formation and effects on enzyme activity and stability, overview
ATP
Q7K6A0, Q7KQK0
residues of the PfPKA catalytic subunit G40, G42, and G45 are involved in ATP fixation, E82 in ATP stabiization, D175 in orienting the phosphate of ATP; residues of the PfPKA catalytic subunit G40, G42, and G45 are involved in ATP fixation, E82 in ATP stabiization, D175 in orienting the phosphate of ATP
cAMP
O00843
dependent on
cAMP
P21137
dependent on
cAMP
P22694
dependent on; dependent on
cAMP
-, P49673
dependent on
cAMP
P40376
nuclear localization is dependent on cAMP
cAMP
-
dependent
N6-benzyl-ATP
-
preferred co-substrate of catalytic subunit mutant M120G, but inhibitory versus kemptide, overview
N6-phenethyl-ATP
-
preferred co-substrate of catalytic subunit mutant M120G, but inhibitory versus kemptide, overview
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
extracellular Ca2+ is required for enzyme activity in sperm
Cd2+
-
can partially substitue Mg2+
Co2+
-
can partially substitue Mg2+
Mg2+
-
activates the enzyme, binds to beta- and gamma-phosphate of ATP and to Asp184
Mg2+
-
-
Mg2+
-
dependent on, chelates the beta- and gamma-phosphate of ATP, Mg2+ is the physiologic metal ion, other divalent cations are able to support nucleotide binding, but only Mn2+, Co2+, and Cd2+ can substitute Mg2+ in supporting the catalytic activity
Mg2+
-
-
Mg2+
Q6ZXJ1
-
Mg2+
-
absolutely required, as MgATP2-, best at 0.5 mM Mg2+, inhibitory at higher Mg2+ concentrations, cannot be substituted by Mn2+
Mg2+
-
as MgATP2-, binding site structure
Mg2+
-
the Mg-positioning loop consists of residues Asp184-Phe187
Mg2+
-
-
Mg2+
-
PKA-Mg2+-ATP-substrate complex formation and effects on enzyme activity and stability, overview
Mg2+
C3W7W0, F2XG10, -
required; required
Mg2+
-
required
Mg2+
-
required
Mg2+
-
required
Mg2+
Q7K6A0, Q7KQK0
required; required
Mn2+
-
can partially substitue Mg2+
additional information
-
in HeLa cells PKA activity follows a biphasic response to thiol oxidation, overview
additional information
-
Ca2+ activates calpain which activates the cAMP-dependent protein kinase
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(Rp)-adenosine 3',5'-cyclic monophosphorothionate triethyl ammonium salt
-
inhibitor of PKA
(Rp)-adenosine 3',5'-cyclic monophosphothioate
-
i.e. (Rp)-cAMPS, analogue of cAMP, competitive inhibition of PKA activation by cAMP, binding site structure
(Rp)-adenosine-3',5'-cyclic monophosphorothioate
-
inhibits PKA
(Rp)-adenosine-3',5'-cyclic monophosphorothioate
-
PKA inhibitor
(Sp)-adenosine 3',5'-cyclic monophosphothioate
-
i.e. (Sp)-cAMPS, analogue of cAMP, competitive inhibition of PKA activation by cAMP, binding site structure
7-hydroxystaurosporine
-
specific protein kinase inhibitor
Acetylsalicylic acid
-
a non-steroidal anti-inflammatory drug, decreases adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes
AdcAhxArg6
-
i.e. adenosine 5'-carboxylic acid-6-aminohexanoic acid-L-arginine, peptide-nucleoside conjugate inhibitor, inhibition of the catalytic subunit, binding mechanism
adenosine 3',5'-cyclic phosphorothioate
-
-
adenosine 5'-(beta,gamma-Imino)triphosphate
-
binding structure at the ATP binding site
ADP
-
noncompetitive inhibition with respect to ATP
alsterpaullone
-
21% inhibition of CDK2 at 0.01 mM
bicarbonate
-
p270 phosphorylation is not observed when sperms are incubated with M2 medium that contains 4.2 mM bicarbonate
Ca2+
-
strong inhibition
ethylmaleimide
-
complete inhibition at 2 mM
genistein
-
partial inhibition
guanethidine
-
noncompetitive inhibiting serine peptide analogue with respect to ATP
H-85
-
unspecific kinase inhibitor, inhibits 23% of the acrosome reaction in sperm at 0.03 mM
H-89
-
PKA inhibitor, inhibits 87% of the acrosome reaction in sperm at 0.03 mM
H-89
-
potent inhibitor of PKA
H-89
-
selective, but not specific inhibitor of PKA
H-89
-
inhibits autophosphorylation of the catalytic subunit C, reversible
H-89
-
PKA inhibitor
H-89
-
selective strong inhibitor
H-89
-
strong inhibition
H-89
-
i.e. N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide
H-89
-
i.e. N-[2-((4-bromocinnamyl)amino)ethyl]5-isoquinolinesulfonamide, as hydrochloride
H-89
-
significant inhibition at 0.003 mM
H-89
-
permeant inhibitor of PKA
H-89
-
PKA specific inhibitor
H-89
-
specific inhibitor
H-89
-
0.01 mM
H-89
-
0.02 mM significantly reduces forskolin- and dibutyryl-cAMP-induced PKA activation
H2O2
-
H2O2 inhibits activation of PKA, but inhibition can be reverted with dithiothreitol or with thioredoxin reductase plus thioredoxin, H2O2 is ineffective if the PKA holoenzyme is preincubated with cAMP, if added to the catalytic alpha-subunit, which is active independently of cAMP activation, or if the catalytic alpha-subunit is substituted by ist C199A mutant in the reconstituted holoenzyme
H89
-
specific inhibition
H89
-
i.e. N-[2-(4-bromocinnamylamino) ethyl]-5-isoquinoline
H89
-
a permeant inhibitor of PKA
H89
Q7K6A0, Q7KQK0
inhibits PfPKA catalytic subunit activity in vitro, leads to parasite growth arrest and morphological alteration; inhibits PfPKA catalytic subunit activity in vitro, leads to parasite growth arrest and morphological alteration
HA1077
-
partial inhibition
imatinib
Q7K6A0, Q7KQK0
competes for the ATP binding site; competes for the ATP binding site
indirubin-3'-monoxime
-
20% inhibition of CDK2 at 0.01 mM
inhibitor H89
-
ATP competitive chemical inhibitor H89
-
inhibitor peptide PKI5-24
-
inhibits the catalytic subunit
-
IP20
-
iodinated inhibitor peptide substrate
IP20
-
inhibitory peptide TTYADFIASGRTGRRN, residues 5-24 of inhibitor PKI, inhibits the ATPase function of the enzyme
IP20
-
peptide RRNAI, derived from the inhibitory sequence of RIalpha comprising residues 94-98, inhibition mechanism
KT-5720
-
specific inhibitor
KT5720
-
PKA inhibitor
KT5720
-
specific for PKA
myristoylated PKA peptide inhibitor
-
14-22 amide, blocks egg jelly layer induction of PKA
-
myristoylated PKI
-
specific inhibitor
-
myristoylated PKI14-22 amide
-
selective peptide inhibitor of P KA
-
myristoylated protein kinase A inhibitor
-
0.01 mM, specific inhibitor
-
myristoylated protein kinase I (14-22) amide
-
specific PKA inhibitor
-
myristoylated-PKI
-
cAMP-PKA-specific inhibitory peptide PKI
-
N-[2-(4-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide dihydrochloride
-
-
N6-benzyl-ATP
-
preferred co-substrate of catalytic subunit mutant M120G, but inhibitory for the mutant, not the wild-type enzyme, versus kemptide, overview
N6-phenethyl-ATP
-
preferred co-substrate of catalytic subunit mutant M120G, but inhibitory for the mutant, not the wild-type enzyme, versus kemptide, overview
Naproxen
-
a non-steroidal anti-inflammatory drug, decreases adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes
Ni2+
-
inhibits sperm protein phosphorylation by the enzyme
nifedipine
-
inhibits sperm protein phosphorylation by the enzyme
nimesulide
-
a non-steroidal anti-inflammatory drug, decreases adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes
peptide inhibitor PKI
-
-
-
piroxicam
-
a non-steroidal anti-inflammatory drug, decreases adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes
PKA regulatory subunit Ialpha
-
pseudosubstrate inhibitor
-
PKI
-
pseudo-substrate inhibitor
-
PKI
-
specific PKA inhibitor protein
-
PKI
-
recombinant His-tagged rabbit PKA inhibitor protein PKI, binding involves Arg133
-
PKI
-
catalytic subunit Calpha
-
PKI
-
-
-
PKI
-
pseudosubstrate inhibitor
-
PKI
-
PKA inhibitor containing a specific PKA pseudosubstrate RRNA
-
PKI
-
-
-
protein kinase A inhibitor peptide PKI
-
-
-
protein kinase A inhibitor PKI peptide
-
significant inhibition at 0.01 mM
-
protein kinase inhibitor
Q7K6A0, Q7KQK0
PKI, a natural endogenous inhibitor; PKI, a natural endogenous inhibitor
-
protein kinase inhibitor
-
natural peptide inhibitor PKI from Bos taurus
-
protein kinase inhibitor peptide
-
PKI
-
protein kinase inhibitor PKI
-
binding structure, overview
-
pseudosubstrate peptides
-
IC50 values for inhibition of the regulatory subunits of PKA by endogenous inhibitors, overview
-
pseudosubstrate peptides
-
IC50 values for inhibition of he regulatory subunits of PKA by endogenous inhibitors, overview
-
purvalanol
-
18% inhibition of CDK2 at 0.01 mM
regulatory subunit 1alpha
-
-
-
RIIalpha subunit
-
-
-
roscovitine
-
7% inhibition of CDK2 at 0.01 mM
Rp-8-CPT-cAMPS
-
-
Rp-cAMP
-
0.5 mM significantly reduces forskolin- and dibutyryl-cAMP-induced PKA activation
staurosporine
-
-
staurosporine
-
partial inhibition
stearate peptide st-Ht31
-
-
-
STVHEILCKLSLEG
-
an acetylated peptide Ac1-14, but not the nonacetylated equivalent N1-14, inhibits PKA-dependent outwardly rectifying Cl- channels, ORCC, and CFTRmediated currents, the peptide sequence is equivalent to the S100A10 binding site on anx 2, it disrupts the anx S100A10/CTFR interaction
Mn2+
-
strong inhibition
additional information
-
phosphorylation of the activation loop leads to enzyme inhibition, in which the phosphorylated activation loop acts as an autoinhibitory substrate blocking the nucleotide binding pocket, competition with ATP
-
additional information
-
modification and concomitant inactivation of the catalytic subunit of bovine heart cAMP-dependent protein kinase with affinity analogs of peptide substrates potentially capable of undergoing disulfide interchange with enzyme-bound sulfhydryl groups
-
additional information
-
no inhibition by KT5823
-
additional information
-
no inhibition of CDK2 by kenpaullone
-
additional information
-
caveolae inhibitors inhibit the internalization of the beta-adrenergic receptor by PKA
-
additional information
-
the regulatory subunits competitively inhibit the PKA kinase activity
-
additional information
-
complete enzyme inhibition inhibits pseudopod formation and cell migration
-
additional information
-
no inhibition of catalytic subunit Cgamma by PKI
-
additional information
-
molecular mechanism of enzyme inhibition by binding of catalytic and regulatory subunits via extended surface of subunit C, overview
-
additional information
-
the two isoforms of the regulatory subunit inhibit the catalytic subunit
-
additional information
-
cyclo-oxygenase-independent inhibitory effect of non-steroidal anti-inflammatory drugs, mechanism, overview
-
additional information
-
PKA is inhibited by oxidation via either glutathionylation of Cys199 in the activation loop, or the formation of an internal disulfide bond between Cys199 and Cys343
-
additional information
-
not inhibited by wortmannin
-
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
-
additional information
-
alpha2A-adrenoceptor stimulation with brimonidine inhibits PKA activity via inhibition of adenylyl cyclase
-
additional information
-
the C subunit is inactivated by Zn2+-metalloprotease-mediated proteolysis
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3-isobutyryl-1-methylxanthine
-
stimulates activity at 0.1 mM
6-benzyl-cAMP
Q7K6A0, Q7KQK0
activator of PfPKA catalytic subunit; activator of PfPKA catalytic subunit
-
8-bromo-cAMP
-
activates to same extent as cAMP
8-bromo-cAMP
-
activates
8-bromo-cAMP
-
-
8-bromo-cAMP
-
-
8-bromo-cAMP
-
stimulates
8-bromo-cAMP
-
-
8-bromo-cAMP
-
0.1 mM
8-bromo-cAMP
-
stimulates activity at 0.1 mM
8-chloro-cAMP
-
activates to same extent as cAMP
8-CPT-cAMP
-
induces release of the active catalytic subunits from the PKA holoenzyme
8-p-chloro-phenylthio-cAMP
-
0.1 mM activates
adipokinetic hormone
-
rapid enzyme activation
Adrenocorticotropin
-
induces PKA activation
-
Calcineurin
-
i.e. CaN, is important for the cAMP/PKA-dependent anx 2S100A10 complex formation
-
calpain
-
activates the PKA holoenzyme in a cAMP-independent fashion. A variety of agents, including inhibitors of the electron transport chain, activate calpain in a Ca2+-dependent manner, which, in turn, catalyzes the proteolysis of the R subunit, thereby releasing the C subunit in its active form, overview
-
cAMP
-
required for activity, activation is mediated by binding of cAMP to the regulatory subunits, causing release of the catalytic subunits
cAMP
-
binds to the 2 catalytic subunits and activates via dissociation of the regulatory dimer
cAMP
-
dependent on, degree of enzyme activation by cAMP or cGMP depends on the substrate
cAMP
-
activates isozymes PKAmyt1 and PKAmyt2
cAMP
-
dependent on, stimulates phosphorylation of RGS protein
cAMP
-
dependent on, activates the enzyme by partly dissociating the regulatory and the catalytic subunits, determination and analysis of the mechanism, the substrate plays a differential role in activation of type I versus type II holoenzyme
cAMP
-
dependent on, binding site
cAMP
-
dependent on
cAMP
-
induces release of the active catalytic subunits from the PKA holoenzyme
cAMP
Q6ZXJ1
dependent on, acts synergistically with cGMP, binding site domain structure on the regulatory subunit RII
cAMP
-
dependent on
cAMP
-
dependent on, 450% activation
cAMP
-
dependent on
cAMP
-
intracellular amount is controlled by the stimulating steroid hormone adrenocorticotropin ACTH in the adrenal cortex increasing PKA enzyme activity, cAMP induces MKP-1 mRNA and protein expression
cAMP
-
required for PKA activity
cAMP
-
each monomer of the tetrameric enzyme contains 2 bindig sites A and B for cAMP, binding involves Arg230 of domain A and Arg359 in domain B of regulatory subunit RIIbeta, cAMP binding releases the catalytic subunits
cAMP
-
dependent on, competitive to regulatory subunit RIalpha, at low concentration the activation of PKA type I, but not of PKA type II, by cAMP is accelerated by the peptide or protein substrate by increased dissociation of subunits Calpha and RIalpha, cAMP has low effect on RII/PKA type II, overview
cAMP
-
dependent on
cAMP
-
required for PKA activation
cAMP
-
dependent on
cAMP
-
dynamics of the binding domain structure, molecular binding mechanism, overview
cAMP
-
dependent on, structural basis of activation mechanism, binding induces conformational changes in the regulatory subunit RIalpha
cAMP
-
exposure of mitochondria to cAMP results in enhanced catalytic subunit catalytic activity. Upon binding of cAMP to the regulatory subunits, the catalytic subunits are released and are thus free to catalyze the phosphorylation of an array of proteins, But cAMP fails to promote R subunit degradation by beta-catenin
cAMP
-
activation of protein kinase A involves the synergistic binding of cAMP to two cAMP binding sites on the inhibitory R subunit, causing release of the C subunit, which subsequently can carry out catalysis
cAMP
Q7K6A0, Q7KQK0
binding of 2 cAMP molecules to each regulatory subunit alters its affinity for the catalytic subunit, resulting in release of the active catalytic subunit; binding of 2 cAMP molecules to each regulatory subunit alters its affinity for the catalytic subunit, resulting in release of the active catalytic subunit
cAMP-response element-binding protein-binding protein/p300
-
PKA coactivator
-
cGMP
-
activates, degree of enzyme activation by cAMP or cGMP depends on the substrate
cGMP
-
activates isozymes PKAmyt1 and PKAmyt2
cGMP
Q6ZXJ1
activates, acts synergistically with cAMP
D-glucose
-
increases phosphorylation of beta-catenin on Ser552 in INS-1E beta-cells
dibutyryl-cAMP
-
induces MKP-1 mRNA and protein expression in H295R cells
dibutyryl-cAMP
-
activates in vitro
dibutyryl-cAMP
-
-
dibutyryl-cAMP
-
PKA activator
forskolin
-
activates at concentration above 0.001 mM
forskolin
-
activates PKA
forskolin
-
forskolin specifically induces tau hyperphosphorylation by PKA at Ser214 resulting in increased phosphorylation at Ser199, Ser22, Ser396, and Ser404 in N2a/tau441 cells
forskolin
-
stimulates the cAMP-dependent enzyme
forskolin
-
activation at 0.01 mM
forskolin
-
0.024 mM, forskolin enhances lamellipodium formation where active PKA is accumulated
forskolin
-
0.005 mM for 48 h
forskolin
-
stimulates activity at 0.025 mM
forskolin
-
0.05 mM activates
forskolin
-
0.01 mM
forskolin
-
0.01 mM
forskolin
-
alone increases activity, which is further increased by the addition of forskolin plus dibutyryl-cAMP and phosphodiesterase inhibitor IBMX
IBMX
-
0.5 mM activates
isoproterenol
-
at concentration below 0.001 mM
isoproterenol
-
stimulates
isoproterenol
-
activation at 0.001 mM
isoproterenol
-
stimulates activity at 2.5 nM
N6,2'-O-dibutyryl-cAMP
-
increases phosphorylation of beta-catenin on Ser552 in INS-1E beta-cells
N6,2'-O-dibutyryladenosine 3',5'-cyclic phosphate
-
induces PKA activation
N6-benzoyl-cAMP
-
0.1 mM activates
N6-benzoyladenosine-3',5'-cyclic monophosphate
-
PKA-specific cAMP analog
N6-monobutyryl-3'-5'-cAMP
-
specific protein kinase A activator, direct stimulation of acivity with 1 mM N6-monobutyryl-3'-5'-cAMP is necessary for the alkaline pH-induced accumulation of vacuolar H+-ATPase in clear cell apical microvilli
N6-Monobutyryl-cAMP
-
0.1 mM activates
prostaglandin E1
-
activates
prostaglandin E2
-
0.05 mM induce activity by elevation of cAMP levels
Ras-2 protein
-
-
-
Sp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt hydrate
-
activates PKA
Sucrose
-
direct inducer of cAMP-PKA signaling
transforming growth factor beta
-
more than 2fold increased activity after 15 min at 0.1 nM
-
Vasoactive intestinal peptide
-
i.e. VIP
Lactic acid
-
increases intracellular cAMP, pCREB and PKA activity
additional information
-
activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated at Thr197, dephosphorylation leads to enzyme activation by 2-3fold
-
additional information
-
activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated at Thr197, dephosphorylation leads to enzyme 2-3fold activation
-
additional information
-
no stimulation by N6,2'-O-dibutyryl-cAMP
-
additional information
-
forskolin activates via stimulation of cAMP production
-
additional information
-
isozyme PKAmyt1 shows 2- and 3.5fold higher affinity for cAMP and cGMP, respectively, than PKAmyt2
-
additional information
-
forskolin induces enzyme activity
-
additional information
-
forskolin stimulates the adenylyl cyclase, which activates the enzyme by increased cAMP level
-
additional information
-
egg jelly layer EJ component fucose sulfate polymer triggers sperm PKA activation
-
additional information
Q6ZXJ1
phosphate-binding cassettes PCB of domain A and B of the regulatory subunits
-
additional information
-
beta-arrestin is not required for phosphorylation activity and receptor substrate endocytosis
-
additional information
-
phosphorylation of CBP by PKA type I is induced by forskolin and ethanol, inhibition of MAPK activates the PKA type I
-
additional information
-
no enzyme activation or induction by adenosine
-
additional information
-
mechanism, transitory activation of tau phosphorylation by PKA in Alzheimer's disease, effects of durative incubation with activators, overview
-
additional information
-
enzyme stimulation via increase of cAMP level trough 1-methyl-3-isobutylxanthine or theophylline
-
additional information
-
PKA is induced by oestrogen 17beta-oestradiol and forskolin
-
additional information
-
forskolin induces PKA activity
-
additional information
-
dephosphorylation activity induced by the pituitary follicle-stimulating hormone FSH
-
additional information
-
beta-adrenergic stimulation of Ser1928 phosphorylation, L-type calcium channel Cav1.2 constitutively associates with the beta2-AR and PKA to efficiently respond to beta-adrenergic activation
-
additional information
-
under mild oxidizing conditions, or short exposure to oxidants, forskolin-stimulated PKA activity is enhanced
-
additional information
-
gamma-hydroxybutyrate induces the enzyme in the hippocampus, the phosphorylation activity is increased via GABAB receptors, but a desensitization of the signaling pathway occurs after repeated administration of gamma-hydroxybutyrate, overview
-
additional information
-
activation loop phosphorylation at Thr197 regulates the enzyme's catalytic activity, molecular mechanism, classical molecular dynamics simulations and ab initio QM/MM calculations are carried out on the wild-type PKA-Mg2+- ATP-substrate complex and its dephosphorylated mutant, T197A, overview
-
additional information
-
not stimulated by glial growth factor, sensory and motor neuron derived factor, or platelet-derived growth factor
-
additional information
-
Ras stimulates adenylate cyclase leading to increasing cAMP levels and in turn increased activity of protein kinase A
-
additional information
-
not activated by 8-(4-chlorophenylthio)-2'-O-methyl-cAMP
-
additional information
-
beta-adrenergic stimulation with isoprenaline leads to activation of PKA via stimulation of adenylyl cyclase
-
additional information
-
treatment of mitochondria with electron transport chain inhibitors rotenone, antimycin A, sodium azide, and oligomycin, as well as an uncoupler of oxidative phosphorylation, elicits enhanced C subunit activity. The catalytic subunit can exist in an inactive state via association with IkappaB in an NF-kappaB-IkappaB-(C subunit) complex. Stimulation of cells with lipopolysaccharide, endotheln-1, or angiotensin II induces IkappaB degradation, resulting in the ensuing C subunit-catalyzed phosphorylation of NF-kappaB p65
-
additional information
-
oligomycin, antimycin A, rotenone, CCCP, sodium azide, or Ca2+ activate calpain which activates the cAMP-dependent protein kinase
-
additional information
-
no intracellular activating effect by sodium lactate
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0174
-
ATP
-
pH 7.0, 37C, recombinant wild-type catalytic subunit
0.019
-
ATP
-
pH 7.0, temperature not specified in the publication, wild-type enzyme
0.023
-
ATP
-
pH 7.0, temperature not specified in the publication, myristoylated wild-type enzyme and enzyme mutant K7C
0.0305
-
ATP
-
pH 7.0, 37C, recombinant mutant M120G catalytic subunit
0.032
-
ATP
-
pH 7.0, temperature not specified in the publication, myristoylated enzyme mutant K7C
0.73
-
Histone
-
pH 7.0, 22C, catalytic subunit
0.0125
-
Kemptide
-
pH 7.0, 30C, recombinant catalytic subunit Cgamma
0.0125
-
Kemptide
-
C-subunit isoform C5, in 50 mM Tris-HCl (pH 7.0), 1 mM dithiothreitol, 5 mM MgCl2, 0.2 mM ATP, at 25C; C-subunit isoform C6, in 50 mM Tris-HCl (pH 7.0), 1 mM dithiothreitol, 5 mM MgCl2, 0.2 mM ATP, at 25C
0.0147
-
Kemptide
-
C-subunit isoform C3, in 50 mM Tris-HCl (pH 7.0), 1 mM dithiothreitol, 5 mM MgCl2, 0.2 mM ATP, at 25C
0.0158
-
Kemptide
-
C-subunit isoform C1, in 50 mM Tris-HCl (pH 7.0), 1 mM dithiothreitol, 5 mM MgCl2, 0.2 mM ATP, at 25C
0.0186
-
Kemptide
-
C-subunit isoform C4, in 50 mM Tris-HCl (pH 7.0), 1 mM dithiothreitol, 5 mM MgCl2, 0.2 mM ATP, at 25C
0.0247
-
Kemptide
-
C-subunit isoform C2, in 50 mM Tris-HCl (pH 7.0), 1 mM dithiothreitol, 5 mM MgCl2, 0.2 mM ATP, at 25C
0.031
-
Kemptide
-
pH 7.0, 22C, catalytic subunit
0.038
-
Kemptide
-
pH 7.0, 30C, recombinant catalytic subunit Calpha
0.023
-
Leu-Arg-Arg-Ala-Ser-Leu-Gly
-
pH 7.0, temperature not specified in the publication, myristoylated wild-type enzyme
0.027
-
Leu-Arg-Arg-Ala-Ser-Leu-Gly
-
pH 7.0, temperature not specified in the publication, enzyme mutant K7C
0.029
-
Leu-Arg-Arg-Ala-Ser-Leu-Gly
-
pH 7.0, temperature not specified in the publication, wild-type enzyme
0.043
-
Leu-Arg-Arg-Ala-Ser-Leu-Gly
-
pH 7.0, temperature not specified in the publication, myristoylated enzyme mutant K7C
0.0019
-
N-(8-([4-[3-(ethoxycarbonyl)-6,8,8-trimethyl-2-oxo-7,8-dihydro-2H-pyrano[3,2-g]quinolin-9(6H)-yl]butanoyl]amino)octanoyl)-GRTGRRFSYP-amide
-
pH and temperature not specified in the publication
0.0022
-
N-(8-([[7-(diethylamino)-2-oxo-2H-chromen-3-yl]carbonyl]amino)octanoyl)-GRTGRRFSYP-amide
-
pH and temperature not specified in the publication
0.0062
-
N-(8-[[(11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-10-yl)carbonyl]amino]octanoyl)-GRTGRRFSYP-amide
-
pH and temperature not specified in the publication
0.0011
-
N6-benzyl-ATP
-
pH 7.0, 37C, recombinant mutant M120G catalytic subunit
0.1
-
N6-benzyl-ATP
-
above, pH 7.0, 37C, recombinant wild-type catalytic subunit
0.0015
-
N6-phenethyl-ATP
-
pH 7.0, 37C, recombinant mutant M120G catalytic subunit
0.0253
-
RFARKGSLREKNV
-
pH 7.0, 30C, recombinant catalytic subunit Cgamma
0.05
-
RFARKGSLREKNV
-
pH 7.0, 30C, recombinant catalytic subunit Calpha
0.0333
-
RKRSRAE
-
pH 7.0, 30C, recombinant catalytic subunit Cgamma
0.293
-
RKRSRAE
-
pH 7.0, 30C, recombinant catalytic subunit Calpha
0.0333
-
RKRSRKE
-
pH 7.0, 30C, recombinant catalytic subunit Cgamma
-
0.5
-
RKRSRKE
-
pH 7.0, 30C, recombinant catalytic subunit Calpha
-
0.021
-
RRASVA
-
pH 7.5, 25C, catalytic subunit
0.0503
-
RRLSSLRA
-
pH 7.0, 30C, recombinant catalytic subunit Cgamma
0.338
-
RRLSSLRA
-
pH 7.0, 30C, recombinant catalytic subunit Calpha
0.039
-
MgATP2-
-
pH 7.0, 22C, catalytic subunit
additional information
-
additional information
-
kinetics of activation and autoinhibition, modeling, pre-steady-state kinetic methods, wild-type and mutant enzymes
-
additional information
-
additional information
-
kinetics, random kinetic mechanism with kemptide as substrate, reaction kinetic can be influenced by the sort of substrate, pre-steady-state kinetics, slow structural changes during reaction
-
additional information
-
additional information
-
kinetics, thermodynamics, isozymes PKAmyt1 and PKAmyt2
-
additional information
-
additional information
-
steady-state kinetics, second order rate constants, for the catalytic subunit
-
additional information
-
additional information
-
kinetics for cAMP binding to wild-type and mutant regulatory subunits RIIbeta, overview
-
additional information
-
additional information
-
kinetics for catalytic subunit Cgamma
-
additional information
-
additional information
-
PKA associates with substrates with a relatively low affinity
-
additional information
-
additional information
-
kinetics of enzyme activity and activation
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
10.6
-
ATP
-
pH 7.0, 37C, recombinant mutant M120G catalytic subunit
19.6
-
ATP
-
pH 7.0, 37C, recombinant wild-type catalytic subunit
18
-
Leu-Arg-Arg-Ala-Ser-Leu-Gly
-
pH 7.0, temperature not specified in the publication, myristoylated wild-type enzyme and enzyme mutant K7C
19
-
Leu-Arg-Arg-Ala-Ser-Leu-Gly
-
pH 7.0, temperature not specified in the publication, wild-type enzyme
29
-
Leu-Arg-Arg-Ala-Ser-Leu-Gly
-
pH 7.0, temperature not specified in the publication, myristoylated enzyme mutant K7C
0.5
-
N6-benzyl-ATP
-
pH 7.0, 37C, recombinant mutant M120G catalytic subunit
0.12
-
N6-phenethyl-ATP
-
pH 7.0, 37C, recombinant mutant M120G catalytic subunit
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0039
-
7-hydroxystaurosporine
-
recombinant wild-type catalytic subunit, pH 7.5
0.0049
-
7-hydroxystaurosporine
-
recombinant mutant S338A catalytic subunit, pH 7.5
0.00013
-
AdcAhxArg6
-
pH 7.5, 30C, recombinant catalytic subunit
0.000048
-
H-89
-
pH 7.0, 22C, catalytic subunit
additional information
-
additional information
-
inhibition kinetics for the catalytic subunit
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.266
-
-
purified catalytic subunit
0.31
-
-
purified recombinant catalytic subunit Cgamma, substrate Kemptide
0.81
-
-
purified recombinant catalytic subunit Cgamma, substrate histone
5.3
-
-
purified recombinant catalytic subunit Calpha
additional information
-
-
-
additional information
-
-
-
additional information
-
-
measurement of cytosolic Ca2+ concentrations
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
-
-
assay at
7
-
-
assay at
7
-
-
assay at
7
-
-
assay at
7.2
-
-
assay at
7.2
-
-
assay at
7.2
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.5
-
Q6ZXJ1
assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.5
-
C3W7W0, F2XG10, -
assay at; assay at
7.5
-
-
assay at
7.6
-
-
assay at
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
-
-
assay at
15
-
-
in vivo assay at
20
-
Q6ZXJ1
assay at
21
-
-
assay at room temperature
22
-
-
assay at room temperature
22
-
-
assay at room temperature
22
-
-
assay at room temperature
22
-
-
assay at room temperature
25
-
-
assay at
25
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
C3W7W0, F2XG10, -
assay at; assay at
30
-
-
assay at
31
-
-
in vivo phosphorylation assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
10
40
-
isozyme PKAmyt1 shows a linear Arrhenius plot, while PKAmyt2 shows a break in Arrhenius plot at 15C being much more temperature-sensitive above 15C compared to isozyme PKAmyt1
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.7
-
-
regulatory subunit Rmyt2, isoelectric focusing
5
-
-
regulatory subunit Rmyt1, isoelectric focusing
5.18
-
C3W7W0, F2XG10, -
regulatory subunit, sequence calculation
7.49
-
Q7K6A0, Q7KQK0
regulatory subunit, sequence calculation
9.11
-
Q7K6A0, Q7KQK0
catalytic subunit, sequence calculation
additional information
-
-
large differences between catalytic and regulatory subunits
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
a pancreatic acinar cell line
Manually annotated by BRENDA team
-
cerebral, microvascular, isolated from cortical vessels
Manually annotated by BRENDA team
-
neuroblastoma cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
mesenchymal cell
Manually annotated by BRENDA team
-
medial prefrontal brain cortex
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
P25321, P68180
; ovary cell line
Manually annotated by BRENDA team
P27791
myoblast L6 cell line
Manually annotated by BRENDA team
-
purified bovine PKA catalytic subunit C
Manually annotated by BRENDA team
-
HEK-293 cells that stably express D1 receptors
Manually annotated by BRENDA team
-
isozyme PKAmyt1 is the main isoform in the digestive tract
Manually annotated by BRENDA team
-
enzyme activity at different developmental stages, overview
Manually annotated by BRENDA team
-
adut skin and NHDF neonatal human dermal fibroblasts
Manually annotated by BRENDA team
-
dorsal root ganglion
Manually annotated by BRENDA team
-
only isoform PKAmyt1 is detected in the cytoplasm of the lateral, frontolateral and frontal ciliated cells of the frontal face, and the cytoplasm of the non-ciliated cells and the mucous cells of the abfrontal face. Conversely, only the PKAmyt2 isozyme occurs in the cilia of lateral, frontolateral and frontal cells
Manually annotated by BRENDA team
Mus musculus FVB/N
-
-
-
Manually annotated by BRENDA team
-
isozyme distribution
Manually annotated by BRENDA team
Mus musculus FVB/N
-
isozyme distribution
-
Manually annotated by BRENDA team
-
embryonic kidney cell
Manually annotated by BRENDA team
-
containing numerous hemocytes
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
immortilized ovarian surface epithelial cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
isozymes PKAmyt1 and PKAmyt2, subunit Rmyt1 is slightly expressed in the cytoplasm of the columnar epithelial cells of the plicated face, whereas subunit Rmyt2 is highly expressed in the cilia
Manually annotated by BRENDA team
-
contains PKA C-subunit isoforms C4, C5, and C6
Manually annotated by BRENDA team
-
posterior adductor muscle, contains PKA C-subunit isoforms C1, C2, and C3
Manually annotated by BRENDA team
-
portal vein smooth muscle myocyte
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
adrenocortical cells
Manually annotated by BRENDA team
-
from sickle cell disease patients
Manually annotated by BRENDA team
-
neuroblastoma x glioma hybrid cell
Manually annotated by BRENDA team
-
precursor-like neuronal cells and differentiated NT2 cells, model neurons
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
portal vein smooth muscle myocyte
Manually annotated by BRENDA team
-
embryonic fibroblast cell line
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
soleus muscle
-
Manually annotated by BRENDA team
-
pulmonary arterial
Manually annotated by BRENDA team
-
portal vein smooth muscle myocyte
Manually annotated by BRENDA team
-
ovarian cancer cell line
Manually annotated by BRENDA team
-
fetal lung fibroblast-like cell line
Manually annotated by BRENDA team
-
isoform PKAmyt1 is uniformly distributed along the muscle fibers of either ABRM or PAM, whereas isoform PKAmyt2 is localized only in the periphery of the muscle fibers of ABRM and PAM
Manually annotated by BRENDA team
additional information
-
C alpha mRNA is widespread and highly expressed in brain, heart, adrenal gland, testis, lung, kidney, spleen and liver, whereas the C beta mRNA is unevenly expressed in the brain and adrenal gland and in much lesser amounts in other tissues
Manually annotated by BRENDA team
additional information
P21137
expressed at a low level in cytosolic and particulate compartments during embryogenesis. As the nematodes progress from late embryonic stages to the newly hatched, first larval stage, C subunit content increases 15fold. High levels of C subunits are observed in several subsequent larval and adult stages of development
Manually annotated by BRENDA team
additional information
-
high PKA activity in ovarian cancer cells
Manually annotated by BRENDA team
additional information
-
expression of the genes kin-1 and F47F2.1b encoding two PK-A-like catalytic subunits during development in mixed stage populations, overview
Manually annotated by BRENDA team
additional information
-
ubiquitous expression of all three isozymes with isozyme C1 showing the highst expression levels in all tissues
Manually annotated by BRENDA team
additional information
-
differential distribution of cAMP-dependent protein kinase isoforms in various tissues of the bivalve mollusc, Rmyt1 is uniformly distributed in the cytoplasm of most cell types, whereas Rmyt2 is localized only in the cell periphery and associated with certain cellular structures, such as the cilia of labial palps and gill filaments, overview. Only Rmyt2 is found in the subepithelial connective tissue and the periphery of the vacuolated cells
Manually annotated by BRENDA team
additional information
Q7K6A0, Q7KQK0
in cytosolic extracts of both the asexual and sexual stages of the parasite, catalytic and regulatory subunits of PfPKA are expressed weakly during the ring and trophozoite stages compared to the schizont stage, and pfpkac mRNA levels are lower in gametocytes and gametes; in cytosolic extracts of both the asexual and sexual stages of the parasite, catalytic and regulatory subunits of PfPKA are expressed weakly during the ring and trophozoite stages compared to the schizont stage, and pfpkac mRNA levels are lower in gametocytes and gametes
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
isozyme PKAmyt2 is the only isoform detected in the cilia of gill filaments
Manually annotated by BRENDA team
-
primarily, enzyme can migrate to the nucleus upon activation
Manually annotated by BRENDA team
-
activated type I PKA is not translocated to the nucleus
Manually annotated by BRENDA team
P40376
diffusely present in the cytoplasm under normal growth conditions
Manually annotated by BRENDA team
Saccharomyces cerevisiae Y258
-
-
-
Manually annotated by BRENDA team
-
subunit RIalpha localizes at the membrane/cytosolic area, subunit RIIalpha is concentrated around the Golgi-centrosomal area, subunits Calpha1 and Cbeta2 in colocalized with RIalpha and RIIalpha
Manually annotated by BRENDA team
-
cAMP/PKA-dependent anx 2S100A10 complex
Manually annotated by BRENDA team
-
localization of cAMP-dependent protein kinase, composed of the components C-PKA, R-PKA, and AKAP121, associated with the A-kinase anchor protein in the inner mitochondrial compartment
Manually annotated by BRENDA team
-
associated with the inner membrane/matrix
Manually annotated by BRENDA team
-
enzyme can migrate from the cytoplasm to the nucleus upon activation
Manually annotated by BRENDA team
-
activated type II PKA is translocated to the nucleus
Manually annotated by BRENDA team
P40376
concentrated in the nucleus under normal growth conditions
Manually annotated by BRENDA team
-
54 S subunit of the yeast mitochondrial ribosome
Manually annotated by BRENDA team
additional information
-
substrate ezrin is localized at the cytoskeleton of the apical plasma membrane
-
Manually annotated by BRENDA team
additional information
-
the enzyme binds to and colocalizes with the kinase-anchoring protein gravin in the neuronal cortex membrane which is enriched in the inner peripheral cortex in close proximity to the plasma membrane
-
Manually annotated by BRENDA team
additional information
-
subcellular localization study, overview
-
Manually annotated by BRENDA team
additional information
-
individually phosphorylated PKA-R isozymes are differentially targeted to distinct cellular compartments by AKAP-isozymes
-
Manually annotated by BRENDA team
additional information
-
the enzyme is anchored to a variety of intracellular locations via interaction with A-kinase anchoring proteins
-
Manually annotated by BRENDA team
additional information
Mus musculus FVB/N
-
individually phosphorylated PKA-R isozymes are differentially targeted to distinct cellular compartments by AKAP-isozymes
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37700
-
-
catalytic subunit, gel filtration
41300
-
-
C-subunit isoform C4, estimated by SDS-PAGE
41900
-
-
C-subunit isoform C1, estimated by SDS-PAGE
42800
-
-
C-subunit isoform C3, estimated by SDS-PAGE; C-subunit isoform C5, estimated by SDS-PAGE
43400
-
-
C-subunit isoform C2, estimated by SDS-PAGE
44500
-
-
C-subunit isoform C6, estimated by SDS-PAGE
90000
-
C3W7W0, F2XG10, -
holoenzyme, gel filtration; holoenzyme, gel filtration
additional information
-
-
amino acid sequence of the catalytic subunit
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 50000, about, regulatory subunit RII, SDS-PAGE
?
-
x * 40800, recombinant catalytic subunit PKA Calpha, SDS-PAGE
?
-
x * 41000-44000, SDS-PAGE
?
-
x * 57000, C-subunit, SDS-PAGE, x * 48000, RII-subunit, SDS-PAGE, x * 121000, AKAP121, SDS-PAGE
?
-
x * 40600, isozyme C1, x * 48200, isozyme C2, x * 52500, isozyme C3
?
-
x * 69000, recombinant GST-tagged TgPKA catalytic subunit, SDS-PAGE
?
Komagataella pastoris JC100
-
x * 50000, about, regulatory subunit RII, SDS-PAGE
-
dimer
-
2 * 54000, (Rmyt1)2, nonreducing SDS-PAGE
dimer
C3W7W0, F2XG10, -
1 * 42800, about, regulatory subunit, + 1 x 39000, catalytic subunit, sequence calculation; 1 * 42800, about, regulatory subunit, + 1 x 39000, catalytic subunit, sequence calculation
dimer
-
beta2, the cAMP-dependent protein kinase is a serine/threonine kinase that exists as an inactive tetrameric holoenzyme consisting of two regulatory subunits and two catalytic subunits. It is activated by digestion of the regulatory subunits through calpain releasing the active catalytic ssubunits
dimer
-
in Caenorhabditis elegans, in addition to tetrameric (R2C2) PK-A holoenzymes, there is also a sub-population of dimeric (RC) PK-A enzymes that are not tethered by AKAPs
heterotetramer
-
the inactive enzyme is composed of two catalytic and two regulatory subunits
heterotetramer
Q7K6A0, Q7KQK0
alpha2beta2, 2 * 42200, about, catalytic subunit, + 2 * 50800, about, regulatory subunit, sequence calculation; alpha2beta2, 2 * 42200, about, catalytic subunit, + 2 * 50800, about, regulatory subunit, sequence calculation
monomer
-
1 * 54000, Rmyt2, reducing or nonreducing SDS-PAGE, 1 * 54000, Rmyt1, reducing SDS-PAGE
monomer
-
1 x 40000, activated catalytic subunit Calpha1, 1 x 47000, activated catalytic subunit Cbeta2
monomer
-
1 * 45100, isolated catalytic subunit, SDS-PAGE
monomer
-
1 * 41000, isolated recombinant catalytic subunit Cgamma from Sf9 cells, SDS-PAGE
monomer
-
1 * 42000, isolated recombinant catalytic subunit Calpha from Escherichia coli, SDS-PAGE
monomer
-
1 * 40000, catalytic subunit, SDS-PAGE
oligomer
-
-
tetramer
-
alpha2beta2, the tetramer is inactive, binding of ATP causes release of the 2 catalytic subunits in active conformation
tetramer
-
a heterotetramer composed of a regulatory dimer and 2 catalytic subunits, the tetramer is inactive, dissociation of the tetramer occurs during activation and cAMP binding
tetramer
-
2 regulatory subunits in a dimer bound to 2 catalytic subunits, the latter are released during activation by cAMP
tetramer
-
consists of two regulatory and two catalytic subunits, the regulatory subunits of PKA bind to free catalytic subunits (alpha, beta, gamma, or PRkX) and their primary function appears to keep the catalytic subunits in an inactive state, two molecules of cAMP bind to each regulatory subunit of PKA and causes the subsequent release and activation of the catalytic subunits
tetramer
-
alpha2beta2, the cAMP-dependent protein kinase is a serine/threonine kinase that exists as an inactive tetrameric holoenzyme consisting of two regulatory subunits and two catalytic subunits. It is activated by digestion of the regulatory subunits through calpain
tetramer
-
in Caenorhabditis elegans, in addition to tetrameric (R2C2) PK-A holoenzymes, there is also a sub-population of dimeric (RC) PK-A enzymes that are not tethered by AKAPs
monomer
C3W7W0, F2XG10, -
1 * 48000, isolated recombinant His-tagged regulatory subunit, SDS-PAGE
additional information
-
the enzyme possesses a regulatory and a catalytic subunit, 2 lobes are comprised in the core scaffold, the N-terminal beta-sheet and C-terminal alpha-helix lobe, which are joined by a polypeptide chain, the active is located at the interface of the 2 lobes
additional information
-
structure modeling, structural elements, overview
additional information
-
MW of the catalytic subunit determined by amino acid sequence is 40580 Da
additional information
-
three different genes encode the catalytic subunits of the cAMP-dependent protein kinase
additional information
P21137
MW of the catalytic subunit C is 39000-41000 Da
additional information
-
PkaC is a catalytic subunit of the Dictyostelium discoideum cAPK
additional information
-
the product of pka1 is a catalytic subunit of protein kinase A
additional information
-
2 isoforms of regulatory subunit termed Rmyt1, type 1, and Rmyt2, one form of catalytic subunit C, peptide mapping of Rmyt1
additional information
-
isozymes PKAmyt1 and PKAmyt2 contain regulatory subunits Rmyt1 and Rmyt2, respectively
additional information
-
the enzyme consists of an N-terminal small lobe and a C-terminal large lobe giving the catalytic core a bean-like structure and stabilizing the enzyme
additional information
-
the substrate binds to the regulatory subunit which is released from the catalytic subunit for enzyme activity
additional information
-
substrates have differential effects on type I and type II PKA holoenzyme dissociation, X-ray scattering measurements, overview
additional information
-
structure of residues 1-91 of the regulatory subunit
additional information
-
catalytic subunit residue Ser338 stabilizes the enzyme
additional information
-
enzyme consists of 2 catalytic subunits bound to a regulatory subunit dimer of subunits RIalpha and RIIalpha, the catalytic subunits are released upon activation by cAMP, 2 isoforms of catalytic subunit C exist, subunits Calpha1 and Cbeta2, which can colocalize in 1 holoenzyme complex
additional information
Q6ZXJ1
structure, deduced from DNA and amino acid sequence, analysis and comparison
additional information
-
structure of catalytic subunit C with ATP binding cleft and activation loop, overview
additional information
-
2 catalytic subunits and 2 regulatory subunits form a tetramer, the inactive holoenzyme, upon cAMP binding the catalytic subunits are released as monomers and become catalytically active
additional information
-
holoenzyme structure
additional information
-
Arg133 is essential for binding of the catalytic subunit C to the regulatory subunit RII
additional information
-
apoenzyme structure analysis, hydrophobic core network, overview
additional information
-
determination of Stoke's radius of purified recombinant catalytic subunit Cgamma
additional information
-
determination of Stoke's radius of purified recombinant catalytic subunit Calpha
additional information
-
determination of cAMP binding and interaction structures of subunits C and RIalpha, overview
additional information
-
structure of subunit C, subunit R, the cAMP binding site, and the activation loop, interaction sites, overview
additional information
-
the catalytic subunit has a cluster of nonconserved acidic residues, Glu127, Glu170, Glu203, Glu230, and Asp241, that are crucial for substrate recognition and binding, protein dynamics of the catalytic C-subunit, overview
additional information
-
PKA is composed of the components C-PKA, R-PKA, and AKAP121
additional information
-
identification of protein kinase A regulatory isoforms and of 11 different A-kinase anchoring proteins, AKAPs, in ventricular tissue, overview
additional information
-
structure of the ternary PKA-substrate complex, overview
additional information
-
the regulatory subunit of PKA inhibits its kinase activity by shielding the catalytic subunit from physiological substrates, interdependence between the Asp170 relay site and the regulatory-catalytic subunit interaction interface
additional information
-
two PKA isoforms that differ at their regulatory subunit, namely, Rmyt1 or Rmyt2<
additional information
-
the enzyme contains the catalytic C subunit, the regulatory R subunit and an A-kinase anchor protein encoded by single genes kin-1, kin-2, and AKAP, respectively. R-subunit isoforms containing exon B- or exon Q-encoded polypeptide sequences lack the dimerisation/docking domains conventionally seen in R-subunits, and are unlikely to participate in the formation of tetrameric PK-A holoenzymes and are, additionally, unlikely to interact with AKAP(s)
additional information
Q7K6A0, Q7KQK0
structure comparison with mammalian enzymes, overview; structure comparison with mammalian enzymes, overview
additional information
Mus musculus FVB/N
-
identification of protein kinase A regulatory isoforms and of 11 different A-kinase anchoring proteins, AKAPs, in ventricular tissue, overview
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
lipoprotein
-
isozyme C1 cotains a consensus sequence for N-myristoylation
phosphoprotein
-
phosphate groups at Thr196 and Ser337
proteolytic modification
-
regulatory subunits of the PKA holoenzyme, but not the catalytic subunits, suffer proteolysis, selectively in a calpain-dependent fashion, upon exposure of bovine heart mitochondria to digitonin, Ca2+, and a myriad of electron transport inhibitors. Attenuation of proteolysis in the presence of calpain inhibitor I. The C subunit is inactivated by Zn2+-metalloprotease-mediated proteolysis
proteolytic modification
-
the cAMP-dependent protein kinase is a serine/threonine kinase that exists as an inactive tetrameric holoenzyme consisting of two regulatory subunits and two catalytic subunits. It is activated by digestion of the regulatory subunits through calpain releasing the active catalytic ssubunits
phosphoprotein
-
autophosphorylation at Ser10, Ser139, Thr197, and Ser338
phosphoprotein
-
the enzyme is regulated by reversible phosphorylation of the activation loop at Thr197, a polypeptide region outside the active site cleft, the enzyme is inhibited by phosphorylation, which also increases the affinity for ATP by 2fold, and activated by dephosphorylation
phosphoprotein
-
activation loop phosphorylation at Thr197 regulates the enzyme's catalytic activity, molecular mechanism, classical molecular dynamics simulations and ab initio QM/MM calculations are carried out on the wild-type PKA-Mg2+- ATP-substrate complex and its dephosphorylated mutant, T197A, overview
phosphoprotein
-
the enzyme performs autophosphorylation
phosphoprotein
Komagataella pastoris JC100
-
the enzyme performs autophosphorylation
-
phosphoprotein
-
autophosphorylation at Thr197 required for activation
phosphoprotein
-
phosphorylation at T197 by exogenous kinase PDK-I, the enzyme performs autophosphorylation at K72, S338 and T197, the latter is phosphorylated first and required for activity, phosphorylation of the other 2 positions take place only if T197 is already phosphorylated, mechanism
phosphoprotein
-
the enzyme autophosphorylates at Ser10, Thr197, and Ser338 of catalytic subunit PKA Calpha
phosphoprotein
-
the enzyme can be phosphorylated at Thr197, Ser338, Ser10, and Ser139, the phosphorylation status of the enzyme varies, and is chronically reduced in enzyme mutant E230Q
phosphoprotein
-
the catalytically active subunit mutant M120G is phosphorylated on Thr197 and Ser338
phosphoprotein
-
analysis of in vivo phosphorylation sites on PKA-R reveals the presence of several differentially phosphorylated PKA-R isoforms, using semiquantitative mass spectrometry, overview
phosphoprotein
-
phosphorylation on Ser10, Ser139, Thr197, and Ser338
phosphoprotein
Mus musculus FVB/N
-
analysis of in vivo phosphorylation sites on PKA-R reveals the presence of several differentially phosphorylated PKA-R isoforms, using semiquantitative mass spectrometry, overview
-
phosphoprotein
-
autophosphorylation of PKA catalytic subunit is necessary for its enzymatic activation and interaction with PKA regulatory subunits
phosphoprotein
C3W7W0, F2XG10, -
the catalytic subunits phosphorylate the regulatory subunits; the catalytic subunits phosphorylate the regulatory subunits
phosphoprotein
-
regulation by phosphorylation at Thr197 of the activation loop, enhances ATP binding and phosphotransfer, but only slightly the substrate binding
additional information
-
unmyristylated Calpha2 may be essential for fertility in the male
lipoprotein
-
irreversible covalent N-myristylation of PKA or occupancy of the myristyl binding pocket may serve as a site for allosteric regulation in the catalytic C-subunit. And N-myristylation enhances the thermal stability of the enzyme, the myristylated C-subunit has a higher affinity for membranes alone. PKA cannot be myristylated if Asn2 is mutated to Asp
additional information
-
the C-subunit of PKA may be regulated by irreversible deamidation of Asn2. With PKA that is purified from tissues, irreversible deamidation of Asn2 to Asp or isoAsp occurs in about 1/3 of the total C-subunit protein. Also, the deamidated form of the protein has a higher cytosolic-to-nuclear ratio than the non-deamidated protein
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystal structure of the protein kinase catalytic subunit with staurosporine bound to the adenosine pocket
-
crystal structures of catalytic subunit of cAMP-dependent protein kinase in complex with isoquinolinesulfonyl protein kinase inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide
-
purified recombinant regulatory subunit deletion mutant RIalpha bound to cAMP analogue ligands (Rp)-cAMPS or (Sp)-cAMPS resulting in (Rp)-RIalpha and (Sp)-RIalpha, hanging drop vapour diffusion method, mixing of 0.002ml protein solution containing 12 mg/ml protein in 50 mM MES, pH 7.5, 0.2 M NaCl, 2 mM EDTA, 2 mM EGTA, and 10 mM DTT, with 0.002 ml reservoir solution containing 1.0 M ammonium sulfate, 12.5% glycerol, 10 mM DTT, 0.1 M sodium acetate, pH 5.5, 22.5C, 1 week, X-ray diffraction structure determination and analysis at 2.3-2.4 A resolution
-
X-ray diffraction structure analysis
-
X-ray diffraction structure analysis of the catalytic subunits and the regulatory R2 dimer, enzyme cocrystallized with ATP and a peptide inhibitor
-
crystallization in active conformation
-
complex between the catalytic subunit and a deletion mutant regulatory subunit RIalpha comprising residues 91-244, structure determination and analysis
-
crystallization of the muatnt E230Q with MgATP2- and protein kinase inhibitor is only possible as apoenzyme, analysis of the mechanism preventing ternary complex formation by relaxed-complex method
-
modification and computational analysis of the crystal structure of catalytic subunit in complex with two Mg2+ and a phosphorylated substrate peptide, molecular dynamics simulation overview
-
purified myristylated wild-type PKA and a K7C mutant as binary complex with bound substrate SP20 peptide and as ternary complex with bound substrate SP20 peptide and adenosine-5'-(beta,gamma-imido)triphosphate, hanging drop vapor diffusion method, 8-10 mg/ml protein in 50 mM N,N-bis(2-hydroxyethyl)glycine, 150 mM ammonium acetate, and 10 mM DTT, pH 8.0, is combined in 1:10:20:5 molar ratio of protein:AMP-PNP:Mg2+:SP20 for the ternary complex or 1:5 protein:SP20 for the binary complex, screening and method optimization, mixing of equal volumes of protein and well solution, the latter containing 2-18% 2-methyl-2,4-pentanediol, and mother liquor or buffers ranging from pH 5.35 to pH 8.5, 100 mM 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl) propane-1,3-diol, pH 6.5, and 9% MeOH, 8-10 weeks, 4C, X-ray diffraction structure determination and analysis at 1.35-2.0 A resolution, modeling
-
purified recombinant catalytic apo-subunit apo-PKA Calpha phosphorylated at Ser10, Thr197, and Ser338, hanging drop vapour diffusion method, 4C, 0.02 ml of 7.5 mg/ml protein in solution 0.1 mM bicine buffer, pH 8.0, 150 mM ammonium acetate, 10 mM 2-mercaptoethanol, and 3% 2-methyl-2,4-pentanediol versus 1 ml reservoir solution containing 0.1 mM Tris-HCl, pH 7.5, and 10-20% v/v 2-methyl-2,4-pentanediol, temperature-sensitive crystals need 6 months to 1 year to grow, cryoprotection by a gradient of 2-methyl-2,4-pentanediol, X-ray diffraction structure determination and analysis at 2.9 A resolution, molecular replacement
-
purified recombinant catalytic subunit C mutant E230Q in ternary complex with ATP, Mg2+, and IP20, hanging drop vapour diffusion method, protein solution versus reservoir solution containing 0.1 M bicine, pH 8.0, 13% 2-methyl-2,4-pentanediol, and 11% methanol, 4C, cryoprotection by 15% glycerol, X-ray diffraction structure determination and analysis at 2.8 A resolution
-
purified recombinant wild-type and mutant PKA catalytic subunits, 0.002 ml 5 mg/ml protein in 50 mM bicine, pH 8.0, 200 mM ammonium acetate, 2 mM DTT, MgCl2, ATP, and IP20, is mixed with 0.001 ml well solution containing 8-12% v/v 2-methyl-2,4-pentanediol and 10 mM DTT, addition of 7% v/v methanol before sealing, X-ray diffraction structure determination and analysis at 1.26 A resolution, modeling
-
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
N-terminal and C-terminal extensions stabilize the catalytic core
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70C, purified recombinant catalytic subunit Cgamma, 0.5 M NaCl, 10 mM potassium phosphate, pH 6.9, 1 mM EDTA, 30% glycerol, on freeze-thaw cycle, stable up to one year
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
PKAII holoenzyme from bee brain by ion exchange, adsorption, and cAMP-affinity chromatography, thereby dissociation of regulatory and catalytic subunits, and reconstitution
Q6ZXJ1
recombinant regulatory subunit deletion mutant RIalpha by affinity chromatography, elution with cGMP, and dialysis
-
recombinant wild-type and mutant subunit RIalpha residues 91-244 construct dimers from Escherichia coli strain BL21(DE3) by cAMP affinity chromatography, dialysis, and gel filtration
-
recombinant wild-type and mutant PKAs from Escherichia coli strain BL21(DE3)
-
recombinant His-tagged catalytic subunit Cgamma from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, recombinant catalytic subunit Cgamma 273fold from Sf9 insect cells by adsorption chromatography and gel filtration
-
by ammonium sulfate fractionation, dialysis, DEAE ion exchange and P11 cellulose chromatography, and hydroxyapatite chromatography, concentration steps on PEG20000
-
enzyme catalytic subunit from fat body 1773fold to homogeneity by ultracentrifugation and 3 steps of ion exchange chromatography
-
recombinant catalytic subunit C mutant E230Q from Escherichia coli
-
recombinant catalytic subunit Calpha from Escherichia coli by nickel affinity chromatography, recombinant catalytic subunit Calpha from Sf9 insect cells 62fold by adsorption chromatography and gel filtration
-
recombinant catalytic subunit PKA Calpha from Escherichia coli strain BL21 by P11 cellulose and ion exchange chromatography
-
recombinant His-tagged mutant catalytic subunit M120G from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant wild-type and mutant Y204A from Escherichia coli by ion exchange chromatography and gel filtration
-
DEAE-cellulose chromatography and Mono-S column chromatography
-
native enzyme from posterior adductor muscle by anion exchange chromatography, ultrafiltration, and gel filtration
-
partial purification of 2 isozymes PKAmyt1 and PKAmyt2 from posterior aductor muscle and mantle tissue by 2 steps of ionexchange chromatography, ammonium sulfate precipitation, and immunoaffinity chromatography
-
purification of the type 1 regulatory subunit Rmyt1 from mussel by DEAE ion exchange and immunoaffinity chromatography, the latter based on antibodies and cGMP-agarose, and gel filtration
-
gel filtration
-
recombinant His-tagged catalytic subunit C, and His-tagged wild-type and mutant regulatory subunits RIIbeta, by nickel affinity chromatography and dialysis
-
regulatory subunit RII from C6 cells by affinity chromatography on an 8-(6-aminohexyl)-amino-cAMP-resin
-
recombinant GST-tagged enzyme and GST-tagged Whi3 protein from Saccharomyces cerevisiae by glutathione affinity chromatography
-
recombinant GST-tagged TgPKA catalytic subunit from wheat germ cell-free protein synthesis system by glutathione affinity chromatography
-
recombinant N-terminally His6-tagged wild-type and mutant catalytic subunits C from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
native catalytic subunit from by anion exchange and cAMP affinity chromatography; recombinant His6-tagged R subunit from Escherichia coli strain BL21(DE3) by cobalt affinity chromatography
C3W7W0, F2XG10, -
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
DNA and amino acid sequence determination of three isozymes resulting from alternative 5'-splicing
-
regulatory subunit RII, DNA sequence determination and analysis, phylogenetic analysis
Q6ZXJ1
-
-, P49673
the catalytic subunit of PKA (pkaC1) is overexpressed in Aspergillus fumigatus, strains overexpressing pkaC1 show high PKA activity, reduced growth, sporulation deficiency, and formation of a dark pigment in the mycelium
-
distinct expression of catalytic subunit C, regulatory subunit RIalpha, and regulatory subunit RIIbeta in Escherichia coli strain 222
-
expressed in HeLa cells
-
expression of regulatory subunit deletion mutant RIalpha comprising residues 1-91
-
expression of wild-type and mutant subunit RIalpha residues 91-244 constructs, containing the minimal motifs for cAMP-dependent tight binding of subunit C, in Escherichia coli strain BL21(DE3)
-
isolation of a full-length cDNA clone coding for Cbeta2 isoform of the bovine C-subunit
-
genes kin-1 and F47F2.1b encode two PK-A-like catalytic subunits, DNA and amino acid sequence determination and analysis, expression profiles
-
DNA and amino acid sequence determination and analysis, PK-A R-subunit exons and introns, modified version of that published in WormBase, overview.Gene models R07E4.6a, R07E4.6b, and R07E4.6q, encoding isoforms A, B, and Q, RT-PCR expression analysis
-
genes kin-1 and F47F2.1b encode two PK-A-like catalytic subunits, DNA and amino acid sequence determination and analysis, expression profiles
-
-
P25321, P68180
expression of wild-type and mutant PKAs in Escherichia coli strain BL21(DE3)
-
expression of the catalytic subunit DdPK3 in Escherichia coli
-
isolation of cDNA
-
;
P22694
expressed in Neuro2a cells
-
expression of His-tagged catalytic subunit Cgamma in Escherichia coli strain BL21(DE3), stable expression of catalytic subunit Cgamma in cAMP-resistant mouse Y1 adrenal mutant cell line, expression of catalytic subunit Cgamma in Spodoptera frugiperda Sf9 cells via baculovirus infection system
-
expression of the catalytic subunit C in HEK-293 cells
-
characterization of genomic clones coding for the Calpha and Cbeta subunits
-
expressed in C2C12 cells
-
expression of catalytic subunit C mutant E230Q in Escherichia coli
-
expression of catalytic subunit PKA Calpha in Escherichia coli strain BL21
-
expression of His-tagged catalytic subunit Calpha in Escherichia coli strain BL21(DE3), expression of catalytic subunit Calpha in Spodoptera frugiperda Sf9 cells via baculovirus infection system
-
expression of PKA catalytic subunit Calpha as His-tagged protein in Escherichia coli strain BL21(DE3) and of HA-tagged wild-type and mutant PKA Calpha in COS cells
-
expression of wild-type and mutant Y204A in Escherichia coli
-
functional expression of His-tagged mutant catalytic subunit M120G in Escherichia coli strain BL21(DE3) requiring co-expression with PDK1 for stabilization, overview
-
isolation of a full-length cDNA clone encoding the C beta catalytic subunit of cAMP-dependent protein kinase from a brain cDNA library
-
recombinant expression of paralemmin 2-AKAP2 fusion protein in ventricular tissue
-
gene pfpkac encoding the catalytic subunit, phylogenetic analysis; gene pfpkar encoding the regulatory subunit, phylogenetic analysis and sequence comparison
Q7K6A0, Q7KQK0
expressed in HEK293 cells
-
expression of His-tagged catalytic subunit C, and His-tagged wild-type and mutant regulatory subunits RIIbeta
-
isolation of a full length cDNA clone encoding the C alpha type catalytic subunit of cAMP-dependent protein kinase
P27791
subcloning and expression of His-tagged wild-type and mutant PKA catalytic subunits in Escherichia coli strain BL21(DE3), introduction of a tobacco etch virus cleavage site to remove the tag, expression of deuterated catalytic subunit in Escherichia coli strain CT19
-
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
-
DNA and amino acid sequence determination and analysis of the catalytic subunit, sequence comparison
-
expression of the TgPKA catalytic subunit as GST-tagged protein in the wheat germ cell-free protein synthesis system
-
expressed in Saccharomyces cerevisiae
-
expression of N-terminally His6-tagged wild-type and mutant catalytic subunits C in Escherichia coli strain BL21(DE3)
-
gene RKA1, regulatory subunit, located in the F chromosome, expression of His6-tagged R subunit in Escherichia coli strain BL21(DE3); gene TPK1
C3W7W0, F2XG10, -
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C199A
-
the mutant of the catalytic alpha-subunit in the holoenzyme leads to insensitivity towards H2O2
D170A
-
site-directed mutagenesis of the regulatory subunit RIalpha, the mutation selectively reduces the negative cooperativity between the cAMP- and C-recognition sites, i.e. the KD for the regulatory-catalytic subunit complex in the presence of cAMP is reduced by more than 12fold, without significantly compromising the high affinity of the regulatory subunit for both binding partners, conformational shifts upon mutation, and physiological implications of the dual functionality of the D170A mutant, overview
I204A
-
site-directed mutagenesis, subunit RIalpha residue mutation, slightly impaired activation of subunit C, mutant show a slightly lower melting temperature compared to the wild-type subunit RIalpha
R241A
-
site-directed mutagenesis, subunit RIalpha residue mutation, slightly impaired activation of subunit C, mutant show a slightly lower melting temperature compared to the wild-type subunit RIalpha
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
T197A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme
R165A
-
site-directed mutagenesis, the mutant cannot be phosphorylated at Thr197 of the activation loop, molecular dynamics simulations, overview
T197A
-
site-directed mutagenesis, the side-chain conformations of the P-site Ser in the R165A mutant are similar to that in the wild-type PKA, although the replacement of Arg165 with Ala disconnects the interactions between the pThr 197 and the active site, molecular dynamics simulations, overview
E230Q
-
site-directed mutagenesis, mutation of an acidic residue from the cluster around the active site of the catalytic subunit C, E230 forms the salt bridge required for interaction with the substrate, mutant shows decreased substrate recognition, phosphorylation degree, and activity compared to the wild-type subunit C, mutant has an open conformation and does not bind ligands like MgATP2- or IP20 inhibitor
E230Q
-
site-directed mutagenesis of the catalytic subunit, the mutation affects the local structure of the the F-to-G helix loop and asp241, and the binding of protein kinase inhibitor PKI, the mutant protein can only be crystallizes as apoenzyme
K72A
-
site-directed mutagenesis, inactive unphosphorylated mutant
K72H
-
site-directed mutagenesis, inactive unphosphorylated mutant
K72M
-
site-directed mutagenesis, inactive unphosphorylated mutant
K72R
-
site-directed mutagenesis, inactive unphosphorylated mutant
K7C
-
site-directed mutagenesis, the mutant exhibits altered kinetics in a myristylated state compared to the wild-type enzyme
M120G
-
site-directed mutagenesis in the ATP-binding pocket of the catalytic subunit, engineering of the PKA catalytic subunit to accept bulky N6-substituted ATP analogs, using a chemical genetics approach initially pioneered with v-Src, overview, N6(benzyl)-ATP and N6(phenethyl)-ATP are the prefrred cofactors of the mutant
N2D
-
site-directed mutagenesis, the mutant cannot be myristoylated at Asn2
S338A
-
site-directed mutagenesis, mutant is phosphorylated at T197, reduced activity compared to the wild-type enzyme
T197A
-
site-directed mutagenesis, mutant is not phosphorylated, inactive mutant
Y204A
-
site-directed mutagenesis, mutation in the catalytic subunit, reduced catalytic efficiency compared to the wild-type enzyme
R230K
-
site-directed mutagenesis, mutation of an A domain residue of regulatory subunit RIIbeta, the mutant possesses one high-affinity cAMP binding site and one low active binding site resulting in reduced overall cAMP binding
R359K
-
site-directed mutagenesis, mutation of a B domain residue of regulatory subunit RIIbeta, the mutant possesses one high-affinity cAMP binding site and one low active binding site resulting in reduced overall cAMP binding
R96D
-
the mutation mimics phosphorylated regulatory subunit RII
RS96A
-
the mutation mimics unphosphorylated regulatory subunit RII
S338A
-
site-specific mutagenesis, mutation of a residue in the hydrophobic motif at the C-terminus of the catalytic subunit, catalytic activity is similar to the wild-type catalytic subunit, reduced protein stability compared to the wild-type enzyme
T197A
-
site-specific mutagenesis, mutation of activation loop residue of the catalytic subunit, inactive mutant, conformational changes and reduced protein stability compared to the wild-type enzyme
T197A/S338A
-
site-specific mutagenesis, highly unstable protein, tends to aggregation
D328A
-
site-directed mutagenesis of the catalytic subunit, mutant shows decreased interaction with the regulatory RI subunit
D328A/K72H
-
site-directed mutagenesis of the catalytic subunit, inactive mutant showing decreased interaction with the regulatory RII subunit
K72H
-
site-directed mutagenesis of the catalytic subunit, inactive mutant
R133A
-
site-directed mutagenesis of the catalytic subunit, mutant shows decreased interaction with the regulatory RII subunit
R133A/K72H
-
site-directed mutagenesis of the catalytic subunit, inactive mutant showing decreased interaction with the regulatory RII subunit
L203A
-
site-directed mutagenesis, subunit RIalpha residue mutation, slightly impaired activation of subunit C, mutant show a slightly lower melting temperature compared to the wild-type subunit RIalpha
additional information
-
generation of a construct RIalpha-(98-381) subunit comprising both cyclic nucleotide binding domains, in the presence and absence of cAMP, mapping the effects of cAMP binding at single residue resolution, NMR study, overview
Y229A
-
site-directed mutagenesis, subunit RIalpha residue mutation, slightly impaired activation of subunit C, mutant show a slightly lower melting temperature compared to the wild-type subunit RIalpha
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
T197D
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
additional information
-
construction and expression of a mouse mutant beta-adrenergic receptor lacking the PKA phosphorylation sites in HEK-293 cells, and coexpression of murine GFP-tagged beta-arrestin
additional information
-
construction and expression of enzyme with inactive cAMP binding sites at the regulatory subunits resulting in impaired beta1-adrenergic receptor recycling in recombinant HEK-293 cells, overview
additional information
-
the beta-gene of the catalytic subunit of protein kinase A encodes mRNAs that lack 99 bp due to loss of exon 4 lead to catalytically inactive proteins
C199A
-
the mutant of the catalytic alpha-subunit in the holoenzyme leads to insensitivity towards H2O2
additional information
-
construction of a deletion mutant of regulatory subunit RIIbeta lacking the complete domain B
additional information
-
deletion of the AKAP150 gene abrogates stimulation of alpha11.2 phosphorylation on Ser1928 in vivo, overview
K336A/H338A
-
i.e. Tpk1K336A/H338A, site-directed mutagenesis, a catalytically inactive PKA variant, that exhibits a stable binding to the substrate
additional information
-
TPK1 overexpression resulted in a severe growth defect
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
-
silencing of pKA using a constructed PKA-C-silencing vector
K72R
-
site-directed mutagenesis of the catalytic subunit, inactive mutant
additional information
-
microinjection of mutant subunits C in Xenopus oocytes, overview
additional information
-
reconstitution of the PKA cascade in Xenopus laevis oocytes, overview
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
reconstitution of holoenzyme from purified subunits in 50 mM Tris-HCl, pH 7.8, 1 mM EDTA, 1 mM EGTA, 10 mM 2-mercaptoethanol, and 0.1 M NaCl
Q6ZXJ1
recombinant catalytic subunit C, regulatory subunit RIalpha, and regulatory subunit RIIbeta from Escherichia coli strain 222 by cAMP-affinity chromatography, gel filtration, and dialysis
-
reversible unfolding and folding in 8.5 M urea of recombinant His-tagged wild-type and mutant regulatory subunits RIIbeta, overview
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
medicine
-
hepatitis C virus infection activates PKA in a cAMP-dependent manner to promote virus release and transmission
medicine
-
activation of protein kinase A by elevation of the intracellular cAMP level inhibits skeletal myogenesis
medicine
-
cAMP-dependent protein kinase acts synergistically with exchange protein directly activated by cAMP to promote adipogenesis
drug development
Q7K6A0, Q7KQK0
the enzyme represents an attractive target for the development of anti-malarial drugs; the enzyme represents an attractive target for the development of anti-malarial drugs
medicine
-
PKA is a target for the therpeutical treatement of Alzheimer's disease and other tauopathies