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This gene encodes one of the catalytic subunits of protein kinase A, which exists as a tetrameric holoenzyme with two regulatory subunits and two catalytic subunits, in its inactive form. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. cAMP-dependent phosphorylation of proteins by protein kinase A is important to many cellular processes, including differentiation, proliferation, and apoptosis. Constitutive activation of this gene caused either by somatic mutations, or genomic duplications of regions that include this gene, have been associated with hyperplasias and adenomas of the adrenal cortex and are linked to corticotropin-independent Cushing's syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. Tissue-specific isoforms that differ at the N-terminus have been described, and these isoforms may differ in the post-translational modifications that occur at the N-terminus of some isoforms. [provided by RefSeq, Jan 2015]
PRKACA has been studied in breast cancer and has been found to mediate resistance to HER2 targeted therapies. It has also been found to contain a mutation hotspot that contributes to neoplastic behavior in neuroendocrine cancers. In hepatocellular fibrolamellar carcinoma (FL-HCC), the fusion DNAJB1 to PRKACA is suggested to be a diagnostic marker for this rare subtype of HCC. In one study, this fusion was observed in 15/15 FL-HCC cases examined and functional studies found that the fusion retained kinase activity.
PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha) is a Protein Coding gene. Diseases associated with PRKACA include Pigmented Nodular Adrenocortical Disease, Primary, 4 and Fibrolamellar Carcinoma. Among its related pathways are Adenylate cyclase inhibitory pathway and DAG and IP3 signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is PRKACB.
Protein kinase A (PKA, aka cAMP-dependent protein kinase) is involved in the regulation of lipid and glucose metabolism and is a component of the signal transduction mechanism of certain GPCRs. PKA is composed of two regulatory subunits and two catalytic subunits.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0000287 | magnesium ion binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA,IDA | 12475942 |
GO:0004674 | protein serine/threonine kinase activity | IEA,IMP | 26537248 |
GO:0004679 | AMP-activated protein kinase activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001669 | acrosomal vesicle | ISS | -- |
GO:0005623 | cell | IEA | -- |
GO:0005634 | nucleus | IBA,IDA | 21085490 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005737 | cytoplasm | IEA,IDA | 21085490 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | DAG and IP3 signaling |
.93
Beta-2 adrenergic-dependent CFTR expression
.50
|
Neurophysiological process PGE2-induced pain processing
.38
Signal transduction Calcium signaling
.35
Inhibitory action of Lipoxin A4 on PDGF, EGF and LTD4 signaling
.33
Development Beta-adrenergic receptors signaling via cAMP
.32
Development Role of Activin A in cell differentiation and proliferation
.32
.01
|
2 | RET signaling |
.92
.92
|
|
3 | Regulation of PLK1 Activity at G2/M Transition |
.50
|
|
4 | Aldosterone synthesis and secretion |
.41
|
.41
|
5 | G-Beta Gamma Signaling |
G-Beta Gamma Signaling
.46
GHRH Signaling
.46
CRHR Pathway
.44
|
Relaxin Pathway
.37
Hedgehog Signaling in Mammals
.32
Signaling in Gap Junctions
.30
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000086 | G2/M transition of mitotic cell cycle | TAS | -- |
GO:0001707 | mesoderm formation | IEA | -- |
GO:0001843 | neural tube closure | IEA | -- |
GO:0002027 | regulation of heart rate | TAS | 23507255 |
GO:0002223 | stimulatory C-type lectin receptor signaling pathway | TAS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
fostamatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors | 0 | |
H-89 | Experimental | Pharma | Target | 0 | ||
Pentanal | Experimental | Pharma | Target | 0 | ||
A-674563 | Experimental | Pharma | Target | Akt1/PKA/CDK2 inhibitor,potent and selective | 0 | |
cyclic amp | Experimental | Pharma | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
H 89 dihydrochloride |
|
130964-39-5 |
|
|
Compound | Action | Cas Number |
---|---|---|
cGMP Dependent Kinase Inhibitor Peptide | Inhibitor of protein kinases G and A | 82801-73-8 |
H 89 dihydrochloride | Protein kinase A inhibitor | 130964-39-5 |
KT 5720 | Selective protein kinase A inhibitor | 108068-98-0 |
PKA inhibitor fragment (6-22) amide | Potent protein kinase A inhibitor | 121932-06-7 |
PKI 14-22 amide, myristoylated | Cell-permeable protein kinase A inhibitor | 201422-03-9 |
Compound | Action | Cas Number |
---|---|---|
A-674563 | Akt1/PKA/CDK2 inhibitor,potent and selective | 552325-73-2 |
AT7867 | Akt1/2/3 and p70S6K/PKA inhibitor | 857531-00-1 |
cGMP Dependent Kinase Inhibitor Peptide | 82801-73-8 | |
Daphnetin | Protein kinases inhibitor for EGFR/PKA/PKC | 486-35-1 |
GF 109203X | Protein kinase C,MLCK,PKG and PKA inhibitor | 133052-90-1 |
H 89 2HCl | Potent PKA inhibitor | 130964-39-5 |
K-252c | Protein kinase inhibitor | 85753-43-1 |
PKA inhibitor fragment (6-22) amide | 121932-06-7 | |
PKI 14-22 amide, myristoylated | PKA inhibitor | 201422-03-9 |
ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7a | · | 7b | ^ | 8a | · | 8b | ^ | 9 | ^ | 10a | · | 10b | ^ | 11 | ^ | 12 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | |||||||||||||||||||||||||||
SP2: | - | - | - | - | |||||||||||||||||||||||||
SP3: | - | ||||||||||||||||||||||||||||
SP4: | - | - | |||||||||||||||||||||||||||
SP5: |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | PRKACA 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | PRKACA 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | PRKACA 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Prkaca 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | -- 31 |
|
OneToMany | |
Rat (Rattus norvegicus) |
Mammalia | Prkaca 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
OneToMany | |
Chicken (Gallus gallus) |
Aves | -- 31 |
|
ManyToMany | |
Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
OneToMany | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | prkaca 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | prkacaa 31 |
|
ManyToMany | |
prkacab 30 31 |
|
ManyToMany | |||
CABZ01071153.1 31 |
|
ManyToMany | |||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.1053 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Pka-C1 32 |
|
|
|
Pka-C3 32 |
|
|
|||
CG12069 32 |
|
|
|||
Pka-C2 31 32 |
|
ManyToMany | |||
Worm (Caenorhabditis elegans) |
Secernentea | F47F2.1a 32 |
|
|
|
F47F2.1b 32 |
|
|
|||
kin-1 31 |
|
OneToMany | |||
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_AFL090W 30 |
|
||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | TPK2 30 31 |
|
ManyToMany | |
TPK1 31 33 |
|
ManyToMany | |||
TPK3 31 |
|
ManyToMany | |||
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0D03190g 30 |
|
||
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | pka1 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 19 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
708471 | Benign: not provided | 14,107,354(-) | G/A | SYNONYMOUS_VARIANT | |
731258 | Benign: not provided | 14,100,864(-) | C/T | SYNONYMOUS_VARIANT | |
733752 | Likely Benign: not provided | 14,106,894(-) | G/A | INTRON_VARIANT | |
737730 | Likely Benign: not provided | 14,097,597(-) | A/C | SYNONYMOUS_VARIANT | |
739600 | Likely Benign: not provided | 14,100,917(-) | A/G | INTRON_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv49n68 | CNV | loss | 17160897 |
dgv6274n54 | CNV | loss | 21841781 |
dgv6276n54 | CNV | gain | 21841781 |
dgv6279n54 | CNV | loss | 21841781 |
esv22154 | CNV | gain | 19812545 |
esv2677290 | CNV | deletion | 23128226 |
nsv1071913 | CNV | deletion | 25765185 |
nsv1143911 | CNV | deletion | 24896259 |
nsv578642 | CNV | gain | 21841781 |
nsv578645 | CNV | loss | 21841781 |
nsv578658 | CNV | loss | 21841781 |
nsv578661 | CNV | loss | 21841781 |
nsv578663 | CNV | loss | 21841781 |
nsv828452 | CNV | loss | 20364138 |
nsv828454 | CNV | gain | 20364138 |
nsv828455 | CNV | gain | 20364138 |
nsv833761 | CNV | loss | 17160897 |
nsv953980 | CNV | deletion | 24416366 |
Disorder | Aliases | PubMed IDs |
---|---|---|
pigmented nodular adrenocortical disease, primary, 4 |
|
|
fibrolamellar carcinoma |
|
|
primary pigmented nodular adrenocortical disease |
|
|
mixed fibrolamellar hepatocellular carcinoma |
|
|
acth-independent cushing syndrome |
|
|