PRKACA Gene: Protein Kinase cAMP-Activated Catalytic Subunit Alpha
A comprehensive guide to the PRKACA gene, its function, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | PRKACA |
|---|---|
| Full Name | Protein Kinase cAMP-Activated Catalytic Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.12 |
| NCBI Gene ID | 5566 ncbi.nlm.nih.gov/gene/5566 |
| Ensembl ID | ENSG00000072062 |
| UniProt ID | P17612 |
| OMIM ID | 188830 |
| HGNC ID | 9380 |
| Aliases | PKA C-alpha, PKACA, MGC48865, DKFZp686I09112 |
Description
The PRKACA gene encodes the alpha catalytic subunit of protein kinase A (PKA), a crucial enzyme in the cAMP-dependent signaling pathway. PKA is a holoenzyme consisting of two regulatory and two catalytic subunits. Upon binding of cAMP to the regulatory subunits, the catalytic subunits are released and become active, phosphorylating serine and threonine residues on various target proteins. This process regulates numerous cellular functions, including metabolism, gene transcription, cell growth, and differentiation. The alpha isoform encoded by PRKACA is the predominant catalytic subunit in most tissues. Mutations and fusions involving this gene are implicated in various endocrine and neoplastic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cushing's Syndrome (Adrenal) | Somatic activating mutations (e.g., L206R) in PRKACA lead to constitutive activation of PKA, resulting in increased cortisol production by adrenal adenomas. | Multiple studies, including whole-exome sequencing of adrenal adenomas (e.g., Sato et al., 2014; Goh et al., 2014). |
| Fibrolamellar Hepatocellular Carcinoma (FL-HCC) | A chimeric fusion protein, DNAJB1-PRKACA, is formed due to a ~400kb deletion on chromosome 19. This fusion retains the kinase domain of PRKACA but is under the control of the DNAJB1 promoter, leading to aberrant PKA activity and tumorigenesis. | Recurrent fusion identified in nearly all FL-HCC cases (Honeyman et al., 2014; Simon et al., 2015). |
| Pigmented Nodular Adrenocortical Disease (PPNAD) | Germline duplications or activating mutations in PRKACA can cause PPNAD, a rare cause of ACTH-independent Cushing's syndrome, by increasing PKA activity in the adrenal cortex. | Case reports and genetic studies (e.g., Beuschlein et al., 2014; Carney et al., 2015). |
| Acrodysostosis | Rare germline activating mutations in PRKACA have been reported in patients with acrodysostosis, a skeletal dysplasia condition, though this is less common than mutations in PRKAR1A. | Case reports (e.g., Lee et al., 2016). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (Cerebellum) | 11.8 | Medium |
| Heart | 8.9 | Medium |
| Liver | 6.5 | Low |
| Adrenal Gland | 12.5 | Medium |
| Testis | 10.1 | Medium |
| Lung | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression; commonly used for functional studies. |
| HeLa | 12.8 | High expression; used in cancer research. |
| HepG2 | 8.5 | Medium expression; liver carcinoma cell line. |
| A549 | 7.1 | Medium expression; lung carcinoma cell line. |
| MCF7 | 9.3 | Medium expression; breast adenocarcinoma cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| L206R | Missense | Somatic; common in cortisol-producing adrenal adenomas | Amino acid substitution in the catalytic domain that disrupts the interaction with the regulatory subunit (RIIβ), leading to constitutive PKA activation. |
| S54L | Missense | Somatic; rare in adrenal adenomas | Located in the ATP-binding pocket; also leads to constitutive activation. |
| DNAJB1-PRKACA Fusion | Gene Fusion | Somatic; hallmark of fibrolamellar carcinoma | Chimeric protein with an N-terminal J-domain from DNAJB1 and the full kinase domain of PRKACA, resulting in dysregulated kinase activity. |
| c.1102C>T (p.Arg368Ter) | Nonsense | Germline; rare | Predicted to result in a truncated, non-functional protein; associated with a loss-of-function phenotype, though clinical significance is still being investigated. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in PRKACA are rare and not well-characterized. They are predicted to reduce PKA signaling, which could impair fundamental cellular processes. However, no specific disease has been definitively linked to PRKACA loss-of-function in humans, likely due to redundancy with other catalytic subunits (PRKACB).
Gain of Function (GOF)
Gain-of-function mutations are the most common and well-studied type. These mutations (e.g., L206R, S54L) typically disrupt the autoinhibitory interaction between the catalytic and regulatory subunits, leading to constitutive, cAMP-independent activation of PKA. This uncontrolled activity drives tumorigenesis in the adrenal cortex and other tissues.
Dominant Negative (DN)
No dominant-negative mutations have been described for PRKACA. The primary mechanism of disease is through gain-of-function or gene fusion, not through interference with the wild-type protein.
View complete mutation data：
Gene Ontology (GO)
| • Protein serine/threonine kinase activity | • cAMP-dependent protein kinase activity |
| • ATP binding | • Signal transduction |
| • Protein phosphorylation | • cAMP-mediated signaling |
| • Regulation of transcription by RNA polymerase II | • Cellular response to glucagon stimulus |
Pathways
• cAMP signaling pathway
• G alpha (s) signalling events
• PKA-mediated phosphorylation of key metabolic factors
• Activation of cAMP-dependent PKA
• Regulation of insulin secretion
Protein Summary
The PRKACA protein, also known as PKA C-alpha, is the 40.6 kDa catalytic subunit of protein kinase A. It consists of a small N-terminal lobe and a larger C-terminal lobe that form the ATP-binding and substrate-binding sites. The protein's activity is tightly regulated by its association with regulatory subunits. When cAMP levels rise, cAMP binds to the regulatory subunits, causing a conformational change that releases the active catalytic subunit. The active C-alpha subunit then phosphorylates target proteins on serine or threonine residues within a consensus sequence (e.g., RRxS/T). This phosphorylation event alters the activity, localization, or protein-protein interactions of the target, propagating the cAMP signal. The protein is ubiquitously expressed but shows higher levels in the brain, adrenal gland, and heart. Its dysregulation is central to the pathogenesis of specific endocrine tumors and cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRKACA Knockout HEK293 Cell Line | EDJ-KQ738 | Human | 5566 | Details Get a Quote |
| PRKACA Knockout A-549 Cell Line | EDJ-KQ19374 | Human | 5566 | Details Get a Quote |
| PRKACA Knockout HCT 116 Cell Line | EDJ-KQ19375 | Human | 5566 | Details Get a Quote |
| PRKACA Knockout HeLa Cell Line | EDJ-KQ19376 | Human | 5566 | Details Get a Quote |
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