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Symbol PRKACA contributors: mct/shn - updated : 18-11-2020
HGNC name protein kinase, cAMP-dependent, catalytic, alpha
HGNC id 9380
Corresponding disease
PPAVSD1 postaxial polydactyly with atrioventricular septal defect (AVSD) 1
PPNAD4 pigmented nodular adrenocortical disease, primary, 4
Location 19p13      Physical location : 14.202.508 - 14.228.559
Synonym name
  • PKA C-alpha
  • protein kinase A catalytic subunit
  • Synonym symbol(s) MGC102831, MGC48865, PKACa, Cs, PKA, PKCD
    TYPE functioning gene
    STRUCTURE 26.06 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    Map pter - D19S914 - D19S840 - PRKACA - D19S892 - D19S226 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2689 - 351 - 1996 8884279
    10 - 2490 - 343 - 1996 8884279
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Reproductivefemale systembreastmammary gland highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    a N terminus segment involved in the sensitivity to dequalinium
    interspecies ortholog to Prkaca, Rattus norvegicus
    ortholog to Prkaca, Mus musculus
    FAMILY PRK family
    CATEGORY enzyme
        plasma membrane
    text PRKACA is localized at the leading edge of membrane protrusions and colocalized with WASF2
    basic FUNCTION
  • involved in the regulation of AICDA function and in the control of T cell-dependent immune responses modulated, via AICDA, by signals that activate PRKACA
  • phosphorylating AICDA and regulating its activity in germinal center B cells
  • its activation is both necessary and sufficient to trigger irreversible growth arrest during keratinocyte differentiation
  • critical role for its signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors CDKN1A, CDKN1B and activation of AKT1 and ERK-dependent proliferative pathways
  • can negatively regulate ESR1, at least in part, through FOXH1
  • key component that controls MYD88-dependent cytokine gene expression in human and mouse but differentially regulates production of TRIF-dependent cytokines
  • affects cell cycle progression and proliferation in human RPE cells through the downregulation of CDKN1B
  • PKCalpha-dependent stimulation of arginine transport requires the activation of MEK/ERK1/2 cascade, which leads to the stimulation of AP-1 and to the consequent induction of SLC7A2 expression
  • plays an important role in redistributing GluN2BR at synapses and pain hypersensitivity (
  • enhances the osteogenic function of DLX5, at least in part, through protein stabilization
  • novel role of PRKACA in the regulation of RCAN1 activity through phosphorylation
  • PRKACA and PRKACB encode the principal catalytic (C) subunits of protein kinase A (PKA) Calpha and Cbeta, respectively
  • AKAP1-PRKACA-PDE4A distribution and integrity have a key role in cellular survival
  • PRKACA directly phosphorylates ATR at Ser435, which actively recruits the key NER protein xeroderma pigmentosum complementation group A (XPA)
  • PRKACA, PRKACB playing critical role in human development
    a component
  • PRKACA, AKT1 and RAPGEF3 were all shown to establish complexes with neuronal A-kinase anchoring protein 150 (AKAP5)
  • WASF2-PRKACA complex is potentially localized at membrane protrusions
  • SPATC1L-PRKACA complex in maintaining the stability of the sperm head-tail junction
    small molecule
  • Grb2 and EGF-receptor (
  • A-kinase-anchoring proteins (AKAPs) (
  • PKA-interacting protein, AKIP1 (
  • AKAP12 target PRKACA and other binding partners to the plasma membrane
  • interactions between endogenous RPS6KA1 and PKAc in intact cells regulate the ability of cAMP to activate PRKACA
  • PRKACA interacts directly with HDAC5 and phosphorylates HDAC5 at serine 280, an evolutionarily conserved site
  • interaction with WASF2 (WASF2 is necessary for the localization of PRKACA under quiescent conditions as well as for membrane protrusions induced by PRKACA activation)
  • interacting with DLX5 (phosphorylates DLX5 and PRKACA activation increases the protein stability, osteogenic activity and transcriptional activity of DLX5)
  • PJA2 forms a stable complex with, and is phosphorylated by PRKACA
  • interplay between PRKACA phosphorylation and TAL1-mediated epigenetic regulation that regulates hematopoietic transcription and differentiation programs during hematopoiesis and leukemogenesis
  • AKAP13 may serve an ancillary cardioprotective role by favouring the association of PRKACA with HSPB6
  • PRKACA and PDE4D anchoring to AKAP9 provides distinct regulation of cAMP signals at the centrosome
  • direct anchoring of both PRKACA and ADCY1 to TRPV1 by AKAP5 facilitates the response to inflammatory mediators and may be critical in the pathogenesis of thermal hyperalgesia
  • WEE2 acts as a direct downstream substrate of protein kinase A (PRKACA)
  • anchoring of not only PRKACA but also ADCY1 by AKAP5 is important for regulation of postsynaptic functions and specifically AMPA receptor activity
  • PRKACA destabilizes PP2CB upon inflammatory stimuli via phosphorylation of Ser-195 in PP2CB
  • DLX3 is a novel target of PRKACA, and PRKACA mediates BMP signaling during osteoblast differentiation, at least in part, by phosphorylating DLX3 and modulating the protein stability and function of DLX3
  • PRKACA regulates calcineurin function through the phosphorylation of RCAN1
  • IMMT is a PRKACA substrate
  • EZR-anchored PRKACA phosphorylates serine 369 and 373 on GJA1 to enhance gap junction assembly, communication, and cell fusion
  • cell & other
  • ciliary axonemes (
    activated by phorbol esters or thymeleatoxin which causes a transient increase of arginine transport through system y(+), referable to the induction of SLC7A2 mRNAs and to the increased expression of SLC7A2 transporters
    ABCA1 that activates PRKACA
    corresponding disease(s) PPNAD4 , PPAVSD1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in colorectal cancers with constitutive activation of the Wnt-APC pathway
    tumoral somatic mutation      
    in hypothalamic hamartoma with gelastic epilepsy
    tumoral fusion      
    DNAJB1-PRKACA fusion gene characterizeshepatocellular fibrolamellar carcinoma
    tumoral somatic mutation      
    in up to 70p100 of cortisol-secreting adrenocortical adenoma
    Variant & Polymorphism
    Candidate gene
  • marker for poor prognosis of breast cancer and correlates to and is important for cell functions associated with breast cancer progression
  • Therapy target
  • hippocampal PKA inhibition by infusion of Rp-cAMPS restored long-term memory in R6/2 mice
  • SystemTypeDisorderPubmed
    targeting PRKACA may provide novel therapeutic options in endometrial tumors
    inhibition of PKA activation, together with standard AR-targeted therapies, may be more efficacious for treatment of patients with prostate cancer
  • hippocampal cAMP-dependent protein kinase (PKA) hyper-activation in na
  • ve R6/1 mice compared with wild-type (WT) mice, whereas extracellular signal-regulated kinase 1/2 and calcineurin activities were not modified