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FLASH GENE
Symbol PRKCA contributors: mct - updated : 28-04-2017
HGNC name protein kinase C, alpha
HGNC id 9393
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two zinc-dependent phorbol-ester and DAG binding domains
  • a C2 domain including a phosphatidyl-binding site
  • a protein kinase catalytic domain
  • an AGC-kinase C-terminal domain
  • HOMOLOGY
    interspecies homolog to rattus Prkca (99.2 pc)
    homolog to murine Prkca (98.2 pc)
    Homologene
    FAMILY
  • Ser/Thr kinase superfamily
  • AGC Ser/Thr protein kinase family
  • PKC class I subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • translocating to cytoplasm after autophosphorylation
  • G3BP2 and PRKCA, relocate to and co-localize in stress granules, but not to P-bodies, when cells are subjected to stress
  • basic FUNCTION
  • acting as a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme
  • playing a fundamental role in regulation of cardiac contractility and calcium handling in myocytes
  • may play a role in cell motility by phosphorylating CSPG4
  • involved in inactivation of MAPK activity
  • involved in induction of apoptosis by extracellular and intracellular signal
  • inducing posive chemotaxis
  • regulating negatively glucose import, insulin receptor signaling pathway, protein amino acid phosphorylation, protein kinase activity
  • regulating positively inflammatory response, protein amino acid phosphorylation
  • involved in regulation of the force of heart contraction and muscle contraction
  • PRKCA and PRKCQ have overlapping functions in alloimmunoreactivity and both PRKCQ and PRKCA isotypes must be targeted to prevent organ allograft rejection
  • serving as major receptors for phorbol esters
  • nodal regulator of heart failure propensity
  • may have a pivotal role in cell signaling that modulates the differentiation and proliferation of osteoblasts
  • ARPC5 and HMMR, in addition to PRKCA, were required for migration of neointimal smooth muscle cells
  • PRKCA and PRKCB1, are involved in most platelet responses implicated in thrombus formation
  • its activation elicits a cascade of orchestrated phosphorylation events that may modulate EIF4G1 structure and control interaction with the EIF4E kinase, MKNK1
  • important role of a novel signalling pathway mediated by PRKCA-HDAC6-CTNNB1 in controlling IRF3-mediated transcription
  • role in the regulation of stress granule formation during cellular stress
  • having a role in memory capacity in healthy subjects and in risk for posttraumatic stress disorder in genocide survivors
  • role in the regulation of stress granule formation during cellular stress
  • likely AKAP5, PRKCA, and TRPV4 channels form dynamic subcellular signaling domains that control Ca(2+) influx into arterial myocytes
  • PRKCA promotes the downregulation of VSIG4 and upregulation of ITGAM expression and TNF and IL6 production, a mechanism that may promote inflammation
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    cell communication
    cell migration & motility
    PHYSIOLOGICAL PROCESS
    text
  • beta 1-integrin mediated cell migration
  • cellular calcium ion homeostasis
  • chondrocyte differentation
  • PATHWAY
    metabolism
    signaling signal transduction
  • intracellular cellular signaling
  • signaling pathway consisting of PRKCA and integrin-linked kinase (ILK) mediates the negative guidance effects of high concentration of SHH on retinal ganglion cell (RGC) axons
  • a component
  • forming a complex with ezrin
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide, other,
  • Ca2+ (3 ions per subunit via the C2 domain)
  • Zn2+
  • ATP
  • diacylglycerol
  • protein
  • targeting ERM proteins MSN, RDX, EZR in association with ITGB1
  • phosphorylating p47 (phox)/NCF1 and activating NADPH oxidase
  • PRKCABP
  • interacting with CENTA1, CSPG4 and PRKCABP
  • DGKD and PRKCA modulate the levels of ubiquitinated EGFR through AKT1 and USP8
  • PRKCA and PICK1 are NPHS1-binding proteins
  • ID1 is a novel target of PRKCA signaling (PRKCA signaling regulates inhibitor of DNA binding 1 in the intestinal epithelium)
  • mediates agonist-induced receptor-mediated TRPV4 activation in endothelial cells
  • PRKCA, PRKCB, stimulates collecting duct EDN1 synthesis via transcriptional activation of the EDN1 promoter (
  • PRKCA negatively modulates SLC6A5 via rapid and dynamic redistribution of SLC6A5 from raft to non-raft membrane subdomains and increasing ubiquitinated SLC6A5 endocytosis
  • binding to SDPR in the presence of phosphatidylserine
  • phosphorylation by PRKCA is critical for RALB-mediated vesicle trafficking and exocytosis
  • binds G3BP2 and regulates stress granule formation following cellular stress
  • PRKCA and AKT1 modulate platelet function by phosphorylating and inhibiting GSK3A/GSK3B, thereby relieving the negative effect of GSK3A/GSK3B on thrombin-mediated platelet activation
  • MARCKS coordinates native TRPC1 channel activation in VSMCs by acting as a reversible PI(4,5)P2 buffer, which is regulated by PRKCA-mediated TRPC1 phosphorylation
  • PRKCA inhibits MYOCD-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation
  • cell & other
  • binding to phosphatidylserine
  • REGULATION
    activated by calcium and diacylglycerol
    hyperglycemia (hyperglycemia induced up-regulation of PRKCA and led to the formation of a complex of NPHS1, PRKCA, PICK1, and ARRB2)
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL17Q24
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer cells may be correlated with the potential of cell migration and invasion
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    dermatologyskin 
    activation of PRKCA is a new therapeutic strategy for non-healing wounds
    diabetetype 1 
    PRKCA and PICK1 are promising therapeutic targets for diabetic nephropathy
    cardiovascularaquiredheart failure
    novel therapeutic target for the treatment of heart failure
    ANIMAL & CELL MODELS
  • activation of two novel PKC isoforms (Prkcd and Prkce) and a classical PKC isoform (Prkca) during the development of steatohepatitis in mice fed the methionine- and choline-deficient (MCD) diet
  • in Prkca(-/-) mice re-epithelialization is delayed, while in novel bitransgenic mice over-expressing constitutively active Prkca it is accelerated