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FLASH GENE
Symbol PRKCA contributors: mct - updated : 28-04-2017
HGNC name protein kinase C, alpha
HGNC id 9393
DNA
TYPE functioning gene
STRUCTURE 507.94 kb     17 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked Y status confirmed
Physical map
LOC284021 17q24.2 hypothetical protein LOC284021 POLG2 17q polymerase (DNA directed), gamma 2, accessory subunit DDX5 17q21 DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 LOC90799 17q24.2 hypothetical protein BC009518 SMURF2 17q22-q23 hypothetical protein BC009518 LOC388411 17 similar to Importin alpha-2 subunit (Karyopherin alpha-2 subunit) (SRP1-alpha) (RAG cohort protein 1) LOC390807 17 hypothetical gene supported by AK097700 MGC40489 17q24 hypothetical protein MGC40489 LOC388412 17 LOC388412 KIAA0563 17q24.2 LOC388412 LOC390808 17 similar to solute carrier family 16, member 6; monocarboxylate transporter 6 LOC284020 17q24.2 similar to solute carrier family 16, member 6; monocarboxylate transporter 6 FLJ32065 17q24.2 hypothetical protein FLJ32065 GNA13 17q24 guanine nucleotide binding protein (G protein), alpha 13 RGS9 17q24 regulator of G-protein signalling 9 AXIN2 17q23-q24 axin 2 (conductin, axil) MGC33887 17q24.2 hypothetical protein MGC33887 LOC280637 17q24.2 proteasome 26S non-ATPase subunit 7 pseudogene APOH 17q23.2 apolipoprotein H (beta-2-glycoprotein I) PRKCA 17q22-q23.2 protein kinase C, alpha CACNG5 17q24 calcium channel, voltage-dependent, gamma subunit 5 CACNG4 17q24 calcium channel, voltage-dependent, gamma subunit 4 CACNG1 17q24 calcium channel, voltage-dependent, gamma subunit 1 HELZ 17q24.2 helicase with zinc finger domain PSMD12 17q24.3 proteasome (prosome, macropain) 26S subunit, non-ATPase, 12 PITPNC1 17q24.3 phosphatidylinositol transfer protein, cytoplasmic 1 DKFZP586L0724 17q24.3 DKFZP586L0724 protein LOC253924 17q24.3 similar to 60S ribosomal protein L17 (L23) FALZ 17q24 fetal Alzheimer antigen LOC284018 17q24.3 hypothetical protein LOC284018
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 - 8787 76.6 672 - -
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
Endocrineadrenal glandcortex   
Nervousnerve   highly
 spinal cord    
Urinarykidney   moderately
Visualeye   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoietic    
Connectiveadipose  moderately
Connectivebone  highly
Epithelialsecretoryglandularendocrine 
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticneutrophil
cell lineage
cell lines
fluid/secretion
at STAGE
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