PRKCD [The Human Chemical-Genetic Interaction Map Project]

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======= PRKCD =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PRKCD
  * **<color #00a2e8>Official Name</color>**: protein kinase C delta
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5580|5580]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q05655|Q05655]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PRKCD&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRKCD|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/176977|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a member of the protein kinase C family of serine- and threonine-specific protein kinases. The encoded protein is activated by diacylglycerol and is both a tumor suppressor and a positive regulator of cell cycle progression. Also, this protein can positively or negatively regulate apoptosis. Defects in this gene are a cause of autoimmune lymphoproliferative syndrome. [provided by RefSeq, Aug 2017]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor- initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self- antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)- induced inhibition of cell cycle progression at G1/S phase by up- regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro- survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl- phenylalanine (fMLP)-treated cells, is required for NCF1 (p47- phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C- terminal and regulates the interaction between MUC1 and beta- catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). {ECO:0000250, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase Tyr|
|Pkinase C|
|C1 1|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|positive regulation of phospholipid scramblase activity|
|positive regulation of glucosylceramide catabolic process|
|regulation of glucosylceramide catabolic process|
|regulation of sphingomyelin catabolic process|
|positive regulation of sphingomyelin catabolic process|
|regulation of phospholipid scramblase activity|
|positive regulation of lipid transporter activity|
|calcium-independent protein kinase C activity|
|positive regulation of phospholipid catabolic process|
|regulation of lipid transporter activity|
|termination of signal transduction|
|positive regulation of endodeoxyribonuclease activity|
|positive regulation of phospholipid translocation|
|negative regulation of filopodium assembly|
|interleukin-12 production|
|regulation of phospholipid translocation|
|positive regulation of deoxyribonuclease activity|
|interleukin-10 production|
|regulation of phospholipid catabolic process|
|cellular response to hydroperoxide|
|positive regulation of nuclease activity|
|regulation of endodeoxyribonuclease activity|
|negative regulation of glial cell apoptotic process|
|regulation of phospholipid transport|
|positive regulation of phospholipid transport|
|positive regulation of ceramide biosynthetic process|
|regulation of deoxyribonuclease activity|
|regulation of glial cell apoptotic process|
|positive regulation of sphingolipid biosynthetic process|
|insulin receptor substrate binding|
|negative regulation of platelet aggregation|
|protein kinase C activity|
|negative regulation of homotypic cell-cell adhesion|
|regulation of plasma membrane organization|
|intrinsic apoptotic signaling pathway in response to oxidative stress|
|regulation of sphingolipid biosynthetic process|
|regulation of membrane lipid metabolic process|
|regulation of ceramide biosynthetic process|
|regulation of platelet aggregation|
|negative regulation of platelet activation|
|positive regulation of superoxide anion generation|
|cell death in response to oxidative stress|
|response to hydroperoxide|
|cellular response to angiotensin|
|regulation of superoxide anion generation|
|regulation of nuclease activity|
|positive regulation of lipid catabolic process|
|negative regulation of plasma membrane bounded cell projection assembly|
|regulation of homotypic cell-cell adhesion|
|response to angiotensin|
|histone phosphorylation|
|regulation of platelet activation|
|cellular senescence|
|regulation of superoxide metabolic process|
|negative regulation of insulin receptor signaling pathway|
|negative regulation of cellular response to insulin stimulus|
|positive regulation of protein import into nucleus|
|positive regulation of protein import|
|B cell proliferation|
|positive regulation of protein dephosphorylation|
|regulation of filopodium assembly|
|non-membrane spanning protein tyrosine kinase activity|
|enzyme activator activity|
|positive regulation of phospholipid metabolic process|
|negative regulation of blood coagulation|
|positive regulation of anion transport|
|negative regulation of hemostasis|
|regulation of membrane lipid distribution|
|negative regulation of peptidyl-tyrosine phosphorylation|
|negative regulation of coagulation|
|negative regulation of actin filament polymerization|
|regulation of lipid catabolic process|
|regulation of protein import into nucleus|
|positive regulation of dephosphorylation|
|regulation of protein import|
|positive regulation of lipid transport|
|positive regulation of nucleocytoplasmic transport|
|regulation of insulin receptor signaling pathway|
|cell aging|
|negative regulation of protein polymerization|
|cellular response to hydrogen peroxide|
|negative regulation of wound healing|
|interferon-gamma-mediated signaling pathway|
|regulation of cellular response to insulin stimulus|
|positive regulation of protein localization to nucleus|
|negative regulation of MAP kinase activity|
|positive regulation of lipid biosynthetic process|
|regulation of blood coagulation|
|regulation of hemostasis|
|positive regulation of lipid localization|
|regulation of coagulation|
|peptidyl-threonine phosphorylation|
|lymphocyte proliferation|
|regulation of phospholipid metabolic process|
|mononuclear cell proliferation|
|negative regulation of response to wounding|
|peptidyl-threonine modification|
|azurophil granule lumen|
|kinase binding|
|regulation of anion transport|
|positive regulation of reactive oxygen species metabolic process|
|leukocyte proliferation|
|positive regulation of response to DNA damage stimulus|
|negative regulation of protein binding|
|regulation of nucleocytoplasmic transport|
|regulation of lipid transport|
|nuclear matrix|
|positive regulation of transporter activity|
|stimulatory C-type lectin receptor signaling pathway|
|innate immune response activating cell surface receptor signaling pathway|
|regulation of protein localization to nucleus|
|cellular response to antibiotic|
|response to hydrogen peroxide|
|cellular response to reactive oxygen species|
|negative regulation of supramolecular fiber organization|
|negative regulation of protein complex assembly|
|negative regulation of protein serine/threonine kinase activity|
|Fc-gamma receptor signaling pathway involved in phagocytosis|
|immune response-regulating cell surface receptor signaling pathway involved in phagocytosis|
|negative regulation of inflammatory response|
|regulation of lipid localization|
|platelet activation|
|regulation of wound healing|
|Fc receptor mediated stimulatory signaling pathway|
|Fc-gamma receptor signaling pathway|
|negative regulation of cytoskeleton organization|
|regulation of protein dephosphorylation|
|positive regulation of lipid metabolic process|
|peptidyl-tyrosine phosphorylation|
|peptidyl-tyrosine modification|
|intrinsic apoptotic signaling pathway|
|cytokine production|
|positive regulation of cellular amide metabolic process|
|positive regulation of intracellular protein transport|
|B cell activation|
|cellular response to interferon-gamma|
|regulation of actin filament polymerization|
|negative regulation of MAPK cascade|
|regulation of response to wounding|
|negative regulation of binding|
|cell-cell junction|
|regulation of signaling receptor activity|
|positive regulation of apoptotic signaling pathway|
|negative regulation of cell-cell adhesion|
|peptidyl-serine phosphorylation|
|protein stabilization|
|regulation of reactive oxygen species metabolic process|
|regulation of mRNA stability|
|negative regulation of cell projection organization|
|response to interferon-gamma|
|regulation of actin polymerization or depolymerization|
|regulation of actin filament length|
|regulation of RNA stability|
|regulation of lipid biosynthetic process|
|positive regulation of DNA metabolic process|
|response to reactive oxygen species|
|negative regulation of cell activation|
|peptidyl-serine modification|
|regulation of plasma membrane bounded cell projection assembly|
|regulation of mRNA catabolic process|
|regulation of cell projection assembly|
|immunoglobulin mediated immune response|
|negative regulation of defense response|
|positive regulation of intracellular transport|
|B cell mediated immunity|
|cell chemotaxis|
|regulation of dephosphorylation|
|cellular response to toxic substance|
|regulation of response to DNA damage stimulus|
|regulation of protein binding|
|regulation of protein polymerization|
|negative regulation of protein kinase activity|
|regulation of intracellular protein transport|
|innate immune response-activating signal transduction|
|protein kinase activity|
|cellular response to oxidative stress|
|Fc receptor signaling pathway|
|negative regulation of kinase activity|
|regulation of peptidyl-tyrosine phosphorylation|
|activation of innate immune response|
|regulation of actin filament organization|
|lymphocyte mediated immunity|
|cellular response to peptide hormone stimulus|
|negative regulation of cell adhesion|
|positive regulation of ion transport|
|negative regulation of transferase activity|
|regulation of transporter activity|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|aging|
|apoptotic signaling pathway|
|regulation of protein stability|
|blood coagulation|
|coagulation|
|hemostasis|
|response to antibiotic|
|positive regulation of cellular protein localization|
|cellular response to peptide|
|activation of protein kinase activity|
|regulation of mRNA metabolic process|
|phagocytosis|
|defense response to bacterium|
|regulation of inflammatory response|
|positive regulation of innate immune response|
|regulation of MAP kinase activity|
|regulation of actin cytoskeleton organization|
|enzyme binding|
|regulation of intracellular transport|
|regulation of supramolecular fiber organization|
|regulation of DNA metabolic process|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|histone modification|
|negative regulation of response to external stimulus|
|positive regulation of cellular catabolic process|
|negative regulation of organelle organization|
|covalent chromatin modification|
|regulation of cellular component size|
|regulation of binding|
|lymphocyte activation|
|response to oxidative stress|
|regulation of actin filament-based process|
|response to peptide hormone|
|regulation of lipid metabolic process|
|regulation of apoptotic signaling pathway|
|regulation of cell-cell adhesion|
|regulation of cellular amide metabolic process|
|cellular response to drug|
|negative regulation of protein phosphorylation|
|positive regulation of protein transport|
|positive regulation of catabolic process|
|negative regulation of phosphorylation|
|immune response-activating cell surface receptor signaling pathway|
|regulation of protein complex assembly|
|regulation of innate immune response|
|positive regulation of establishment of protein localization|
|protein kinase binding|
|response to peptide|
|positive regulation of defense response|
|wound healing|
|immune response-regulating cell surface receptor signaling pathway|
|neutrophil degranulation|
|neutrophil activation involved in immune response|
|regulation of body fluid levels|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|negative regulation of intracellular signal transduction|
|response to toxic substance|
|positive regulation of multi-organism process|
|leukocyte degranulation|
|regulation of anatomical structure size|
|regulation of protein serine/threonine kinase activity|
|myeloid leukocyte mediated immunity|
|myeloid cell activation involved in immune response|
|regulation of response to biotic stimulus|
|posttranscriptional regulation of gene expression|
|positive regulation of protein kinase activity|
|response to inorganic substance|
|regulation of cellular protein localization|
|regulation of cytoskeleton organization|
|chemotaxis|
|taxis|
|cell population proliferation|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|immune response-activating signal transduction|
|response to wounding|
|positive regulation of kinase activity|
|myeloid leukocyte activation|
|negative regulation of protein modification process|
|immune response-regulating signaling pathway|
|cellular response to organonitrogen compound|
|positive regulation of response to external stimulus|
|cellular response to hormone stimulus|
|adaptive immune response|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|activation of immune response|
|regulation of cell activation|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|cytokine-mediated signaling pathway|
|regulation of cell adhesion|
|response to bacterium|
|regulation of plasma membrane bounded cell projection organization|
|perinuclear region of cytoplasm|
|positive regulation of cell death|
|chromatin organization|
|regulation of ion transport|
|regulated exocytosis|
|negative regulation of cellular component organization|
|regulation of protein transport|
|regulation of cell projection organization|
|regulation of cellular response to stress|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of MAPK cascade|
|regulation of defense response|
|leukocyte mediated immunity|
|innate immune response|
|positive regulation of hydrolase activity|
|regulation of multi-organism process|
|negative regulation of catalytic activity|
|exocytosis|
|regulation of protein kinase activity|
|regulation of cellular catabolic process|
|membrane organization|
|positive regulation of immune response|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to hormone|
|regulation of cellular localization|
|apoptotic process|
|leukocyte activation|
|defense response to other organism|
|regulation of cellular component biogenesis|
|cell migration|
|protein phosphorylation|
|regulation of transferase activity|
|positive regulation of transport|
|regulation of catabolic process|
|negative regulation of cell death|
|response to organonitrogen compound|
|secretion by cell|
|cellular response to cytokine stimulus|
|endoplasmic reticulum|
|positive regulation of protein phosphorylation|
|response to drug|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|export from cell|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|chromosome organization|
|cell activation|
|cell motility|
|localization of cell|
|response to nitrogen compound|
|immune effector process|
|cell death|
|regulation of response to external stimulus|
|response to cytokine|
|negative regulation of protein metabolic process|
|secretion|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of molecular function|
|positive regulation of immune system process|
|regulation of immune response|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|regulation of hydrolase activity|
|phosphorylation|
|regulation of organelle organization|
|response to other organism|
|response to external biotic stimulus|
|locomotion|
|response to biotic stimulus|
|defense response|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|extracellular region|
|vesicle-mediated transport|
|positive regulation of cellular biosynthetic process|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp12|Chloramphenicol 2μM R00 exp12]]|-1.85|
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|1.71|
|[[:results:exp77|Prochlorperazine 5.2μM R02 exp77]]|1.74|
|[[:results:exp514|Phorbol-12-myristate-13-acetate 0.57μM R08 exp514]]|4.13|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 15355
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.73 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PRKCD Expression in NALM6 Cells: 4.73'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>