======= PRKCA =======
== Gene Information ==
* **Official Symbol**: PRKCA
* **Official Name**: protein kinase C alpha
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5578|5578]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P17252|P17252]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=PRKCA&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRKCA|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/176960|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [provided by RefSeq, Jul 2008].
* **UniProt Summary**: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)- dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B- ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF- kappa-B-induced genes, through IL1A-dependent induction of NF- kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O- tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. {ECO:0000269|PubMed:10848585, ECO:0000269|PubMed:11909826, ECO:0000269|PubMed:12724315, ECO:0000269|PubMed:12832403, ECO:0000269|PubMed:15016832, ECO:0000269|PubMed:15504744, ECO:0000269|PubMed:15526160, ECO:0000269|PubMed:18056764, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21576361, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:28028151, ECO:0000269|PubMed:9738012, ECO:0000269|PubMed:9830023, ECO:0000269|PubMed:9873035, ECO:0000269|PubMed:9927633}.
|C1 1|
|Pkinase C|
|Pkinase Tyr|
|C2|
|Pkinase|
|histone H3-T6 phosphorylation|
|positive regulation of dense core granule biogenesis|
|histone kinase activity (H3-T6 specific)|
|alphav-beta3 integrin-PKCalpha complex|
|regulation of dense core granule biogenesis|
|desmosome assembly|
|positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway|
|histone-threonine phosphorylation|
|positive regulation of lipopolysaccharide-mediated signaling pathway|
|negative regulation of glial cell apoptotic process|
|desmosome organization|
|regulation of glial cell apoptotic process|
|mitotic nuclear envelope disassembly|
|regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway|
|positive regulation of macrophage differentiation|
|protein kinase C activity|
|nuclear envelope disassembly|
|membrane disassembly|
|positive regulation of bone remodeling|
|positive regulation of bone resorption|
|regulation of platelet aggregation|
|regulation of macrophage differentiation|
|positive regulation of cAMP-mediated signaling|
|regulation of homotypic cell-cell adhesion|
|regulation of lipopolysaccharide-mediated signaling pathway|
|positive regulation of G protein-coupled receptor signaling pathway|
|histone phosphorylation|
|positive regulation of cardiac muscle hypertrophy|
|regulation of platelet activation|
|positive regulation of tissue remodeling|
|positive regulation of muscle hypertrophy|
|ERBB2 signaling pathway|
|regulation of bone resorption|
|regulation of bone remodeling|
|regulation of cAMP-mediated signaling|
|nuclear envelope organization|
|positive regulation of myeloid leukocyte differentiation|
|positive regulation of blood vessel endothelial cell migration|
|regulation of cardiac muscle hypertrophy|
|regulation of muscle hypertrophy|
|ERBB signaling pathway|
|regulation of tissue remodeling|
|regulation of blood coagulation|
|regulation of hemostasis|
|regulation of coagulation|
|peptidyl-threonine phosphorylation|
|regulation of muscle adaptation|
|regulation of blood vessel endothelial cell migration|
|peptidyl-threonine modification|
|positive regulation of myeloid cell differentiation|
|positive regulation of endothelial cell proliferation|
|positive regulation of endothelial cell migration|
|mitochondrial membrane|
|cell-cell junction assembly|
|regulation of myeloid leukocyte differentiation|
|regulation of endothelial cell proliferation|
|integrin binding|
|nucleus organization|
|platelet activation|
|regulation of wound healing|
|cell-cell junction organization|
|positive regulation of epithelial cell migration|
|regulation of G protein-coupled receptor signaling pathway|
|positive regulation of leukocyte differentiation|
|positive regulation of mitotic cell cycle|
|regulation of endothelial cell migration|
|positive regulation of angiogenesis|
|regulation of response to wounding|
|cell junction assembly|
|peptidyl-serine phosphorylation|
|regulation of insulin secretion|
|regulation of mRNA stability|
|positive regulation of vasculature development|
|regulation of RNA stability|
|positive regulation of hemopoiesis|
|positive regulation of epithelial cell proliferation|
|response to interleukin-1|
|peptidyl-serine modification|
|regulation of mRNA catabolic process|
|regulation of peptide hormone secretion|
|positive regulation of ERK1 and ERK2 cascade|
|cell junction organization|
|regulation of epithelial cell migration|
|regulation of myeloid cell differentiation|
|regulation of muscle system process|
|protein kinase activity|
|axon guidance|
|neuron projection guidance|
|regulation of hormone secretion|
|regulation of leukocyte differentiation|
|apoptotic signaling pathway|
|regulation of angiogenesis|
|blood coagulation|
|regulation of ERK1 and ERK2 cascade|
|coagulation|
|hemostasis|
|angiogenesis|
|regulation of vasculature development|
|regulation of mRNA metabolic process|
|regulation of epithelial cell proliferation|
|enzyme binding|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|histone modification|
|axonogenesis|
|covalent chromatin modification|
|positive regulation of cell cycle|
|regulation of cell-cell adhesion|
|cellular component disassembly|
|positive regulation of cell adhesion|
|blood vessel morphogenesis|
|axon development|
|endomembrane system organization|
|cell morphogenesis involved in neuron differentiation|
|regulation of hemopoiesis|
|regulation of protein secretion|
|wound healing|
|neuron projection morphogenesis|
|plasma membrane bounded cell projection morphogenesis|
|blood vessel development|
|cell projection morphogenesis|
|regulation of peptide secretion|
|regulation of body fluid levels|
|positive regulation of cell migration|
|positive regulation of multi-organism process|
|vasculature development|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|cell part morphogenesis|
|cardiovascular system development|
|positive regulation of cellular component biogenesis|
|positive regulation of cell motility|
|regulation of response to biotic stimulus|
|posttranscriptional regulation of gene expression|
|regulation of hormone levels|
|positive regulation of cellular component movement|
|positive regulation of MAPK cascade|
|chemotaxis|
|positive regulation of locomotion|
|taxis|
|cell morphogenesis involved in differentiation|
|response to wounding|
|regulation of system process|
|mitotic cell cycle process|
|positive regulation of response to external stimulus|
|regulation of mitotic cell cycle|
|regulation of cell activation|
|tube morphogenesis|
|neuron projection development|
|regulation of cell adhesion|
|mitotic cell cycle|
|perinuclear region of cytoplasm|
|chromatin organization|
|regulation of protein transport|
|enzyme linked receptor protein signaling pathway|
|cell morphogenesis|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of multi-organism process|
|regulation of secretion|
|neuron development|
|cellular component morphogenesis|
|regulation of cellular catabolic process|
|zinc ion binding|
|tube development|
|regulation of cell migration|
|membrane organization|
|circulatory system development|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|anatomical structure formation involved in morphogenesis|
|negative regulation of programmed cell death|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|apoptotic process|
|cell adhesion|
|biological adhesion|
|regulation of cellular component biogenesis|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of locomotion|
|negative regulation of cell death|
|regulation of catabolic process|
|regulation of cellular component movement|
|cell cycle process|
|endoplasmic reticulum|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|programmed cell death|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|chromosome organization|
|cell activation|
|cell death|
|regulation of response to external stimulus|
|response to cytokine|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|positive regulation of immune system process|
|cell projection organization|
|regulation of cell cycle|
|positive regulation of protein modification process|
|mitochondrion|
|phosphorylation|
|locomotion|
|cell cycle|
|positive regulation of developmental process|
|regulation of protein phosphorylation|
|regulation of response to stress|
|ATP binding|
|generation of neurons|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|cell development|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp13|Chloramphenicol 20μM R00 exp13]]|2.32|
^Gene^Correlation^
|[[:human genes:r:rrm1|RRM1]]|0.448|
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 6793
* **Expression level (log2 read counts)**: 5.21
{{:chemogenomics:nalm6 dist.png?nolink |}}