======= PRKCZ =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PRKCZ
  * **<color #00a2e8>Official Name</color>**: protein kinase C zeta
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5590|5590]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q05513|Q05513]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PRKCZ&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRKCZ|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/176982|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a kinase activity which is independent of calcium and diacylglycerol but not of phosphatidylserine. Furthermore, it is insensitive to typical PKC inhibitors and cannot be activated by phorbol ester. Unlike the classical PKC isoenzymes, it has only a single zinc finger module. These structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. Phosphorylates VAMP2 in vitro (PubMed:17313651). {ECO:0000269|PubMed:11035106, ECO:0000269|PubMed:12162751, ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:18321849, ECO:0000269|PubMed:9447975}.

<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 C|
|Pkinase Tyr|
|C1 1|
|PB1|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|positive regulation of interleukin-5 secretion|
|myelin sheath abaxonal region|
|positive regulation of interleukin-13 secretion|
|apical cortex|
|activation of phospholipase D activity|
|positive regulation of interleukin-10 secretion|
|positive regulation of T-helper 2 cell cytokine production|
|positive regulation of T-helper 2 cell differentiation|
|regulation of interleukin-5 secretion|
|axon hillock|
|membrane hyperpolarization|
|regulation of interleukin-10 secretion|
|regulation of neurotransmitter receptor localization to postsynaptic specialization membrane|
|regulation of interleukin-13 secretion|
|regulation of T-helper 2 cell differentiation|
|regulation of T-helper 2 cell cytokine production|
|insulin receptor substrate binding|
|positive regulation of interleukin-5 production|
|protein kinase C signaling|
|protein kinase C activity|
|positive regulation of interleukin-13 production|
|positive regulation of type 2 immune response|
|phospholipase binding|
|regulation of receptor localization to synapse|
|positive regulation of T cell cytokine production|
|positive regulation of T-helper cell differentiation|
|regulation of interleukin-5 production|
|regulation of interleukin-13 production|
|positive regulation of insulin receptor signaling pathway|
|positive regulation of interleukin-4 production|
|positive regulation of cellular response to insulin stimulus|
|regulation of protein localization to synapse|
|regulation of interleukin-4 production|
|positive regulation of excitatory postsynaptic potential|
|positive regulation of CD4-positive, alpha-beta T cell differentiation|
|14-3-3 protein binding|
|regulation of type 2 immune response|
|regulation of T cell cytokine production|
|long-term memory|
|activation of protein kinase B activity|
|regulation of T-helper cell differentiation|
|positive regulation of CD4-positive, alpha-beta T cell activation|
|negative regulation of insulin receptor signaling pathway|
|negative regulation of cellular response to insulin stimulus|
|positive regulation of interleukin-10 production|
|potassium channel regulator activity|
|modulation of excitatory postsynaptic potential|
|cell leading edge|
|vesicle transport along microtubule|
|positive regulation of alpha-beta T cell differentiation|
|regulation of CD4-positive, alpha-beta T cell differentiation|
|long-term synaptic potentiation|
|positive regulation of T cell mediated immunity|
|vesicle cytoskeletal trafficking|
|membrane depolarization|
|positive regulation of cell-matrix adhesion|
|negative regulation of peptidyl-tyrosine phosphorylation|
|regulation of interleukin-10 production|
|positive regulation of cytokine production involved in immune response|
|positive regulation of phospholipase activity|
|positive regulation of alpha-beta T cell activation|
|neuron projection extension|
|regulation of CD4-positive, alpha-beta T cell activation|
|regulation of alpha-beta T cell differentiation|
|positive regulation of nervous system process|
|regulation of insulin receptor signaling pathway|
|stress fiber|
|regulation of T cell mediated immunity|
|regulation of phospholipase activity|
|positive regulation of lipase activity|
|regulation of cellular response to insulin stimulus|
|organelle transport along microtubule|
|Schaffer collateral - CA1 synapse|
|positive regulation of T cell differentiation|
|regulation of cytokine production involved in immune response|
|developmental cell growth|
|cell growth|
|regulation of alpha-beta T cell activation|
|positive regulation of lymphocyte differentiation|
|positive regulation of production of molecular mediator of immune response|
|regulation of lipase activity|
|positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|transforming growth factor beta receptor signaling pathway|
|positive regulation of adaptive immune response|
|positive regulation of lymphocyte mediated immunity|
|protein heterooligomerization|
|nuclear matrix|
|regulation of cell-matrix adhesion|
|regulation of protein localization to cell periphery|
|developmental growth involved in morphogenesis|
|establishment of cell polarity|
|memory|
|positive regulation of cell-substrate adhesion|
|bicellular tight junction|
|negative regulation of protein complex assembly|
|positive regulation of leukocyte mediated immunity|
|regulation of nervous system process|
|regulation of T cell differentiation|
|positive regulation of cytokine secretion|
|regulation of production of molecular mediator of immune response|
|vesicle|
|regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|positive regulation of leukocyte differentiation|
|regulation of lymphocyte mediated immunity|
|positive regulation of synaptic transmission|
|positive regulation of NF-kappaB transcription factor activity|
|cellular response to transforming growth factor beta stimulus|
|transport along microtubule|
|microtubule organizing center|
|regulation of adaptive immune response|
|response to transforming growth factor beta|
|cellular response to insulin stimulus|
|regulation of lymphocyte differentiation|
|cell-cell junction|
|peptidyl-serine phosphorylation|
|establishment of vesicle localization|
|cytoskeleton-dependent intracellular transport|
|nuclear envelope|
|microtubule-based transport|
|protein localization to plasma membrane|
|vesicle localization|
|positive regulation of hemopoiesis|
|regulation of synaptic plasticity|
|regulation of protein localization to membrane|
|establishment or maintenance of cell polarity|
|transmembrane receptor protein serine/threonine kinase signaling pathway|
|peptidyl-serine modification|
|positive regulation of T cell activation|
|regulation of cytokine secretion|
|regulation of leukocyte mediated immunity|
|regulation of cell-substrate adhesion|
|positive regulation of ERK1 and ERK2 cascade|
|positive regulation of leukocyte cell-cell adhesion|
|positive regulation of immune effector process|
|membrane raft|
|response to insulin|
|protein localization to cell periphery|
|protein kinase activity|
|postsynaptic density|
|regulation of peptidyl-tyrosine phosphorylation|
|positive regulation of cell-cell adhesion|
|learning or memory|
|positive regulation of DNA-binding transcription factor activity|
|cellular response to peptide hormone stimulus|
|endosome|
|positive regulation of protein secretion|
|microtubule-based movement|
|regulation of leukocyte differentiation|
|positive regulation of peptide secretion|
|regulation of ERK1 and ERK2 cascade|
|regulation of leukocyte cell-cell adhesion|
|cognition|
|regulation of T cell activation|
|apical plasma membrane|
|cellular response to peptide|
|activation of protein kinase activity|
|glutamatergic synapse|
|positive regulation of lymphocyte activation|
|establishment of organelle localization|
|protein serine/threonine kinase activity|
|developmental growth|
|response to peptide hormone|
|growth|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of secretion by cell|
|positive regulation of leukocyte activation|
|negative regulation of protein phosphorylation|
|positive regulation of cell activation|
|positive regulation of protein transport|
|regulation of DNA-binding transcription factor activity|
|regulation of membrane potential|
|positive regulation of secretion|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|negative regulation of phosphorylation|
|positive regulation of cytokine production|
|regulation of protein complex assembly|
|regulation of hemopoiesis|
|negative regulation of hydrolase activity|
|positive regulation of establishment of protein localization|
|protein kinase binding|
|regulation of protein secretion|
|regulation of immune effector process|
|response to peptide|
|microtubule cytoskeleton organization|
|protein localization to membrane|
|neuron projection morphogenesis|
|plasma membrane bounded cell projection morphogenesis|
|cell projection morphogenesis|
|regulation of peptide secretion|
|inflammatory response|
|cellular response to growth factor stimulus|
|cell part morphogenesis|
|regulation of lymphocyte activation|
|protein complex oligomerization|
|response to growth factor|
|positive regulation of protein kinase activity|
|regulation of cellular protein localization|
|positive regulation of MAPK cascade|
|cell junction|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|behavior|
|positive regulation of kinase activity|
|organelle localization|
|regulation of system process|
|negative regulation of protein modification process|
|cellular response to organonitrogen compound|
|regulation of leukocyte activation|
|cellular response to hormone stimulus|
|regulation of cell activation|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|neuron projection development|
|microtubule-based process|
|regulation of cell adhesion|
|regulation of cytokine production|
|perinuclear region of cytoplasm|
|negative regulation of cellular component 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|
|positive regulation of hydrolase activity|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|regulation of secretion|
|neuron development|
|cellular component morphogenesis|
|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|
|positive regulation of cell population proliferation|
|regulation of cellular localization|
|regulation of cellular component biogenesis|
|cell migration|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|positive regulation of transport|
|negative regulation of cell death|
|response to organonitrogen compound|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|localization of cell|
|cell motility|
|response to nitrogen compound|
|negative regulation of protein metabolic process|
|cytoskeleton organization|
|plasma membrane bounded cell projection organization|
|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|
|cell projection organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|regulation of hydrolase activity|
|phosphorylation|
|locomotion|
|defense response|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|nervous system process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|ATP binding|
|intracellular transport|
|generation of neurons|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|cell development|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|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|
|establishment of localization in cell|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|system process|
|membrane|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' 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:exp478|Doxorubicin 0.02μM R08 exp478]]|-1.72|
|[[:results:exp140|Nicotinate 1000μM R03 exp140]]|-1.7|
|[[:results:exp10|CCCP 0.1μM R00 exp10]]|1.79|
|[[:results:exp235|Geldanamycin 0.01μM R05 exp235]]|1.89|
|[[:results:exp249|Vinorelbine 0.001μM R05 exp249]]|1.9|
|[[:results:exp277|Curcumin 6.5μM R06 exp277]]|2.22|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:a:arcn1|ARCN1]]|0.46|
|[[:human genes:m:mt1e|MT1E]]|0.454|
|[[:human genes:p:pola1|POLA1]]|0.445|
|[[:human genes:c:copb2|COPB2]]|0.438|
|[[:human genes:s:sf3a1|SF3A1]]|0.438|
|[[:human genes:p:psmd11|PSMD11]]|0.434|
|[[:human genes:a:ankle2|ANKLE2]]|0.426|
|[[:human genes:v:vasn|VASN]]|0.424|
|[[:human genes:p:psmd3|PSMD3]]|0.417|
|[[:human genes:c:chd4|CHD4]]|0.416|
|[[:human genes:c:cdc73|CDC73]]|0.413|
|[[:human genes:h:hgc6.3|HGC6.3]]|0.408|
|[[:human genes:p:pan3|PAN3]]|0.406|
|[[:human genes:r:rbm39|RBM39]]|0.406|
|[[:human genes:t:tceb3cl2|TCEB3CL2]]|0.405|
</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>**: 2556
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.95 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PRKCZ Expression in NALM6 Cells: 5.95'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>