PRKD2 [The Human Chemical-Genetic Interaction Map Project]

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======= PRKD2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PRKD2
  * **<color #00a2e8>Official Name</color>**: protein kinase D2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=25865|25865]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9BZL6|Q9BZL6]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PRKD2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRKD2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/607074|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress- induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:15604256, PubMed:14743217, PubMed:17077180, PubMed:16928771, PubMed:17962809, PubMed:17951978, PubMed:18262756, PubMed:19192391, PubMed:19001381, PubMed:23503467, PubMed:28428613). May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (PubMed:17962809). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin- 2 (IL2) promoter up-regulation (PubMed:17077180). During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (By similarity). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (PubMed:16928771). During TCR- induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (PubMed:19192391). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (PubMed:14743217). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion (PubMed:23503467). {ECO:0000250|UniProtKB:Q8BZ03, ECO:0000269|PubMed:14743217, ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:16928771, ECO:0000269|PubMed:17077180, ECO:0000269|PubMed:17951978, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:18262756, ECO:0000269|PubMed:19001381, ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613}.

<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|
|Pkinase Tyr|
|C1 1|
|PH|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|protein kinase D signaling|
|positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway|
|positive regulation of histone deacetylase activity|
|positive regulation of fibroblast growth factor receptor signaling pathway|
|positive regulation of cell migration by vascular endothelial growth factor signaling pathway|
|positive regulation of deacetylase activity|
|regulation of histone deacetylase activity|
|regulation of deacetylase activity|
|endothelial tube morphogenesis|
|morphogenesis of an endothelium|
|positive regulation of T cell receptor signaling pathway|
|positive regulation of vascular endothelial growth factor receptor signaling pathway|
|protein kinase C activity|
|positive regulation of endothelial cell chemotaxis|
|positive regulation of histone deacetylation|
|positive regulation of CREB transcription factor activity|
|vascular endothelial growth factor signaling pathway|
|regulation of endothelial cell chemotaxis|
|positive regulation of antigen receptor-mediated signaling pathway|
|positive regulation of protein deacetylation|
|regulation of histone deacetylation|
|regulation of fibroblast growth factor receptor signaling pathway|
|positive regulation of interleukin-2 production|
|regulation of vascular endothelial growth factor receptor signaling pathway|
|regulation of T cell receptor signaling pathway|
|cellular response to vascular endothelial growth factor stimulus|
|regulation of protein deacetylation|
|positive regulation of interleukin-8 production|
|protein kinase C binding|
|regulation of interleukin-2 production|
|positive regulation of blood vessel endothelial cell migration|
|regulation of antigen receptor-mediated signaling pathway|
|vascular endothelial growth factor receptor signaling pathway|
|positive regulation of DNA biosynthetic process|
|regulation of interleukin-8 production|
|peptidyl-threonine phosphorylation|
|regulation of blood vessel endothelial cell migration|
|peptidyl-threonine modification|
|sphingolipid biosynthetic process|
|positive regulation of histone modification|
|positive regulation of endothelial cell proliferation|
|endothelium development|
|positive regulation of endothelial cell migration|
|positive regulation of chromatin organization|
|positive regulation of peptidyl-serine phosphorylation|
|regulation of DNA biosynthetic process|
|regulation of endothelial cell proliferation|
|membrane lipid biosynthetic process|
|positive regulation of chemotaxis|
|regulation of peptidyl-serine phosphorylation|
|positive regulation of epithelial cell migration|
|regulation of histone modification|
|positive regulation of NF-kappaB transcription factor activity|
|sphingolipid metabolic process|
|regulation of endothelial cell migration|
|positive regulation of angiogenesis|
|peptidyl-serine phosphorylation|
|positive regulation of chromosome organization|
|T cell receptor signaling pathway|
|positive regulation of vasculature development|
|regulation of chromatin organization|
|positive regulation of epithelial cell proliferation|
|protein autophosphorylation|
|positive regulation of DNA metabolic process|
|peptidyl-serine modification|
|membrane lipid metabolic process|
|positive regulation of ERK1 and ERK2 cascade|
|regulation of chemotaxis|
|regulation of epithelial cell migration|
|protein kinase activity|
|positive regulation of DNA-binding transcription factor activity|
|regulation of cellular response to growth factor stimulus|
|regulation of angiogenesis|
|regulation of ERK1 and ERK2 cascade|
|antigen receptor-mediated signaling pathway|
|epithelial tube morphogenesis|
|angiogenesis|
|regulation of vasculature development|
|regulation of epithelial cell proliferation|
|regulation of chromosome organization|
|regulation of DNA metabolic process|
|protein serine/threonine kinase activity|
|positive regulation of cell adhesion|
|blood vessel morphogenesis|
|regulation of DNA-binding transcription factor activity|
|morphogenesis of an epithelium|
|positive regulation of cytokine production|
|immune response-activating cell surface receptor signaling pathway|
|immune response-regulating cell surface receptor signaling pathway|
|blood vessel development|
|positive regulation of cell migration|
|cellular response to growth factor stimulus|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|vasculature development|
|cardiovascular system development|
|positive regulation of cell motility|
|response to growth factor|
|positive regulation of cellular component movement|
|positive regulation of MAPK cascade|
|positive regulation of locomotion|
|immune response-activating signal transduction|
|tissue morphogenesis|
|lipid biosynthetic process|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|adaptive immune response|
|positive regulation of organelle organization|
|activation of immune response|
|tube morphogenesis|
|regulation of cell adhesion|
|regulation of cytokine production|
|enzyme linked receptor protein signaling pathway|
|regulation of MAPK cascade|
|positive regulation of hydrolase activity|
|tube development|
|regulation of cell migration|
|positive regulation of immune response|
|circulatory system development|
|peptidyl-amino acid modification|
|anatomical structure formation involved in morphogenesis|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|cell adhesion|
|biological adhesion|
|cellular lipid metabolic process|
|protein phosphorylation|
|regulation of locomotion|
|Golgi apparatus|
|regulation of cellular component movement|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|cell death|
|regulation of response to external stimulus|
|epithelium development|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of immune system process|
|regulation of immune response|
|positive regulation of cellular component organization|
|lipid metabolic process|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of protein modification process|
|regulation of hydrolase activity|
|phosphorylation|
|regulation of organelle organization|
|positive regulation of developmental process|
|organonitrogen compound biosynthetic process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|ATP binding|
|positive regulation of transcription, DNA-templated|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|regulation of immune system process|
|positive regulation of signal transduction|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|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|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</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:exp363|GSK-J4 1-1.25μM to day4 R07 exp363]]|-2.23|
|[[:results:exp333|All-trans-Retinoic-Acid 8μM R07 exp333]]|-1.88|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:r:rrm1|RRM1]]|0.483|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 4617
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.7 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PRKD2 Expression in NALM6 Cells: 5.7'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>