======= PDK4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PDK4
  * **<color #00a2e8>Official Name</color>**: pyruvate dehydrogenase kinase 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5166|5166]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q16654|Q16654]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PDK4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PDK4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602527|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, thereby contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism. {ECO:0000269|PubMed:15955060, ECO:0000269|PubMed:18658136, ECO:0000269|PubMed:21816445, ECO:0000269|PubMed:21852536}.

<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'>
|HATPase c|
|BCDHK Adom3|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|pyruvate dehydrogenase (acetyl-transferring) kinase activity|
|regulation of acetyl-CoA biosynthetic process from pyruvate|
|regulation of acyl-CoA biosynthetic process|
|regulation of coenzyme metabolic process|
|regulation of sulfur metabolic process|
|negative regulation of anoikis|
|regulation of anoikis|
|regulation of fatty acid oxidation|
|regulation of cofactor metabolic process|
|regulation of purine nucleotide biosynthetic process|
|regulation of nucleotide biosynthetic process|
|regulation of bone resorption|
|regulation of fatty acid biosynthetic process|
|regulation of bone remodeling|
|cellular response to fatty acid|
|regulation of tissue remodeling|
|response to fatty acid|
|regulation of fatty acid metabolic process|
|insulin receptor signaling pathway|
|regulation of pH|
|reactive oxygen species metabolic process|
|glucose metabolic process|
|regulation of glucose metabolic process|
|regulation of purine nucleotide metabolic process|
|regulation of nucleotide metabolic process|
|regulation of cellular carbohydrate metabolic process|
|monovalent inorganic cation homeostasis|
|cellular response to starvation|
|hexose metabolic process|
|cellular response to insulin stimulus|
|regulation of cellular ketone metabolic process|
|glucose homeostasis|
|carbohydrate homeostasis|
|regulation of lipid biosynthetic process|
|response to starvation|
|monosaccharide metabolic process|
|regulation of carbohydrate metabolic process|
|cellular response to acid chemical|
|response to insulin|
|cellular response to nutrient levels|
|protein kinase activity|
|cellular response to extracellular stimulus|
|cellular response to peptide hormone stimulus|
|cellular response to peptide|
|cellular response to external stimulus|
|response to acid chemical|
|mitochondrial matrix|
|response to peptide hormone|
|regulation of lipid metabolic process|
|regulation of cellular amide metabolic process|
|regulation of small molecule metabolic process|
|response to peptide|
|carbohydrate metabolic process|
|response to nutrient levels|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|cellular response to lipid|
|response to extracellular stimulus|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|cellular response to nitrogen compound|
|cation homeostasis|
|enzyme linked receptor protein signaling pathway|
|inorganic ion homeostasis|
|ion homeostasis|
|response to lipid|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to hormone|
|protein phosphorylation|
|negative regulation of cell death|
|response to organonitrogen compound|
|cellular response to oxygen-containing compound|
|response to nitrogen compound|
|chemical homeostasis|
|cellular response to endogenous stimulus|
|mitochondrion|
|phosphorylation|
|response to endogenous stimulus|
|ATP binding|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|homeostatic process|
|regulation of cell death|
|cellular response to stress|
|small molecule metabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic 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:exp59|UMK57 1μM R01 exp59]]|1.7|
</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>**: 10986
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -6.6 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PDK4 Expression in NALM6 Cells: -6.6'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>