PDK3

Gene Information

Official Symbol: PDK3
Official Name: pyruvate dehydrogenase kinase 3
Aliases and Previous Symbols: N/A
Entrez ID: 5165
UniProt: Q15120
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle, and thus is one of the major enzymes responsible for the regulation of glucose metabolism. The enzymatic activity of PDH is regulated by a phosphorylation/dephosphorylation cycle, and phosphorylation results in inactivation of PDH. The protein encoded by this gene is one of the three pyruvate dehydrogenase kinases that inhibits the PDH complex by phosphorylation of the E1 alpha subunit. This gene is predominantly expressed in the heart and skeletal muscles. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010].
UniProt Summary: Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species. {ECO:0000269|PubMed:10748134, ECO:0000269|PubMed:11486000, ECO:0000269|PubMed:15861126, ECO:0000269|PubMed:16436377, ECO:0000269|PubMed:17683942, ECO:0000269|PubMed:18718909, ECO:0000269|PubMed:22865452}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Hypoxia 5%O2 R04 exp191	-2.53
Deguelin 0.05μM R02 exp69	-2.32
SGC0649 7μM R03 exp150	-2.14
Rotenone 0.07μM R08 exp431	-2.01
JQ1 0.01μM R03 exp130	-2
Nicotinamide Riboside 100μM R03 exp139	-1.84
S-DABN 8μM R03 exp112	-1.82
NN-Diethyl-meta-toluamide 100μM R05 exp237	-1.7
Bafilomycin-A1 0.009μM R08 exp454	1.74
Deferoxamine 11μM R07 exp350	1.84
2-Deoxy-D-glucose 800μM R05 exp214	2.65

Global Fraction of Cell Lines Where Essential: 1/694

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	1/26
bone	0/26
breast	0/30
central nervous system	0/49
cervix	0/4
colorectal	0/17
esophagus	0/11
fibroblast	0/1
gastric	0/14
kidney	0/18
liver	0/19
lung	0/72
lymphocyte	0/16
ovary	0/25
pancreas	0/22
peripheral nervous system	0/15
plasma cell	0/12
prostate	0/1
skin	0/20
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/28
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 17040
Expression level (log2 read counts): 3.5

Expression Distribution

HATPase c
BCDHK Adom3

hypoxia-inducible factor-1alpha signaling pathway
pyruvate dehydrogenase (acetyl-transferring) kinase activity
peroxisome proliferator activated receptor signaling pathway
regulation of acetyl-CoA biosynthetic process from pyruvate
regulation of acyl-CoA biosynthetic process
regulation of coenzyme metabolic process
regulation of sulfur metabolic process
regulation of cofactor metabolic process
regulation of purine nucleotide biosynthetic process
regulation of nucleotide biosynthetic process
cellular response to fatty acid
cellular response to glucose stimulus
cellular response to hexose stimulus
cellular response to monosaccharide stimulus
cellular response to carbohydrate stimulus
response to fatty acid
regulation of fatty acid metabolic process
cellular glucose homeostasis
glucose metabolic process
regulation of glucose metabolic process
regulation of purine nucleotide metabolic process
regulation of nucleotide metabolic process
response to glucose
regulation of cellular carbohydrate metabolic process
response to hexose
response to monosaccharide
hexose metabolic process
intracellular receptor signaling pathway
response to carbohydrate
regulation of cellular ketone metabolic process
peptidyl-serine phosphorylation
regulation of reactive oxygen species metabolic process
glucose homeostasis
carbohydrate homeostasis
cellular response to hypoxia
cellular response to decreased oxygen levels
peptidyl-serine modification
monosaccharide metabolic process
regulation of carbohydrate metabolic process
cellular response to acid chemical