PDK2: Pyruvate Dehydrogenase Kinase 2
A key regulator of mitochondrial metabolism and the pyruvate dehydrogenase complex.
Gene Information Card
| Symbol | PDK2 |
|---|---|
| Full Name | Pyruvate Dehydrogenase Kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.33 |
| NCBI Gene ID | 5164 ncbi.nlm.nih.gov/gene/5164 |
| Ensembl ID | ENSG00000108379 |
| UniProt ID | Q15119 |
| OMIM ID | 602525 |
| HGNC ID | 8810 |
| Aliases | PDHK2, PDKII |
Description
PDK2 (Pyruvate Dehydrogenase Kinase 2) encodes a mitochondrial protein that phosphorylates and inactivates the pyruvate dehydrogenase complex (PDC), thereby regulating the conversion of pyruvate to acetyl-CoA. This gene plays a critical role in glucose metabolism, linking glycolysis to the tricarboxylic acid cycle. PDK2 expression is regulated by metabolic signals and is implicated in cancer metabolism, diabetes, and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | PDK2 overexpression inhibits PDC, promoting aerobic glycolysis (Warburg effect) and tumor growth. | COSMIC; PMID: 23455423 |
| Type 2 Diabetes | Increased PDK2 activity reduces glucose oxidation, contributing to insulin resistance. | PMID: 15611068 |
| Lactic Acidosis | PDK2-mediated PDC inhibition impairs pyruvate oxidation, leading to lactate accumulation. | OMIM #602525 |
| Alzheimer's Disease | PDK2 upregulation reduces brain glucose metabolism, linked to cognitive decline. | PMID: 28753428 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 12.5 | Medium |
| Heart | 9.8 | Medium |
| Liver | 6.2 | Low |
| Kidney | 8.1 | Medium |
| Brain | 7.4 | Medium |
| Pancreas | 5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical cancer cell line |
| MCF7 | 11.2 | Breast cancer cell line |
| HepG2 | 9.5 | Hepatocellular carcinoma cell line |
| A549 | 13.8 | Lung cancer cell line |
| SH-SY5Y | 7.1 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.01% | p.Met1Val; potential loss of start codon |
| c.101C>T | Missense | <0.01% | p.Thr34Met; functional impact unknown |
| c.1123G>A | Missense | <0.01% | p.Gly375Ser; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants may reduce kinase activity, leading to increased PDC activity and altered metabolism.
Gain of Function (GOF)
Not well characterized; overexpression in tumors suggests potential gain-of-function via increased expression.
Dominant Negative (DN)
No dominant-negative mutations reported in PDK2.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein kinase activity |
| • pyruvate dehydrogenase (acetyl-transferring) kinase activity | • mitochondrion |
| • regulation of glucose metabolic process | • response to hypoxia |
Pathways
• Pyruvate metabolism
• Glycolysis / Gluconeogenesis
• Metabolic reprogramming in cancer
• Insulin signaling
Protein Summary
PDK2 is a 407-amino acid mitochondrial serine/threonine kinase that phosphorylates the E1 alpha subunit of the pyruvate dehydrogenase complex (PDC). This phosphorylation inactivates PDC, reducing the conversion of pyruvate to acetyl-CoA and shifting metabolism toward lactate production. PDK2 is a key metabolic checkpoint in glucose homeostasis and is a therapeutic target in cancer and metabolic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDK2 Knockout HEK293 Cell Line | EDJ-KQ3278 | Human | 5164 | Details Get a Quote |
| PDK2 Knockout HCT 116 Cell Line | EDJ-KQ23446 | Human | 5164 | Details Get a Quote |
| PDK2 Knockout A-549 Cell Line | EDJ-KQ24831 | Human | 5164 | Details Get a Quote |
| PDK2 Knockout HeLa Cell Line | EDJ-KQ24833 | Human | 5164 | Details Get a Quote |
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