The PDK3 gene (3-Phosphoinositide-Dependent Protein Kinase 3) encodes a member of the phosphoinositide-dependent protein kinase (PDK) family. PDK3 is a serine/threonine kinase that plays important roles in cell survival, metabolism, and stress responses. It is expressed in various tissues, with high expression in brain, and is implicated in neurodegenerative diseases and cancer.
| Attribute |
Value |
| Symbol |
PDK3 |
| Full Name |
3-Phosphoinositide-Dependent Protein Kinase 3 |
| Chromosomal Location |
Xp22.11 |
| NCBI Gene ID |
5165 |
| OMIM ID |
300341 |
| Ensembl ID |
ENSG00000168268 |
| UniProt ID |
O95819 |
| Protein Size |
350 amino acids |
| Molecular Weight |
~39 kDa |
PDK3 contains characteristic features:
- Kinase Domain: Serine/threonine kinase activity
- PH Domain: Phosphoinositide binding (present in some isoforms)
- Regulatory Regions: Autoinhibitory and activation segments
- Akt Activation: PDK3 phosphorylates and activates Akt/PKB
- PKC Activation: Regulates protein kinase C isoforms
- Cell Survival: Promotes cell survival under stress conditions
- Glucose Metabolism: Insulin signaling pathway component
- Lipid Metabolism: Affects lipid synthesis and storage
- Mitochondrial Function: Regulates mitochondrial activity
- Oxidative Stress: Activated in response to ROS
- DNA Damage: Involved in DNA damage responses
- Hypoxia: Regulates hypoxic responses
PDK3 is widely expressed:
Expression is regulated by developmental stage and metabolic conditions.
- Tau Phosphorylation: May contribute to tau pathology
- Cell Survival: Dysregulation affects neuronal viability
- Metabolic Dysfunction: Links to brain metabolic deficits
- Dopaminergic Neurons: Altered expression in substantia nigra
- Mitochondrial Function: Regulates mitochondrial health
- Oncogenic Role: Overexpressed in various cancers
- Cell Proliferation: Promotes cancer cell growth
- Therapeutic Target: PDK3 inhibitors in development
- Diabetes: Altered insulin signaling
- Obesity: Metabolic dysfunction
PDK3 participates in multiple pathways:
- PI3K/Akt Pathway: Central cell survival pathway
- mTOR Pathway: Growth and metabolism regulation
- AMPK Pathway: Energy sensing
- MAPK Pathway: Stress responses
| Compound |
Mechanism |
Status |
| BX-517 |
PDK1/3 selective inhibitor |
Research |
| OSU-03012 |
Multi-PDK inhibitor |
Preclinical |
| Compound 20 |
PDK3 selective |
Research |
- PDK3 knockout mice show developmental abnormalities
- PDK3 promotes neuronal survival under stress conditions
- Targeting PDK3 shows therapeutic potential in models