Molecule Information

General Information of the Molecule (ID: Mol01902)

• Name: Pyruvate dehydrogenase kinase 2 (PDK2) ,Homo sapiens
• Synonyms: PDK2; PDHK2
• Molecule Type: Protein
• Gene Name: PDK2
• Gene ID: 5164
• Location: chr17:50,094,737-50,112,152[+]
• Sequence:
  MRWVWALLKNASLAGAPKYIEHFSKFSPSPLSMKQFLDFGSSNACEKTSFTFLRQELPVR
  LANIMKEINLLPDRVLSTPSVQLVQSWYVQSLLDIMEFLDKDPEDHRTLSQFTDALVTIR
  NRHNDVVPTMAQGVLEYKDTYGDDPVSNQNIQYFLDRFYLSRISIRMLINQHTLIFDGST
  NPAHPKHIGSIDPNCNVSEVVKDAYDMAKLLCDKYYMASPDLEIQEINAANSKQPIHMVY
  VPSHLYHMLFELFKNAMRATVESHESSLILPPIKVMVALGEEDLSIKMSDRGGGVPLRKI
  ERLFSYMYSTAPTPQPGTGGTPLAGFGYGLPISRLYAKYFQGDLQLFSMEGFGTDAVIYL
  KALSTDSVERLPVYNKSAWRHYQTIQEAGDWCVPSTEPKNTSTYRVS
• Function: Kinase that plays a key role in the 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. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. 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. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.
• Uniprot ID: PDK2_HUMAN
• Ensembl ID: ENSG00000005882
• HGNC ID: HGNC:8810

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian clear cell Carcinoma [1]

• Resistant Disease: Ovarian clear cell Carcinoma [ICD-11: 2C73.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: RMG5 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: RMG1 cells; Ovary; Homo sapiens (Human); CVCL_1662
• In Vivo Model: ICR/nu female mice model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR; Western blotting assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: Patients with high expression of pyruvate dehydrogenase kinase 2 (PDK2) had a worse prognosis than those with low PDK2 expression. Furthermore, inhibition of PDK2 synergistically enhanced cisplatin sensitivity by activating the electron transport chain and by increasing the production of mitochondrial reactive oxygen species.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.93E-02; Fold-change: -1.63E-01; Z-score: -4.38E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.14E-02; Fold-change: 1.60E-01; Z-score: 5.08E-01

References

• Ref 1: PDK2 leads to cisplatin resistance through suppression of mitochondrial function in ovarian clear cell carcinoma .Cancer Sci. 2021 Nov;112(11):4627-4640. doi: 10.1111/cas.15125. Epub 2021 Sep 13. 10.1111/cas.15125