PCK2: Phosphoenolpyruvate Carboxykinase 2 (Mitochondrial)
Key enzyme in gluconeogenesis and glyceroneogenesis, implicated in metabolic disorders and cancer.
Gene Information Card
| Symbol | PCK2 |
|---|---|
| Full Name | Phosphoenolpyruvate Carboxykinase 2 (Mitochondrial) |
| Gene Type | Protein coding |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 5106 ncbi.nlm.nih.gov/gene/5106 |
| Ensembl ID | ENSG00000100889 |
| UniProt ID | Q16822 |
| OMIM ID | 261650 |
| HGNC ID | 8727 |
| Aliases | PEPCK-M, PEPCK2, M-PEPCK |
Description
PCK2 encodes the mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK-M), a key enzyme in gluconeogenesis, glyceroneogenesis, and serinogenesis. It catalyzes the GTP-dependent decarboxylation of oxaloacetate to phosphoenolpyruvate, bypassing the cytosolic PEPCK1. PCK2 is expressed in multiple tissues and plays a role in metabolic adaptation, including in cancer cells where it supports anabolic pathways.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Metabolic syndrome | Altered gluconeogenesis and lipid metabolism | OMIM #261650; GWAS studies |
| Type 2 diabetes | Dysregulation of hepatic glucose production | PMID: 23493553 |
| Non-alcoholic fatty liver disease (NAFLD) | Increased PCK2 expression linked to steatosis | PMID: 25635004 |
| Cancer (various) | Supports serine biosynthesis and redox balance in tumors | COSMIC; PMID: 28991257 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Adipose tissue | 8.7 | Medium |
| Brain | 6.3 | Low |
| Heart | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line |
| HEK293 | 9.8 | Embryonic kidney cells |
| MCF7 | 7.2 | Breast cancer cell line |
| A549 | 6.5 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Potential loss of start codon; ClinVar |
| c.104C>T (p.Thr35Met) | Missense | 0.02% | Unknown significance; ClinVar |
| c.1246G>A (p.Gly416Ser) | Missense | 0.01% | Reported in COSMIC; cancer sample |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Met1?) likely abolish protein expression or catalytic activity.
Gain of Function (GOF)
Not well characterized; some cancer-associated variants may increase enzyme stability.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • phosphoenolpyruvate carboxykinase activity (GO:0004611) | • gluconeogenesis (GO:0006094) |
| • mitochondrion (GO:0005739) | • carboxylic acid metabolic process (GO:0019752) |
| • GTP binding (GO:0005525) |
Pathways
• Gluconeogenesis (Reactome: R-HSA-70263)
• Glyceroneogenesis (Reactome: R-HSA-70263)
• Serine biosynthesis (Reactome: R-HSA-389542)
Protein Summary
PCK2 is a 640-amino acid mitochondrial enzyme that catalyzes the rate-limiting step of gluconeogenesis. It uses GTP to convert oxaloacetate to phosphoenolpyruvate and CO2. Unlike the cytosolic isoform PCK1, PCK2 is not regulated by insulin but is induced by fasting and cAMP. In cancer, PCK2 supports serine synthesis and redox balance, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PCK2 Knockout HEK293 Cell Line | EDJ-KQ1544 | Human | 5106 | Details Get a Quote |
| PCK2 Knockout HCT 116 Cell Line | EDJ-KQ21216 | Human | 5106 | Details Get a Quote |
| PCK2 Knockout A-549 Cell Line | EDJ-KQ19851 | Human | 5106 | Details Get a Quote |
| PCK2 Knockout HeLa Cell Line | EDJ-KQ21217 | Human | 5106 | Details Get a Quote |
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