PKM

Function

Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723). In addition to its role in glycolysis, also regulates transcription (PubMed:18191611, PubMed:21620138). Stimulates POU5F1-mediated transcriptional activation (PubMed:18191611). Promotes in a STAT1-dependent manner, the expression of the immune checkpoint protein CD274 in ARNTL/BMAL1-deficient macrophages (By similarity). Also acts as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a general role in caspase independent cell death of tumor cells (PubMed:17308100).

Pathway

Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5.

Post-translational modifications

ISGylated.

Under hypoxia, hydroxylated by EGLN3.

Acetylation at Lys-305 is stimulated by high glucose concentration, it decreases enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy.

FGFR1-dependent tyrosine phosphorylation is reduced by interaction with TRIM35.

Sequence similarities

Belongs to the pyruvate kinase family.

Tissue specificity

Specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells, as well as cancer cells.

Cellular localization

• Cytoplasm
• Nucleus
• Translocates to the nucleus in response to different apoptotic stimuli. Nuclear translocation is sufficient to induce cell death that is caspase independent, isoform-specific and independent of its enzymatic activity.

Alternative names

• Pyruvate kinase PKM
• Cytosolic thyroid hormone-binding protein
• Opa-interacting protein 3
• Pyruvate kinase 2/3
• Pyruvate kinase muscle isozyme
• Thyroid hormone-binding protein 1
• Tumor M2-PK
• p58
• CTHBP
• OIP-3
• THBP1
• PKM2
• PKM
• OIP3
• PK2
• PK3

Database links

• entrezGene:5315
• omim:179050
• swissprot:P14618

Target type

Proteins

Primary research area

Epigenetics

Other research areas

• Immunology & Infectious Disease

Molecular weight

57937Da