Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. 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. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.
Isoform M2
Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (By similarity). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (By similarity). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (By similarity). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (By similarity). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (By similarity). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (PubMed:29996098). May also act 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 (PubMed:28575669). Plays a role in caspase independent cell death of tumor cells (By similarity).
Isoform M1
Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth. In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity.
Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5.
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.
Isoform M2
Acetylated at Lys-433 by EP300, leading to impair phosphoenolpyruvate substrate-binding and promote its homodimerization and subsequent translocation to the nucleus. Deacetylation at Lys-433 by SIRT6 promotes its nuclear export into the cytoplasm, leading to suppress its nuclear localization and oncogenic function.
Isoform M2
S-nitrosylation at Cys-423 and Cys-424 inhibits homotetramerization and pyruvate kinase activity (PubMed:30487609). S-nitrosylation is indirectly inhibited by AKR1A1 which degrades S-nitroso-CoA, a cofactor required to S-nitrosylate proteins (PubMed:30487609).
FGFR1-dependent tyrosine phosphorylation is reduced by interaction with TRIM35.
Belongs to the pyruvate kinase family.
Embryonic stem cells and embryonal carcinoma cells.
Pk3, Pkm2, Pykm, Pkm, Pyruvate kinase PKM, Pyruvate kinase muscle isozyme, Threonine-protein kinase PKM2, Tyrosine-protein kinase PKM2
Proteins
Metabolism
57845Da
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