Recombinant human PKM2 protein (His tag)

일반 정보

기능

Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed : 15996096, PubMed : 1854723, PubMed : 20847263). 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, PubMed : 20847263). 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, PubMed : 20847263).. 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 (PubMed : 18337823, PubMed : 20847263). 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 (PubMed : 18191611, PubMed : 21620138, PubMed : 22056988, PubMed : 22306293, PubMed : 22901803, PubMed : 24120661). 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 (PubMed : 22056988, PubMed : 22306293, PubMed : 22901803, PubMed : 24120661, PubMed : 26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed : 22306293, PubMed : 22901803, PubMed : 24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed : 18337823, PubMed : 22901803, PubMed : 26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). 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 (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed : 17308100).. Isoform M1. Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed : 18337823). 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 (PubMed : 20847263).

서열 유사성

Belongs to the pyruvate kinase family.

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.. Isoform M2. Acetylated at Lys-433 by EP300, leading to impair phosphoenolpyruvate substrate-binding and promote its homodimerization and subsequent translocation to the nucleus (PubMed:24120661). Deacetylation at Lys-433 by SIRT6 promotes its nuclear export into the cytoplasm, leading to suppress its nuclear localization and oncogenic function (PubMed:26787900).. 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.