Mouse Recombinant PKM1 protein, His Tag (V2LY-0526-LY1124)

pyruvate kinase M1/2

Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:20847263, 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:20847263, 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:20847263, PubMed:15996096, PubMed:1854723).
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 ARNTL/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).

Cellular response to insulin stimulusManual Assertion Based On ExperimentIBA:GO_Central
Glycolytic processManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of cytoplasmic translationISS:UniProtKB
Positive regulation of sprouting angiogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Programmed cell deathManual Assertion Based On ExperimentIDA:UniProtKB

Isoform M2
Cytoplasm
Nucleus
Translocates to the nucleus in response to various signals, such as EGF receptor activation or apoptotic stimuli (PubMed:17308100, PubMed:22056988, PubMed:24120661).
Nuclear translocation is promoted by acetylation by EP300 (PubMed:24120661).
Deacetylation by SIRT6 promotes its nuclear export in a process dependent of XPO4, thereby suppressing its ability to activate transcription and promote tumorigenesis (PubMed:26787900).
Isoform M1
Cytoplasm

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