PKM

This gene encodes a protein involved in glycolysis. The encoded protein is a pyruvate kinase that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate to ADP, generating ATP and pyruvate. This protein has been shown to interact with thyroid hormone and may mediate cellular metabolic effects induced by thyroid hormones. This protein has been found to bind Opa protein, a bacterial outer membrane protein involved in gonococcal adherence to and invasion of human cells, suggesting a role of this protein in bacterial pathogenesis. Several alternatively spliced transcript variants encoding a few distinct isoforms have been reported.

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.