Pkm
entrez
18746
canonical
uniprot
P52480
canonical
ensembl
ENSMUSG00000032294
resolver
ensp
ENSMUSP00000034834
resolver
ensp
ENSMUSP00000128770
resolver
ensp
ENSMUSP00000226656
resolver
ensp
ENSMUSP00000226694
resolver
ensp
ENSMUSP00000226696
resolver
ensp
ENSMUSP00000331515
resolver
ensp
ENSMUSP00000331523
resolver
ensp
ENSMUSP00000331524
resolver
ensp
ENSMUSP00000358022
resolver
genesymbol
Pkm
resolver
genesymbol_syn
Pk3
resolver
genesymbol_syn
Pkm2
resolver
genesymbol_syn
Pykm
resolver
uniprot
Q3TBV8
resolver
uniprot
Q3TBW5
resolver
uniprot
Q3TC59
resolver
uniprot
Q3U1X3
resolver
uniprot
Q3U5P6
resolver
uniprot
Q4VC20
resolver
uniprot
Q64484
resolver
uniprot
Q91YI8
resolver
uniprot
Q9CWB1
resolver
uniprot_entry
KPYM_MOUSE
resolver
uniprot_sec
Q3TBV8
resolver
uniprot_sec
Q3TBW5
resolver
uniprot_sec
Q3TC59
resolver
uniprot_sec
Q3U1X3
resolver
uniprot_sec
Q3U5P6
resolver
uniprot_sec
Q4VC20
resolver
uniprot_sec
Q64484
resolver
uniprot_sec
Q91YI8
resolver
uniprot_sec
Q9CWB1
resolver
activity_regulation
ACTIVITY REGULATION: [Isoform M2]: Isoform M2 is allosterically activated by D-fructose 1,6-bisphosphate (FBP). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3). The activity of the tetrameric form is inhibited by PML. Selective binding to tyrosine-phosphorylated peptides releases the allosteric activator FBP, leading to inhibition of PKM enzymatic activity, this diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Glycolytic flux are highly dependent on de novo biosynthesis of serine and glycine, and serine is a natural ligand and allosteric activator of isoform M2. Acetylation at Lys-433 promotes its translocation into the nucleus and homodimerization, promoting the protein kinase activity. {ECO:0000250|UniProtKB:P14618}.; ACTIVITY REGULATION: [Isoform M1]: Has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity. {ECO:0000250|UniProtKB:P14618}.
uniprot
proteins
amino_acid_sequence
MPKPHSEAGTAFIQTQQLHAAMADTFLEHMCRLDIDSAPITARNTGIICTIGPASRSVEMLKEMIKSGMNVARLNFSHGTHEYHAETIKNVREATESFASDPILYRPVAVALDTKGPEIRTGLIKGSGTAEVELKKGATLKITLDNAYMEKCDENILWLDYKNICKVVEVGSKIYVDDGLISLQVKEKGADFLVTEVENGGSLGSKKGVNLPGAAVDLPAVSEKDIQDLKFGVEQDVDMVFASFIRKAADVHEVRKVLGEKGKNIKIISKIENHEGVRRFDEILEASDGIMVARGDLGIEIPAEKVFLAQKMMIGRCNRAGKPVICATQMLESMIKKPRPTRAEGSDVANAVLDGADCIMLSGETAKGDYPLEAVRMQHLIAREAEAAIYHLQLFEELRRLAPITSDPTEAAAVGAVEASFKCCSGAIIVLTKSGRSAHQVARYRPRAPIIAVTRNPQTARQAHLYRGIFPVLCKDAVLNAWAEDVDLRVNLAMDVGKARGFFKKGDVVIVLTGWRPGSGFTNTMRVVPVP
uniprot
proteins
ec_number
2.7.1.40
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: 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. {ECO:0000250|UniProtKB:P14618}.; FUNCTION: [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). {ECO:0000250|UniProtKB:P14618, ECO:0000269|PubMed:28575669, ECO:0000269|PubMed:29996098}.; FUNCTION: [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. {ECO:0000250|UniProtKB:P14618}.
uniprot
proteins
mass_dalton
57845
uniprot
proteins
mutagenesis
MUTAGEN 367; /note="K->M: Abolishes pyruvate kinase activity without affecting interaction with the ribosome."; /evidence="ECO:0000269|PubMed:28575669"; MUTAGEN 423..424; /note="CC->AA: In knockin mice; abolished S-nitrosylation, leading to increased pyruvate kinase activity."; /evidence="ECO:0000269|PubMed:30487609"; MUTAGEN 464; /note="H->A: Abolishes amino-acid binding without affecting interaction with the translating ribosome."; /evidence="ECO:0000269|PubMed:28575669
uniprot
proteins
pathway_participation
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5. {ECO:0000250|UniProtKB:P14618}.
uniprot
proteins
post_translational_modification
PTM: ISGylated. {ECO:0000269|PubMed:16139798}.; PTM: Under hypoxia, hydroxylated by EGLN3. {ECO:0000250|UniProtKB:P14618}.; PTM: Acetylation at Lys-305 is stimulated by high glucose concentration, it decreases enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy. {ECO:0000250|UniProtKB:P14618}.; PTM: [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. {ECO:0000250|UniProtKB:P14618}.; PTM: [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). {ECO:0000269|PubMed:30487609}.; PTM: FGFR1-dependent tyrosine phosphorylation is reduced by interaction with TRIM35. {ECO:0000250|UniProtKB:P14618}.
uniprot
proteins
protein_family
Pyruvate kinase family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16139798
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
18034455
uniprot
proteins
pubmed
18191611
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
28575669
uniprot
proteins
pubmed
29996098
uniprot
proteins
pubmed
30487609
uniprot
proteins
pubmed
7612666
uniprot
proteins
pubmed
9545585
uniprot
proteins
sequence_length
531
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform M2]: Cytoplasm {ECO:0000250|UniProtKB:P14618}. Nucleus {ECO:0000250|UniProtKB:P14618}. Note=Translocates to the nucleus in response to various signals, such as EGF receptor activation or apoptotic stimuli. Nuclear translocation is promoted by acetylation by EP300. Deacetylation by SIRT6 promotes its nuclear export in a process dependent of XPO4, thereby suppressing its ability to activate transcription and promote tumorigenesis. {ECO:0000250|UniProtKB:P14618}.; SUBCELLULAR LOCATION: [Isoform M1]: Cytoplasm {ECO:0000250|UniProtKB:P14618}.
uniprot
proteins