PKM
entrez
5315
canonical
uniprot
P14618
canonical
ensembl
ENSG00000067225
resolver
ensp
ENSP00000320171
resolver
ensp
ENSP00000334983
resolver
ensp
ENSP00000373745
resolver
ensp
ENSP00000455736
resolver
ensp
ENSP00000455901
resolver
ensp
ENSP00000513903
resolver
ensp
ENSP00000562019
resolver
ensp
ENSP00000562023
resolver
ensp
ENSP00000639913
resolver
enst
ENST00000389093
resolver
enst
ENST00000565154
resolver
enst
ENST00000565184
resolver
enst
ENST00000698741
resolver
genesymbol
HEL-S-30
resolver
genesymbol
PKM
resolver
genesymbol_syn
OIP3
resolver
genesymbol_syn
PK2
resolver
genesymbol_syn
PK3
resolver
genesymbol_syn
PKM2
resolver
hgnc
HGNC:9021
resolver
uniprot
A0A0A0MRZ0
resolver
uniprot
A0A804F6T5
resolver
uniprot
A0A804F729
resolver
uniprot
A0A8V8TNX9
resolver
uniprot
A6NFK3
resolver
uniprot
B2R5N8
resolver
uniprot
B3KRY0
resolver
uniprot
B4DFX8
resolver
uniprot
B4DNK4
resolver
uniprot
B4DUU6
resolver
uniprot
P14786
resolver
uniprot
Q53GK4
resolver
uniprot
Q96E76
resolver
uniprot
Q9BWB5
resolver
uniprot
Q9UCV6
resolver
uniprot
Q9UPF2
resolver
uniprot
V9HWB8
resolver
uniprot_entry
A0A0A0MRZ0_HUMAN
resolver
uniprot_entry
A0A804F6T5_HUMAN
resolver
uniprot_entry
A0A804F729_HUMAN
resolver
uniprot_entry
A0A8V8TNX9_HUMAN
resolver
uniprot_entry
B4DNK4_HUMAN
resolver
uniprot_entry
KPYM_HUMAN
resolver
uniprot_entry
V9HWB8_HUMAN
resolver
uniprot_sec
A6NFK3
resolver
uniprot_sec
B2R5N8
resolver
uniprot_sec
B3KRY0
resolver
uniprot_sec
B4DFX8
resolver
uniprot_sec
B4DUU6
resolver
uniprot_sec
P14786
resolver
uniprot_sec
Q53GK4
resolver
uniprot_sec
Q96E76
resolver
uniprot_sec
Q9BWB5
resolver
uniprot_sec
Q9UCV6
resolver
uniprot_sec
Q9UPF2
resolver
activity_regulation
ACTIVITY REGULATION: [Isoform M2]: Isoform M2 is allosterically activated by D-fructose 1,6-bisphosphate (FBP) (PubMed:15996096, PubMed:18337815, PubMed:1854723, PubMed:2813362). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3) (PubMed:15996096). The activity of the tetrameric form is inhibited by PML (PubMed:18298799). 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 (PubMed:18337815). 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 (PubMed:23064226). Acetylation at Lys-433 promotes its translocation into the nucleus and homodimerization, promoting the protein kinase activity (PubMed:24120661). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:18298799, ECO:0000269|PubMed:18337815, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:23064226, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:2813362}.; 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:0000269|PubMed:20847263}.
uniprot
proteins
amino_acid_sequence
MSKPHSEAGTAFIQTQQLHAAMADTFLEHMCRLDIDSPPITARNTGIICTIGPASRSVETLKEMIKSGMNVARLNFSHGTHEYHAETIKNVRTATESFASDPILYRPVAVALDTKGPEIRTGLIKGSGTAEVELKKGATLKITLDNAYMEKCDENILWLDYKNICKVVEVGSKIYVDDGLISLQVKQKGADFLVTEVENGGSLGSKKGVNLPGAAVDLPAVSEKDIQDLKFGVEQDVDMVFASFIRKASDVHEVRKVLGEKGKNIKIISKIENHEGVRRFDEILEASDGIMVARGDLGIEIPAEKVFLAQKMMIGRCNRAGKPVICATQMLESMIKKPRPTRAEGSDVANAVLDGADCIMLSGETAKGDYPLEAVRMQHLIAREAEAAIYHLQLFEELRRLAPITSDPTEATAVGAVEASFKCCSGAIIVLTKSGRSAHQVARYRPRAPIIAVTRNPQTARQAHLYRGIFPVLCKDPVQEAWAEDVDLRVNFAMNVGKARGFFKKGDVVIVLTGWRPGSGFTNTMRVVPVP
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 (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). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; 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 (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). Promotes transcription of VEGFA following translocation to the nucleus along with the NFKB1/p50 and RELA/p65 subunits of the NF-kappa-B transcription factor complex which is triggered by interaction with FOXM1 isoform 5 (FOXM1D) and leads to increased angiogenesis (PubMed:33314660). 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). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900, ECO:0000269|PubMed:33314660}.; FUNCTION: [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). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}.
uniprot
proteins
mass_dalton
57937
uniprot
proteins
mutagenesis
MUTAGEN 367; /note="K->M: Abolishes both pyruvate kinase and protein kinase activities."; /evidence="ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22901803"; MUTAGEN 399; /note="R->E: Impaired homotetramerization, leading to homodimerization and subsequent activation of the protein kinase activity."; /evidence="ECO:0000269|PubMed:22306293"; MUTAGEN 403; /note="P->A: Significant reduction in hydroxylation and in PKM-mediated transcriptional activity of HIF1A; when associated with A-408."; /evidence="ECO:0000269|PubMed:21620138"; MUTAGEN 408; /note="P->A: Significant reduction in hydroxylation and in PKM-mediated transcriptional activity of HIF1A; when associated with A-403."; /evidence="ECO:0000269|PubMed:21620138"; MUTAGEN 423..424; /note="CC->AA: Abolished S-nitrosylation, leading to increased pyruvate kinase activity."; /evidence="ECO:0000269|PubMed:30487609"; MUTAGEN 433; /note="K->E: Abolished interaction with phosphorylated CTNNB1. Impaired phosphorylation of histone H3."; /evidence="ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22901803"; MUTAGEN 433; /note="K->Q: Mimics acetylation, promoting homodimerization and activation of the protein kinase activity."; /evidence="ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900"; MUTAGEN 433; /note="K->R: Abolished acetylation by EP300. Abolished deacetylation by SIRT6."; /evidence="ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900"; MUTAGEN 437; /note="S->Y: Unable to bind FBP but still activated by serine."; /evidence="ECO:0000269|PubMed:23064226"; MUTAGEN 464; /note="H->A: Abolishes serine binding and allosteric activation."; /evidence="ECO:0000269|PubMed:23064226
uniprot
proteins
pathway_participation
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5. {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723}.
uniprot
proteins
post_translational_modification
PTM: ISGylated. {ECO:0000269|PubMed:16139798}.; PTM: Under hypoxia, hydroxylated by EGLN3. {ECO:0000269|PubMed:21620138}.; 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:0000269|PubMed:21700219, ECO:0000269|Ref.11}.; 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 (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). {ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; 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:0000269|PubMed:25263439}.
uniprot
proteins
protein_family
Pyruvate kinase family
uniprot
proteins
pubmed
12650930
uniprot
proteins
pubmed
12665801
uniprot
proteins
pubmed
14654843
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
15996096
uniprot
proteins
pubmed
16139798
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17308100
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18191611
uniprot
proteins
pubmed
18298799
uniprot
proteins
pubmed
18337815
uniprot
proteins
pubmed
18337823
uniprot
proteins
pubmed
1854723
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
2040271
uniprot
proteins
pubmed
20847263
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21483450
uniprot
proteins
pubmed
21620138
uniprot
proteins
pubmed
21700219
uniprot
proteins
pubmed
22056988
uniprot
proteins
pubmed
22306293
uniprot
proteins
pubmed
22901803
uniprot
proteins
pubmed
23064226
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23530218
uniprot
proteins
pubmed
24120661
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25263439
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26787900
uniprot
proteins
pubmed
27199445
uniprot
proteins
pubmed
27573352
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
2813362
uniprot
proteins
pubmed
2854097
uniprot
proteins
pubmed
30487609
uniprot
proteins
pubmed
32268273
uniprot
proteins
pubmed
33314660
uniprot
proteins
pubmed
9466265
uniprot
proteins
sequence_length
531
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform M2]: Cytoplasm {ECO:0000269|PubMed:25263439, ECO:0000269|PubMed:26787900, ECO:0000269|PubMed:27573352, ECO:0000269|PubMed:32268273}. Nucleus {ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900, ECO:0000269|PubMed:27573352, ECO:0000269|PubMed:32268273}. Note=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). {ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; SUBCELLULAR LOCATION: [Isoform M1]: Cytoplasm {ECO:0000305}.
uniprot
proteins