Activating Compound | Comment | Organism | Structure |
---|---|---|---|
D-fructose 1,6-bisphosphate | induces an association of two inactive dimers to the active tetrameric form | Homo sapiens | |
D-fructose 1,6-bisphosphate | induces an association of two inactive dimers to the active tetrameric form. M2-PK showing ProTalpha kinase activity is a trimeric association and possesses no observable pyruvate kinase activity. This association can be shifted by fructose 1,6-P2 to the tetrameric form which results in a reduction of ProTalpha-kinase activity | Mus musculus |
Application | Comment | Organism |
---|---|---|
diagnostics | M2-PK in stool is a screening marker for colorectal cancer. M2-PK in plasma is a marker for follow-up studies during tumor therapy | Homo sapiens |
drug development | M2-PK is a potential target for tumor therapy, detailed overview | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | IgE receptor FcepsilonRI rapid phosphorylation of tyrosine residues in M2-PK leads to its inhibition and initiation of mast cell degranulation | Homo sapiens | |
suppressor of cytokine signaling 3 | in dendritic cells the interaction of M2-PK with suppressor of cytokine signaling 3, SOCS3, induces a decrease of M2-PK activity and ATP production as well as an impairment of dendritic cell-based immunotherapy against tumors | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Homo sapiens | 5829 | - |
additional information | nuclear translocation of M2-PK by the somatostatin analogue TT232, H2O2 or UV light | Homo sapiens | - |
- |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Mus musculus | |
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + prothymosin alpha | Mus musculus | in normal murine lymphocytes and in tumor cells M2-PK phosphorylates prothymosin alpha on a threonine | ADP + phospho-prothymosin alpha | - |
? | |
ATP + pyruvate | Mus musculus | - |
ADP + phosphoenolpyruvate | - |
r | |
ATP + pyruvate | Homo sapiens | - |
ADP + phosphoenolpyruvate | - |
r | |
additional information | Homo sapiens | nuclear M2-PK participates in the phosphorylation of the epsilon-amino group of histone 1 by direct phosphate transfer from PEP without requiring ATP. M2-PK directly inters with different oncoproteins and components of the protein kinase cascade, such as HPV-16 E7, the tyrosine kinases pp60v-src, BCR-ABL, ETV6-NTRK3, FGFR-1, FLT3 and JAK-2, the serine/threonine kinase A-Raf, cytoplasmic promyelocytic leukemia tumor suppressor protein as well as phosphotyrosine peptides | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | IgE receptor FcepsilonRI rapid phosphorylation of tyrosine residues in M2-PK leads to its inhibition and initiation of mast cell degranulation | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
adipocyte | expression of M2-type pyruvate kinase isoenzyme | Homo sapiens | - |
embryo | expression of M2-type pyruvate kinase isoenzyme | Homo sapiens | - |
Henles loop | expression of M2-type pyruvate kinase isoenzyme | Homo sapiens | - |
lung | expression of M2-type pyruvate kinase isoenzyme | Homo sapiens | - |
lymphocyte | - |
Mus musculus | - |
additional information | M2-type pyruvate kinase isoenzyme is expressed in different differentiated cells and tissues as well as in all proliferating cells | Mus musculus | - |
additional information | M2-type pyruvate kinase isoenzyme is expressed in different differentiated cells and tissues as well as in all proliferating cells. Increase of tumor M2-PK in plasma of patients with renal cell carcinoma, melanoma, lung, breast, cervical, ovarian, oesopharyngeal, gastric, pancreatic and colorectal cancer as well as in pleural fluid of patients with chest malignancies which correlates with tumor stages | Homo sapiens | - |
pancreatic islet | expression of M2-type pyruvate kinase isoenzyme | Homo sapiens | - |
renal medulla | expression of M2-type pyruvate kinase isoenzyme | Homo sapiens | - |
renal tubule | distal, expression of M2-type pyruvate kinase isoenzyme | Homo sapiens | - |
retina | expression of M2-type pyruvate kinase isoenzyme | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + prothymosin alpha | in normal murine lymphocytes and in tumor cells M2-PK phosphorylates prothymosin alpha on a threonine | Mus musculus | ADP + phospho-prothymosin alpha | - |
? | |
ATP + prothymosin alpha | ProTalpha kinase activity | Mus musculus | ADP + phospho-prothymosin alpha | - |
? | |
ATP + pyruvate | - |
Mus musculus | ADP + phosphoenolpyruvate | - |
r | |
ATP + pyruvate | - |
Homo sapiens | ADP + phosphoenolpyruvate | - |
r | |
additional information | nuclear M2-PK participates in the phosphorylation of the epsilon-amino group of histone 1 by direct phosphate transfer from PEP without requiring ATP. M2-PK directly inters with different oncoproteins and components of the protein kinase cascade, such as HPV-16 E7, the tyrosine kinases pp60v-src, BCR-ABL, ETV6-NTRK3, FGFR-1, FLT3 and JAK-2, the serine/threonine kinase A-Raf, cytoplasmic promyelocytic leukemia tumor suppressor protein as well as phosphotyrosine peptides | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | nearly inactive dimeric form | Mus musculus |
dimer | nearly inactive dimeric form | Homo sapiens |
More | in tumors, the dimeric form of M2-PK is predominant due to direct interaction with different oncoproteins and components of the protein kinase cascade, such as HPV-16 E7, the tyrosine kinases pp60v-src, BCR-ABL, ETV6-NTRK3, FGFR-1, FLT3 and JAK-2, the serine/threonine kinase A-Raf, cytoplasmic promyelocytic leukemia tumor suppressor protein as well as phosphotyrosine peptides | Homo sapiens |
tetramer | highly active tetrameric form | Mus musculus |
tetramer | highly active tetrameric form | Homo sapiens |
trimer | M2-PK showing ProTalpha kinase activity is a trimeric association and possesses no observable pyruvate kinase activity | Mus musculus |
Synonyms | Comment | Organism |
---|---|---|
M2-PK | - |
Mus musculus |
M2-PK | - |
Homo sapiens |
PKM2 | - |
Mus musculus |
PKM2 | - |
Homo sapiens |
pyruvate kinase M2 | - |
Mus musculus |
pyruvate kinase M2 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ADP | - |
Mus musculus | |
ADP | - |
Homo sapiens | |
ATP | - |
Mus musculus | |
ATP | - |
Homo sapiens |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | HIF-1alpha induces an increased transcription of the pyruvate kinase M gene.. Induction of M2-PK expression by hypermethylated secreted frizzled related protein and mutated adenomatous polyposis coli protein, APC, overview | up |
General Information | Comment | Organism |
---|---|---|
malfunction | missense mutations of M2-PK are described in the lymphocytes of an Indian Bloom syndrome patient. Inhibition of M2-PK isdirectly linked with the initiation of mast cell degranulation | Homo sapiens |
additional information | expression of M2-PK is under the control of nutrients, insulin, different transcription factors such as SP1, SP3, HIF-1alpha, as well as c-myc, the zonula occludens protein 2 (ZO-2), Ras and microRNA 133a and 133b | Homo sapiens |
physiological function | pyruvate kinase is a glycolytic enzyme catalyzing the ATP regenerating dephosphorylation of phosphoenolpyruvate to pyruvate. Pyruvate kinase is responsible for net ATP production within the glycolytic sequence. Besides its role as glycolytic enzyme M2-PK may also function as protein kinase | Mus musculus |
physiological function | pyruvate kinase is a glycolytic enzyme catalyzing the ATP regenerating dephosphorylation of phosphoenolpyruvate to pyruvate. Pyruvate kinase is responsible for net ATP production within the glycolytic sequence. Besides its role as glycolytic enzyme M2-PK may also function as protein kinase. In tumor metabolism the quaternary structure of M2-PK (tetramer:dimer ratio) determines whether glucose is used for glycolytic energy regeneration (highly active tetrameric form, Warburg effect) or synthesis of cell building blocks (nearly inactive dimeric form) which are both prerequisites for cells with a high proliferation rate. In tumor cells the nearly inactive dimeric form of M2-PK is predominant due to direct interactions with different oncoproteins. Besides its key functions in tumor metabolism, M2-PK may also react as protein kinase as well as co activator of transcription factors. The mTOR/HIF-1a/c-myc/M2-PK cascade may be one explanation for the increased aerobic glycolysis in tumor cells first described by Otto Warburg, overview. Nuclear translocation of M2-PK by the somatostatin analogue TT232, H2O2 or UV light are linked to the induction of caspase independent apoptosis. M2-PK binds to the mast cell IgE receptor FcepsilonRI and plays a crucial role in responses to allergens | Homo sapiens |