| + |
EGLN3 | up-regulates activity 
hydroxylation
|
PKM |
0.447 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267476 |
Pro403 |
EELRRLApITSDPTE |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 21620138 |
Interaction of PKM2 with prolyl hydroxylase 3 (PHD3) enhances PKM2 binding to HIF-1α and PKM2 coactivator function. Mass spectrometry and anti-hydroxyproline antibody assays demonstrate PKM2 hydroxylation on proline-403/408. PHD3 knockdown inhibits PKM2 coactivator function, reduces glucose uptake and lactate production, and increases O(2) consumption in cancer cells. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267477 |
Pro408 |
LAPITSDpTEATAVG |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 21620138 |
Interaction of PKM2 with prolyl hydroxylase 3 (PHD3) enhances PKM2 binding to HIF-1α and PKM2 coactivator function. Mass spectrometry and anti-hydroxyproline antibody assays demonstrate PKM2 hydroxylation on proline-403/408. PHD3 knockdown inhibits PKM2 coactivator function, reduces glucose uptake and lactate production, and increases O(2) consumption in cancer cells. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CyclinD3/CDK6 | down-regulates activity 
phosphorylation
|
PKM |
0.263 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273032 |
Ser37 |
MCRLDIDsPPITARN |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 28607489 |
Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3–CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2.|Phosphomimicking mutants of PFKP (S679E) or PKM2 (S37E) displayed decreased catalytic activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276453 |
Ser37 |
MCRLDIDsPPITARN |
Homo sapiens |
T-cell Acute Lymphoblastic Leukemia Cell |
| pmid |
sentence |
| 28607489 |
We show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2. Phosphomimicking mutants of PFKP (S679E) or PKM2 (S37E) displayed decreased catalytic activity, which was not further affected by pre-incubation with cyclin D3-CDK6 (Extended Data Fig. 3a, b). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276454 |
Ser37 |
MCRLDIDsPPITARN |
Homo sapiens |
|
| pmid |
sentence |
| 28607489 |
We show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2. Phosphomimicking mutants of PFKP (S679E) or PKM2 (S37E) displayed decreased catalytic activity, which was not further affected by pre-incubation with cyclin D3-CDK6 (Extended Data Fig. 3a, b). |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
TRIB2 | up-regulates activity
phosphorylation
|
PKM |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275431 |
Ser37 |
MCRLDIDsPPITARN |
Homo sapiens |
A-549 Cell |
| pmid |
sentence |
| 35790734 |
This study demonstrated that TRIB2, not a "pseudokinase", has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDC25A | up-regulates activity
dephosphorylation
|
PKM |
0.5 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276967 |
Ser37 |
MCRLDIDsPPITARN |
Homo sapiens |
|
| pmid |
sentence |
| 27485204 |
Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2 dependent beta-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.|Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent \u03b2-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PKM | up-regulates activity
phosphorylation
|
RBBP8 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277413 |
Thr126 |
ELMNERNtLQEENKK |
Homo sapiens |
U-87MG Cell |
| pmid |
sentence |
| 30297868 |
Here, we uncover an unexpected mechanism through which pyruvate kinase M2 (PKM2), the highly expressed PK isoform in cancer cells and a master regulator of cancer metabolic reprogramming, integrates with the DDR to directly promote DNA double-strand break (DSB) repair. In response to ionizing radiation and oxidative stress, ATM phosphorylates PKM2 at T328 resulting in its nuclear accumulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK8 | up-regulates activity
phosphorylation
|
PKM |
0.38 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276933 |
Thr365 |
CIMLSGEtAKGDYPL |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 26258887 |
Active JNK1 specifically activates PKM2 but not PKM1. Mechanistically, PARP14 inhibits the pro-apoptotic kinase JNK1, which results in the activation of PKM2 through phosphorylation of Thr365. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PIM2 | up-regulates quantity by stabilization
phosphorylation
|
PKM |
0.379 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267472 |
Thr454 |
RAPIIAVtRNPQTAR |
Homo sapiens |
|
| pmid |
sentence |
| 24142698 |
Here, we identified the protein-serine/threonine kinase PIM2, a known oncogene, as a novel binding partner of PKM2. The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells. Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. Compared with wild type, PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260905 |
Thr454 |
RAPIIAVtRNPQTAR |
Homo sapiens |
|
| pmid |
sentence |
| 24142698 |
Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PTPN6 | down-regulates activity
dephosphorylation
|
PKM |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276997 |
Tyr105 |
FASDPILyRPVAVAL |
Homo sapiens |
|
| pmid |
sentence |
| 26959741 |
SHP-1 dephosphorylates PKM2 at Y105 to inhibit nuclear function of PKM2 and determines the efficacy of targeted drugs.|SHP-1 directly dephosphorylated PKM2 at Y105 and further decreased the proliferative activity of PKM2; similar effects were found in sorafenib-treated hepatocellular carcinoma cells.|SHP-1 dephosphorylates p-PKM2Y105 and further affects the nucleus-related cell proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EGFR | down-regulates activity
phosphorylation
|
PKM |
0.463 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277197 |
Tyr148 |
KITLDNAyMEKCDEN |
Homo sapiens |
MDA-MB-468 Cell |
| pmid |
sentence |
| 26759242 |
EGFR binds to and phosphorylates PKM2 to inhibit its activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PKM | up-regulates activity
phosphorylation
|
STAT3 |
0.457 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267716 |
Tyr705 |
DPGSAAPyLKTKFIC |
in vitro |
|
| pmid |
sentence |
| 22306293 |
PKM2 activates transcription of MEK5 by phosphorylating stat3 at Y705. In vitro phosphorylation assays show that PKM2 is a protein kinase using PEP as a phosphate donor |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | FLT3-ITD signaling |
| + |
PKM | up-regulates
phosphorylation
|
STAT3 |
0.457 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-195766 |
Tyr705 |
DPGSAAPyLKTKFIC |
Homo sapiens |
|
| pmid |
sentence |
| 22306293 |
Pkm2 activates transcription of mek5 by phosphorylating stat3 at y705. pkm2 regulates mek5 transcription via activation of stat3 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
PKM | down-regulates quantity
chemical modification
|
phosphonatoenolpyruvate |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266534 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15996096 |
Pyruvate kinase (PK)1 is an important regulatory enzyme that is able to generate ATP under hypoxic conditions as well as regulate glucose consumption. Pyruvate kinase catalyzes the last step in glycolysis converting the substrate phosphoenolpyruvate (PEP) into pyruvate, while producing one molecule of ATP per reaction per cycle (Figure 1A). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glycolysis and Gluconeogenesis |
| + |
PKM | up-regulates activity
binding
|
HIF-1 complex |
0.399 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267473 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 21620138 |
PKM2 interacts directly with the HIF-1α subunit and promotes transactivation of HIF-1 target genes by enhancing HIF-1 binding and p300 recruitment to hypoxia response elements, |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glycolysis and Gluconeogenesis |
| + |
SREBF1 | up-regulates quantity by expression
transcriptional regulation
|
PKM |
0.295 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-142297 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16308421 |
Well-described targets of srebp-1 and the carbohydrate response element binding protein (chrebp), which include the following: fatty acid synthase (fas), acetyl coa carboxylase (acc1), and liver pyruvate kinase (l-pk) |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-166381 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20577053 |
Well-described targets of srebp-1 and the carbohydrate response element binding protein (chrebp), which include the following: fatty acid synthase (fas), acetyl coa carboxylase (acc1), and liver pyruvate kinase (l-pk) |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
ACP1 | up-regulates activity
dephosphorylation
|
PKM |
0.283 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277134 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30251652 |
Indeed, it is evident that LMW-PTP, hydrolyzing phosphotyrosine residues, contributes to maintain PKM2 in its active form.|We speculate that this effect is in large part due to LMW-PTP inhibition, which leads a fast PKM2 phosphorylation and inactivation.|we demonstrate that in melanoma cells the overexpression of LMW-PTP is functional to maintain PKM2 in its dephosphorylate status – the tetrameric, “full active” form - which is retained in the cytoplasm |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CREB1 | up-regulates quantity by expression 
transcriptional regulation
|
PKM |
0.252 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-142103 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16308421 |
In fasted mammals, glucose homeostasis is maintained through induction of the camp response element-binding protein (creb) coactivator transducer of regulated creb activity 2 (torc2), which stimulates the gluconeogenic program in concert with the forkhead factor foxo1 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-166346 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20577053 |
In fasted mammals, glucose homeostasis is maintained through induction of the camp response element-binding protein (creb) coactivator transducer of regulated creb activity 2 (torc2), which stimulates the gluconeogenic program in concert with the forkhead factor foxo1 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
L-serine | up-regulates activity
chemical activation
|
PKM |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251557 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23064226 |
We show that serine can bind to and activate human PKM2, and that PKM2 activity in cells is reduced in response to serine deprivation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Shikonin | down-regulates activity
chemical inhibition
|
PKM |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262008 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21516121 |
Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. |Shikonin and alkannin are potent inhibitors of recombinant human PKM2|Shikonin and alkannin significantly inhibited the glycolytic rate, as manifested by cellular lactate production and glucose consumption in drug-sensitive and resistant cancer cell lines (MCF-7, MCF-7/Adr, MCF-7/Bcl-2, MCF-7/Bcl-x(L) and A549) that primarily express PKM2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Alkannin | down-regulates activity
chemical inhibition
|
PKM |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262009 |
|
|
Homo sapiens |
MCF-7 Cell, A-549 Cell |
| pmid |
sentence |
| 21516121 |
Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. |Shikonin and alkannin are potent inhibitors of recombinant human PKM2|Shikonin and alkannin significantly inhibited the glycolytic rate, as manifested by cellular lactate production and glucose consumption in drug-sensitive and resistant cancer cell lines (MCF-7, MCF-7/Adr, MCF-7/Bcl-2, MCF-7/Bcl-x(L) and A549) that primarily express PKM2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PKM | up-regulates quantity
chemical modification
|
pyruvate |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266536 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15996096 |
Pyruvate kinase (PK)1 is an important regulatory enzyme that is able to generate ATP under hypoxic conditions as well as regulate glucose consumption. Pyruvate kinase catalyzes the last step in glycolysis converting the substrate phosphoenolpyruvate (PEP) into pyruvate, while producing one molecule of ATP per reaction per cycle (Figure 1A). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glycolysis and Gluconeogenesis |
3.0
PKM
- 
- 