| + |
PRKAA1 | up-regulates activity 
phosphorylation
|
NFE2L2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277494 |
Ser374 |
GDTLLGLsDSEVEEL |
in vitro |
|
| pmid |
sentence |
| 31805502 |
MS-based analysis of immunoprecipitated Nrf2 revealed serine 374, 408 and 433 in human Nrf2 to be hyperphosphorylated as a function of activated AMPK. A direct phosphate-transfer by AMPK to those sites was indicated by in vitro kinase assays with recombinant proteins as well as interaction of AMPK and Nrf2 in cells, evident by co-immunoprecipitation. Mutation of serine 374, 408 and 433 to alanine did not markedly affect half-life, nuclear accumulation or induction of reporter gene expression upon Nrf2 activation with sulforaphane. However, some selected endogenous Nrf2 target genes responded with decreased induction when the identified phosphosites were mutated, whereas others remained unaffected. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277496 |
Ser408 |
GDMVQPLsPSQGQST |
in vitro |
|
| pmid |
sentence |
| 31805502 |
MS-based analysis of immunoprecipitated Nrf2 revealed serine 374, 408 and 433 in human Nrf2 to be hyperphosphorylated as a function of activated AMPK. A direct phosphate-transfer by AMPK to those sites was indicated by in vitro kinase assays with recombinant proteins as well as interaction of AMPK and Nrf2 in cells, evident by co-immunoprecipitation. Mutation of serine 374, 408 and 433 to alanine did not markedly affect half-life, nuclear accumulation or induction of reporter gene expression upon Nrf2 activation with sulforaphane. However, some selected endogenous Nrf2 target genes responded with decreased induction when the identified phosphosites were mutated, whereas others remained unaffected. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277495 |
Ser433 |
PEKELPVsPGHRKTP |
in vitro |
|
| pmid |
sentence |
| 31805502 |
MS-based analysis of immunoprecipitated Nrf2 revealed serine 374, 408 and 433 in human Nrf2 to be hyperphosphorylated as a function of activated AMPK. A direct phosphate-transfer by AMPK to those sites was indicated by in vitro kinase assays with recombinant proteins as well as interaction of AMPK and Nrf2 in cells, evident by co-immunoprecipitation. Mutation of serine 374, 408 and 433 to alanine did not markedly affect half-life, nuclear accumulation or induction of reporter gene expression upon Nrf2 activation with sulforaphane. However, some selected endogenous Nrf2 target genes responded with decreased induction when the identified phosphosites were mutated, whereas others remained unaffected. |
|
| Publications: |
3 |
Organism: |
In Vitro |
| + |
PRKCD | up-regulates activity
phosphorylation
|
NFE2L2 |
0.371 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249161 |
Ser40 |
SREVFDFsQRRKEYE |
in vitro |
|
| pmid |
sentence |
| 12198130 |
Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
PRKCB | up-regulates
phosphorylation
|
NFE2L2 |
0.417 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91830 |
Ser40 |
SREVFDFsQRRKEYE |
Homo sapiens |
|
| pmid |
sentence |
| 12198130 |
Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKCA | up-regulates
phosphorylation
|
NFE2L2 |
0.534 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91826 |
Ser40 |
SREVFDFsQRRKEYE |
Homo sapiens |
|
| pmid |
sentence |
| 12198130 |
Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PAK4 | down-regulates quantity by destabilization 
phosphorylation
|
NFE2L2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277583 |
Thr369 |
ESSSYGDtLLGLSDS |
Mus musculus |
Hepatocyte |
| pmid |
sentence |
| 35108418 |
PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
FYN | down-regulates quantity
phosphorylation
|
NFE2L2 |
0.403 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278358 |
Tyr576 |
RDEDGKPySPSEYSL |
Homo sapiens |
|
| pmid |
sentence |
| 23434765 |
Fyn phosphorylates Nrf2 Y568, resulting in nuclear export and degradation of Nrf2.|Fyn phosphorylates Nrf2Y568 resulting in nuclear export and degradation of Nrf2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
NQO1 |
0.49 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279860 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.NFE2L2-mediated upregulation of NQO1 is implicated in promoting resistance to ferroptosis inducers, such as erastin and sorafenib, in HCC cells |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
HMOX1 |
0.682 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279861 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Heme oxygenase 1 (HMOX1, also known as HO-1), an NFE2L2-dependent inducible enzyme, plays a crucial role in the degradation of heme, a pro-oxidant, into three biologically active products: biliverdin, free iron, and carbon monoxide |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256276 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24024136 |
In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs). |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
Ferritin |
0.3 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279862 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. In HCC cells, NFE2L2-mediated upregulation of FTH1 enhances the cellular antioxidant defense by increasing the capacity for iron storage, thereby reducing erastin- or sorafenib-induced ferroptosis |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
SLC40A1 |
0.258 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279863 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. SLC40A1 is a target gene of NFE2L2, with a putative ARE identified approximately -7 kb upstream of the SLC40A1 core promoter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
MT1G |
0.287 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279866 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. The expression of MT1G during ferroptosis is regulated by the NFE2L2 signaling pathway. In the context of cancer, particularly HCC, the upregulation of MT1G has been linked to resistance against sorafenib, a kinase inhibitor commonly used in cancer therapy |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
SLC7A11 |
0.427 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279867 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. NFE2L2 directly binds to the promoter region of SLC7A11, leading to increased expression of this transporter, which in turn contributes to the resistance to ferroptosis and to radiotherapy |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
GCLC |
0.473 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279868 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256277 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24024136 |
In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs). |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
GCLM |
0.442 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279869 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
GSS |
0.312 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279870 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
GSTA1 |
0.344 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256278 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24024136 |
In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
NFE2L2 | down-regulates quantity by repression 
transcriptional regulation
|
GSTA1 |
0.344 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254644 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22459801 |
Different expression pattern of Nrf2 regulated genes in end-stage liver disease samples were observed: glutamate-cysteine ligase (GCLC) and glutathione-S-transferase A1 (GSTA1) were significantly down-regulated in most liver disease groups, whereas heme oxidase 1 (HMOX1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) were not significantly suppressed. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
PXDN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265248 |
|
|
Homo sapiens |
HeLa Cell, HEK-293 Cell |
| pmid |
sentence |
| 29953917 |
PXDN expression in response to H2O2 and the Nrf2-specific inducers, tert-butylhydroquinone (tBHQ) and sulforaphane (SFN), was determined by western blotting and immunofluorescence microscopy, in HeLa and HEK293 cells.We found that Nrf2 binds to and increases luciferase reporter gene expression from the PXDN promoter via a putative Nrf2-binding site. In summary, we show that PXDN is a novel target of the redox sensitive transcription factor Nrf2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression 
transcriptional regulation
|
PGD |
0.282 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267355 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22789539 |
We identified six genes involved in the PPP and NADPH production pathways as direct targets of Nrf2. To identify the target genes of NRF2 responsible for cell proliferation, we performed microarray analysis in A549 cells treated with NRF2 siRNA or control siRNA. We used three independent NRF2 siRNAs and selected genes whose expression levels were reduced to less than 66.7% of that of the control sample by all three siRNAs to minimize off-target effects (Table S1). In addition to the typical target genes of NRF2 encoding detoxifying enzymes and antioxidant proteins (cytoprotective genes), genes whose products are involved in the PPP (glucose-6-phosphate dehydrogenase [G6PD], phosphogluconate dehydrogenase [PGD], transketolase [TKT], and transaldolase 1 [TALDO1]) and de novo nucleotide synthesis (phosphoribosyl pyrophosphate amidotransferase [PPAT] and methylenetetrahydrofolate dehydrogenase 2 [MTHFD2]) were decreased by the NRF2 knockdown (Figure 1B). Genes encoding enzymes for NADPH synthesis (malic enzyme 1 [ME1] and isocitrate dehydrogenase 1 [IDH1]) were also decreased (Figure 1B). We also confirmed the reduction of the enzyme proteins encoded by these genes in the NRF2-knockdown cells (Figure 1C). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Pentose phosphate pathway |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
TALDO1 |
0.369 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267357 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22789539 |
We identified six genes involved in the PPP and NADPH production pathways as direct targets of Nrf2. To identify the target genes of NRF2 responsible for cell proliferation, we performed microarray analysis in A549 cells treated with NRF2 siRNA or control siRNA. We used three independent NRF2 siRNAs and selected genes whose expression levels were reduced to less than 66.7% of that of the control sample by all three siRNAs to minimize off-target effects (Table S1). In addition to the typical target genes of NRF2 encoding detoxifying enzymes and antioxidant proteins (cytoprotective genes), genes whose products are involved in the PPP (glucose-6-phosphate dehydrogenase [G6PD], phosphogluconate dehydrogenase [PGD], transketolase [TKT], and transaldolase 1 [TALDO1]) and de novo nucleotide synthesis (phosphoribosyl pyrophosphate amidotransferase [PPAT] and methylenetetrahydrofolate dehydrogenase 2 [MTHFD2]) were decreased by the NRF2 knockdown (Figure 1B). Genes encoding enzymes for NADPH synthesis (malic enzyme 1 [ME1] and isocitrate dehydrogenase 1 [IDH1]) were also decreased (Figure 1B). We also confirmed the reduction of the enzyme proteins encoded by these genes in the NRF2-knockdown cells (Figure 1C). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Pentose phosphate pathway |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
TFB2M |
0.251 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268996 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15684387 |
Here, we establish that the expression of human TFB1M and TFB2M promoters is governed by nuclear respiratory factors (NRF-1 and NRF-2), key transcription factors implicated in mitochondrial biogenesis. In addition, we show that NRF recognition sites within both TFB promoters are required for maximal trans activation by the PGC-1 family coactivators, PGC-1alpha and PRC |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268998 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15684387 |
Here, we establish that the expression of human TFB1M and TFB2M promoters is governed by nuclear respiratory factors (NRF-1 and NRF-2), key transcription factors implicated in mitochondrial biogenesis. In addition, we show that NRF recognition sites within both TFB promoters are required for maximal trans activation by the PGC-1 family coactivators, PGC-1alpha and PRC |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | down-regulates quantity by repression
transcriptional regulation
|
GCLC |
0.473 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254643 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22459801 |
Different expression pattern of Nrf2 regulated genes in end-stage liver disease samples were observed: glutamate-cysteine ligase (GCLC) and glutathione-S-transferase A1 (GSTA1) were significantly down-regulated in most liver disease groups, whereas heme oxidase 1 (HMOX1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) were not significantly suppressed. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
SOD2 |
0.453 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254652 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22493435 |
BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ROS | up-regulates
|
NFE2L2 |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267353 |
|
|
Homo sapiens |
A-549 Cell |
| pmid |
sentence |
| 22789539 |
Nrf2 is a master transcriptional activator of cytoprotective genes. It activates transcription in response to electrophiles and reactive oxygen species (ROS) (Itoh et al., 1997, Uruno and Motohashi, 2011). Under normal conditions, Nrf2 is constantly ubiquitinated by Keap1 and degraded by the proteasome. Exposure to the stimuli inactivates Keap1 and stabilizes Nrf2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Pentose phosphate pathway |
| + |
NFE2L2 | up-regulates
|
Metastasis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259285 |
|
|
Homo sapiens |
Hep-G2 Cell |
| pmid |
sentence |
| 26194347 |
Nrf2 was up-regulated in HCC, and expression of Nrf2 was correlated with tumor differentiation, metastasis, and tumor size. Further studies demonstrated that inhibition of Nrf2 expression inhibited proliferation by inducing apoptosis and repressed invasion, and up-regulation of Nrf2 expression resulted in opposite phenotypes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
PPAT |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267358 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22789539 |
We identified six genes involved in the PPP and NADPH production pathways as direct targets of Nrf2. To identify the target genes of NRF2 responsible for cell proliferation, we performed microarray analysis in A549 cells treated with NRF2 siRNA or control siRNA. We used three independent NRF2 siRNAs and selected genes whose expression levels were reduced to less than 66.7% of that of the control sample by all three siRNAs to minimize off-target effects (Table S1). In addition to the typical target genes of NRF2 encoding detoxifying enzymes and antioxidant proteins (cytoprotective genes), genes whose products are involved in the PPP (glucose-6-phosphate dehydrogenase [G6PD], phosphogluconate dehydrogenase [PGD], transketolase [TKT], and transaldolase 1 [TALDO1]) and de novo nucleotide synthesis (phosphoribosyl pyrophosphate amidotransferase [PPAT] and methylenetetrahydrofolate dehydrogenase 2 [MTHFD2]) were decreased by the NRF2 knockdown (Figure 1B). Genes encoding enzymes for NADPH synthesis (malic enzyme 1 [ME1] and isocitrate dehydrogenase 1 [IDH1]) were also decreased (Figure 1B). We also confirmed the reduction of the enzyme proteins encoded by these genes in the NRF2-knockdown cells (Figure 1C). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Nucleotide Biosynthesis |
| + |
NFE2L2 | up-regulates
|
Proliferation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256262 |
|
|
Homo sapiens |
Hep-G2 Cell |
| pmid |
sentence |
| 26194347 |
Nrf2 was up-regulated in HCC, and expression of Nrf2 was correlated with tumor differentiation, metastasis, and tumor size. Further studies demonstrated that inhibition of Nrf2 expression inhibited proliferation by inducing apoptosis and repressed invasion, and up-regulation of Nrf2 expression resulted in opposite phenotypes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
MTHFD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267359 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22789539 |
We identified six genes involved in the PPP and NADPH production pathways as direct targets of Nrf2. To identify the target genes of NRF2 responsible for cell proliferation, we performed microarray analysis in A549 cells treated with NRF2 siRNA or control siRNA. We used three independent NRF2 siRNAs and selected genes whose expression levels were reduced to less than 66.7% of that of the control sample by all three siRNAs to minimize off-target effects (Table S1). In addition to the typical target genes of NRF2 encoding detoxifying enzymes and antioxidant proteins (cytoprotective genes), genes whose products are involved in the PPP (glucose-6-phosphate dehydrogenase [G6PD], phosphogluconate dehydrogenase [PGD], transketolase [TKT], and transaldolase 1 [TALDO1]) and de novo nucleotide synthesis (phosphoribosyl pyrophosphate amidotransferase [PPAT] and methylenetetrahydrofolate dehydrogenase 2 [MTHFD2]) were decreased by the NRF2 knockdown (Figure 1B). Genes encoding enzymes for NADPH synthesis (malic enzyme 1 [ME1] and isocitrate dehydrogenase 1 [IDH1]) were also decreased (Figure 1B). We also confirmed the reduction of the enzyme proteins encoded by these genes in the NRF2-knockdown cells (Figure 1C). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
TBXAS1 |
0.246 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268993 |
|
|
|
|
| pmid |
sentence |
| 14565864 |
Ecotopic expression of NF-E2 related factors showed that Nrf2, but not Nrf1, Nrf3, or Bach1, activated TXAS promoter in a dose-dependent manner. |
|
| Publications: |
1 |
| + |
MYC | up-regulates quantity by expression
transcriptional regulation
|
NFE2L2 |
0.521 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267363 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29731393 |
Oncogenic proteins that regulate proliferation, such as KRAS, BRAF, and MYC increase the transcription of NRF2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Nucleotide Biosynthesis, Pentose phosphate pathway |
| + |
NFE2L2 | down-regulates
|
Cell_death |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256652 |
|
|
Homo sapiens |
Hep-G2 Cell |
| pmid |
sentence |
| 26194347 |
Nrf2 was up-regulated in HCC, and expression of Nrf2 was correlated with tumor differentiation, metastasis, and tumor size. Further studies demonstrated that inhibition of Nrf2 expression inhibited proliferation by inducing apoptosis and repressed invasion, and up-regulation of Nrf2 expression resulted in opposite phenotypes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SIRT5 | up-regulates quantity by expression
transcriptional regulation
|
NFE2L2 |
0.308 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261208 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31815138 |
Western blot showed that Sirt5 overexpression upregulated Nrf2. Sirt5 attenuates apoptosis through Nrf2/HO-1 and Bcl-2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
SOD1 |
0.411 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254653 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22493435 |
BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BRAF | up-regulates quantity by expression
transcriptional regulation
|
NFE2L2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267362 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29731393 |
Oncogenic proteins that regulate proliferation, such as KRAS, BRAF, and MYC increase the transcription of NRF2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
NFE2L2 | up-regulates quantity
transcriptional regulation
|
HMOX1 |
0.682 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259334 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31257023 |
Nrf2 accumulation in lung cancers causes the stabilization of Bach1 by inducing Ho1, the enzyme catabolizing heme. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
NFE2L2 | down-regulates
|
Apoptosis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256263 |
|
|
Homo sapiens |
Hep-G2 Cell |
| pmid |
sentence |
| 26194347 |
Nrf2 was up-regulated in HCC, and expression of Nrf2 was correlated with tumor differentiation, metastasis, and tumor size. Further studies demonstrated that inhibition of Nrf2 expression inhibited proliferation by inducing apoptosis and repressed invasion, and up-regulation of Nrf2 expression resulted in opposite phenotypes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
G6PD |
0.329 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267354 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22789539 |
We identified six genes involved in the PPP and NADPH production pathways as direct targets of Nrf2. To identify the target genes of NRF2 responsible for cell proliferation, we performed microarray analysis in A549 cells treated with NRF2 siRNA or control siRNA. We used three independent NRF2 siRNAs and selected genes whose expression levels were reduced to less than 66.7% of that of the control sample by all three siRNAs to minimize off-target effects (Table S1). In addition to the typical target genes of NRF2 encoding detoxifying enzymes and antioxidant proteins (cytoprotective genes), genes whose products are involved in the PPP (glucose-6-phosphate dehydrogenase [G6PD], phosphogluconate dehydrogenase [PGD], transketolase [TKT], and transaldolase 1 [TALDO1]) and de novo nucleotide synthesis (phosphoribosyl pyrophosphate amidotransferase [PPAT] and methylenetetrahydrofolate dehydrogenase 2 [MTHFD2]) were decreased by the NRF2 knockdown (Figure 1B). Genes encoding enzymes for NADPH synthesis (malic enzyme 1 [ME1] and isocitrate dehydrogenase 1 [IDH1]) were also decreased (Figure 1B). We also confirmed the reduction of the enzyme proteins encoded by these genes in the NRF2-knockdown cells (Figure 1C). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Pentose phosphate pathway |
| + |
BTG2 | up-regulates activity
binding
|
NFE2L2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254647 |
|
|
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 22493435 |
BTG2 stimulation of antioxidant gene expression is also NFE2L2-dependent. We further demonstrate that BTG2 is a binding partner for NFE2L2 and increases its transcriptional activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SYVN1 | down-regulates quantity by destabilization
ubiquitination
|
NFE2L2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267360 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29731393 |
NRF2 is negatively regulated by three E3 ubiquitin ligase complexes: the KEAP1-CUL3-RBX1 complex, the β-TrCP-SKP1-CUL1-RBX1 complex, and HRD1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
CAT |
0.429 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254651 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22493435 |
BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
KRT16 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254645 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18629308 |
When overexpressed in HaCaT cells, NRF2 was also directly involved in not only the up-regulation of the detoxification gene thioredoxin but also K16 gene expression. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
NQO1 |
0.49 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256275 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24024136 |
In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
KEAP1 | down-regulates quantity
ubiquitination
|
NFE2L2 |
0.815 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259335 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31257023 |
Keap1 is a substrate receptor of a Cul3-RING ubiquitin ligase (CRL3) that, in physiological conditions, constitutively binds and targets Nrf2 for degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
TXN |
0.406 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254646 |
|
|
Homo sapiens |
HaCaT Cell |
| pmid |
sentence |
| 18629308 |
When overexpressed in HaCaT cells, NRF2 was also directly involved in not only the up-regulation of the detoxification gene thioredoxin but also K16 gene expression. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates
|
Purine biosynthesis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267352 |
|
|
Homo sapiens |
A-549 Cell |
| pmid |
sentence |
| 22789539 |
Nrf2 promotes purine nucleotide synthesis and glutamine use in proliferating cells |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
GSR |
0.408 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279871 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279873 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
GPX4 |
0.386 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279872 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279874 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
NQO1 |
0.49 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256279 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8962164 |
These results indicated that hARE-mediated expression of the NQO1 gene and its induction by xenobiotics and antioxidants are mediated by Nrf1 and Nrf2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
TKT |
0.268 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267356 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22789539 |
We identified six genes involved in the PPP and NADPH production pathways as direct targets of Nrf2. To identify the target genes of NRF2 responsible for cell proliferation, we performed microarray analysis in A549 cells treated with NRF2 siRNA or control siRNA. We used three independent NRF2 siRNAs and selected genes whose expression levels were reduced to less than 66.7% of that of the control sample by all three siRNAs to minimize off-target effects (Table S1). In addition to the typical target genes of NRF2 encoding detoxifying enzymes and antioxidant proteins (cytoprotective genes), genes whose products are involved in the PPP (glucose-6-phosphate dehydrogenase [G6PD], phosphogluconate dehydrogenase [PGD], transketolase [TKT], and transaldolase 1 [TALDO1]) and de novo nucleotide synthesis (phosphoribosyl pyrophosphate amidotransferase [PPAT] and methylenetetrahydrofolate dehydrogenase 2 [MTHFD2]) were decreased by the NRF2 knockdown (Figure 1B). Genes encoding enzymes for NADPH synthesis (malic enzyme 1 [ME1] and isocitrate dehydrogenase 1 [IDH1]) were also decreased (Figure 1B). We also confirmed the reduction of the enzyme proteins encoded by these genes in the NRF2-knockdown cells (Figure 1C). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Pentose phosphate pathway |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
TBXAS1 |
0.246 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253907 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14565864 |
Ecotopic expression of NF-E2 related factors showed that Nrf2, but not Nrf1, Nrf3, or Bach1, activated TXAS promoter in a dose-dependent manner. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KRAS | up-regulates quantity by expression
transcriptional regulation
|
NFE2L2 |
0.427 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267361 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29731393 |
Oncogenic proteins that regulate proliferation, such as KRAS, BRAF, and MYC increase the transcription of NRF2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CUL3-RBX1-KEAP1 | down-regulates quantity by destabilization
ubiquitination
|
NFE2L2 |
0.584 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279844 |
|
|
Homo sapiens |
Pancreatic Ductal Adenocarcinoma Cell |
| pmid |
sentence |
| 39534872 |
NFE2L2 is primarily regulated by the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex, which, under normal conditions, promotes the ubiquitination and proteasomal degradation of NFE2L2, keeping its cellular levels low. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
ABCB6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279864 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KEAP1 | down-regulates
binding
|
NFE2L2 |
0.815 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205229 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24997453 |
Keap1 is an oxidative stress-sensing protein and is a negative regulator of nuclear factor-erythroid-2-related factor 2 (nrf2). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
FECH |
0.323 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279865 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39534872 |
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NFE2L2 | up-regulates quantity by expression
transcriptional regulation
|
PIR |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279850 |
|
|
Homo sapiens |
Pancreatic Ductal Adenocarcinoma Cell |
| pmid |
sentence |
| 39534872 |
The activation of NFE2L2 is pivotal in protecting cells from ferroptotic death. To achieve this protective function, NFE2L2 regulates a broad spectrum of genes involved in multiple cellular pathways, including those that modulate ROS, detoxify harmful agents, and repair damaged proteins. In human pancreatic cancer cell lines, the expression of PIR is upregulated by NFE2L2 in response to ferroptosis-inducing agents (erastin or RSL3) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PIR | up-regulates activity
binding
|
NFE2L2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279852 |
|
|
Homo sapiens |
Pancreatic Ductal Adenocarcinoma Cell |
| pmid |
sentence |
| 33373853 |
In contrast, the depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
NFE2L2
- 
- 