Summary of NFE2L2
Nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2 or Nrf2, is a protein (transcription factor). Nrf2 increases the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation.
Substances that stimulate the Nrf2 pathway are being studied for the treatment of diseases that are caused by oxidative stress.
It responds to injury and inflammation [R].
The Function of NFE2L2
Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region.
Protein names
Recommended name:
Nuclear factor erythroid 2-related factor 2Short name:
HEBP1Alternative name(s):
NF-E2-related factor 2NFE2-related factor 2
Nuclear factor, erythroid derived 2, like 2
- RS10183914 (NFE2L2) ??
- RS16865105 (NFE2L2) ??
- RS1806649 (NFE2L2) ??
- RS1962142 (NFE2L2) ??
- RS2001350 (NFE2L2) ??
- RS2886161 (NFE2L2) ??
- RS35652124 (NFE2L2) ??
- RS6706649 (NFE2L2) ??
- RS6721961 (NFE2L2) ??
- RS6726395 (NFE2L2) ??
- RS7557529 (NFE2L2) ??
To see your genotype, you should be logged in and have a file with your genotype uploaded.
Top Gene-Substance Interactions
NFE2L2 Interacts with These Diseases
| Disease | Score |
Fixes
Top Ways to Increase Nrf2:
- Exercise (R)
- Calorie Restriction (R)
- Ketosis (R)
- LLLT (R)
- Fish oil/DHA (R)
- Vitamin D (R)
- Sulforaphane/Broccoli sprouts (R) -and other Isothiocyanates from cruciferous vegetables (R)
- Lipoic Acid
- Butyrate (R)
- Garlic (R)
- Curcumin (R)
Fixes Advanced
Other Ways to Activate Nrf2:
- PGC-1a (R)
- Molecular Hydrogen (R),
- Thyroid hormones (R)
- Luteolin (R) “ luteolin is ideal because it inhibits Nrf2 in many cancer cells (R),
- Berberine (R),
- PQQ (R),
- Cinnamaldehyde (R),
- Anthocyanins (R, R2)
- Carnitine (R),
- Andrographolide/Andrographis (R),
- Black Cumin Oil (R),
- EGCG (R),
- Astaxanthin (R),
- Lycopene (R),
- Tocopherols and tocotrienols (R),
- Quercetin (R),
- Naringenin (R),
- Resveratrol
- Chlorella (R),
- Cocoa (R),
- Schisandra (R),
- Licorice (R),
- Chinese Skullcap - Baicalin (R), Baicalein (R, R2) and Wogonin (R)
- Citrus Flavanoids/Citrus Bioflavonoids (R),
- Withanolide A/Ashwagandha (R),
- Pau Darco (R),
- Ginkgolide B (prevents suppression)/Ginkgo (R),
- Oleanolic acid (R)
- Apigenin
(R)
- Melatonin (R)
- Ginger/6-Shigoal (R)
- Pterostilbene (R),
- Hops (R)
- High-dose Vitamin C (R)
- Celastrol found in Thunder God Vine Extract (R)
- Artemisia (R)
- Kaempferol (R),
- Genistein (R), Soy Isoflavones (R),
- Bilirubin (R),
- Betanin/Beets (R),
- Chlorogenic acid (R),
- Carnosic acid/Rosemary (R)
- Grapes (R)
- Propolis (Brazilian green) (R)
- Kiwi peel (R), Geranium (R),
Inhibitors of Nrf2: SIRT1 decreases Nrf2-related gene production since acetylation allows Nrf2 to bind to DNA better and produce antioxidant genes (R). This is a downside of SIRT1.
Substances That Increase NFE2L2
| Substances | Interaction | Organism | Category |
Substances That Decrease NFE2L2
| Substances | Interaction | Organism | Category |
Advanced Summary
Read: About NRF2 and Natural Ways to Increase It.
Nrf2 increases the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation.
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Nrf2 is found in the highest concentrations (in descending order) in the kidney, muscle, lung, heart, liver, and brain (R). Nrf2 stimulates NQO1 , which donates electrons and detoxifies a variety of chemicals and drugs.
NQO1 is important for phase 2 detox. I suspect that people sensitive to everything have less NQO1 or less of an electron supply. Nrf2 produces two of the most important rate-limiting steps in glutathione (GSH) production.
Glutamate-cysteine ligase, catalytic (Gclc) and glutamate-cysteine ligase, modifier (GCLM) bind together to form glutathione . These are produced by Nrf2.
The glutathione S-transferase (GST) allow glutathione to bind with drugs and toxins, which then allow the body to eliminate potentially harmful and toxic compounds. GSTs are produced by Nrf2 activation and represent an important route of detoxification.
Sulfiredoxin 1 (SRXN1) and Thioredoxin reductase 1 (TXNRD1) give over electrons to peroxiredoxins, proteins important in the detoxification of hydrogen peroxide and peroxynitrite.
Nrf2 stimulates Heme oxygenase-1. Heme oxygenase-1 (HMOX1, HO-1) is an enzyme that catalyzes the breakdown of heme into the antioxidant biliverdin, the anti-inflammatory agent carbon monoxide, and iron. HO-1 defends against sepsis, hypertension, atherosclerosis, acute lung injury, kidney injury, and pain.
The UDP-glucuronosyltransferase (UGT) family catalyze the conjugation of a glucuronic acid to drugs, chemicals, and toxins, making them more water-soluble and readily excreted. Nrf2 has been shown to induce UGT1A1 and UGT1A6 . Bilirubin and Tylenol are examples of substances that are glucuronidated.
My clients are more likely to have higher bilirubin and this can come from less of an ability to glucuronidation enzymes. Multidrug resistance-associated proteins (Mrps) are important membrane transporters that eject various compounds from various organs into bile or plasma, with subsequent excretion in the feces or urine, respectively. Mrps have been shown to be increased by Nrf2 and alteration in their expression can dramatically alter the pharmacokinetics and toxicity of compounds.
People with CIRS or biotoxin related issues usually have a problem excreting toxins in an efficient way and almost certainly the Nrf2 pathway will help excrete these toxins more easily. Reference.
The Negatives of Nrf2 Activation: Activation of NRF2 may promote the development of cancerous tumors. It can also contribute to the development of heart disease by raising cholesterol levels and cholesterol content in the liver. Having low cholesterol might be an indicator of less Nrf2 function (although there are many other pathways that lower cholesterol). Reference.
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Technical
The following transcription factors affect gene expression:
Tissue specificity:
Widely expressed. Highest expression in adult muscle, kidney, lung, liver and in fetal muscle.
Gene Pathways:
Induction:
Down-regulated by ENC1 via a proteasomal ubiquitin-independent protein catabolic process.
Molecular Function:
- Transcription Regulatory Region Sequence-Specific Dna Binding
- Rna Polymerase Ii Distal Enhancer Sequence-Specific Dna Binding
- Rna Polymerase Ii Activating Transcription Factor Binding
- Transcriptional Activator Activity, Rna Polymerase Ii Distal Enhancer Sequence-Specific Binding
- Dna Binding
- Transcription Factor Activity, Sequence-Specific Dna Binding
- Protein Domain Specific Binding
- Transcription Regulatory Region Dna Binding
Biological Processes:
- Transcription From Rna Polymerase Ii Promoter
- Inflammatory Response
- Aging
- Proteasomal Ubiquitin-Independent Protein Catabolic Process
- Positive Regulation Of Gene Expression
- Negative Regulation Of Cardiac Muscle Cell Apoptotic Process
- Positive Regulation Of Neuron Projection Development
- Protein Ubiquitination
- Positive Regulation Of Blood Coagulation
- Endoplasmic Reticulum Unfolded Protein Response
- Cellular Response To Oxidative Stress
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter In Response To Stress
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter In Response To Oxidative Stress
- Perk-Mediated Unfolded Protein Response
- Cellular Response To Glucose Starvation
- Proteasome-Mediated Ubiquitin-Dependent Protein Catabolic Process
- Positive Regulation Of Blood Vessel Endothelial Cell Migration
- Cell Redox Homeostasis
- Positive Regulation Of Angiogenesis
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Regulation Of Embryonic Development
- Positive Regulation Of Glucose Import
- Cellular Response To Hydrogen Peroxide
- Cellular Response To Tumor Necrosis Factor
- Cellular Response To Hypoxia
- Cellular Response To Fluid Shear Stress
- Cellular Response To Laminar Fluid Shear Stress
- Negative Regulation Of Hematopoietic Stem Cell Differentiation
- Negative Regulation Of Oxidative Stress-Induced Intrinsic Apoptotic Signaling Pathway
- Positive Regulation Of Er-Associated Ubiquitin-Dependent Protein Catabolic Process
- Negative Regulation Of Hydrogen Peroxide-Induced Cell Death
- Positive Regulation Of Glutathione Biosynthetic Process
- Negative Regulation Of Vascular Associated Smooth Muscle Cell Migration
- Regulation Of Removal Of Superoxide Radicals
- Negative Regulation Of Endothelial Cell Apoptotic Process
- Positive Regulation Of Reactive Oxygen Species Metabolic Process