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Molecule Details

General Information of the Molecule
Name
Nuclear factor erythroid 2-related factor 2 (Nrf2)
Synonyms
Nuclear factor, erythroid derived 2, like 2; NRF2; NFE2-related factor 2; NF-E2-related factor 2; HEBP1
Gene Name
NFE2L2
Gene ID
4780
Sequence
MMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREVFDFSQRRKEYELEKQKKLEKERQE
QLQKEQEKAFFAQLQLDEETGEFLPIQPAQHIQSETSGSANYSQVAHIPKSDALYFDDCM
QLLAQTFPFVDDNEVSSATFQSLVPDIPGHIESPVFIATNQAQSPETSVAQVAPVDLDGM
QQDIEQVWEELLSIPELQCLNIENDKLVETTMVPSPEAKLTEVDNYHFYSSIPSMEKEVG
NCSPHFLNAFEDSFSSILSTEDPNQLTVNSLNSDATVNTDFGDEFYSAFIAEPSISNSMP
SPATLSHSLSELLNGPIDVSDLSLCKAFNQNHPESTAEFNDSDSGISLNTSPSVASPEHS
VESSSYGDTLLGLSDSEVEELDSAPGSVKQNGPKTPVHSSGDMVQPLSPSQGQSTHVHDA
QCENTPEKELPVSPGHRKTPFTKDKHSSRLEAHLTRDELRAKALHIPFPVEKIINLPVVD
FNEMMSKEQFNEAQLALIRDIRRRGKNKVAAQNCRKRKLENIVELEQDLDHLKDEKEKLL
KEKGENDKSLHLLKKQLSTLYLEVFSMLRDEDGKPYSPSEYSLQQTRDGNVFLVPKSKKP
DVKKN
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Function
Important for the coordinated up-regulation of genes in response to oxidative stress and the regulation of cellular redox conditions. 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. Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes.
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Uniprot ID
NF2L2_HUMAN
Pfam
PF03131
KEGG ID
hsa4780
TTD ID
T88505
Natural Product(s) of This Target
1 Brusatol  NP Info  Investigative Brucea javanica
2 Cucurbitacin I  NP Info  Investigative Citrullus lanatus
3 Daphnetin  NP Info  Investigative Euphorbia
4 Ginsenoside Rh2  NP Info  Investigative Panax ginseng
5 Isoliquiritigenin  NP Info  Investigative Robinia pseudoacacia
6 Lycopene  NP Info  Phase 2 Daucus carota
7 Neferine  NP Info  Investigative Nelumbo nucifera
8 Oridonin  NP Info  Investigative Isodon rubescens
9 Polydatin  NP Info  Investigative Polygonum cuspidatum
10 Salvianolic acid A  NP Info  Investigative Salvia
11 Xanthohumol  NP Info  Investigative Humulus lupulus
Drug(s) of This Target
1 Diazinon  Drug Info  Investigative Scabies
2 MST312  Drug Info  Investigative Lung cancer
References
Reference 1 Free heme regulates placenta growth factor through NRF2-antioxidant response signaling. Free Radic Biol Med. 2019 Nov 1;143:300-308.
Reference 2 Low nanomolar concentrations of Cucurbitacin-I induces G2/M phase arrest and apoptosis by perturbing redox homeostasis in gastric cancer cells in vitro and in vivo. Cell Death Dis. 2016 Feb 18;7(2):e2106.
Reference 3 Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death. Free Radic Biol Med. 2017 May;106:38-52.
Reference 4 Calycosin suppresses expression of pro-inflammatory cytokines via the activation of p62/Nrf2-linked heme oxygenase 1 in rheumatoid arthritis synovial fibroblasts. Pharmacol Res. 2016 Nov;113(Pt A):695-704.
Reference 5 Isoliquiritigenin alleviates early brain injury after experimental intracerebral hemorrhage via suppressing ROS- and/or NF-KappaB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway. J Neuroinflammation. 2017 Jun 13;14(1):119.
Reference 6 Natural ingredients-derived antioxidants attenuate H(2)O(2)-induced oxidative stress and have chondroprotective effects on human osteoarthritic chondrocytes via Keap1/Nrf2 pathway. Free Radic Biol Med. 2020 May 20;152:854-864.
Reference 7 Mitochondrial protective effect of neferine through the modulation of nuclear factor erythroid 2-related factor 2 signalling in ischaemic stroke. Br J Pharmacol. 2019 Feb;176(3):400-415.
Reference 8 Oridonin protects LPS-induced acute lung injury by modulating Nrf2-mediated oxidative stress and Nrf2-independent NLRP3 and NF-KappaB pathways. Cell Commun Signal. 2019 Jun 11;17(1):62.
Reference 9 Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway. Redox Biol. 2018 Sep;18:124-137.
Reference 10 Salvianolic acid A protects RPE cells against oxidative stress through activation of Nrf2/HO-1 signaling. Free Radic Biol Med. 2014 Apr;69:219-28.
Reference 11 Activated AMPK boosts the Nrf2/HO-1 signaling axis--A role for the unfolded protein response. Free Radic Biol Med. 2015 Nov;88(Pt B):417-426.
Reference 12 Thearubigin regulates the production of Nrf2 and alleviates LPS-induced acute lung injury in neonatal rats. 3 Biotech. 2019 Dec;9(12):451.
Reference 13 Fernblock? Upregulates NRF2 Antioxidant Pathway and Protects Keratinocytes from PM(2.5)-Induced Xenotoxic Stress. Oxid Med Cell Longev. 2020 Apr 14;2020:2908108.
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China