产品: 磷酸化 Nrf2 (Ser40) 抗体
货号: DF7519
描述: Rabbit polyclonal antibody to Phospho-Nrf2 (Ser40)
应用: WB IHC IF/ICC
反应: Human, Mouse, Rat
预测: Pig, Bovine, Horse, Rabbit, Dog, Chicken
分子量: 100~120kD; 68kD(Calculated).
蛋白号: Q16236
RRID: AB_2841018

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产品描述

来源:
Rabbit
应用:
WB 1:500-1:3000, IHC 1:50-1:200, IF/ICC 1:100-1:500
*The optimal dilutions should be determined by the end user.
*Tips:

WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.

反应:
Human,Mouse,Rat
预测:
Pig(100%), Bovine(91%), Horse(89%), Rabbit(82%), Dog(100%), Chicken(91%)
克隆:
Polyclonal
特异性:
Phospho-Nrf2 (Ser40) Antibody detects endogenous levels of Nrf2 only when phosphorylated at S40.
RRID:
AB_2841018
引用格式: Affinity Biosciences Cat# DF7519, RRID:AB_2841018.
偶联:
Unconjugated.
纯化:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
别名:

展开/折叠

erythroid derived 2; HEBP1; like 2; NF E2 related factor 2; NF-E2-related factor 2; NF2L2_HUMAN; NFE2 related factor 2; NFE2-related factor 2; Nfe2l2; Nrf 2; NRF2; Nuclear factor (erythroid derived 2) like 2; Nuclear factor; nuclear factor erythroid 2 like 2; Nuclear factor erythroid 2 related factor 2; Nuclear factor erythroid 2-related factor 2; Nuclear factor erythroid derived 2 like 2;

抗原和靶标

免疫原:
Uniprot:
基因/基因ID:
表达:
Q16236 NF2L2_HUMAN:

Widely expressed. Highest expression in adult muscle, kidney, lung, liver and in fetal muscle.

序列:
MMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREVFDFSQRRKEYELEKQKKLEKERQEQLQKEQEKAFFAQLQLDEETGEFLPIQPAQHIQSETSGSANYSQVAHIPKSDALYFDDCMQLLAQTFPFVDDNEVSSATFQSLVPDIPGHIESPVFIATNQAQSPETSVAQVAPVDLDGMQQDIEQVWEELLSIPELQCLNIENDKLVETTMVPSPEAKLTEVDNYHFYSSIPSMEKEVGNCSPHFLNAFEDSFSSILSTEDPNQLTVNSLNSDATVNTDFGDEFYSAFIAEPSISNSMPSPATLSHSLSELLNGPIDVSDLSLCKAFNQNHPESTAEFNDSDSGISLNTSPSVASPEHSVESSSYGDTLLGLSDSEVEELDSAPGSVKQNGPKTPVHSSGDMVQPLSPSQGQSTHVHDAQCENTPEKELPVSPGHRKTPFTKDKHSSRLEAHLTRDELRAKALHIPFPVEKIINLPVVDFNEMMSKEQFNEAQLALIRDIRRRGKNKVAAQNCRKRKLENIVELEQDLDHLKDEKEKLLKEKGENDKSLHLLKKQLSTLYLEVFSMLRDEDGKPYSPSEYSLQQTRDGNVFLVPKSKKPDVKKN

种属预测

种属预测:

score>80的预测可信度较高,可尝试用于WB检测。*预测模型主要基于免疫原序列比对,结果仅作参考,不作为质保凭据。

Species
Results
Score
Pig
100
Dog
100
Bovine
91
Chicken
91
Horse
89
Rabbit
82
Xenopus
73
Sheep
0
Zebrafish
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

翻译修饰 - Q16236 作为底物

Site PTM Type Enzyme
S40 Phosphorylation P05771 (PRKCB) , P17252 (PRKCA)
K44 Ubiquitination
K64 Ubiquitination
T80 Phosphorylation
S215 Phosphorylation
S301 Phosphorylation
S344 Phosphorylation P49841 (GSK3B)
S347 Phosphorylation P49841 (GSK3B)
S351 Phosphorylation
S356 Phosphorylation
T395 Phosphorylation Q00535 (CDK5)
S408 Phosphorylation
S433 Phosphorylation Q00535 (CDK5)
R437 Methylation
K438 Acetylation
T439 Phosphorylation Q00535 (CDK5)
K443 Acetylation
K445 Acetylation
S447 Phosphorylation
K462 Acetylation
K462 Ubiquitination
K472 Acetylation
K487 Acetylation
K506 Acetylation
K508 Acetylation
K516 Acetylation
K516 Ubiquitination
K518 Acetylation
K518 Sumoylation
K518 Ubiquitination
K533 Acetylation
K536 Acetylation
K538 Acetylation
K541 Acetylation
K543 Acetylation
K548 Acetylation
K548 Ubiquitination
K554 Acetylation
K554 Ubiquitination
K555 Acetylation
S558 Phosphorylation
T559 Phosphorylation
Y561 Phosphorylation
K574 Ubiquitination
Y576 Phosphorylation P06241 (FYN)
S577 Phosphorylation
K596 Acetylation
K599 Acetylation

研究背景

功能:

Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerization with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes. The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes. May also 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.

翻译修饰:

Ubiquitinated in the cytoplasm by the BCR(KEAP1) E3 ubiquitin ligase complex leading to its degradation. In response to oxidative stress, electrophile metabolites, such as sulforaphane, modify KEAP1, leading to inhibit activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and activity. In response to autophagy, the BCR(KEAP1) complex is inactivated (By similarity).

Phosphorylation of Ser-40 by PKC in response to oxidative stress dissociates NFE2L2 from its cytoplasmic inhibitor KEAP1, promoting its translocation into the nucleus.

Acetylation at Lys-596 and Lys-599 increases nuclear localization whereas deacetylation by SIRT1 enhances cytoplasmic presence.

Glycation impairs transcription factor activity by preventing heterodimerization with small Maf proteins. Deglycation by FN3K restores activity.

细胞定位:

Cytoplasm>Cytosol. Nucleus.
Note: Cytosolic under unstressed conditions: ubiquitinated and degraded by the BCR(KEAP1) E3 ubiquitin ligase complex (PubMed:15601839, PubMed:21196497). Translocates into the nucleus upon induction by electrophilic agents that inactivate the BCR(KEAP1) E3 ubiquitin ligase complex (PubMed:21196497).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
组织特异性:

Widely expressed. Highest expression in adult muscle, kidney, lung, liver and in fetal muscle.

亚基结构:

Heterodimer; heterodimerizes with small Maf proteins (By similarity). Interacts (via the bZIP domain) with MAFG and MAFK; required for binding to antioxidant response elements (AREs) on DNA (By similarity). Interacts with KEAP1; the interaction is direct and promotes ubiquitination by the BCR(KEAP1) E3 ubiquitin ligase complex. Forms a ternary complex with PGAM5 and KEAP1. Interacts with EEF1D at heat shock promoter elements (HSE). Interacts via its leucine-zipper domain with the coiled-coil domain of PMF1. Interacts with CHD6; involved in activation of the transcription (By similarity). Interacts with ESRRB; represses NFE2L2 transcriptional activity (By similarity).

(Microbial infection) Interacts with herpes virus 8 protein LANA1.

蛋白家族:

The ETGE motif, and to a lower extent the DLG motif, mediate interaction with KEAP1.

Belongs to the bZIP family. CNC subfamily.

研究领域

· Genetic Information Processing > Folding, sorting and degradation > Protein processing in endoplasmic reticulum.   (View pathway)

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

文献引用

1). Amelioratory effects of astragaloside IV on hepatocarcinogenesis via Nrf2-mediated pSmad3C/3L transformation. Phytomedicine, 2023 (PubMed: 37301185) [IF=7.9]

2). KAN0438757, a novel PFKFB3 inhibitor, prevent the progression of severe acute pancreatitis via the Nrf2/HO-1 pathway in infiltrated macrophage. Free radical biology & medicine, 2024 (PubMed: 37984751) [IF=7.4]

Application: WB    Species: Mouse    Sample:

Fig. 4. Effects of KAN0438757 on the regulation of Nrf2/HO-1 pathways. (A) The levels of HO-1, Nrf2, P-Nrf2, Keap 1, and NQO-1 proteins in mice with induced FAEE-SAP, determined by Western blot among DMSO + NS, 757 + NS, DMSO + FAEE-SAP, and K-757 + FAEE-SAP groups their quantification. (B) Western blot assessment of the protein levels of HO-1, Nrf2, P-Nrf2, Keap 1, and NQO-1 in RAW264.7 cells stimulated with LPS. (C) Quantification of the levels of the Bax, Bcl-2, Caspase-3, and Cleaved Caspase-3 proteins in mice with induced FAEE-SAP and (D) RAW264.7 cells stimulated with LPS by Western blot. Significance (exact p values as indicated) was determined by a one-way ANOVA test. Data represent three or more experiments and as mean value ± SEM: n = 5, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

3). Phosphodiesterase 4B is required for NLRP3 inflammasome activation by positive feedback with Nrf2 in the early phase of LPS- induced acute lung injury. Free Radical Biology and Medicine, 2021 (PubMed: 34644617) [IF=7.4]

4). Ellagic acid ameliorates arsenic-induced neuronal ferroptosis and cognitive impairment via Nrf2/GPX4 signaling pathway. Ecotoxicology and environmental safety, 2024 (PubMed: 39128446) [IF=6.8]

Application: WB    Species: Rat    Sample: hippocampus

Fig. 6. The impact of ellagic acid treatment on arsenic-induced Nrf2/Keap1 signaling pathway in the hippocampus and HT22 cells. (A) Western blot for p-Nrf2, Nrf2 and Keap1 in the hippocampus. (B-D) Relative density analysis of the p-Nrf2, Nrf2 and Keap1 protein bands in the hippocampus. (E) Quantification of Keap1 mRNA levels in the hippocampus. (F) Western blot for Nucleus Nrf2, Nrf2 and Keap1 in HT22 cells. (G-I) Relative density analysis of the Nucleus Nrf2, Nrf2 and Keap1 protein bands in HT22 cells. (J) Quantification of Keap1 mRNA levels in HT22 cells. Data are presented as mean ± SD (n=3). * significant difference compared to the control group (*P

5). Eriodictyol ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation. Molecular Medicine, 2022 (PubMed: 35093024) [IF=5.7]

Application: WB    Species: Mouse    Sample: brain

Fig. 7 Eriodictyol up-regulates VDR expression and activates the Nrf2/HO-1 signaling pathway. A VDR expression in the mouse brain was detected using immunohistochemical staining. Then, B the VDR protein expression level in the mouse cortex and hippocampus was measured using Western blotting. C The VDR protein expression level in HT-22 cells was measured using Western blotting, and D its relative mRNA expression level was detected using q-PCR. E The levels of Nrf2, p-Nrf2 and HO-1 in the mouse cortex and hippocampus were measured using Western blotting. F The levels of Nrf2, p-Nrf2 and HO-1 in HT-22 cells were measured using Western blotting. G The level of Nrf2 in the nucleus and cytoplasm of HT-22 cells was detected using Western blotting, and Lamin B1 and β-actin were used as loading controls for the nuclear and cytoplasmic proteins, respectively. The data are presented as the means ± SD of three experiments. **P < 0.01 and ***P < 0.001 compared with the Aβ1–42 oligomer group. ##P < 0.01 compared with the control group

6). Ginsenoside Rg1 attenuates chronic inflammation-induced renal fibrosis in mice by inhibiting AIM2 inflammasome in an Nrf2-dependent manner. Journal of Functional Foods, 2024 [IF=5.6]

Application: WB    Species: Mouse    Sample:

Fig. 4. Effects of Rg1 treatment on Nrf2/HO-1 signaling in LPS-induced CKD mice. (A) Representative immunofluorescence (IF) images of p-Nrf2 (×400, bar: 20 μm). (B) Statistical results of p-Nrf2 IF. (C) Representative WB images of p-Nrf2, Nrf2, and HO-1. (D) Statistical results of Nrf2. (E) Statistical results of p-Nrf2/Nrf2. (F) Statistical results of HO-1. Data are expressed as mean ± SD, n = 4. #P < 0.05, ##P < 0.01 versus Model.

7). The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat. Biomedical Journal, 2019 (PubMed: 30987703) [IF=5.5]

Application: WB    Species: rat    Sample: intestine

Fig. 6 | IL-1Ra activates Nrf2/HO-1 signaling in I/R intestine. (A) The protein expression levels of p-Nrf2, Nrf2 and HO-1.

8). A diarylheptanoid compound from Alpinia officinarum Hance ameliorates high glucose-induced insulin resistance by regulating PI3K/AKT-Nrf2-GSK3β signaling pathways in HepG2 cells. JOURNAL OF ETHNOPHARMACOLOGY, 2022 (PubMed: 35605918) [IF=5.4]

9). Astragaloside IV inhibits hepatocellular carcinoma by continually suppressing the development of fibrosis and regulating pSmad3C/3L and Nrf2/HO-1 pathways. JOURNAL OF ETHNOPHARMACOLOGY, 2021 (PubMed: 34157326) [IF=5.4]

Application: WB    Species: Mice    Sample: liver tissue

Fig. 5. AS-IV modulates pSmad3C/3L and Nrf2/HO-1 pathways in mice treated with DCC for 12 weeks. (A), (B), (C), (F), (G), (H), (I), (M) Hepatic expression and distribution pattern of proteins (TGF-β1, pSmad3C, pSmad3L, pNrf2) by immunofluorescent staining, and relative fluorescent intensity of TGF-β1, pSmad3C, pSmad3L, pNrf2 in the liver (Magnification × 400); (D), (E), (K), (L) Representative immunoblots and relative protein levels of TGF-β1, pSmad3C, pSmad3L, pSmad2C, pSmad2L, PAI-1, pNrf-2, Nrf-2, HO-1, NQO1. (J), (N) The Nrf-2 expression was evaluated by immunohistochemistry (Magnification × 400), and quantitation (% of the positively stained area) of Nrf2 by immunohistochemistry; (O) the correlation analysis of pSmad3C and pNrf2; (P) the correlation analysis of pSmad3L and pNrf2. Data are presented as mean ± SD (n = 3 for each group). #P < 0.05 VS. Control. # #P < 0.01 VS. Control. *P < 0.05 VS. Model. **P < 0.01 VS. Model.

10). Zhen-Wu decoction and lactiflorin, an ingredient predicted by in silico modelling, alleviate uremia induced cardiac endothelial injury via Nrf2 activation. JOURNAL OF ETHNOPHARMACOLOGY, 2022 (PubMed: 35963415) [IF=5.4]

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