製品: Phospho-IRE1 (Ser724) Antibody
カタログ: DF8322
タンパク質の説明: Rabbit polyclonal antibody to Phospho-IRE1 (Ser724)
アプリケーション: WB
反応性: Human, Mouse, Rat
予測: Pig, Bovine, Horse, Sheep, Rabbit, Dog, Chicken, Xenopus
分子量: 110 kDa; 110kD(Calculated).
ユニプロット: O75460
RRID: AB_2841598

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製品説明

ソース:
Rabbit
アプリケーション:
WB 1:1000-3000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human,Mouse,Rat
予測:
Pig(100%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(100%), Xenopus(90%)
クローナリティ:
Polyclonal
特異性:
Phospho-IRE1 (Ser724) Antibody detects endogenous levels of IRE1 only when phosphorylated at Ser724.
RRID:
AB_2841598
引用形式: Affinity Biosciences Cat# DF8322, RRID:AB_2841598.
コンジュゲート:
Unconjugated.
精製:
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.
別名:

折りたたみ/展開

Endoplasmic reticulum (ER) to nucleus signalling 1; Endoplasmic reticulum to nucleus signaling 1; Endoplasmic reticulum-to-nucleus signaling 1; Endoribonuclease; ER to nucleus signaling 1; ERN 1; Ern1; ERN1_HUMAN; hIRE 1p; hIRE1p; Inositol requiring 1; Inositol requiring 1, S. cerevisiae, homolog of; Inositol requiring enzyme 1, S. cerevisiae, homolog of; Inositol requiring protein 1; inositol-requiring enzyme 1; Inositol-requiring protein 1; IRE 1; IRE 1a; IRE 1P; Ire1 alpha; Ire1-alpha; IRE1a; Ire1alpha; IRE1P; MGC163277; MGC163279; Protein kinase/endoribonuclease; RGD1559716; Serine/threonine protein kinase/endoribonuclease IRE1;

免疫原

免疫原:
Uniprot:
遺伝子(ID):
発現特異性:
O75460 ERN1_HUMAN:

Ubiquitously expressed. High levels observed in pancreatic tissue.

タンパク質配列:
MPARRLLLLLTLLLPGLGIFGSTSTVTLPETLLFVSTLDGSLHAVSKRTGSIKWTLKEDPVLQVPTHVEEPAFLPDPNDGSLYTLGSKNNEGLTKLPFTIPELVQASPCRSSDGILYMGKKQDIWYVIDLLTGEKQQTLSSAFADSLCPSTSLLYLGRTEYTITMYDTKTRELRWNATYFDYAASLPEDDVDYKMSHFVSNGDGLVVTVDSESGDVLWIQNYASPVVAFYVWQREGLRKVMHINVAVETLRYLTFMSGEVGRITKWKYPFPKETEAKSKLTPTLYVGKYSTSLYASPSMVHEGVAVVPRGSTLPLLEGPQTDGVTIGDKGECVITPSTDVKFDPGLKSKNKLNYLRNYWLLIGHHETPLSASTKMLERFPNNLPKHRENVIPADSEKKSFEEVINLVDQTSENAPTTVSRDVEEKPAHAPARPEAPVDSMLKDMATIILSTFLLIGWVAFIITYPLSMHQQQQLQHQQFQKELEKIQLLQQQQQQLPFHPPGDTAQDGELLDTSGPYSESSGTSSPSTSPRASNHSLCSGSSASKAGSSPSLEQDDGDEETSVVIVGKISFCPKDVLGHGAEGTIVYRGMFDNRDVAVKRILPECFSFADREVQLLRESDEHPNVIRYFCTEKDRQFQYIAIELCAATLQEYVEQKDFAHLGLEPITLLQQTTSGLAHLHSLNIVHRDLKPHNILISMPNAHGKIKAMISDFGLCKKLAVGRHSFSRRSGVPGTEGWIAPEMLSEDCKENPTYTVDIFSAGCVFYYVISEGSHPFGKSLQRQANILLGACSLDCLHPEKHEDVIARELIEKMIAMDPQKRPSAKHVLKHPFFWSLEKQLQFFQDVSDRIEKESLDGPIVKQLERGGRAVVKMDWRENITVPLQTDLRKFRTYKGGSVRDLLRAMRNKKHHYRELPAEVRETLGSLPDDFVCYFTSRFPHLLAHTYRAMELCSHERLFQPYYFHEPPEPQPPVTPDAL

種類予測

種類予測:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
100
Horse
100
Bovine
100
Sheep
100
Dog
100
Chicken
100
Rabbit
100
Xenopus
90
Zebrafish
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - O75460 基板として

Site PTM Type Enzyme
T49 Phosphorylation
K88 Ubiquitination
K95 Ubiquitination
T132 Phosphorylation
Y161 Phosphorylation
Y166 Phosphorylation
Y179 Phosphorylation
T283 Phosphorylation
Y289 Phosphorylation
K374 Acetylation
K374 Ubiquitination
K485 Ubiquitination
S533 Phosphorylation
S536 Phosphorylation
S544 Phosphorylation
S548 Phosphorylation
S551 Phosphorylation
Y628 Phosphorylation O75460 (ERN1)
K633 Ubiquitination
K706 Ubiquitination
S724 Phosphorylation O75460 (ERN1)
S726 Phosphorylation
S729 Phosphorylation
K851 Ubiquitination
K860 Ubiquitination
T973 Phosphorylation

PTMs - O75460 酵素として

Substrate Site Source
O75460 (ERN1) Y628 Uniprot
O75460 (ERN1) S724 Uniprot

研究背景

機能:

Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endoribonuclease activity. The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA. The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes. Acts as an upstream signal for ER stress-induced GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane by modulating the expression and localization of SEC16A.

PTMs:

Autophosphorylated following homodimerization. Autophosphorylation promotes activation of the endoribonuclease domain.

ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities.

細胞の位置付け:

Endoplasmic reticulum membrane>Single-pass type I membrane protein.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

Ubiquitously expressed. High levels observed in pancreatic tissue.

サブユニット構造:

Monomer. Homodimer; disulfide-linked; homodimerization takes place in response to endoplasmic reticulum stress and promotes activation of the kinase and endoribonuclease activities. Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges. Interacts (via the luminal region) with DNAJB9/ERdj4; interaction takes place in unstressed cells and promotes recruitment of HSPA5/BiP. Interacts (via the luminal region) with HSPA5/BiP; HSPA5/BiP is a negative regulator of the unfolded protein response (UPR) that prevents homodimerization of ERN1/IRE1 and subsequent activation of the protein. Interacts with PDIA6, a negative regulator of the UPR; the interaction is direct and disrupts homodimerization. Interacts with DAB2IP (via PH domain); the interaction occurs in a endoplasmic reticulum stress-induced dependent manner and is required for subsequent recruitment of TRAF2 to ERN1/IRE1 (By similarity). Interacts with TAOK3 and TRAF2. Interacts with RNF13.

タンパク質ファミリー:

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

研究領域

· Cellular Processes > Transport and catabolism > Autophagy - animal.   (View pathway)

· Cellular Processes > Cell growth and death > Apoptosis.   (View pathway)

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

· Human Diseases > Endocrine and metabolic diseases > Non-alcoholic fatty liver disease (NAFLD).

· Human Diseases > Neurodegenerative diseases > Alzheimer's disease.

参考文献

1). TRAPPC1 is essential for the maintenance and differentiation of common myeloid progenitors in mice. EMBO reports, 2023 (PubMed: 36440617) [IF=7.7]

2). Polystyrene nanoplastics promote CHIP-mediated degradation of tight junction proteins by activating IRE1α/XBP1s pathway in mouse Sertoli cells. Ecotoxicology and Environmental Safety, 2022 (PubMed: 36446169) [IF=6.8]

Application: WB    Species: Mouse    Sample: TM4 cells

Fig. 4. PS-NPs activated UPR in TM4 Sertoli cells. (a) TM4 cells were treated with indicated concentrations of PS-NPs for 24 h. The protein levels of p-IRE1α, GRP78, ATF6α, and β-actin were measured using the Western blot analysis. Results were presented as the mean ± SD (n = 3). *p 

3). Acute exposure to polystyrene nanoplastics induces unfolded protein response and global protein ubiquitination in lungs of mice. Ecotoxicology and environmental safety, 2024 (PubMed: 38865938) [IF=6.8]

4). Icariin improves the cognitive function of APP/PS1 mice via suppressing endoplasmic reticulum stress. LIFE SCIENCES, 2019 (PubMed: 31400352) [IF=6.1]

Application: WB    Species: mouse    Sample: hippocampus

Fig.5| Effects of ICA on ER stress in the hippocampus of APP/PS1 mice. ER stress was activated in the hippocampus of APP/PS1 mice evidenced by the high levels of GRP78, ATF6, and p-IRE1α. ICA treatment decreased GRP78 level, not affected the ATF6, IRE1α and IRE1αphosphorylation. (A) Immunoblots.

5). Protective Effect of Patchouli Alcohol Against High-Fat Diet Induced Hepatic Steatosis by Alleviating Endoplasmic Reticulum Stress and Regulating VLDL Metabolism in Rats. Frontiers in Pharmacology, 2019 (PubMed: 31632274) [IF=5.6]

Application: WB    Species: rat    Sample: liver

FIGURE 4 | PA treatment attenuated HFD-induced ER stress in rats. (A) Representative immunoreactive bands of GRP78, PERK, p-PERK, IRE1α, p-IRE1α, and ATF6

6). Dl-3-n-Butylphthalide Ameliorates Diabetic Nephropathy by Ameliorating Excessive Fibrosis and Podocyte Apoptosis. Frontiers in Pharmacology, 2021 (PubMed: 34497508) [IF=5.6]

Application: WB    Species: Mice    Sample: kidney tissues

FIGURE 6 DL-NBP treatment inhibits diabetes-induced elevated ERS in kidney. (A–F) Western blotting and quantification of ERS-elevated protein expression [p-PERK (A,B), p-IRE1α (A,C), GRP78 (A,D), ATF-6 (A,E), CHOP (A,F)] in kidney of mice from each group (n = 3). Protein expression was normalized to the expression of β-actin. (G,H) Representative images of immunohistochemical staining of CHOP in kidney of mice from each group (n = 3). Scale bar = 20 μm. Data are presented as mean ± SEM; *p < 0.05, **p < 0.01, ***p < 0.001 vs. db/m control; # p < 0.05, ## p < 0.01, ### p < 0.001 vs. db/db mice.

7). The endocrine disruptor vinclozolin causes endothelial injury via eNOS/Nox4/IRE1α signaling. European journal of pharmacology, 2024 (PubMed: 38901528) [IF=5.0]

8). Modulation of non‐steroidal anti‐inflammatory drug‐induced, ER stress‐mediated apoptosis in Caco‐2 cells by different polyphenolic antioxidants: a mechanistic study. Journal of Pharmacy and Pharmacology, 2020 (PubMed: 32716561) [IF=3.3]

Application: WB    Species: human    Sample: Caco-2 cells

Figure 7| Expression of IRE-1a/JNK1/2 proteins and their phosphorylated forms (a) in Caco-2 cells after treatment with ER stressors (INDO, DIC,TUN, TGN) in the presence of the test compounds (EGCG, HYPO, PHY, ML385) for 48 h.

9). Dihydroartemisinin promotes CHAC1 transcription to induce ferroptosis in primary liver cancer cells: activation of unfolded protein responses. Research Square, 2020

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