The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Please could you let me know if CSB-EP007795HU is phosphorylated or not?
A:
Thanks for your inquiry. This protein is expressed in E.coli, which is a prokaryotic expression system, so it's not phosphorylated.
Target Background
Function
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 proteins 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.
Gene References into Functions
results suggest that apocynin protects ECs against ER stress-induced apoptosis via IRE1alpha involvement. These findings may provide a novel mechanistic explanation for the anti-apoptotic effect of apocynin in ER stress.PMID:29696609
Study results provide evidence that DDRGK1 is essential for endoplasmic reticulum (ER) homeostasis regulation in both human cancer cells and mouse hematopoietic stem cells. Depletion of DDRGK1 activates apoptotic pathway by targeting the ER-stress sensor IRE1alpha. DDRGK1 regulates IRE1alpha protein stability via its interaction with the kinase domain of IRE1alpha.PMID:28128204
IRE1 was up-regulated during excisional wound healing at the time in wound healing consistent with that of the proliferative phase. Inhibition of IRE1 led to decreased scar formation.PMID:29316036
urinary levels of the spliced X-box binding protein 1 (sXBP1) mRNA as a proxy of inositol-requiring enzyme 1alpha (IRE1alpha) activity because sXBP1 is absolutely sensitive and specific for endoplasmic reticulum stress.PMID:29276149
Here, the authors show that similar to yeast, human IRE1alpha's endoplasmic reticulum-lumenal domain (hIRE1alpha LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1alpha LD's MHC-like groove and induce allosteric changes that lead to its oligomerization.PMID:28971800
Three branches of the Unfolded Protein Response (UPR) have been described, including the activation of the inositol-requiring enzyme 1 (IRE1), the pancreatic ER kinase (PKR)-like ER kinase (PERK), and the activating transcription factor 6 (ATF6).PMID:28105371
IRE1alpha is expressed at lower levels in higher-grade gliomas, suggesting greater antitumor efficacy of the oncolytic virus M1. Taken together, these findings illustrate a defensive mechanism of glioma cells against the oncolytic virus M1 and identify possible approaches to enhance the oncolytic viral protein accumulation and the subsequent lysis of tumor cells.PMID:29263275
Systematic mutation of the AREs (ARE1-3) in the LDLR 3'UTR and expression of each mutant coupled to a luciferase reporter in Huh7 cells demonstrated that ARE1 is required for rapid LDLR mRNA decay and 5-AzaC-induced mRNA stabilization via the IRE1alpha-EGFR-ERK1/2 signaling cascade.PMID:29208426
Pharmacologic modulation of IRE1 counteracts metaflammation and alleviates atherosclerosis.PMID:28137856
Present study demonstrates that fine-tuning of the expression of proliferation related transcription factor genes depends upon glucose and glutamine deprivation in IRE1-dependent manner and possibly contributes to slower tumor growth after inhibition of IRE1.PMID:29537195
The activation of IRE1alpha by the hepatitis C virus protein NS4B in XBP1-proficient cells conferred apoptosis resistance and promoted viral replication.PMID:28588082
this study highlights an important role for Nck1 in fine-tuning IRE1alpha expression and signaling that regulate PTP1B expression and subsequent activation of the PI3K-Akt pathway in HepG2 cells.PMID:28455143
IRE1alpha-XBP1 pathway regulates Mel-RMu cell proliferation and progression by activating IL-6/STAT3 signaling.PMID:28222747
The authors propose that the Sec61-IRE1alpha complex defines the extent of IRE1alpha activity and may determine cell fate decisions during endoplasmic reticulum stress conditions.PMID:28504640
ERN1 and ALPK1 inhibit differentiation of bi-potential tumor-initiating cells in human triple negative breast cancer.PMID:27829216
IRE1 deficiency fully restored the learning and memory capacity of AD mice, associated with improved synaptic function and improved long-term potentiation (LTP). At the molecular level, IRE1 deletion reduced the expression of amyloid precursor protein (APP) in cortical and hippocampal areas of AD mice.PMID:28341998
The biologic processes altered by aberrant IRE1alpha-XBP1 signaling in these innate immune cells.PMID:26979393
Inhibition of IRE1 modifies the hypoxic regulation of GADD34 family gene expression in cultured glioma cells.PMID:29227599
Changes in the expression level of nuclear genes encoding mitochondrial proteins possibly reflect metabolic reprogramming of mitochondria by hypoxia and IRE1-mediated endoplasmic reticulum stress signaling and correlate with suppression of glioma cell proliferation under inhibition of the IRE1 enzyme function.PMID:29235326
The inhibition of IRE1 changes sensitivity of the expression of down-stream genes to glutamine deprivation in cultured glial tumor cells.PMID:29235329
The present study demonstrated that the inhibition of IRE1 in glioma cells affected the hypoxic regulation of the expression of down-stream genes in various directions, though hypoxic conditions did not abolish the effect of IRE1 inhibition on the expression of respective genes.PMID:29235836
Inhibition of IRE1 modifies hypoxic regulation of pentose-phosphate pathway genes expression in cultured glioma cells.PMID:29236388
Study reports that the endoplasmic reticulum luminal co-chaperone ERdj4/DNAJB9 is a selective IRE1 repressor that promotes a complex between the luminal Hsp70 BiP and the luminal stress-sensing domain of IRE1alpha.PMID:29198525
The present study is the first to uncover a key prosurvival modulator, Yip1A, which coordinates IRE1 signaling with PERK signaling to support the survival of HeLa and CaSki cervical cancer cells.PMID:28358375
Inositol-requiring kinase 1 may be a useful biomarker to predict recurrence in surgically resected lung adenocarcinoma patients.PMID:28334878
Fortilin directly interacts with the cytoplasmic domain of IRE1alpha, inhibits both kinase and endoribonuclease (RNase) activities of this stress sensor, and protects cells against apoptotic cell death at both cellular and whole animal levels.PMID:28550308
Overall, these data demonstrate that hypoxia can suppress adiponectin expression and activate the PERK and IRE1 signaling pathways in differentiated adipocytes, and this two pathways are involved in the suppression of adiponectin expression induced by hypoxia.PMID:28888981
ER stress-regulated IRE1 dependent decay is involved in regulation of hepatic diseases. (review)PMID:27774654
The unfolded protein response reduces glucose metabolism via IRE1 signaling.PMID:28093214
Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function affects the expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells in gene specific manner and these changes possibly contribute to the suppression of the cell proliferation. Most of these genes are regulated by hypoxia and preferentially through IRE1 signaling pathway of endoplasmic reticulum stressPMID:28222026
IRE1alpha was shown to cleave miR-150 and thereby to release the suppressive effect that miR-150 exerted on alphaSMA expression through c-Myb. Inhibition of IRE1alpha was also demonstrated to block endoplasmic reticulum expansion through an XBP-1-dependent pathway.PMID:27226027
IRE-1 has an ancient function as a cytoplasmic sentinel that activates p38 and SKN-1(Nrf2). csteine modifications induced by ROS signals can direct proteins to adopt unexpected functions and may coordinate many cellular processes.PMID:27540856
The findings indicate that IRE1-XBP1 downregulation distinguishes germinal center B-cell-like diffuse large B-cell lymphoma (DLBCL) from other DLBCL subtypes and contributes to tumor growth.PMID:28167662
Western blot analysis of subcutaneously implanted AsPC-1 and BxPC-3 tumors as well as orthotopically implanted Panc-1 tumors demonstrated upregulation of BIP, CHOP, and IRE1alpha expression in the tumor lysates from penfluridol-treated mice as compared to tumors from control micePMID:28618969
the ABL family of tyrosine kinases rheostatically enhances IRE1alpha's enzymatic activities, thereby potentiating endoplasmic reticulum stress-induced apoptosis.PMID:28380378
Pre-ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress-dependent autophagy via PERK and IRE1 signalingsPMID:28178380
IRE1 is involved in multivesicular body information during endoplasmic reticulum stress.PMID:27725157
Comparison of this structure with other existing structures of IRE1alpha and integration of our extensive structure activity relationship (SAR) data has led us to formulate a model to rationalize how ATP-binding site ligands are able to control the IRE1alpha oligomeric state and subsequent RNase domain activityPMID:27227314
Our data indicate that reduced response of IRE1alpha/Xbp-1 signaling pathway to bortezomib may contribute to drug resistance in myeloma cellsPMID:27647225
heat stress simultaneously activates both the unfolded protein response (UPR) and autophagy, followed by the activation of a negative feedback system in UPR by modulating the responses related to the IRE1alpha-XBP-1 axis.PMID:27743894
these findings underscore the essential role of cytosine nucleotide at +1 in the 3' splice site for determining cleavage specificity of hIRE1alpha.PMID:28027394
Crucially, Chlamydia trachomatis infection resulted in robust IRE1alpha RNAse activity that was dependent on TLR4 signalling and inhibition of IRE1alpha RNAse activity prevented PKR activation.PMID:27021640
Pretreatment by IRE1 agonist tunicamycin or JNK agonist anisomycin attenuated the effect of psoralen on osteoporotic osteoblasts. Psoralen inhibited apoptosis of osteoporotic osteoblasts by regulating IRE1-ASK1-JNK pathwayPMID:28349059
Results indicate that excessive activation of the endoplasmic reticulum stress-associated IRE1alpha pathway is involved in LC neuronal apoptosis induced by single prolonged stress exposure; this may be a crucial mechanism of the pathogenesis of post- traumatic stress disorderPMID:27059130
these results confirmed that ER stress-mediated apoptosis contributes to the protection effects of naringenin against H/R injury, which is potentially involved in ATF6, IRE1alpha and PERK signaling activation.PMID:27785700
Structural and mechanistic studies of IRE1PMID:27686654
Inhibition of IRE1 signaling enzyme function affects the expression of NR3C1 and related genes in U87 glioma cells in gene specific manner and all these genes are regulated by hypoxia preferentially through IRE1 signaling pathway of the endoplasmic reticulum stress.PMID:27560795
Data suggest that ubiquitin D (UBD) provides a negative feedback on cytokine-induced activation of the endoplasmic reticulum to nucleus signaling 1 (IRE1alpha)/c-Jun N-terminal kinase (JNK) pro-apoptotic pathway in cytokine-exposed beta cells.PMID:27044747
we used KO hepatocytes to demonstrate that PA-induced EV release was mediated by inositol requiring enzyme 1alpha (IRE1alpha)/X-box binding protein-1PMID:26621917
Using drugs that specifically inhibit or activate the PERK or IRE1alpha sensors, we demonstrate that signalling through the PERK axis activates this expression, through a transcriptional mechanismPMID:26634309
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Subcellular Location
Endoplasmic reticulum membrane; Single-pass type I membrane protein.
Protein Families
Protein kinase superfamily, Ser/Thr protein kinase family
Tissue Specificity
Ubiquitously expressed. High levels observed in pancreatic tissue.