PERK Positive Control is synthetically produced from the sequence and is suitable for use in western blot applications.
Applications
WB
Note
STRICTLY FOR FURTHER SCIENTIFIC RESEARCH USE ONLY (RUO). MUST NOT TO BE USED IN DIAGNOSTIC OR THERAPEUTIC APPLICATIONS.
Product Properties
Dilution Range
WB: 1:500
Formulation
Provided as 100 uL ready-to-use, in SDS-PAGE sample buffer (Laemelli's buffer) containing Tris, pH 6.8, 1 % SDS, Glycerol and Bromophenolblue blue as tracking dye. The sample is reduced by adding 2% beta mercaptoethanol. The protein concentration is
Storage Instruction
Store at-20°C for long term storage. Avoid freeze-thaw cycles.
Ubiquitous. A high level expression is seen in secretory tissues.
Post Translational Modifications
Oligomerization of the N-terminal ER luminal domain by ER stress promotes EIF2AK3/PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr-982 on the kinase activation loop. Autophosphorylated at Tyr-619 following endoplasmic reticulum stress, leading to activate its activity. Dephosphorylated at Tyr-619 by PTPN1/PTP1B, leading to inactivate its enzyme activity. Phosphorylation at Thr-802 by AKT (AKT1, AKT2 and/or AKT3) inactivates EIF2AK3/PERK. ADP-ribosylated by PARP16 upon ER stress, which increases kinase activity.
Function
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR). Key effector of the integrated stress response (ISR) to unfolded proteins: EIF2AK3/PERK specifically recognizes and binds misfolded proteins, leading to its activation and EIF2S1/eIF-2-alpha phosphorylation. EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming. The EIF2AK3/PERK-mediated unfolded protein response increases mitochondrial oxidative phosphorylation by promoting ATF4-mediated expression of COX7A2L/SCAF1, thereby increasing formation of respiratory chain supercomplexes. In contrast to most subcellular compartments, mitochondria are protected from the EIF2AK3/PERK-mediated unfolded protein response due to EIF2AK3/PERK inhibition by ATAD3A at mitochondria-endoplasmic reticulum contact sites. In addition to EIF2S1/eIF-2-alpha, also phosphorylates NFE2L2/NRF2 in response to stress, promoting release of NFE2L2/NRF2 from the BCR(KEAP1) complex, leading to nuclear accumulation and activation of NFE2L2/NRF2. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function.
Endoplasmic Reticulum MembraneSingle-Pass Type I Membrane ProteinLocalizes To The Localizes To Endoplasmic Reticulum MembraneAlso Present At Mitochondria-Endoplasmic Reticulum Contact SitesWhere It Interacts With Atad3a
