Recombinant human PERK protein

Specifications

Form

Liquid

Additional notes

The purity was determined to be >90% by densitometry

General info

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) (PubMed : 10026192, PubMed : 10677345, PubMed : 11907036, PubMed : 12086964, PubMed : 25925385, PubMed : 31023583). 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 (PubMed : 10677345, PubMed : 27917829, PubMed : 31023583). 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 (PubMed : 10026192, PubMed : 10677345, PubMed : 31023583, PubMed : 33384352). 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 (PubMed : 31023583). 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 (PubMed : 39116259). 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 (By similarity). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity). Involved in control of mitochondrial morphology and function (By similarity).

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.

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 (By similarity). Autophosphorylated at Tyr-619 following endoplasmic reticulum stress, leading to activate its activity (PubMed:22169477). Dephosphorylated at Tyr-619 by PTPN1/PTP1B, leading to inactivate its enzyme activity (PubMed:22169477). Phosphorylation at Thr-802 by AKT (AKT1, AKT2 and/or AKT3) inactivates EIF2AK3/PERK (By similarity).. ADP-ribosylated by PARP16 upon ER stress, which increases kinase activity.