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Target intelligence / Profile preview
PKR-like Endoplasmic Reticulum Kinase (PERK)
- Target
- PERK
- Molecular classification
- Enzyme, Protein Kinase, Serine/Threonine Kinase, Transmembrane protein
01
Overview
PERK is a type I transmembrane serine/threonine-protein kinase located in the endoplasmic reticulum (ER) membrane. It is one of three principal ER stress sensors that mediate the unfolded protein response (UPR), alongside IRE1 and ATF6. PERK reduces global protein synthesis during ER stress to alleviate folding load by phosphorylating eIF2α at Ser51, inhibiting formation of active eIF2-GTP-tRNAi^Met complex. This attenuates general mRNA translation but allows selective translation of specific mRNAs such as ATF4 that help restore homeostasis or trigger apoptosis if stress persists.
- Other names
- EIF2AK3Eukaryotic translation initiation factor 2-alpha kinase 3
02
Mechanism of action
Kinase Inhibitor
03
Biological functions
Unfolded Protein Response (UPR)Regulation of protein synthesisCell cycle regulationApoptosisER stress response
04
Disease associations
Wolcott-Rallison syndromeDiabetes mellitusNeurodegenerative diseases
05
Safety considerations
Chronic or excessive activation contributes to neurodegenerative diseases through persistent translational repression and apoptosis.
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