EIF2AK3
EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3, also known as PERK and PEK) is an endoplasmic reticulum membrane kinase that senses unfolded proteins. It phosphorylates eIF-2-alpha to attenuate global protein synthesis during cellular stress. Browse Assay Genie's current range of EIF2AK3 research reagents below, or read on for the biology behind the target.
EIF2AK3 is a metabolic-stress sensing protein kinase and a key effector of the integrated stress response (ISR) to unfolded proteins. It recognises and binds misfolded proteins, which leads to its activation and to phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1, or eIF-2-alpha). Phosphorylated eIF-2-alpha acts as a global inhibitor of protein synthesis, attenuating cap-dependent translation while allowing preferential translation of ISR-specific mRNAs, including the transcriptional activators ATF4 and QRICH1, which drive transcriptional reprogramming.
The EIF2AK3 protein, also called PERK, has further roles in the unfolded protein response (UPR). It increases mitochondrial oxidative phosphorylation by promoting ATF4-mediated expression of COX7A2L/SCAF1, which raises the formation of respiratory chain supercomplexes. It also phosphorylates NFE2L2/NRF2, releasing it from the BCR(KEAP1) complex so that it accumulates in the nucleus and is activated. EIF2AK3 is a critical effector of UPR-induced G1 growth arrest through loss of cyclin-D1 (CCND1), and it is involved in control of mitochondrial morphology and function. Mitochondria are protected from the PERK-mediated UPR because ATAD3A inhibits EIF2AK3 at mitochondria-endoplasmic reticulum contact sites.
The EIF2AK3 gene encodes a type I membrane protein located in the endoplasmic reticulum, where it is induced by ER stress caused by malfolded proteins. It belongs to the protein kinase superfamily, Ser/Thr protein kinase family, GCN2 subfamily, and sits in the HGNC group of eukaryotic translation initiation factor 2 alpha kinases. Mutations in this gene are associated with Wolcott-Rallison syndrome. Orthologues are annotated in mouse and rat as Eif2ak3.
EIF2AK3 binds misfolded proteins and is a key effector of the UPR and the integrated stress response.
Phosphorylation of eIF-2-alpha by EIF2AK3 attenuates cap-dependent translation while favouring ATF4 and QRICH1 mRNAs.
EIF2AK3 influences mitochondrial morphology, function and respiratory supercomplex formation, and is restrained by ATAD3A at ER contact sites.
EIF2AK3 phosphorylates NFE2L2/NRF2, releasing it from the BCR(KEAP1) complex for nuclear accumulation and activation.
EIF2AK3 is an ER-resident stress-sensing kinase. When it binds misfolded proteins it becomes active and phosphorylates eIF-2-alpha, which attenuates global cap-dependent translation and promotes translation of ATF4 and QRICH1. It also phosphorylates NFE2L2/NRF2 and contributes to UPR-induced G1 arrest.
Yes. PERK and PEK are alternative names for the EIF2AK3 gene and protein, whose full name is eukaryotic translation initiation factor 2 alpha kinase 3. UniProt also uses the name EIF2AK3/PERK in its function annotation. HGNC lists no previous full names.
Mutations in the EIF2AK3 gene are associated with Wolcott-Rallison syndrome. Mouse and rat orthologues are both named Eif2ak3, so rodent models can be used to study it. Check the datasheet of any product for its validated reactivity.
Other eIF2 alpha kinases, eIF2 pathway components and translation initiation factors with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9NZJ5; product specifications from Assay Genie datasheets.