LMPD Database

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LMP012626

UniProt Annotations

Entry Information
Gene Nameeukaryotic translation initiation factor 2 alpha kinase 3
Protein EntryE2AK3_RAT
UniProt IDQ9Z1Z1
SpeciesRat
Comments
Comment typeDescription
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
DomainThe lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP.
Enzyme RegulationPerturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction.
FunctionPhosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. 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 (By similarity)
InductionBy ER stress.
PtmADP-ribosylated by PARP16 upon ER stress, which increases kinase activity
PtmAutophosphorylated. Phosphorylated at Tyr-611 following endoplasmic reticulum stress, leading to activate its tyrosine- protein kinase activity. Dephosphorylated by PTPN1/TP1B, leading to inactivate its enzyme activity (By similarity)
PtmN-glycosylated
SimilarityBelongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.
SimilarityContains 1 protein kinase domain
Subcellular LocationEndoplasmic reticulum membrane; Single-pass type I membrane protein.
SubunitInteracts with DNAJC3 and MFN2 (By similarity). Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER- stressed cells
Tissue SpecificityUbiquitous.