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PERK a transmembrane protein kinase of the PEK family resident in the endoplasmic reticulum (ER) membrane and is linked to insulin processing.. Couples ER stress to translation inhibition. Stress induces autophosphorylation of its kinase domain and increases its activity. Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (eIF2alpha), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. A critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin d1. Forms dimers with BiP in resting cells. Oligomerizes in ER-stressed cells. LOF mutations cause Wolcott-Rallison syndrome (WRS), characterized by insulin-dependent diabetes in early infancy and, later, multiple system abnormalities. Neuronal death in Alzheimer?s and Parkinson?s diseases is thought to be due to ER stress and has been weakly linked to PEK. Note: This description may include information from UniProtKB.
Protein type: EC; Kinase, protein; Membrane protein, integral; Other group; PEK family; PEK subfamily; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Translation
Chromosomal Location of Human Ortholog: 2p11.2
Cellular Component: cytoplasm; endoplasmic reticulum; endoplasmic reticulum membrane; integral component of endoplasmic reticulum membrane; membrane; perinuclear region of cytoplasm
Molecular Function: ATP binding; enzyme binding; eukaryotic translation initiation factor 2alpha kinase activity; Hsp90 protein binding; identical protein binding; protein binding; protein homodimerization activity; protein kinase activity; protein phosphatase binding; protein serine/threonine kinase activity
Biological Process: activation of cysteine-type endopeptidase activity involved in apoptotic process; angiogenesis; bone mineralization; calcium-mediated signaling; cellular response to amino acid starvation; cellular response to cold; cellular response to glucose starvation; chondrocyte development; eiF2alpha phosphorylation in response to endoplasmic reticulum stress; endocrine pancreas development; endoplasmic reticulum organization; endoplasmic reticulum unfolded protein response; ER overload response; insulin secretion; insulin-like growth factor receptor signaling pathway; negative regulation of myelination; negative regulation of translation; negative regulation of translational initiation in response to stress; ossification; peptidyl-serine phosphorylation; PERK-mediated unfolded protein response; positive regulation of gene expression; positive regulation of protein localization to nucleus; positive regulation of transcription from RNA polymerase I promoter; positive regulation of vascular endothelial growth factor production; protein amino acid phosphorylation; protein autophosphorylation; protein homooligomerization; regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; regulation of translational initiation by eIF2 alpha phosphorylation; response to manganese-induced endoplasmic reticulum stress; skeletal system development
Disease: Epiphyseal Dysplasia, Multiple, With Early-onset Diabetes Mellitus
Reference #:  Q9NZJ5 (UniProtKB)
Alt. Names/Synonyms: DKFZp781H1925; E2AK3; EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3; Eukaryotic translation initiation factor 2-alpha kinase 3; heme-regulated EIF2-alpha kinase; HRI; HsPEK; Pancreatic eIF2-alpha kinase; PEK; PERK; PRKR-like endoplasmic reticulum kinase; WRS
Gene Symbols: EIF2AK3
Molecular weight: 125,216 Da
Basal Isoelectric point: 5.27  Predict pI for various phosphorylation states
CST Pathways:  Translation: eIF2
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