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: Protein kinase, Other; Translation; Kinase, protein; EC 188.8.131.52; Protein kinase, Ser/Thr (non-receptor); Membrane protein, integral; Other group; PEK family; PEK subfamily
Cellular Component: endoplasmic reticulum membrane; membrane; endoplasmic reticulum; cytoplasm; integral to membrane
Molecular Function: identical protein binding; protein serine/threonine kinase activity; protein binding; enzyme binding; protein phosphatase binding; ATP binding; eukaryotic translation initiation factor 2alpha kinase activity; protein kinase activity
Biological Process: lactation; endoplasmic reticulum organization and biogenesis; fat cell differentiation; caspase activation; ossification; translation; positive regulation of signal transduction; positive regulation of protein binding; negative regulation of myelination; unfolded protein response; protein amino acid autophosphorylation; calcium-mediated signaling; chondrocyte development; SREBP-mediated signaling pathway; endocrine pancreas development; protein amino acid phosphorylation; bone mineralization; unfolded protein response, activation of signaling protein activity; cellular protein metabolic process; insulin-like growth factor receptor signaling pathway; insulin secretion; negative regulation of translation; regulation of fatty acid metabolic process; negative regulation of translation initiation in response to stress; skeletal development; ER overload response; protein homooligomerization
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.