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 18.104.22.168; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Membrane protein, integral; Protein kinase, Other; Translation; Other group; PEK family; PEK subfamily
Cellular Component: endoplasmic reticulum membrane; membrane; cell; endoplasmic reticulum; cytoplasm; integral to membrane; intracellular
Molecular Function: transferase activity; protein serine/threonine kinase activity; identical protein binding; protein binding; enzyme binding; transferase activity, transferring phosphorus-containing groups; nucleotide binding; kinase activity; protein phosphatase binding; ATP binding; eukaryotic translation initiation factor 2alpha kinase activity; protein kinase activity
Biological Process: lactation; fat cell differentiation; translation; positive regulation of protein binding; protein amino acid autophosphorylation; protein amino acid phosphorylation; bone mineralization; positive regulation of transcription from RNA polymerase I promoter; regulation of translation; cellular response to glucose starvation; negative regulation of translation in response to stress; pancreas development; regulation of fatty acid metabolic process; angiogenesis; skeletal development; ER overload response; protein homooligomerization; endoplasmic reticulum organization and biogenesis; caspase activation; ossification; positive regulation of signal transduction; negative regulation of myelination; unfolded protein response; calcium-mediated signaling; chondrocyte development; SREBP-mediated signaling pathway; endocrine pancreas development; response to unfolded protein; peptidyl-serine phosphorylation; insulin-like growth factor receptor signaling pathway; negative regulation of translation; phosphorylation; negative regulation of apoptosis
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.