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: Membrane protein, integral; Protein kinase, Ser/Thr (non-receptor); EC 184.108.40.206; Kinase, protein; Protein kinase, Other; Translation; Other group; PEK family; PEK subfamily
Cellular Component: cytoplasm; endoplasmic reticulum; endoplasmic reticulum membrane; integral to 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; kinase activity; nucleotide binding; protein binding; protein kinase activity; protein phosphatase binding; protein serine/threonine kinase activity; transferase activity
Biological Process: angiogenesis; bone mineralization; calcium-mediated signaling; caspase activation; cellular response to amino acid starvation; cellular response to glucose starvation; chondrocyte development; endocrine pancreas development; endoplasmic reticulum organization and biogenesis; ER overload response; fat cell differentiation; insulin-like growth factor receptor signaling pathway; lactation; negative regulation of apoptosis; negative regulation of myelination; negative regulation of translation; negative regulation of translation in response to stress; ossification; pancreas development; peptidyl-serine phosphorylation; phosphorylation; positive regulation of protein binding; positive regulation of signal transduction; positive regulation of transcription from RNA polymerase I promoter; protein amino acid autophosphorylation; protein amino acid phosphorylation; protein homooligomerization; regulation of fatty acid metabolic process; regulation of translation; response to unfolded protein; skeletal development; SREBP-mediated signaling pathway; translation; unfolded protein response
LTP: 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.