EIF2AK3

Eukaryotic translation initiation factor 2-alpha kinase 3 ;
PRKR-like endoplasmic reticulum kinase ;
Pancreatic eIF2-alpha kinase ;
HsPEK ;

catalytic activity:ATP + a protein = ADP + a phosphoprotein.,disease:Defects in EIF2AK3 are the cause of Wolcott-Rallison syndrome (WRS) [MIM:226980]; also known as multiple epiphyseal dysplasia with early-onset diabetes mellitus. WRS is a rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities.,domain:The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP.,enzyme regulation:Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction.,function:Phosphorylates 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.,induction:By ER stress.,PTM:Autophosphorylated.,PTM:N-glycosylated.,similarity:Belongs to the protein kinase superfamily.,similarity:Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.,similarity:Contains 1 protein kinase domain.,subunit:Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER-stressed cells. Interacts with DNAJC3.,tissue specificity:Ubiquitous. A high level expression is seen in secretory tissues.,

skeletal system development, ossification, chondrocyte differentiation, chondrocyte development, peptide secretion,generation of a signal involved in cell-cell signaling, translation, regulation of translation, regulation of translational initiation, protein complex assembly, protein amino acid phosphorylation, phosphorus metabolic process, phosphate metabolic process, apoptosis, activation of caspase activity, virus-infected cell apoptosis, ER overload response, ER-nuclear signaling pathway, response to unfolded protein, endoplasmic reticulum organization, cell surface receptor linked signal transduction, enzyme linked receptor protein signaling pathway, transmembrane receptor protein tyrosine kinase signaling pathway, intracellular signaling cascade, cell-cell signaling, cell death, negative regulation of biosynthetic process, hormone transport, response to organic substance, negative regulation of macromolecule biosynthetic process, negative regulation of macromolecule metabolic process, posttranscriptional regulation of gene expression, regulation of hormone levels, regulation of cell death, positive regulation of peptidase activity,programmed cell death, peptide transport, death, phosphorylation, negative regulation of translation, calcium-mediated signaling, second-messenger-mediated signaling, peptide hormone secretion, insulin secretion, bone mineralization, endoplasmic reticulum unfolded protein response, pancreas development, endocrine pancreas development, biomineral formation, negative regulation of cellular biosynthetic process, regulation of myelination,negative regulation of myelination, regulation of neurological system process, negative regulation of neurological system process, negative regulation of translation in response to stress, negative regulation of translational initiation in response to stress, positive regulation of protein binding, regulation of cellular protein metabolic process, negative regulation of cellular protein metabolic process, regulation of homeostatic process, secretion by cell, cellular response to stress, cellular response to unfolded protein, response to endoplasmic reticulum stress, endocrine system development, regulation of apoptosis, regulation of programmed cell death, positive regulation of catalytic activity,positive regulation of caspase activity, regulation of caspase activity, regulation of protein binding, regulation of translation in response to stress, regulation of translational initiation in response to stress, macromolecular complex subunit organization, regulation of system process, positive regulation of molecular function, negative regulation of translational initiation, protein amino acid autophosphorylation, hormone secretion, secretion, insulin-like growth factor receptor signaling pathway, regulation of binding, positive regulation of binding, cartilage development,negative regulation of multicellular organismal process, negative regulation of protein metabolic process, protein oligomerization, protein homooligomerization, regulation of hydrolase activity, positive regulation of hydrolase activity,response to protein stimulus, regulation of nervous system development, regulation of transmission of nerve impulse,regulation of peptidase activity, regulation of endopeptidase activity, bone development, macromolecular complex assembly, protein complex biogenesis,

Endoplasmic reticulum membrane; Single-pass type I membrane protein.

Ubiquitous. A high level expression is seen in secretory tissues.