PERK Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily. Ubiquitous. A high level expression is seen in secretory tissues. 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; 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 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-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 by RNA polymerase I; positive regulation of vascular endothelial growth factor production; protein autophosphorylation; protein homooligomerization; protein phosphorylation; regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; regulation of translational initiation by eIF2 alpha phosphorylation; response to endoplasmic reticulum stress; 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; truncated eukaryotic translation initiation factor 2 alpha kinase 3; WRS
Gene Symbols: EIF2AK3
Molecular weight: 125,216 Da
Basal Isoelectric point: 5.27  Predict pI for various phosphorylation states
CST Pathways:  Translation: eIF2
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein