|Other Names||Eukaryotic translation initiation factor 2-alpha kinase 3, PRKR-like endoplasmic reticulum kinase, Pancreatic eIF2-alpha kinase, HsPEK, EIF2AK3, PEK, PERK|
|Target/Specificity||The synthetic peptide sequence used to generate the antibody AP8054a was selected from the N-term region of human PERK. A 10 to 100 fold molar excess to antibody is recommended. Precise conditions should be optimized for a particular assay.|
|Format||Synthetic peptide was lyophilized with 100% acetonitrile and is supplied as a powder. Reconstitute with 0.1 ml DI water for a final concentration of 1 mg/ml.|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C.|
|Precautions||This product is for research use only. Not for use in diagnostic or therapeutic procedures.|
|Function||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.|
|Cellular Location||Endoplasmic reticulum membrane; Single-pass type I membrane protein|
|Tissue Location||Ubiquitous. A high level expression is seen in secretory tissues|
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PERK, a member of the GCN2 subfamily of Ser/Thr protein kinases, 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. It likely serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin D1 Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction Expression of this Type I membrane protein is ubiquitous, with highest levels seen in secretory tissues. Defects in EIF2AK3 are the cause of Wolcott-Rallison syndrome (WRS), 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.
Delepine, M., et al., Nat. Genet. 25(4):406-409 (2000).Shi, Y., et al., J. Biol. Chem. 274(9):5723-5730 (1999).Sood, R., et al., Biochem. J. 346 Pt 2, 281-293 (2000).
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