Eukaryotic translation initiation factor 2-alpha kinase 3

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Common Name:Eukaryotic translation initiation factor 2-alpha kinase 3
Other Names, such as IUPAC Name
PRKR-like endoplasmic reticulum kinase, pancreatic eIF2-alpha kinase, protein kinase RNA–like endoplasmic reticulum kinase, kinase PERK, HsPEK, EC:
Biochemical Information
Molecular Structure
Important Issues in Man
Relevant Clinical Literature
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Eukaryotic translation initiation factor 2-alpha kinase 3 is a 1116 amino acid enzyme coded by the EIF2AK3 gene (PERK) at 2p11.2, most highly expressed in the pancreas. It is a critical kinase activating the unfolded protein response which causes cell apoptosis due to G1 growth arrest when abnormally folded proteins accumulate pathologically with in cells as in prion disease and several neurodegenerative diseases. Its function is understood from the observation that malfolded proteins in the endoplasmic reticulum (ER) inhibit translation initiation. The response is mediated by increased phosphorylation of eIF2-alpha causing loss of cyclin-D1 (CCND1)and is thought to reduce the workload imposed on the folding machinery during stress. Small molecule inhibitors of eukaryotic translation initiation factor 2-alpha kinase 3 have been demonstrated to prevent prion disease progression in mice[1]. However they also caused side effects similar to those of Wolcott-Rallison syndrome.

Mutations of EIF2AK3 cause Wolcott-Rallison syndrome (WRS). This is autosomal recessive disorder with:

  • Neonatal or early infancy insulin-dependent diabetes mellitus
  • Epiphyseal dysplasia
  • Osteoporosis
  • Growth retardation
  • Hepatic and renal dysfunction
  • Mental retardation
  • Cardiovascular abnormalities.


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