Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3 (EIF2aK3)

WRS; PEK; PERK; HsPEK; PRKR-like endoplasmic reticulum kinase; Pancreatic eIF2-alpha kinase

SPN	R825
HGNC	3255
MGI	1341830
PubMed	10932183
RGD	70884
UniProt	Q9NZJ5
Wiki	EIF2AK3

Phosphorylation of eIF2-alpha results in inhibition of the guanine nucleotide exchange factor eIF-2B, thereby reducing the rate of the GDP to GTP exchange that is required for eIF2 to carry out additional rounds of translation initiation. The eukaryotic eIF2-alpha kinases PKR, HRI, and yeast GCN2 share extensive homology within their catalytic domains, but have distinct regulatory domains allowing for different physiologic signals to regulate phosphorylation of eIF2-alpha.The kinase domain of human PEK is similar to that of the other eIF2-alpha kinases, but the 550-residue N-terminal region is unique, perhaps reflecting the different physiologic signals that regulate its activity. Like rat PEK, recombinant human PEK was autophosphorylated and specifically phosphorylated eIF2-alpha.

Reference

"Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells."
J. Biol. Chem. 274:5723-5730(1999) [PubMed] [Europe PMC] [Abstract]

"Pancreatic eukaryotic initiation factor-2alpha kinase (PEK) homologues in humans, Drosophila melanogaster and Caenorhabditis elegans that mediate translational control in response to endoplasmic reticulum stress."
Biochem. J. 346:281-293(2000) [PubMed] [Europe PMC] [Abstract]

"EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome."
Nat. Genet. 25:406-409(2000) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"H2s-induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response."
Sci. Signal. 4:RA86-RA86(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK-and IRE1alpha-mediated unfolded protein response."
Nat. Cell Biol. 14:1223-1230(2012) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]