The protein encoded by this gene 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 is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Jan 2010]
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 (CCND1).
Subunit: Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER-stressed cells. Interacts with DNAJC3.
Subcellular Location: Endoplasmic reticulum membrane; Single-pass type I membrane protein.
Tissue Specificity: Ubiquitous. A high level expression is seen in secretory tissues.
Post-translational modifications: Oligomerization of the N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the SLCterminal cytoplasmic kinase domain at multiple residues including Thr-982 on the kinase activation loop. Autophosphorylated. Phosphorylated at Tyr-619 following endoplasmic reticulum stress, leading to activate its tyrosine-protein kinase activity. Dephosphorylated by PTPN1/TP1B, leading to inactivate its enzyme activity.
N-glycosylated.
ADP-ribosylated by PARP16 upon ER stress, which increases kinase activity.
DISEASE: Wolcott-Rallison syndrome (WRS) [MIM:226196]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.
Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.
Contains 1 protein kinase domain.
SWISS: Q9NZJ5
Gene ID: 9451
Database links:
Entrez Gene: 9451 Human
Entrez Gene: 13666 Mouse
Entrez Gene: 29702 Rat
Omim: 604032 Human
SwissProt: Q9NZJ5 Human
SwissProt: Q9Z2B5 Mouse
SwissProt: Q9Z1Z1 Rat
Unigene: 591589 Human
Unigene: 247167 Mouse
Unigene: 24897 Rat
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Sample:
Cerebrum (Mouse) Lysate at 40 ug
Testis (Mouse) Lysate at 40 ug
NIH/3T3(Mouse) Cell Lysate at 30 ug
Primary: Anti- EIF2AK3’PERK (SLM51385M) at 1/1000 dilution
Secondary: IRDye800CW Goat Anti- Mouse IgG at 1/20000 dilution
Predicted band size: 125 kD
Observed band size: 125 kD
Sample:
Cerebrum (Mouse) Lysate at 40 ug
Primary: Anti- EIF2AK3’PERK (SLM51385M) at 1/1000 dilution
Secondary: IRDye800CW Goat Anti-Mouse IgG at 1/20000 dilution
Predicted band size: 122 kD
Observed band size: 122 kD
Sample:
SY5Y(Human) Cell Lysate at 30 ug
Primary: Anti- EIF2AK3/PERK (SLM51385M) at 1/1000 dilution
Secondary: IRDye800CW Goat Anti-Mouse IgG at 1/20000 dilution
Predicted band size: 122 kD
Observed band size: 122 kD
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Specific References (1) | SLM51385M has been referenced in 1 publications.
[IF=5.793] Chunyue Wang. et al. Neuroprotective effects of verbascoside against Alzheimer’s disease via the relief of endoplasmic reticulum stress in Aβ-exposed U251 cells and APP/PS1 mice. J Neuroinflamm. 2020 Dec;17(1):1-16 WB ; Human.
