EIF2AK3

Eukaryotic translation initiation factor 2-alpha kinase 3, also known as protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), is an enzyme that in humans is encoded by the EIF2AK3 gene.^[5][6][7][8]

EIF2AK3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4G31, 4G34, 4M7I, 4X7H, 4X7J, 4X7K, 4X7L, 4X7N, 4X7O, 4YZS
Identifiers
Aliases	EIF2AK3, PEK, PERK, WRS, eukaryotic translation initiation factor 2 alpha kinase 3
External IDs	OMIM: 604032; MGI: 1341830; HomoloGene: 3557; GeneCards: EIF2AK3; OMA:EIF2AK3 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p11.2 Start 88,556,741 bp[1] End 88,691,518 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 C1 Start 70,821,499 bp[2] End 70,882,229 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in body of pancreas mucosa of paranasal sinus Achilles tendon pylorus parotid gland nasal epithelium mucosa of sigmoid colon tibia epithelium of nasopharynx trachea Top expressed in submandibular gland lacrimal gland parotid gland granulocyte seminal vesicula calvaria islet of Langerhans lumbar spinal ganglion epithelium of stomach decidua More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity protein kinase activity Hsp90 protein binding nucleotide binding protein homodimerization activity kinase activity protein serine/threonine kinase activity protein binding identical protein binding enzyme binding protein phosphatase binding ATP binding eukaryotic translation initiation factor 2alpha kinase activity Cellular component cytoplasm integral component of membrane endoplasmic reticulum membrane membrane integral component of endoplasmic reticulum membrane endoplasmic reticulum perinuclear region of cytoplasm cytosolic ribosome Biological process skeletal system development bone mineralization insulin-like growth factor receptor signaling pathway negative regulation of translation regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation cellular response to glucose starvation negative regulation of translation in response to stress ossification negative regulation of translational initiation in response to stress phosphorylation cellular response to amino acid starvation chondrocyte development regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway insulin secretion endoplasmic reticulum organization response to endoplasmic reticulum stress PERK-mediated unfolded protein response ER overload response response to manganese-induced endoplasmic reticulum stress endoplasmic reticulum unfolded protein response protein phosphorylation response to unfolded protein positive regulation of gene expression cellular response to cold peptidyl-serine phosphorylation angiogenesis eiF2alpha phosphorylation in response to endoplasmic reticulum stress protein autophosphorylation positive regulation of vascular endothelial growth factor production positive regulation of transcription by RNA polymerase I protein homooligomerization activation of cysteine-type endopeptidase activity involved in apoptotic process negative regulation of myelination regulation of translation calcium-mediated signaling endocrine pancreas development positive regulation of protein localization to nucleus regulation of translational initiation by eIF2 alpha phosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9451 13666 Ensembl ENSG00000172071 ENSMUSG00000031668 UniProt Q9NZJ5 Q9Z2B5 RefSeq (mRNA) NM_001313915 NM_004836 NM_010121 NM_001313918 RefSeq (protein) NP_001300844 NP_004827 NP_001300847 NP_034251 Location (UCSC) Chr 2: 88.56 – 88.69 Mb Chr 6: 70.82 – 70.88 Mb PubMed search [3] [4]
Wikidata
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Function

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.^[6]

Clinical significance

Patients with mutations in this gene develop Wolcott-Rallison syndrome.^[9]

Interactions

EIF2AK3 has been shown to interact with DNAJC3,^[10] NFE2L2,^[11] and endoplasmic reticulum chaperone BiP (Hsp70).^[12]

Inhibitors

• GSK2606414
• 3-Fluoro-GSK2606414