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EIF2AK3 (Eukaryotic translation initiation factor 2-alpha kinase 3) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. In the public catalogues the evidence so far is association rather than a proven role. This dossier gathers the 0 products (0 approved), 0 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR). Key effector of the integrated stress response (ISR) to unfolded proteins: EIF2AK3/PERK specifically recognises and binds misfolded proteins, leading to its activation and EIF2S1/eIF-2-alpha phosphorylation. EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming. The EIF2AK3/PERK-mediated unfolded protein response increases mitochondrial oxidative phosphorylation by promoting ATF4-mediated expression of COX7A2L/SCAF1, thereby increasing formation of respiratory chain supercomplexes. In contrast to most subcellular compartments, mitochondria are protected from the EIF2AK3/PERK-mediated unfolded protein response due to EIF2AK3/PERK inhibition by ATAD3A at mitochondria-endoplasmic reticulum contact sites. In addition to EIF2S1/eIF-2-alpha, also phosphorylates NFE2L2/NRF2 in response to stress, promoting release of NFE2L2/NRF2 from the BCR(KEAP1) complex, leading to nuclear accumulation and activation of NFE2L2/NRF2. Location: Endoplasmic reticulum membrane (UniProt). Locus 2p11.2 (HGNC).
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No trial in the corpus names this target or one of its products.
No recorded escape route names this target.
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Query for this target: (TITLE:"EIF2AK3" OR ABSTRACT:"EIF2AK3" OR TITLE:"eukaryotic translation initiation factor 2 alpha kinase 3" OR ABSTRACT:"eukaryotic translation initiation factor 2 alpha kinase 3" OR TITLE:"Eukaryotic translation initiation factor 2-alpha kinase 3" OR ABSTRACT:"Eukaryotic translation initiation factor 2-alpha kinase 3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about EIF2AK3, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/eif2ak3.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/eif2ak3.json. Licence CC BY-NC 4.0.