EIF2AK3
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.
Overview
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.
Open Targets scores its association with cancer at 0.54 (direct and indirect evidence; datatypes literature 0.98, affected pathway 0.83, animal model 0.48, genetic association 0.08).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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).
- 3 · How drugs use it
No product in this corpus aims at EIF2AK3 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:3255 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9NZJ5 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000172071 (association with cancer (MONDO_0004992) 0.54; (GraphQL API, CC0))
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).
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: none stated by the sources. Evidence tier "association-only" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery 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.