EIF2AK3 — Eukaryotic translation initiation factor 2 alpha kinase 3
EIF2AK3 belongs to a gene co-expression module in 4 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
EIF2AK3's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| Gamma-delta T cells | ER Stress Response Stress | ATP1B3, ATP2A2, BACH1, CPD, FAM118A, G3BP2, GRK5, HBP1 +13 more | |
| Macrophages | MAPK Stress Kinase Inflammatory | ARHGAP26, BRAF, BTBD9, CRY1, CYTH3, ESYT2, EXT1, FOXK2 +12 more | View in SCUBA |
| Monocytes | Integrated Stress Response Stress | CDKN1A, CSRNP1, HBEGF, KLF10, MAFF, PIM3, TIPARP | View in SCUBA |
| Mucosal-associated invariant T cell | Hypoxia-ER Stress Stress | ANKHD1, ARID1A, ARID4B, ATXN7, CEMIP2, CPD, CTDP1, ELF1 +5 more |
About the gene
| Synonyms | PEK, PERK |
|---|---|
| Chromosome | 2: 88556741-88691518 |
| Predicted location | Intracellular, Membrane |
| Essential gene | No |
| Protein class | Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins |
| Molecular function | Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
| Biological process | Stress response, Translation regulation, Unfolded protein response |
Function
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 recognizes 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 (By similarity). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity). Involved in control of mitochondrial morphology and function (By similarity).
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.