Description | eukaryotic translation initiation factor 2-alpha kinase 1heme regulated initiation factor 2 alpha kinaseheme sensitive initiation factor 2a kinaseheme-controlled repressorheme-regulated eukaryotic initiation factor eIF-2-alpha kinaseheme-regulated in | serine/threonine-protein phosphatase PP1-alpha catalytic subunitprotein phosphatase 1, catalytic subunit, alpha isozymeserine/threonine protein phosphatase PP1-alpha 1 catalytic subunittesticular tissue protein Li 155 |
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000199389, ENST00000536084, ENST00000495565, | ENST00000312989, ENST00000532446, ENST00000376745, ENST00000358239, |
Hgene | Tgene |
EIF2AK1
Q9BQI3 | PPP1CA
P62136 |
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 conditions (PubMed:32132706, PubMed:32132707, PubMed:37327776). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:32132706, PubMed:32132707, PubMed:37327776). 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 activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707, PubMed:37327776). Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Iron deficiency also triggers activation by full-length DELE1 (PubMed:37327776). Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707). {ECO:0000250|UniProtKB:Q9Z2R9, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:32197074}. | FUNCTION: Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Dephosphorylates CENPA (PubMed:25556658). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (PubMed:26083323). {ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:21712997, ECO:0000269|PubMed:23396208, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26083323}.; FUNCTION: (Microbial infection) Necessary for alphaviruses replication. {ECO:0000269|PubMed:29769351}. |
Kinase | GOID | GO term | P.adjust |
EIF2AK1 | ID | Description | 0.00e+00 |
EIF2AK1 | GO:0071287 | cellular response to manganese ion | 7.58e-03 |
EIF2AK1 | GO:0097050 | type B pancreatic cell apoptotic process | 7.58e-03 |
EIF2AK1 | GO:0036490 | regulation of translation in response to endoplasmic reticulum stress | 7.58e-03 |
EIF2AK1 | GO:0043558 | regulation of translational initiation in response to stress | 7.58e-03 |
EIF2AK1 | GO:0010042 | response to manganese ion | 7.58e-03 |
EIF2AK1 | GO:0036499 | PERK-mediated unfolded protein response | 7.58e-03 |
EIF2AK1 | GO:0043555 | regulation of translation in response to stress | 7.58e-03 |
EIF2AK1 | GO:0045947 | negative regulation of translational initiation | 7.58e-03 |
EIF2AK1 | GO:0034063 | stress granule assembly | 9.49e-03 |
EIF2AK1 | GO:0140467 | integrated stress response signaling | 1.06e-02 |
EIF2AK1 | GO:1904037 | positive regulation of epithelial cell apoptotic process | 1.06e-02 |
EIF2AK1 | GO:0006984 | ER-nucleus signaling pathway | 1.06e-02 |
EIF2AK1 | GO:0034198 | cellular response to amino acid starvation | 1.06e-02 |
EIF2AK1 | GO:1990928 | response to amino acid starvation | 1.06e-02 |
EIF2AK1 | GO:0034605 | cellular response to heat | 1.21e-02 |
EIF2AK1 | GO:0030968 | endoplasmic reticulum unfolded protein response | 1.29e-02 |
EIF2AK1 | GO:0006446 | regulation of translational initiation | 1.31e-02 |
EIF2AK1 | GO:0034620 | cellular response to unfolded protein | 1.31e-02 |
EIF2AK1 | GO:0034644 | cellular response to UV | 1.31e-02 |
EIF2AK1 | GO:0009408 | response to heat | 1.39e-02 |
EIF2AK1 | GO:0035967 | cellular response to topologically incorrect protein | 1.39e-02 |
EIF2AK1 | GO:1904035 | regulation of epithelial cell apoptotic process | 1.39e-02 |
EIF2AK1 | GO:0006413 | translational initiation | 1.39e-02 |
EIF2AK1 | GO:0071482 | cellular response to light stimulus | 1.39e-02 |
EIF2AK1 | GO:0043200 | response to amino acid | 1.39e-02 |
EIF2AK1 | GO:0006986 | response to unfolded protein | 1.42e-02 |
EIF2AK1 | GO:0001101 | response to acid chemical | 1.42e-02 |
EIF2AK1 | GO:1904019 | epithelial cell apoptotic process | 1.42e-02 |
EIF2AK1 | GO:0009411 | response to UV | 1.44e-02 |
EIF2AK1 | GO:0035966 | response to topologically incorrect protein | 1.46e-02 |
EIF2AK1 | GO:0009266 | response to temperature stimulus | 1.51e-02 |
EIF2AK1 | GO:0009267 | cellular response to starvation | 1.51e-02 |
EIF2AK1 | GO:0071478 | cellular response to radiation | 1.51e-02 |
EIF2AK1 | GO:0071248 | cellular response to metal ion | 1.62e-02 |
EIF2AK1 | GO:0042594 | response to starvation | 1.72e-02 |
EIF2AK1 | GO:0071241 | cellular response to inorganic substance | 1.75e-02 |
EIF2AK1 | GO:0031669 | cellular response to nutrient levels | 1.85e-02 |
EIF2AK1 | GO:0034599 | cellular response to oxidative stress | 1.85e-02 |
EIF2AK1 | GO:0034976 | response to endoplasmic reticulum stress | 1.88e-02 |
EIF2AK1 | GO:0031668 | cellular response to extracellular stimulus | 1.94e-02 |
EIF2AK1 | GO:0017148 | negative regulation of translation | 2.03e-02 |
EIF2AK1 | GO:0062197 | cellular response to chemical stress | 2.03e-02 |
EIF2AK1 | GO:0009416 | response to light stimulus | 2.03e-02 |
EIF2AK1 | GO:0071214 | cellular response to abiotic stimulus | 2.03e-02 |
EIF2AK1 | GO:0104004 | cellular response to environmental stimulus | 2.03e-02 |
EIF2AK1 | GO:0034249 | negative regulation of amide metabolic process | 2.03e-02 |
EIF2AK1 | GO:0071496 | cellular response to external stimulus | 2.03e-02 |
EIF2AK1 | GO:0010038 | response to metal ion | 2.06e-02 |
EIF2AK1 | GO:0006979 | response to oxidative stress | 2.25e-02 |