EIF2AK1 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0008285Biological processnegative regulation of cell population proliferation
GO_0046986Biological processnegative regulation of hemoglobin biosynthetic process
GO_0030225Biological processmacrophage differentiation
GO_0140468Biological processHRI-mediated signaling
GO_0060586Biological processmulticellular organismal-level iron ion homeostasis
GO_0002526Biological processacute inflammatory response
GO_0051649Biological processestablishment of localization in cell
GO_1990641Biological processresponse to iron ion starvation
GO_0045993Biological processnegative regulation of translational initiation by iron
GO_0010998Biological processregulation of translational initiation by eIF2 alpha phosphorylation
GO_0006909Biological processphagocytosis
GO_0046501Biological processprotoporphyrinogen IX metabolic process
GO_1901526Biological processpositive regulation of mitophagy
GO_0046777Biological processprotein autophosphorylation
GO_0140467Biological processintegrated stress response signaling
GO_0010999Biological processregulation of eIF2 alpha phosphorylation by heme
GO_0005634Cellular componentnucleus
GO_0005829Cellular componentcytosol
GO_0005737Cellular componentcytoplasm
GO_0042803Molecular functionprotein homodimerization activity
GO_0106310Molecular functionprotein serine kinase activity
GO_0004694Molecular functioneukaryotic translation initiation factor 2alpha kinase activity
GO_0020037Molecular functionheme binding
GO_0005524Molecular functionATP binding
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameEIF2AK1
Protein nameEukaryotic translation initiation factor 2-alpha kinase 1 (EC 2.7.11.1) (Heme-controlled repressor) (HCR) (Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase) (Heme-regulated inhibitor) (hHRI) (Hemin-sensitive initiation factor 2-alpha kinase)
Eukaryotic translation initiation factor 2 alpha kinase 1
SynonymsHRI
KIAA1369
PRO1362
DescriptionFUNCTION: 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 . 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 . 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 . 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 . 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 . .

AccessionsH7C033
ENST00000422786.1
Q9BQI3
F8WCM0
ENST00000431744.5
ENST00000199389.11 [Q9BQI3-1]
C9J7U7
ENST00000446699.1