Reactome | Response of EIF2AK1 (HRI) to heme deficiency

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Response of EIF2AK1 (HRI) to heme deficiency Show undefined attributes

authored	[InstanceEdit:9648881] May, Bruce, 2019-06-10
created	[InstanceEdit:9648890] May, Bruce, 2019-06-10
dbId	9648895
displayName	Response of EIF2AK1 (HRI) to heme deficiency
doi	10.3180/R-HSA-9648895.1
edited	[InstanceEdit:9648881] May, Bruce, 2019-06-10
eventOf	[Pathway:R-HSA-2262752] Cellular responses to stress - Homo sapiens
goBiologicalProcess	[GO_BiologicalProcess:437012] regulation of eIF2 alpha phosphorylation by heme
hasDiagram	true
hasEHLD	false
hasEvent	[Reaction:R-HSA-9648880] Ferriheme dissociates from p-T-EIF2AK1:2xferriheme dimer - Homo sapiens [Reaction:R-HSA-9648883] p-T-EIF2AK1:ferriheme dimer autophosphorylates - Homo sapiens [Reaction:R-HSA-9648888] p-T,T486,T488-EIF2AK1 phosphorylates EIF2S1 (eIF2-alpha) - Homo sapiens [BlackBoxEvent:R-HSA-381128] Translation of ATF4 - Homo sapiens [BlackBoxEvent:R-HSA-9650722] Translation of DDIT3 - Homo sapiens [BlackBoxEvent:R-HSA-9650710] Translation of PPP1R15A - Homo sapiens [BlackBoxEvent:R-HSA-9653745] Translation of ATF5 - Homo sapiens [Reaction:R-HSA-9655086] ATF4 binds the DDIT3 promoter - Homo sapiens [BlackBoxEvent:R-HSA-9655071] Transcription of DDIT3 (CHOP, GADD153) in response to heme deficiency - Homo sapiens [Reaction:R-HSA-9653742] ATF4 and a CEBP protein bind the ATF5 promoter - Homo sapiens [BlackBoxEvent:R-HSA-9653724] Transcription of ATF5 - Homo sapiens [Reaction:R-HSA-9653893] ATF4, CEBPB, and ATF3 bind the CHAC1 promoter - Homo sapiens [BlackBoxEvent:R-HSA-9653894] Expression of CHAC1 - Homo sapiens [Reaction:R-HSA-9635927] ATF4 and a CEBP protein bind the TRIB3 promoter - Homo sapiens [BlackBoxEvent:R-HSA-9635912] Expression of TRIB3 in response to stress - Homo sapiens [Reaction:R-HSA-9654752] ATF4 binds the PPP1R15A (GADD34) promoter - Homo sapiens [BlackBoxEvent:R-HSA-9654774] Transcription of PPP1R15A - Homo sapiens [Reaction:R-HSA-9635915] ATF4 and CEBPB,CEBPG bind the ASNS gene - Homo sapiens [BlackBoxEvent:R-HSA-1791118] Expression of ASNS (Asparagine Synthetase) - Homo sapiens [BlackBoxEvent:R-HSA-9654792] Expression of GRB10 - Homo sapiens
isInDisease	false
isInferred	false
lastUpdatedDate	2021-09-15
literatureReference	[LiteratureReference:9655279] Translation initiation control by heme-regulated eukaryotic initiation factor 2alpha kinase in erythroid cells under cytoplasmic stresses [LiteratureReference:9655276] Translational control by heme-regulated eIF2? kinase during erythropoiesis [LiteratureReference:9635265] The eIF2? kinases: their structures and functions [LiteratureReference:9655551] Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency [LiteratureReference:9655874] Elucidation of molecular mechanism of stability of the heme-regulated eIF2? kinase upon binding of its ligand, hemin in its catalytic kinase domain [LiteratureReference:9655576] Two heme-binding domains of heme-regulated eukaryotic initiation factor-2alpha kinase. N terminus and kinase insertion [LiteratureReference:9655560] Heme-regulated eIF-2alpha kinase purifies as a hemoprotein [LiteratureReference:9655579] Characterization of heme-regulated eIF2alpha kinase: roles of the N-terminal domain in the oligomeric state, heme binding, catalysis, and inhibition [LiteratureReference:9655528] Elucidation of the heme binding site of heme-regulated eukaryotic initiation factor 2alpha kinase and the role of the regulatory motif in heme sensing by spectroscopic and catalytic studies of mutant proteins [LiteratureReference:9655582] Identification of Cys385 in the isolated kinase insertion domain of heme-regulated eIF2 alpha kinase (HRI) as the heme axial ligand by site-directed mutagenesis and spectral characterization [LiteratureReference:9655533] Multiple autophosphorylation is essential for the formation of the active and stable homodimer of heme-regulated eIF2alpha kinase [LiteratureReference:9655534] Autophosphorylation of threonine 485 in the activation loop is essential for attaining eIF2alpha kinase activity of HRI [LiteratureReference:9655550] Autophosphorylation of heme-regulated eukaryotic initiation factor 2? kinase and the role of the modification in catalysis [LiteratureReference:9633883] Regulated translation initiation controls stress-induced gene expression in mammalian cells [LiteratureReference:9650728] HRI coordinates translation necessary for protein homeostasis and mitochondrial function in erythropoiesis [LiteratureReference:9656236] HRI coordinates translation by eIF2?P and mTORC1 to mitigate ineffective erythropoiesis in mice during iron deficiency [LiteratureReference:9664251] The function of heme-regulated eIF2alpha kinase in murine iron homeostasis and macrophage maturation [LiteratureReference:9664250] Heme-regulated eIF2alpha kinase in erythropoiesis and hemoglobinopthies
maxDepth	2
modified	[InstanceEdit:9847082] Weiser, Joel, 2023-10-12
name	Response of EIF2AK1 (HRI) to heme deficiency
releaseDate	2019-12-10
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:9664254] Chen, Jane-Jane, 2019-10-22
schemaClass	Pathway
species	[Species:48887] Homo sapiens
stId	R-HSA-9648895
summation	[Summation:9650720] The kinases of the integrated stress response phosphorylate ...
updateTrackers	[UpdateTracker:9775908] Update Tracker - [Pathway:9648895] Response of EIF2AK1 (HRI) to heme deficiency - v78:[updateContainedRLE]

Referrals

(updatedInstance)	[UpdateTracker:9775908] Update Tracker - [Pathway:9648895] Response of EIF2AK1 (HRI) to heme deficiency - v78:[updateContainedRLE]
(hasEvent)	[Pathway:R-HSA-2262752] Cellular responses to stress

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