Eif2ak1 eukaryotic translation initiation factor 2 alpha kinase 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Eif2ak1provided by MGI
Official Full Name: eukaryotic translation initiation factor 2 alpha kinase 1provided by MGI
Primary source: MGI:MGI:1353448
See related: Ensembl:ENSMUSG00000029613 AllianceGenome:MGI:1353448
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: HCR; Hri
Summary: Enables heme binding activity; protein homodimerization activity; and protein kinase activity. Involved in negative regulation of cell population proliferation; negative regulation of hemoglobin biosynthetic process; and protein autophosphorylation. Acts upstream of or within several processes, including macrophage differentiation; multicellular organismal-level iron ion homeostasis; and regulation of protein metabolic process. Located in cytoplasm. Is expressed in alimentary system; central nervous system; liver; nervous system; and spinal cord. Orthologous to human EIF2AK1 (eukaryotic translation initiation factor 2 alpha kinase 1). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in liver E14.5 (RPKM 46.8), liver E14 (RPKM 43.9) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 5 G2; 5 82.67 cM

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	5	NC_000071.7 (143803586..143839535)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	5	NC_000071.6 (143817792..143902717)

Chromosome 5 - NC_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2alpha HRI kinase.
Title: Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase.
The eIF2alpha kinase HRI triggers the autophagic clearance of cytosolic protein aggregates.
Title: The eIF2α kinase HRI triggers the autophagic clearance of cytosolic protein aggregates.
Study in eIF2alpha kinase quadruple knockout (4KO) and single eIF2alpha kinase-rescued 4KO mouse embryonic fibroblast cells results indicate that the eIF2alpha kinase HRI is responsible for nanosecond pulsed electric fields (nsPEFs)-induced integrated stress response activation and is activated by nsPEF-generated reactive oxygen species.
Title: Nanosecond pulsed electric fields induce the integrated stress response via reactive oxygen species-mediated heme-regulated inhibitor (HRI) activation.
this study proposes that HRI, eIF2alpha, and HSPB8 define a novel cytosolic unfolded protein response (cUPR) essential for optimal innate immune signaling by large molecular platforms, functionally homologous to the PERK/eIF2alpha/HSPA5 axis of the endoplasmic reticulum UPR.
Title: The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling.
HRI coordinates 2 key translation-regulation pathways, eIF2alphaP and mTORC1, to circumvent ineffective erythropoiesis, highlighting heme and translation in the regulation of erythropoiesis.
Title: HRI coordinates translation by eIF2αP and mTORC1 to mitigate ineffective erythropoiesis in mice during iron deficiency.
HRI mediates the cellular confinement and killing of virulent L. monocytogenes.
Title: The eIF2α Kinase Heme-Regulated Inhibitor Protects the Host from Infection by Regulating Intracellular Pathogen Trafficking.
heme-regulated inhibitor (HRI), protein kinase R (PKR), PKR-like endoplasmic reticulum kinase, (PERK) and general control non-depressible 2 (GCN2) are sufficient for the integrated stress response; there are no additional eIF2alpha kinases in vertebrates
Title: Integrated stress response of vertebrates is regulated by four eIF2α kinases.
Heme-Regulated eIF2alpha Kinase Modulates Hepatic FGF21 and Is Activated by PPARbeta/delta Deficiency. Findings suggest that HRI is a potential target for regulating hepatic FGF21 levels.
Title: Heme-Regulated eIF2α Kinase Modulates Hepatic FGF21 and Is Activated by PPARβ/δ Deficiency.
These findings indicate that the anti-proliferative actions of PKR on pancreatic beta-cells may contribute to the pathogenesis of type 2 diabetes.
Title: Activation of double-stranded RNA-dependent protein kinase inhibits proliferation of pancreatic β-cells.
we suggest that Tyr193, Thr485 and Thr490 are essential residues in the catalysis.
Title: Autophosphorylation of heme-regulated eukaryotic initiation factor 2α kinase and the role of the modification in catalysis.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

BE692051 (e-PCR)
- UniSTS:207910

AF028808 (e-PCR)
- UniSTS:163380

RH124577 (e-PCR)
- UniSTS:161399

RH125654 (e-PCR)
- UniSTS:162440

Eif2ak1 (e-PCR), detects polymorphism
- UniSTS:527331

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables eukaryotic translation initiation factor 2alpha kinase activity	ISO Inferred from Sequence Orthology more info
enables eukaryotic translation initiation factor 2alpha kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables heme binding	IDA Inferred from Direct Assay more info	PubMed
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in HRI-mediated signaling	ISO Inferred from Sequence Orthology more info
involved_in HRI-mediated signaling	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within acute inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within establishment of localization in cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in integrated stress response signaling	ISO Inferred from Sequence Orthology more info
involved_in integrated stress response signaling	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within macrophage differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organismal-level iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of hemoglobin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of translation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within phagocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of mitophagy	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of mitophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein autophosphorylation	IEP Inferred from Expression Pattern more info	PubMed
involved_in protein localization to mitochondrion	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within protoporphyrinogen IX metabolic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of eIF2 alpha phosphorylation by heme	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of hemoglobin biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of translation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of translational initiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of translational initiation	IEA Inferred from Electronic Annotation more info
involved_in response to iron ion starvation	ISO Inferred from Sequence Orthology more info
involved_in response to iron ion starvation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: eukaryotic translation initiation factor 2-alpha kinase 1

Names: heme-controlled repressor; heme-regulated eukaryotic initiation factor eIF-2-alpha kinase; heme-regulated inhibitor; hemin-sensitive initiation factor 2-alpha kinase

NP_001407713.1

EC 2.7.11.1

NP_038585.2

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001420784.1 → NP_001407713.1 eukaryotic translation initiation factor 2-alpha kinase 1 isoform 2

Status: VALIDATED

Source sequence(s)

AC136746, AC166900
NM_013557.3 → NP_038585.2 eukaryotic translation initiation factor 2-alpha kinase 1 isoform 1

See identical proteins and their annotated locations for NP_038585.2

Status: VALIDATED

Source sequence(s)

AC136746, AC166900

Consensus CDS

CCDS84994.1

UniProtKB/Swiss-Prot

Q2TA96, Q69ZK8, Q8C024, Q8K123, Q9CTP5, Q9D601, Q9Z2R9

Related

ENSMUSP00000098056.5, ENSMUST00000100487.6

Conserved Domains (2) summary

cd14049
Location:160 → 578

STKc_EIF2AK1_HRI; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase

pfam00069
Location:167 → 580

Pkinase; Protein kinase domain