Eif2ak3 eukaryotic translation initiation factor 2 alpha kinase 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Eif2ak3provided by MGI
Official Full Name: eukaryotic translation initiation factor 2 alpha kinase 3provided by MGI
Primary source: MGI:MGI:1341830
See related: Ensembl:ENSMUSG00000031668 AllianceGenome:MGI:1341830
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Pek; Perk
Summary: The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in a similar gene in human are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]
Expression: Ubiquitous expression in placenta adult (RPKM 10.8), colon adult (RPKM 7.9) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 6 C1; 6 32.09 cM

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	6	NC_000072.7 (70821468..70882225)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	6	NC_000072.6 (70844484..70905241)

Chromosome 6 - NC_000072.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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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?

H2S alleviated sepsis-induced acute kidney injury by inhibiting PERK/Bax-Bcl2 pathway.
Title: H(2)S alleviated sepsis-induced acute kidney injury by inhibiting PERK/Bax-Bcl2 pathway.
Oligodendrocyte-selective deletion of the eIF2alpha kinase Perk/Eif2ak3 limits functional recovery after spinal cord injury.
Title: Oligodendrocyte-selective deletion of the eIF2α kinase Perk/Eif2ak3 limits functional recovery after spinal cord injury.
Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice.
Title: Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice.
DNAJC10 maintains survival and self-renewal of leukemia stem cells through PERK branch of the unfolded protein response.
Title: DNAJC10 maintains survival and self-renewal of leukemia stem cells through PERK branch of the unfolded protein response.
Partial Deletion of Perk Improved High-Fat Diet-Induced Glucose Intolerance in Mice.
Title: Partial Deletion of Perk Improved High-Fat Diet-Induced Glucose Intolerance in Mice.
ALKBH5 protects against stroke by reducing endoplasmic reticulum stress-dependent inflammation injury via the STAT5/PERK/EIF2alpha/CHOP signaling pathway in an m[6]A-YTHDF1-dependent manner.
Title: ALKBH5 protects against stroke by reducing endoplasmic reticulum stress-dependent inflammation injury via the STAT5/PERK/EIF2α/CHOP signaling pathway in an m(6)A-YTHDF1-dependent manner.
Pericentrin deficiency in smooth muscle cells augments atherosclerosis through HSF1-driven cholesterol biosynthesis and PERK activation.
Title: Pericentrin deficiency in smooth muscle cells augments atherosclerosis through HSF1-driven cholesterol biosynthesis and PERK activation.
SEL1L preserves CD8[+] T-cell survival and homeostasis by fine-tuning PERK signaling and the IL-15 receptor-mediated mTORC1 axis.
Title: SEL1L preserves CD8(+) T-cell survival and homeostasis by fine-tuning PERK signaling and the IL-15 receptor-mediated mTORC1 axis.
Role of PERK-mediated pathway in the effect of mild hypothermia after cerebral ischaemia/reperfusion.
Title: Role of PERK-mediated pathway in the effect of mild hypothermia after cerebral ischaemia/reperfusion.
Astrocytic deletion of protein kinase R-like ER kinase (PERK) does not affect learning and memory in aged mice but worsens outcome from experimental stroke.
Title: Astrocytic deletion of protein kinase R-like ER kinase (PERK) does not affect learning and memory in aged mice but worsens outcome from experimental stroke.

Submit: New GeneRIF Correction See all GeneRIFs (159)

Variation

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Alleles

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

Endonuclease-mediated (5) 1 citation
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI427929 (e-PCR)
- UniSTS:159520

Z72375 (e-PCR)
- UniSTS:67437

Eif2ak3 (e-PCR), detects polymorphism
- UniSTS:525219

PMC262586P2 (e-PCR)
- UniSTS:272318

RH91182 (e-PCR)
- UniSTS:86985

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 Hsp90 protein binding	ISO Inferred from Sequence Orthology more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables eukaryotic initiation factor eIF2 binding	IC Inferred by Curator more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
enables eukaryotic translation initiation factor 2alpha kinase activity	IGI Inferred from Genetic Interaction more info	PubMed
enables eukaryotic translation initiation factor 2alpha kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
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 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 H2AXY142 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 H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables misfolded protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein phosphatase binding	ISO Inferred from Sequence Orthology more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in ER overload response	ISO Inferred from Sequence Orthology more info
involved_in ER overload response	ISS Inferred from Sequence or Structural Similarity more info
involved_in ERAD pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in PERK-mediated unfolded protein response	IDA Inferred from Direct Assay more info	PubMed
involved_in PERK-mediated unfolded protein response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within SREBP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in angiogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within bone mineralization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to amino acid starvation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to amino acid starvation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to cold	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cold	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to glucose starvation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to glucose starvation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within chondrocyte development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in eiF2alpha phosphorylation in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in eiF2alpha phosphorylation in response to endoplasmic reticulum stress	ISO Inferred from Sequence Orthology more info
involved_in eiF2alpha phosphorylation in response to endoplasmic reticulum stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in endocrine pancreas development	ISO Inferred from Sequence Orthology more info
involved_in endocrine pancreas development	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within endoplasmic reticulum organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within endoplasmic reticulum unfolded protein response	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within endoplasmic reticulum unfolded protein response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endoplasmic reticulum unfolded protein response	ISO Inferred from Sequence Orthology more info
involved_in endoplasmic reticulum unfolded protein response	ISS Inferred from Sequence or Structural Similarity more info
involved_in endoplasmic reticulum unfolded protein response	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within fat cell differentiation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within insulin-like growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lactation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of myelination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of translation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of translation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of translation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of translation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of translation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of translation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of translation in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of translation in response to stress	ISO Inferred from Sequence Orthology more info
involved_in ossification	ISO Inferred from Sequence Orthology more info
involved_in ossification	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within pancreas development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERAD pathway	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within positive regulation of cysteine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of glutathione biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase I	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase I	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vascular endothelial growth factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of vascular endothelial growth factor production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein autophosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of fatty acid metabolic process	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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of translational initiation by eIF2 alpha phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of translational initiation by eIF2 alpha phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to endoplasmic reticulum stress	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within skeletal system development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within translation	IDA Inferred from Direct Assay more info	PubMed

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
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum quality control compartment	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: eukaryotic translation initiation factor 2-alpha kinase 3

Names: PRKR-like endoplasmic reticulum kinase; pancreatic eIF2-alpha kinase

NP_001300847.1

EC 2.7.11.1

NP_034251.2

EC 2.7.11.1

XP_006505564.1

EC 2.7.11.1

XP_011239504.1

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_001313918.1 → NP_001300847.1 eukaryotic translation initiation factor 2-alpha kinase 3 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks multiple alternate 3' exons and uses an alternate 3' terminal exon, compared to variant 1. The encoded isoform (2) has a distinct and shorter C-terminus, compared to isoform 1.

Source sequence(s)

AC156398, AK010397

Consensus CDS

CCDS85063.1

UniProtKB/TrEMBL

A0A0R4J1Y1

Related

ENSMUSP00000123759.2, ENSMUST00000162950.2

Conserved Domains (1) summary

cl14874
Location:100 → 127

Luminal_IRE1_like; The Luminal domain, a dimerization domain, of Inositol-requiring protein 1-like proteins
NM_010121.3 → NP_034251.2 eukaryotic translation initiation factor 2-alpha kinase 3 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC155842, BC054809, BP762515

Consensus CDS

CCDS20223.1

UniProtKB/Swiss-Prot

Q9CTK8, Q9CWT5, Q9Z2B5

UniProtKB/TrEMBL

E9QQ30, Q7TQC8

Related

ENSMUSP00000034093.9, ENSMUST00000034093.15

Conserved Domains (4) summary

cd09768
Location:100 → 416

Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3

smart00220
Location:879 → 1071

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14048
Location:874 → 1073

STKc_EIF2AK3_PERK; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase

cl21453
Location:583 → 671

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000072.7 Reference GRCm39 C57BL/6J

Range

70821468..70882225

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011241202.3 → XP_011239504.1 eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1

UniProtKB/Swiss-Prot

Q9CTK8, Q9CWT5, Q9Z2B5

UniProtKB/TrEMBL

Q7TQC8

Conserved Domains (3) summary

cd09768
Location:100 → 416

Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3

cd14048
Location:873 → 1072

STKc_EIF2AK3_PERK; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase

cl21453
Location:582 → 670

PKc_like; Protein Kinases, catalytic domain
XM_006505501.2 → XP_006505564.1 eukaryotic translation initiation factor 2-alpha kinase 3 isoform X2

Conserved Domains (3) summary

cd14048
Location:637 → 836

STKc_EIF2AK3_PERK; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase

cl14874
Location:28 → 179

Luminal_IRE1_like; The Luminal domain, a dimerization domain, of Inositol-requiring protein 1-like proteins

cl21453
Location:346 → 434

PKc_like; Protein Kinases, catalytic domain