Eif2ak2 eukaryotic translation initiation factor 2-alpha kinase 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Eif2ak2provided by RGD
Official Full Name: eukaryotic translation initiation factor 2-alpha kinase 2provided by RGD
Primary source: RGD:3402
See related: Ensembl:ENSRNOG00000048315 AllianceGenome:RGD:3402
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Pkr; Prkr
Summary: Predicted to enable double-stranded RNA binding activity; eukaryotic translation initiation factor 2alpha kinase activity; and identical protein binding activity. Involved in several processes, including response to exogenous dsRNA; response to lipopolysaccharide; and response to vitamin E. Located in nucleus. Biomarker of pulmonary venoocclusive disease. Human ortholog(s) of this gene implicated in Alzheimer's disease; Huntington's disease; Parkinson's disease; and hepatitis B. Orthologous to human EIF2AK2 (eukaryotic translation initiation factor 2 alpha kinase 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Spleen (RPKM 178.3), Lung (RPKM 134.5) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 6q12

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	6	NC_086024.1 (21941147..21977115)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	6	NC_051341.1 (16189000..16224972)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	6	NC_005105.4 (1428845..1466193, complement)

Chromosome 6 - NC_086024.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Regulation of the cerebrovascular smooth muscle cell phenotype by mitochondrial oxidative injury and endoplasmic reticulum stress in simulated microgravity rats via the PERK-eIF2alpha-ATF4-CHOP pathway.
Title: Regulation of the cerebrovascular smooth muscle cell phenotype by mitochondrial oxidative injury and endoplasmic reticulum stress in simulated microgravity rats via the PERK-eIF2α-ATF4-CHOP pathway.
Upregulation of PKR pathway mediates glucolipotoxicity induced diabetic cardiomyopathy in vivo in wistar rats and in vitro in cultured cardiomyocytes.
Title: Upregulation of PKR pathway mediates glucolipotoxicity induced diabetic cardiomyopathy in vivo in wistar rats and in vitro in cultured cardiomyocytes.
tudy reports, for the first time, that PKR-mediated harmful effects of PA in cultured cardiomyocytes via activation of JNK, NF-kB, and NLRP3 pathways. Inhibition of PKR is one of the possible mechanistic approaches to inhibit inflammation, oxidative stress, and apoptosis in lipotoxicity-induced cardiomyocyte damage.
Title: Inhibition of protein kinase R protects against palmitic acid-induced inflammation, oxidative stress, and apoptosis through the JNK/NF-kB/NLRP3 pathway in cultured H9C2 cardiomyocytes.
PKR plays a pivotal role in LPS-induced bone loss in periodontal disease.
Title: PKR regulates LPS-induced osteoclast formation and bone destruction in vitro and in vivo.
Increased levels of PKR and HMGB1 in synovium or blood appear to be involved in the occurrence and development ofrheumatoid arthritis (RA )in a rat model. Selective inhibition of PKR improves the symptoms of RA perhaps by inhibiting the release of HMGB1
Title: PKR and HMGB1 expression and function in rheumatoid arthritis.
Zn(2+) stimulated the phosphorylation of eIF2a and promoted the nuclear accumulation of activating transcription factor 4 (ATF4). Treatment with salubrinal enhanced Zn(2+)-induced ATF4 accumulation and IL-23 p19 mRNA expression.
Title: Zinc regulates expression of IL-23 p19 mRNA via activation of eIF2α/ATF4 axis in HAPI cells.
PERK pathway is involved in oxygen-glucose-serum deprivation-induced NF-kappaB activation via reactive oxygen species generation in spinal cord astrocytes.
Title: PERK pathway is involved in oxygen-glucose-serum deprivation-induced NF-kB activation via ROS generation in spinal cord astrocytes.
Taken together, these data suggest that PP1-12 protects cardiomyocytes from TM- and I/R-induced apoptosis, and this effect is achieved at least in part through the inhibition of cell apoptosis and the induction of eIF2alpha phosphorylation
Title: Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin-induced apoptosis and I/R through the upregulation of p-eIF2α.
The results suggested that the diminished hypertrophic response in the obese Zucker rat may be mediated, at least in part, by the hyperactivation of AMPK- and double-stranded-RNA-dependent protein kinase-related signaling.
Title: Diminished muscle growth in the obese Zucker rat following overload is associated with hyperphosphorylation of AMPK and dsRNA-dependent protein kinase.
Activation of the PERK/eIF2a signaling pathway contributes to the occurrence and development of hepatocyte apoptosis in alcoholic liver injury.
Title: [Role of PERK/eIF2a signaling pathway in hepatocyte apoptosis of alcoholic liver injury rats].

Submit: New GeneRIF Correction See all GeneRIFs (20)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D6Wox23 (e-PCR)
- UniSTS:518805

BF390837 (e-PCR)
- UniSTS:249586

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables double-stranded RNA binding	IEA Inferred from Electronic Annotation more info
enables double-stranded RNA binding	ISO Inferred from Sequence Orthology 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	IEA Inferred from Electronic Annotation more info
enables eukaryotic translation initiation factor 2alpha kinase activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables kinase activity	ISO Inferred from Sequence Orthology more info
enables non-membrane spanning protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	ISO Inferred from Sequence Orthology more info
enables protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in antiviral innate immune response	IEA Inferred from Electronic Annotation more info
involved_in antiviral innate immune response	ISO Inferred from Sequence Orthology more info
involved_in cellular response to amino acid starvation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amino acid starvation	ISO Inferred from Sequence Orthology more info
involved_in eiF2alpha phosphorylation in response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within endoplasmic reticulum unfolded protein response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of osteoblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of osteoblast proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of osteoblast proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of translation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of translation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of translation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of viral genome replication	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of viral genome replication	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of viral genome replication	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of chemokine production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of chemokine production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cytokine production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cytokine production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of non-canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of non-canonical NF-kappaB signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of stress-activated MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of stress-activated MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of NLRP3 inflammasome complex assembly	ISO Inferred from Sequence Orthology more info
involved_in regulation of NLRP3 inflammasome complex assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of hematopoietic progenitor cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in regulation of hematopoietic progenitor cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of hematopoietic stem cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in regulation of hematopoietic stem cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of hematopoietic stem cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in regulation of hematopoietic stem cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to exogenous dsRNA	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to interferon-alpha	IEA Inferred from Electronic Annotation more info
involved_in response to interferon-alpha	ISO Inferred from Sequence Orthology more info
involved_in response to interferon-alpha	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to lipopolysaccharide	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to organic substance	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to toxic substance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to virus	ISO Inferred from Sequence Orthology more info
involved_in response to virus	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to vitamin E	IPI Inferred from Physical Interaction more info	PubMed
acts_upstream_of_or_within translation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: interferon-induced, double-stranded RNA-activated protein kinase

Names: Protein kinase, interferon-inducible double stranded RNA dependent; eIF-2A protein kinase 2; interferon-inducible RNA-dependent protein kinase; protein kinase R; protein kinase RNA-activated; tyrosine-protein kinase EIF2AK2

NP_062208.2

EC 2.7.10.2

EC 2.7.11.1

XP_008762647.2

EC 2.7.10.2

EC 2.7.11.1

XP_038968708.1

EC 2.7.10.2

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_019335.2 → NP_062208.2 interferon-induced, double-stranded RNA-activated protein kinase

Status: PROVISIONAL

Source sequence(s)

JAXUCZ010000006

UniProtKB/Swiss-Prot

Q63184

UniProtKB/TrEMBL

A0A0G2K100, A6H9V3

Related

ENSRNOP00000071646.1, ENSRNOT00000089185.2

Conserved Domains (3) summary

cd19903
Location:7 → 74

DSRM_EIF2AK2_rpt1; first double-stranded RNA binding motif of eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and similar proteins

cd19904
Location:94 → 160

DSRM_EIF2AK2_rpt2; second double-stranded RNA binding motif of eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and similar proteins

cl21453
Location:229 → 498

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086024.1 Reference GRCr8

Range

21941147..21977115

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039112780.2 → XP_038968708.1 interferon-induced, double-stranded RNA-activated protein kinase isoform X2

UniProtKB/Swiss-Prot

Q63184

Conserved Domains (3) summary

cd19903
Location:7 → 74

DSRM_EIF2AK2_rpt1; first double-stranded RNA binding motif of eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and similar proteins

cd19904
Location:94 → 160

DSRM_EIF2AK2_rpt2; second double-stranded RNA binding motif of eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and similar proteins

cl21453
Location:229 → 455

PKc_like; Protein Kinases, catalytic domain
XM_008764425.2 → XP_008762647.2 interferon-induced, double-stranded RNA-activated protein kinase isoform X1

UniProtKB/Swiss-Prot

Q63184

UniProtKB/TrEMBL

A0A0G2K100, A6H9V3

Related

ENSRNOP00000094921.1, ENSRNOT00000105846.1

Conserved Domains (3) summary

cd19903
Location:7 → 74

DSRM_EIF2AK2_rpt1; first double-stranded RNA binding motif of eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and similar proteins

cd19904
Location:94 → 160

DSRM_EIF2AK2_rpt2; second double-stranded RNA binding motif of eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and similar proteins

cl21453
Location:229 → 498

PKc_like; Protein Kinases, catalytic domain