Eif2ak3 eukaryotic translation initiation factor 2 alpha kinase 3 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Eif2ak3provided by RGD
Official Full Name: eukaryotic translation initiation factor 2 alpha kinase 3provided by RGD
Primary source: RGD:70884
See related: EnsemblRapid:ENSRNOG00000006069 AllianceGenome:RGD:70884
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: PEK
Summary: Enables Hsp90 protein binding activity and eukaryotic translation initiation factor 2alpha kinase activity. Involved in negative regulation of translation in response to stress; protein autophosphorylation; and response to manganese-induced endoplasmic reticulum stress. Located in perinuclear region of cytoplasm. Biomarker of pulmonary venoocclusive disease. Human ortholog(s) of this gene implicated in Wolcott-Rallison syndrome and type 1 diabetes mellitus. Orthologous to human EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Thymus (RPKM 137.6), Kidney (RPKM 111.4) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 4q32

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	4	NC_086022.1 (104363838..104425271)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	4	NC_051339.1 (102805495..102866914)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	4	NC_005103.4 (98648513..98709695)

Chromosome 4 - NC_086022.1 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?

HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway.
Title: HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway.
Changes in UPR-PERK pathway and muscle hypertrophy following resistance training and creatine supplementation in rats.
Title: Changes in UPR-PERK pathway and muscle hypertrophy following resistance training and creatine supplementation in rats.
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.
High PEK expression is associated with reduced bone growth and shortened long bones.
Title: Sirtuin-1 (SIRT1) stimulates growth-plate chondrogenesis by attenuating the PERK-eIF-2α-CHOP pathway in the unfolded protein response.
These results suggest that the administration of Pien Tze Huang ameliorated the severity of alcoholic and high-fat diet rats possibly by inhibiting the Hcy-induced PERK/eIF2alpha pathway.
Title: Pien Tze Huang ameliorates liver injury by inhibiting the PERK/eIF2α signaling pathway in alcohol and high-fat diet rats.
AS-IV may attenuate inflammatory responses by disrupting the crosstalk between autophagy and the PERK-eIF2alpha pathway and may be an ideal agent for treating inflammatory pulmonary diseases.
Title: Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy.
Pre-ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress-dependent autophagy via PERK and IRE1 signalings
Title: Pre-ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress-dependent autophagy via PERK and IRE1 signalings.
these results confirmed that ER stress-mediated apoptosis contributes to the protection effects of naringenin against H/R injury, which is potentially involved in ATF6, IRE1alpha and PERK signaling activation.
Title: Naringenin ameliorates hypoxia/reoxygenation-induced endoplasmic reticulum stress-mediated apoptosis in H9c2 myocardial cells: involvement in ATF6, IRE1α and PERK signaling activation.
Cirrhotic rats with diabetes showed higher intrahepatic ET-1 vasoresponsiveness than normoglycemic cirrhotic rats. This effect may be related, at least in part, to intrahepatic ETA R receptor and pERK over-expression.
Title: Diabetes enhances the intrahepatic vascular response to endothelin-1 in cirrhotic rats: association with the ETA receptor and pERK up-regulation.
Data suggest that down-regulation of PERK kinase-activating transcription factor 4 (ATF4)-tramscription factor CHOP pathway by Astragaloside IV (AS-IV) may be a strategy for the treatment of diabetic nephropathy (DN).
Title: Down-regulation of PERK-ATF4-CHOP pathway by Astragaloside IV is associated with the inhibition of endoplasmic reticulum stress-induced podocyte apoptosis in diabetic rats.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by RGD

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	IDA Inferred from Direct Assay more info	PubMed
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 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	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	ISO Inferred from Sequence Orthology more info
enables misfolded protein binding	ISO Inferred from Sequence Orthology more info
enables misfolded protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein kinase activity	ISO Inferred from Sequence Orthology more info
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 tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
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	ISO Inferred from Sequence Orthology more info
involved_in PERK-mediated unfolded protein response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within SREBP signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in angiogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within bone mineralization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within calcium-mediated signaling	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within chondrocyte development	ISO Inferred from Sequence Orthology more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
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	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within endoplasmic reticulum unfolded protein response	ISO Inferred from Sequence Orthology more info
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
acts_upstream_of_or_within fat cell differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within insulin-like growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lactation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of gene expression	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of myelination	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of translation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of translation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of translation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of translation in response to endoplasmic reticulum stress	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of translation in response to stress	IDA Inferred from Direct Assay more info	PubMed
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	ISO Inferred from Sequence Orthology more info
involved_in peptidyl-serine phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of glutathione biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein localization to nucleus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of signal transduction	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein autophosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
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	ISO Inferred from Sequence Orthology more info
involved_in regulation of translational initiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of translational initiation	ISO Inferred from Sequence Orthology more info
involved_in regulation of translational initiation by eIF2 alpha phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in response to endoplasmic reticulum stress	ISO Inferred from Sequence Orthology more info
involved_in response to endoplasmic reticulum stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to manganese-induced endoplasmic reticulum stress	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within skeletal system development	ISO Inferred from Sequence Orthology more info
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
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum membrane	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum quality control compartment	ISO Inferred from Sequence Orthology more info
located_in mitochondria-associated endoplasmic reticulum membrane contact site	IEA Inferred from Electronic Annotation more info
is_active_in mitochondria-associated endoplasmic reticulum membrane contact site	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	IDA Inferred from Direct Assay more info	PubMed

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; protein tyrosine kinase EIF2AK3

NP_113787.1

EC 2.7.10.2

EC 2.7.11.1

XP_006236686.1

EC 2.7.10.2

EC 2.7.11.1

XP_008761199.1

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_031599.2 → NP_113787.1 eukaryotic translation initiation factor 2-alpha kinase 3 precursor

See identical proteins and their annotated locations for NP_113787.1

Status: PROVISIONAL

Source sequence(s)

AF096835

UniProtKB/Swiss-Prot

Q9Z1Z1

UniProtKB/TrEMBL

A6IA60, A6IA61

Related

ENSRNOP00000008451.4, ENSRNOT00000008451.7

Conserved Domains (4) summary

cd09768
Location:99 → 412

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

smart00220
Location:873 → 1065

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14048
Location:868 → 1067

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:579 → 667

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_086022.1 Reference GRCr8

Range

104363838..104425271

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006236624.5 → XP_006236686.1 eukaryotic translation initiation factor 2-alpha kinase 3 isoform X2

UniProtKB/TrEMBL

A6IA61

Conserved Domains (3) summary

cd09768
Location:99 → 412

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

COG1520
Location:97 → 258

PQQ; Outer membrane protein assembly factor BamB, contains PQQ-like beta-propeller repeat [Cell wall/membrane/envelope biogenesis]

cl21453
Location:579 → 667

PKc_like; Protein Kinases, catalytic domain
XM_008762977.4 → XP_008761199.1 eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1

See identical proteins and their annotated locations for XP_008761199.1

UniProtKB/TrEMBL

A6IA61

Conserved Domains (4) summary

cd09768
Location:1 → 266

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

smart00220
Location:727 → 919

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14048
Location:722 → 921

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:433 → 521

PKc_like; Protein Kinases, catalytic domain