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Eif2ak3 - eukaryotic translation initiation factor 2 alpha kinase 3 Gene

Also Known as Pek; Perk

Species: Mus musculus

Gene Type: protein coding

Gene ID: 13666

About Eif2ak3

Chromosome 6: 70,821,499-70,882,229 forward strand.GRCm39:CM000999.3

This gene has 5 transcripts (splice variants), 197 orthologues, 8 paralogues and is associated with 41 phenotypes. Ubiquitous expression in placenta adult (RPKM 1.8), colon adult (RPKM 7.9) and 28 other tissues.

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]

Eif2ak3 Products (2)

mRNA	Protein	Name
NM_001313918.1	NP_001300847.1	eukaryotic translation initiation factor 2-alpha kinase 3 isoform 2 precursor
NM_010121.3	NP_034251.2	eukaryotic translation initiation factor 2-alpha kinase 3 isoform 1 precursor

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables eukaryotic translation initiation factor 2alpha kinase activity	IDA IDA: Inferred from direct assay	9930704	MGI
enables eukaryotic translation initiation factor 2alpha kinase activity	IGI IGI: Inferred from genetic interaction	14729979	MGI
enables eukaryotic translation initiation factor 2alpha kinase activity	IMP IMP: Inferred from mutant phenotype	14729979	MGI
enables identical protein binding	IPI IPI: Inferred from physical interaction	16973740	MGI
enables protein binding	IPI IPI: Inferred from physical interaction	12610133	MGI
enables protein kinase activity	IDA IDA: Inferred from direct assay	14517290	MGI
enables protein kinase activity	IMP IMP: Inferred from mutant phenotype	15542627	MGI
enables protein serine/threonine kinase activity	IDA IDA: Inferred from direct assay	9930704	MGI

Biological Process GO Annotation	Evidence	References	Source
involved in ERAD pathway	IMP IMP: Inferred from mutant phenotype	17707796	MGI
involved in PERK-mediated unfolded protein response	IMP IMP: Inferred from mutant phenotype	14729979	MGI
acts upstream of or within SREBP signaling pathway	IDA IDA: Inferred from direct assay	18852460	MGI
acts upstream of or within activation of cysteine-type endopeptidase activity involved in apoptotic process	IMP IMP: Inferred from mutant phenotype	10882126	MGI
acts upstream of or within bone mineralization	IMP IMP: Inferred from mutant phenotype	11997520	MGI
acts upstream of or within calcium-mediated signaling	IMP IMP: Inferred from mutant phenotype	16352659	MGI
involved in cellular response to glucose starvation	IMP IMP: Inferred from mutant phenotype	22915762	MGI
acts upstream of or within chondrocyte development	IMP IMP: Inferred from mutant phenotype	12865332	MGI
involved in eiF2alpha phosphorylation in response to endoplasmic reticulum stress	IMP IMP: Inferred from mutant phenotype	17707796	MGI
acts upstream of or within endoplasmic reticulum organization	IMP IMP: Inferred from mutant phenotype	11430819	MGI
acts upstream of or within endoplasmic reticulum unfolded protein response	IDA IDA: Inferred from direct assay	9930704	MGI
acts upstream of or within endoplasmic reticulum unfolded protein response	IMP IMP: Inferred from mutant phenotype	10882126	MGI
acts upstream of or within fat cell differentiation	IDA IDA: Inferred from direct assay	18852460	MGI
acts upstream of or within insulin-like growth factor receptor signaling pathway	IMP IMP: Inferred from mutant phenotype	12865332	MGI
acts upstream of or within intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP IMP: Inferred from mutant phenotype	11430819	MGI
acts upstream of or within lactation	IMP IMP: Inferred from mutant phenotype	18852460	MGI
acts upstream of or within negative regulation of apoptotic process	IMP IMP: Inferred from mutant phenotype	15542627	MGI
acts upstream of or within negative regulation of gene expression	IMP IMP: Inferred from mutant phenotype	23152784	MGI
acts upstream of or within negative regulation of myelination	IMP IMP: Inferred from mutant phenotype	15911877	MGI
acts upstream of or within negative regulation of translation	IDA IDA: Inferred from direct assay	9930704	MGI
acts upstream of or within negative regulation of translation	IGI IGI: Inferred from genetic interaction	16176978	MGI
acts upstream of or within negative regulation of translation	IMP IMP: Inferred from mutant phenotype	10882126	MGI
involved in negative regulation of translation	IMP IMP: Inferred from mutant phenotype	12610133	MGI
involved in negative regulation of translation in response to endoplasmic reticulum stress	IDA IDA: Inferred from direct assay	9930704	MGI
acts upstream of or within pancreas development	IMP IMP: Inferred from mutant phenotype	11997520	MGI
involved in peptidyl-serine phosphorylation	IDA IDA: Inferred from direct assay	9930704	MGI
acts upstream of or within positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IGI IGI: Inferred from genetic interaction	22240901	MGI
involved in positive regulation of gene expression	IMP IMP: Inferred from mutant phenotype	14729979	MGI
involved in positive regulation of glutathione biosynthetic process	IMP IMP: Inferred from mutant phenotype	14978030	MGI
acts upstream of or within positive regulation of protein binding	IMP IMP: Inferred from mutant phenotype	16352659	MGI
involved in positive regulation of protein localization to nucleus	IMP IMP: Inferred from mutant phenotype	14517290	MGI
acts upstream of or within positive regulation of signal transduction	IDA IDA: Inferred from direct assay	18852460	MGI
involved in positive regulation of transcription by RNA polymerase I	IMP IMP: Inferred from mutant phenotype	22915762	MGI
involved in positive regulation of vascular endothelial growth factor production	IMP IMP: Inferred from mutant phenotype	22915762	MGI
acts upstream of or within protein autophosphorylation	IDA IDA: Inferred from direct assay	9930704	MGI
involved in protein autophosphorylation	IDA IDA: Inferred from direct assay	12610133	MGI
acts upstream of or within protein autophosphorylation	IMP IMP: Inferred from mutant phenotype	15542627	MGI
acts upstream of or within protein phosphorylation	IDA IDA: Inferred from direct assay	9930704	MGI
involved in protein phosphorylation	IDA IDA: Inferred from direct assay	14517290	MGI
acts upstream of or within protein phosphorylation	IMP IMP: Inferred from mutant phenotype	10882126	MGI
involved in protein phosphorylation	IMP IMP: Inferred from mutant phenotype	10882126	MGI
involved in regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation	IMP IMP: Inferred from mutant phenotype	11106749	MGI
acts upstream of or within regulation of fatty acid metabolic process	IMP IMP: Inferred from mutant phenotype	18852460	MGI
involved in regulation of translational initiation	IMP IMP: Inferred from mutant phenotype	14729979	MGI
involved in regulation of translational initiation by eIF2 alpha phosphorylation	IDA IDA: Inferred from direct assay	14676213	MGI
involved in regulation of translational initiation by eIF2 alpha phosphorylation	IMP IMP: Inferred from mutant phenotype	10882126	MGI
involved in response to endoplasmic reticulum stress	IDA IDA: Inferred from direct assay	11106749	MGI
involved in response to endoplasmic reticulum stress	IMP IMP: Inferred from mutant phenotype	14978030	MGI
acts upstream of or within skeletal system development	IMP IMP: Inferred from mutant phenotype	11997520	MGI
acts upstream of or within translation	IDA IDA: Inferred from direct assay	12388085	MGI

Cellular Component GO Annotation	Evidence	References	Source
located in cytoplasm	IDA IDA: Inferred from direct assay	11747369	MGI
located in endoplasmic reticulum	IDA IDA: Inferred from direct assay	11430819	MGI
located in endoplasmic reticulum membrane	IDA IDA: Inferred from direct assay	9930704	MGI
located in endoplasmic reticulum quality control compartment	IDA IDA: Inferred from direct assay	17707796	MGI

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

Eif2ak3 Protein Structure

Luminal_EIF2AK3

PKc_like

STKc_EIF2AK3_PERK

0
200
400
600
800
1000
1114 a.a.

Protein Preferred Names	Protein Names
eukaryotic translation initiation factor 2-alpha kinase 3	PRKR-like endoplasmic reticulum kinase pancreatic eIF2-alpha kinase

Eif2ak3 Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	Eif2ak3	Q9Z2B5	EIF2S1	Homo sapiens	P05198	Far-WB	16288713
Intra	Eif2ak3	Q9Z2B5	EIF2S1	Homo sapiens	P05198	FRET	16288713
Intra	Eif2ak3	Q9Z2B5	Eif2s1	Mus musculus	Q6ZWX6	Protein Kinase Assay	28869608
Intra	Eif2ak3	Q9Z2B5	Cnpy2	Mus musculus	Q9QXT0	Anti Tag CoIP	28869608
Intra	Eif2ak3	Q9Z2B5	Eif2ak3	Mus musculus	Q9Z2B5	Solution Sedimentation	16973740
Intra	Eif2ak3	Q9Z2B5	Eif2ak3	Mus musculus	Q9Z2B5	GMS	16973740
Cross	Eif2ak3	Q9Z2B5	HSPA5	Homo sapiens	P11021	Anti Tag CoIP	28869608
Intra	Eif2ak3	Q9Z2B5	Mfn2	Mus musculus	Q80U63	Anti Bait CoIP	23921556
Intra	Eif2ak3	Q9Z2B5	P27958-PRO_0000037569	Hepatitis C virus	P27958-PRO_0000037569	Pull Down	23667408
Intra	Eif2ak3	Q9Z2B5	aspat_myctu	Mycobacterium tuberculosis	O69689	Y2H Array	29165646
Cross	Eif2ak3	Q9Z2B5	P27958-PRO_0000037570	Hepatitis C virus	P27958-PRO_0000037570	Pull Down	23667408

Cross: Cross-species interaction Intra: Intraspecies interaction

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (4)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-119240	CCT020312	Activator	99.05%	Unkown
HY-RS04244	EIF2AK3 Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS04245	Eif2ak3 Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS04246	Eif2ak3 Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Homo sapiens	Eif2ak3	NCBI	NCBI:9451