Eif2ak4 eukaryotic translation initiation factor 2 alpha kinase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Eif2ak4provided by MGI
Official Full Name: eukaryotic translation initiation factor 2 alpha kinase 4provided by MGI
Primary source: MGI:MGI:1353427
See related: Ensembl:ENSMUSG00000005102 AllianceGenome:MGI:1353427
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: GCN2; MGCN2; 2610011M03
Summary: Enables eukaryotic translation initiation factor 2alpha kinase activity and tRNA binding activity. Involved in several processes, including GCN2-mediated signaling; learning or memory; and regulation of translational initiation. Acts upstream of or within cellular response to starvation; endoplasmic reticulum unfolded protein response; and regulation of translation. Located in cytoplasm. Is expressed in several structures, including gut; hemolymphoid system gland; liver; lung; and ovary. Human ortholog(s) of this gene implicated in pulmonary venoocclusive disease 2. Orthologous to human EIF2AK4 (eukaryotic translation initiation factor 2 alpha kinase 4). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in ovary adult (RPKM 8.2), limb E14.5 (RPKM 7.9) and 28 other tissues See more
Orthologs: human all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 2 E5; 2 59.4 cM

Exon count:: 41

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (118219065..118305715)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (118388583..118475234)

Chromosome 2 - NC_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: Mouse ENCODE transcriptome data 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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

GCN2 kinase activation mediates pulmonary vascular remodeling and pulmonary arterial hypertension.
Title: GCN2 kinase activation mediates pulmonary vascular remodeling and pulmonary arterial hypertension.
GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency.
Title: GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency.
Computational modeling of the synergistic role of GCN2 and the HPA axis in regulating the integrated stress response in the central circadian timing system.
Title: Computational modeling of the synergistic role of GCN2 and the HPA axis in regulating the integrated stress response in the central circadian timing system.
GCN2 is required to maintain core body temperature in mice during acute cold.
Title: GCN2 is required to maintain core body temperature in mice during acute cold.
Role of liver AMPK and GCN2 kinases in the control of postprandial protein metabolism in response to mid-term high or low protein intake in mice.
Title: Role of liver AMPK and GCN2 kinases in the control of postprandial protein metabolism in response to mid-term high or low protein intake in mice.
The amino acid sensor GCN2 suppresses terminal oligopyrimidine (TOP) mRNA translation via La-related protein 1 (LARP1).
Title: The amino acid sensor GCN2 suppresses terminal oligopyrimidine (TOP) mRNA translation via La-related protein 1 (LARP1).
The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages.
Title: The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages.
GCN2 adapts protein synthesis to scavenging-dependent growth.
Title: GCN2 adapts protein synthesis to scavenging-dependent growth.
Inhibition of GCN2 alleviates hepatic steatosis and oxidative stress in obese mice: Involvement of NRF2 regulation.
Title: Inhibition of GCN2 alleviates hepatic steatosis and oxidative stress in obese mice: Involvement of NRF2 regulation.
Intermittent Leucine Deprivation Produces Long-lasting Improvement in Insulin Sensitivity by Increasing Hepatic Gcn2 Expression.
Title: Intermittent Leucine Deprivation Produces Long-lasting Improvement in Insulin Sensitivity by Increasing Hepatic Gcn2 Expression.

Submit: New GeneRIF Correction See all GeneRIFs (87)

Variation

Go to the top of the page Help

Alleles

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

Chemically induced (ENU) (1)
Endonuclease-mediated (4)
Targeted (3) 1 citation

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

AI447567 (e-PCR)
- UniSTS:165191

PMC134046P1 (e-PCR)
- UniSTS:270720

D2Mit276 (e-PCR), detects polymorphism
- UniSTS:129158

RH140887 (e-PCR)
- UniSTS:222903

Eif2ak4 (e-PCR), detects polymorphism
- UniSTS:527074

Eif2ak4 (e-PCR), detects polymorphism
- UniSTS:527075

Eif2ak4 (e-PCR), detects polymorphism
- UniSTS:527076

Eif2ak4 (e-PCR), detects polymorphism
- UniSTS:527077

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation 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 histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
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 tRNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage checkpoint signaling	IEA Inferred from Electronic Annotation more info
involved_in GCN2-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in GCN2-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in GCN2-mediated signaling	ISO Inferred from Sequence Orthology more info
involved_in T cell activation involved in immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in cellular response to UV	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to amino acid starvation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to amino acid starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to amino acid starvation	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 cold	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cold	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within cellular response to starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in defense response to virus	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
acts_upstream_of_or_within endoplasmic reticulum unfolded protein response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in long-term memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation by host of viral genome replication	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of CREB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of neuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of translation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of translational initiation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of translational initiation in response to stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of translational initiation in response to stress	IDA Inferred from Direct Assay more info	PubMed
involved_in neuron projection extension	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of adaptive immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of defense response to virus by host	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of long-term synaptic potentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of translational initiation in response to starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of translational initiation in response to starvation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cytoplasmic translational initiation in response to stress	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of feeding behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of translational initiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of translational initiation	ISS Inferred from Sequence or Structural Similarity 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 regulation of translational initiation by eIF2 alpha phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of translational initiation in response to stress	IDA Inferred from Direct Assay more info	PubMed
involved_in response to endoplasmic reticulum stress	IGI Inferred from Genetic Interaction more info	PubMed
involved_in viral 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
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosolic ribosome	ISS Inferred from Sequence or Structural Similarity more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

Go to the top of the page Help

Preferred Names: eIF-2-alpha kinase GCN2

Names: GCN2 eIF2alpha kinase; GCN2-like protein

NP_001171277.1

EC 2.7.11.1

NP_001342312.1

EC 2.7.11.1

NP_001408350.1

EC 2.7.11.1

NP_001408351.1

EC 2.7.11.1

NP_038747.2

EC 2.7.11.1

XP_006499689.1

EC 2.7.11.1

XP_006499690.1

EC 2.7.11.1

XP_017174398.1

EC 2.7.11.1

XP_036018145.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_001177806.2 → NP_001171277.1 eIF-2-alpha kinase GCN2 isoform 2

See identical proteins and their annotated locations for NP_001171277.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence and lacks an alternate internal exon in the 5' end compared to variant 1, that causes a frameshift. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AL929163

Consensus CDS

CCDS50669.1

UniProtKB/TrEMBL

A2AUM2

Related

ENSMUSP00000099586.4, ENSMUST00000102527.10

Conserved Domains (4) summary

PLN02972
Location:958 → 1378

PLN02972; Histidyl-tRNA synthetase

cd14012
Location:187 → 425

PK_eIF2AK_GCN2_rpt1; Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cd14046
Location:470 → 886

STKc_EIF2AK4_GCN2_rpt2; Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cl00266
Location:1284 → 1528

HGTP_anticodon; HGTP anticodon binding domain, as found at the C-terminus of histidyl, glycyl, threonyl and prolyl tRNA synthetases, which are classified as a group of class II aminoacyl-tRNA synthetases (aaRS). In aaRSs, the anticodon binding domain is responsible for ...
NM_001355383.2 → NP_001342312.1 eIF-2-alpha kinase GCN2 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks three alternate internal exons in the 5' end compared to variant 1, that causes a frameshift. The resulting isoform (3) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AL929163

UniProtKB/TrEMBL

A2AUM2

Conserved Domains (4) summary

cd14012
Location:109 → 347

PK_eIF2AK_GCN2_rpt1; Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cd14046
Location:392 → 808

STKc_EIF2AK4_GCN2_rpt2; Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cl00266
Location:1206 → 1450

HGTP_anticodon; HGTP anticodon binding domain, as found at the C-terminus of histidyl, glycyl, threonyl and prolyl tRNA synthetases, which are classified as a group of class II aminoacyl-tRNA synthetases (aaRS). In aaRSs, the anticodon binding domain is responsible for ...

cl28413
Location:880 → 1300

HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]
NM_001421421.1 → NP_001408350.1 eIF-2-alpha kinase GCN2 isoform 2

Status: VALIDATED

Source sequence(s)

AL929163
NM_001421422.1 → NP_001408351.1 eIF-2-alpha kinase GCN2 isoform 4

Status: VALIDATED

Source sequence(s)

AL929163
NM_013719.4 → NP_038747.2 eIF-2-alpha kinase GCN2 isoform 1

Status: VALIDATED

Description

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

Source sequence(s)

AL929163

Consensus CDS

CCDS16576.1

UniProtKB/Swiss-Prot

A2AUM3, A2AUM4, Q6GQT4, Q6ZPT5, Q8C5S0, Q8CIF5, Q9CT30, Q9CUV9, Q9ESB6, Q9ESB7, Q9ESB8, Q9QZ05

UniProtKB/TrEMBL

A2AUM0

Related

ENSMUSP00000005233.6, ENSMUST00000005233.12

Conserved Domains (7) summary

smart00220
Location:589 → 1000

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00591
Location:26 → 137

RWD; domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain

COG0124
Location:1049 → 1485

HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

cd14012
Location:299 → 537

PK_eIF2AK_GCN2_rpt1; Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cd14046
Location:582 → 998

STKc_EIF2AK4_GCN2_rpt2; Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cl00266
Location:1394 → 1640

HGTP_anticodon; HGTP anticodon binding domain, as found at the C-terminus of histidyl, glycyl, threonyl and prolyl tRNA synthetases, which are classified as a group of class II aminoacyl-tRNA synthetases (aaRS). In aaRSs, the anticodon binding domain is responsible for ...

cl00268
Location:1060 → 1384

class_II_aaRS-like_core; Class II tRNA amino-acyl synthetase-like catalytic core domain. Class II amino acyl-tRNA synthetases (aaRS) share a common fold and generally attach an amino acid to the 3' OH of ribose of the appropriate tRNA. PheRS is an exception in that it attaches ...

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_000068.8 Reference GRCm39 C57BL/6J

Range

118219065..118305715

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036162252.1 → XP_036018145.1 eIF-2-alpha kinase GCN2 isoform X2

UniProtKB/TrEMBL

A2AUM1, A2AUM2

Related

ENSMUSP00000106498.2, ENSMUST00000110874.8

Conserved Domains (5) summary

smart00591
Location:9 → 59

RWD; domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain

PLN02972
Location:992 → 1412

PLN02972; Histidyl-tRNA synthetase

cd14012
Location:221 → 459

PK_eIF2AK_GCN2_rpt1; Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cd14046
Location:504 → 920

STKc_EIF2AK4_GCN2_rpt2; Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cl00266
Location:1318 → 1562

HGTP_anticodon; HGTP anticodon binding domain, as found at the C-terminus of histidyl, glycyl, threonyl and prolyl tRNA synthetases, which are classified as a group of class II aminoacyl-tRNA synthetases (aaRS). In aaRSs, the anticodon binding domain is responsible for ...
XM_017318909.3 → XP_017174398.1 eIF-2-alpha kinase GCN2 isoform X1

UniProtKB/Swiss-Prot

A2AUM3, A2AUM4, Q6GQT4, Q6ZPT5, Q8C5S0, Q8CIF5, Q9CT30, Q9CUV9, Q9ESB6, Q9ESB7, Q9ESB8, Q9QZ05

Conserved Domains (5) summary

smart00591
Location:26 → 137

RWD; domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain

PLN02972
Location:1043 → 1463

PLN02972; Histidyl-tRNA synthetase

cd14012
Location:272 → 510

PK_eIF2AK_GCN2_rpt1; Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cd14046
Location:555 → 971

STKc_EIF2AK4_GCN2_rpt2; Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cl00266
Location:1369 → 1613

HGTP_anticodon; HGTP anticodon binding domain, as found at the C-terminus of histidyl, glycyl, threonyl and prolyl tRNA synthetases, which are classified as a group of class II aminoacyl-tRNA synthetases (aaRS). In aaRSs, the anticodon binding domain is responsible for ...
XM_006499626.5 → XP_006499689.1 eIF-2-alpha kinase GCN2 isoform X4

UniProtKB/TrEMBL

A2AUM2

Conserved Domains (4) summary

PLN02972
Location:947 → 1367

PLN02972; Histidyl-tRNA synthetase

cd14012
Location:176 → 414

PK_eIF2AK_GCN2_rpt1; Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cd14046
Location:459 → 875

STKc_EIF2AK4_GCN2_rpt2; Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cl00266
Location:1273 → 1517

HGTP_anticodon; HGTP anticodon binding domain, as found at the C-terminus of histidyl, glycyl, threonyl and prolyl tRNA synthetases, which are classified as a group of class II aminoacyl-tRNA synthetases (aaRS). In aaRSs, the anticodon binding domain is responsible for ...
XM_006499627.5 → XP_006499690.1 eIF-2-alpha kinase GCN2 isoform X5

UniProtKB/TrEMBL

A2AUM2

Related

ENSMUSP00000106494.2, ENSMUST00000110870.8

Conserved Domains (4) summary

PLN02972
Location:920 → 1340

PLN02972; Histidyl-tRNA synthetase

cd14012
Location:149 → 387

PK_eIF2AK_GCN2_rpt1; Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cd14046
Location:432 → 848

STKc_EIF2AK4_GCN2_rpt2; Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2

cl00266
Location:1246 → 1490

HGTP_anticodon; HGTP anticodon binding domain, as found at the C-terminus of histidyl, glycyl, threonyl and prolyl tRNA synthetases, which are classified as a group of class II aminoacyl-tRNA synthetases (aaRS). In aaRSs, the anticodon binding domain is responsible for ...