Atf4 activating transcription factor 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Atf4provided by MGI
Official Full Name: activating transcription factor 4provided by MGI
Primary source: MGI:MGI:88096
See related: Ensembl:ENSMUSG00000042406 AllianceGenome:MGI:88096
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: Atf-4; C/ATF; CREB2; CREB-2; TAXREB67
Summary: Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; cAMP response element binding protein binding activity; and promoter-specific chromatin binding activity. Contributes to DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including PERK-mediated unfolded protein response; animal organ development; and regulation of gene expression. Acts upstream of or within several processes, including gluconeogenesis; positive regulation of sodium-dependent phosphate transport; and positive regulation of vascular associated smooth muscle cell apoptotic process. Located in cytoplasm and nucleus. Part of ATF1-ATF4 transcription factor complex and ATF4-CREB1 transcription factor complex. Is expressed in several structures, including central nervous system; embryo ectoderm; eye; genitourinary system; and long bone. Human ortholog(s) of this gene implicated in prostate carcinoma. Orthologous to human ATF4 (activating transcription factor 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in liver E14 (RPKM 153.4), liver E14.5 (RPKM 138.1) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 15 E1; 15 37.85 cM

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	15	NC_000081.7 (80139385..80141746)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	15	NC_000081.6 (80255184..80257545)

Chromosome 15 - NC_000081.7 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: 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?

Study of ATF4/CHOP axis-mediated mitochondrial unfolded protein response in neuronal apoptosis induced by methylmercury.
Title: Study of ATF4/CHOP axis-mediated mitochondrial unfolded protein response in neuronal apoptosis induced by methylmercury.
Gut-derived ammonia contributes to alcohol-related fatty liver development via facilitating ethanol metabolism and provoking ATF4-dependent de novo lipogenesis activation.
Title: Gut-derived ammonia contributes to alcohol-related fatty liver development via facilitating ethanol metabolism and provoking ATF4-dependent de novo lipogenesis activation.
ATF4 expression in thermogenic adipocytes is required for cold-induced thermogenesis in mice via FGF21-independent mechanisms.
Title: ATF4 expression in thermogenic adipocytes is required for cold-induced thermogenesis in mice via FGF21-independent mechanisms.
C/EBPalpha alleviates hepatic ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress via HDAC1-mediated deacetylation of ATF4.
Title: C/EBPα alleviates hepatic ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress via HDAC1-mediated deacetylation of ATF4.
Endometrial stromal cell autophagy-dependent ferroptosis caused by iron overload in ovarian endometriosis is inhibited by the ATF4-xCT pathway.
Title: Endometrial stromal cell autophagy-dependent ferroptosis caused by iron overload in ovarian endometriosis is inhibited by the ATF4-xCT pathway.
The Critical Role of The Piezo1/beta-catenin/ATF4 Axis on The Stemness of Gli1[+] BMSCs During Simulated Microgravity-Induced Bone Loss.
Title: The Critical Role of The Piezo1/β-catenin/ATF4 Axis on The Stemness of Gli1(+) BMSCs During Simulated Microgravity-Induced Bone Loss.
ATF4 knockdown in macrophage impairs glycolysis and mediates immune tolerance by targeting HK2 and HIF-1alpha ubiquitination in sepsis.
Title: ATF4 knockdown in macrophage impairs glycolysis and mediates immune tolerance by targeting HK2 and HIF-1α ubiquitination in sepsis.
Oxidized phospholipids facilitate calcific aortic valve disease by elevating ATF4 through the PERK/eIF2alpha axis.
Title: Oxidized phospholipids facilitate calcific aortic valve disease by elevating ATF4 through the PERK/eIF2α axis.
Activating transcription factor 4 drives the progression of diabetic cardiac fibrosis.
Title: Activating transcription factor 4 drives the progression of diabetic cardiac fibrosis.
ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis.
Title: ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis.

Submit: New GeneRIF Correction See all GeneRIFs (183)

Variation

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Alleles

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

Targeted (10) 1 citation
Endonuclease-mediated (4)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

UniSTS:274176 (e-PCR)
- UniSTS:274176

Atf4 (e-PCR), detects polymorphism
- UniSTS:274176

NoName (e-PCR)
- UniSTS:548144

AW050190 (e-PCR)
- UniSTS:180785

Atf4 (e-PCR), detects polymorphism
- UniSTS:141126

PMC19934P1 (e-PCR)
- UniSTS:271863

Atf4 (e-PCR), detects polymorphism
- UniSTS:532479

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IGI Inferred from Genetic Interaction more info	PubMed
enables DNA binding	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
contributes_to DNA-binding transcription factor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
contributes_to RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables cAMP response element binding protein binding	IDA Inferred from Direct Assay more info	PubMed
enables general transcription initiation factor binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables leucine zipper domain binding	ISO Inferred from Sequence Orthology more info
enables promoter-specific chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables promoter-specific chromatin binding	ISO Inferred from Sequence Orthology more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific double-stranded DNA binding	ISO Inferred from Sequence Orthology more info
contributes_to transcription cis-regulatory region binding	ISO Inferred from Sequence Orthology more info
enables transcription cis-regulatory region binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in HRI-mediated signaling	ISO Inferred from Sequence Orthology more info
involved_in L-asparagine metabolic process	ISO Inferred from Sequence Orthology more info
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
involved_in bone mineralization	IMP Inferred from Mutant Phenotype more info	PubMed
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 glucose starvation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to leucine starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to leucine starvation	ISO Inferred from Sequence Orthology more info	PubMed
involved_in cellular response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in circadian regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in circadian rhythm	IEP Inferred from Expression Pattern more info	PubMed
involved_in embryonic hemopoiesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endoplasmic reticulum unfolded protein response	IDA Inferred from Direct Assay more info	PubMed
involved_in gamma-aminobutyric acid signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within gluconeogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in integrated stress response signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in integrated stress response signaling	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within intracellular calcium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lens fiber cell morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mRNA transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cold-induced thermogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of potassium ion transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of biomineral tissue development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of gene expression	IMP Inferred from Mutant Phenotype 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 neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of sodium-dependent phosphate transport	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
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of vascular associated smooth muscle cell apoptotic process	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 regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of osteoblast differentiation	ISO Inferred from Sequence Orthology more info
involved_in regulation of synaptic plasticity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay 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
involved_in response to nutrient levels	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within rhythmic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
part_of ATF1-ATF4 transcription factor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of ATF1-ATF4 transcription factor complex	IDA Inferred from Direct Assay more info	PubMed
part_of ATF1-ATF4 transcription factor complex	ISO Inferred from Sequence Orthology more info
part_of ATF4-CREB1 transcription factor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of ATF4-CREB1 transcription factor complex	IDA Inferred from Direct Assay more info	PubMed
part_of ATF4-CREB1 transcription factor complex	ISO Inferred from Sequence Orthology more info
part_of CHOP-ATF4 complex	ISO Inferred from Sequence Orthology more info
located_in Lewy body core	ISO Inferred from Sequence Orthology more info
part_of RNA polymerase II transcription regulator complex	IDA Inferred from Direct Assay more info	PubMed
part_of RNA polymerase II transcription regulator complex	IPI Inferred from Physical Interaction more info	PubMed
part_of RNA polymerase II transcription regulator complex	ISO Inferred from Sequence Orthology more info
colocalizes_with centrosome	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in dendrite membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in neuron projection	ISO Inferred from Sequence Orthology more info
located_in nuclear periphery	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	NAS Non-traceable Author Statement more info	PubMed
part_of transcription regulator complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cyclic AMP-dependent transcription factor ATF-4

Names: c/EBP-related ATF; cAMP-dependent transcription factor ATF-4; cAMP-responsive element-binding protein 2; cyclic AMP-responsive element-binding protein 2; tax-responsive enhancer element-binding protein 67 homolog; taxREB67 homolog

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_001287180.1 → NP_001274109.1 cyclic AMP-dependent transcription factor ATF-4

See identical proteins and their annotated locations for NP_001274109.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an internal segment in the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AA003141, AK003001, BC085169, BE992821

Consensus CDS

CCDS37145.1

UniProtKB/Swiss-Prot

Q06507, Q5U4B2, Q61906

UniProtKB/TrEMBL

Q3U2J1

Conserved Domains (1) summary

cd14692
Location:277 → 339

bZIP_ATF4; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-4 (ATF-4) and similar proteins: a DNA-binding and dimerization domain
NM_009716.3 → NP_033846.2 cyclic AMP-dependent transcription factor ATF-4

See identical proteins and their annotated locations for NP_033846.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AK003001, BC085169, BE992821

Consensus CDS

CCDS37145.1

UniProtKB/Swiss-Prot

Q06507, Q5U4B2, Q61906

UniProtKB/TrEMBL

Q3U2J1

Related

ENSMUSP00000105234.4, ENSMUST00000109605.5

Conserved Domains (1) summary

cd14692
Location:277 → 339

bZIP_ATF4; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-4 (ATF-4) and similar proteins: a DNA-binding and dimerization domain