Atf4 activating transcription factor 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Atf4provided by RGD
Official Full Name: activating transcription factor 4provided by RGD
Primary source: RGD:621863
See related: Ensembl:ENSRNOG00000017801 AllianceGenome:RGD:621863
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Enables DNA-binding transcription factor binding activity; general transcription initiation factor binding activity; and protein C-terminus binding activity. Involved in several processes, including cellular response to oxygen-glucose deprivation; positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress; and response to manganese-induced endoplasmic reticulum stress. Located in cytoplasm; dendrite membrane; and nucleus. Biomarker of borna disease and pulmonary venoocclusive disease. 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: Biased expression in Muscle (RPKM 892.6), Lung (RPKM 714.1) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 7q34

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	7	NC_086025.1 (113684681..113686739)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	7	NC_051342.1 (111804135..111806457)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	7	NC_005106.4 (121480723..121482781)

Chromosome 7 - NC_086025.1 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?

Activating Transcription Factor 4-mediated Mitochondrial Unfolded Protein Response Alleviates Hippocampal Neuronal Damage in an In Vitro Model of Epileptiform Discharges.
Title: Activating Transcription Factor 4-mediated Mitochondrial Unfolded Protein Response Alleviates Hippocampal Neuronal Damage in an In Vitro Model of Epileptiform Discharges.
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.
Silencing ATF4 inhibits JMJD3-dependent JUNB/ETS1 axis and mitigates cerebral ischemic injury.
Title: Silencing ATF4 inhibits JMJD3-dependent JUNB/ETS1 axis and mitigates cerebral ischemic injury.
ATF4 Protects the Heart From Failure by Antagonizing Oxidative Stress.
Title: ATF4 Protects the Heart From Failure by Antagonizing Oxidative Stress.
Possible effects of fibroblast growth factor 21 on vascular calcification via suppressing activating transcription factor 4 mediated apoptosis and osteogenic transformation in rats.
Title: Possible effects of fibroblast growth factor 21 on vascular calcification via suppressing activating transcription factor 4 mediated apoptosis and osteogenic transformation 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.
PRMT1 suppresses ATF4-mediated endoplasmic reticulum response in cardiomyocytes.
Title: PRMT1 suppresses ATF4-mediated endoplasmic reticulum response in cardiomyocytes.
This study demonstrated that ATF4 is able to alleviate cerebral ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation through parkin-dependent mitophagy activity.
Title: Parkin-Dependent Mitophagy is Required for the Inhibition of ATF4 on NLRP3 Inflammasome Activation in Cerebral Ischemia-Reperfusion Injury in Rats.
These findings reveal a critical role for ATF4 in regulating the modulation of neuronal excitability by metabotropic GABAB receptors
Title: Activating Transcription Factor 4 (ATF4) Regulates Neuronal Activity by Controlling GABA(B)R Trafficking.
Results find that ATF4 down-regulation in both hippocampal and cortical neuron cultures reduces protein and RNA levels of RhoGDIalpha. The study identified a new cellular pathway in which ATF4 regulates the expression of RhoGDIalpha that in turn affects Rho GTPase protein levels, and thereby, controls cellular functions as diverse as memory and cell motility.
Title: Activating Transcription Factor 4 (ATF4) modulates Rho GTPase levels and function via regulation of RhoGDIα.

Submit: New GeneRIF Correction See all GeneRIFs (28)

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

RH127863 (e-PCR)
- UniSTS:211173

PMC19934P1 (e-PCR)
- UniSTS:271863

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

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables DNA binding	ISO Inferred from Sequence Orthology more info
enables DNA binding	ISS Inferred from Sequence or Structural Similarity 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	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
contributes_to DNA-binding transcription factor activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
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	ISO Inferred from Sequence Orthology more info
enables cAMP response element binding protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables general transcription initiation factor binding	IPI Inferred from Physical Interaction more info	PubMed
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	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein heterodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
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 HRI-mediated signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in L-asparagine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in PERK-mediated unfolded protein response	ISO Inferred from Sequence Orthology more info
involved_in PERK-mediated unfolded protein response	ISS Inferred from Sequence or Structural Similarity more info
involved_in bone mineralization	ISO Inferred from Sequence Orthology more info
involved_in bone mineralization	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to UV	ISS Inferred from Sequence or Structural Similarity 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 glucose starvation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to leucine starvation	ISO Inferred from Sequence Orthology more info
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 cellular response to oxidative stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in circadian regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in circadian regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in circadian rhythm	ISO Inferred from Sequence Orthology more info
involved_in embryonic hemopoiesis	ISO Inferred from Sequence Orthology more info
involved_in embryonic hemopoiesis	ISS Inferred from Sequence or Structural Similarity 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
involved_in gamma-aminobutyric acid signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within gluconeogenesis	ISO Inferred from Sequence Orthology more info
involved_in integrated stress response signaling	ISO Inferred from Sequence Orthology more info
involved_in integrated stress response signaling	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within intracellular calcium ion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	ISO Inferred from Sequence Orthology more info
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in lens fiber cell morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in lens fiber cell morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in mRNA transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in mRNA transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cold-induced thermogenesis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of translational initiation in response to stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron differentiation	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of biomineral tissue development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of gene expression	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 neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of sodium-dependent phosphate transport	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 transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of vascular associated smooth muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
involved_in regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of osteoblast differentiation	ISO Inferred from Sequence Orthology more info
involved_in regulation of osteoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of synaptic plasticity	ISO Inferred from Sequence Orthology more info
involved_in regulation of synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
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	ISO Inferred from Sequence Orthology more info
involved_in regulation of transcription by RNA polymerase II	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
involved_in response to nutrient levels	ISO Inferred from Sequence Orthology more info
involved_in response to toxic substance	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info

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	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	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	ISO Inferred from Sequence Orthology more info
located_in centrosome	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in dendrite membrane	IDA Inferred from Direct Assay more info	PubMed
located_in neuron projection	ISO Inferred from Sequence Orthology more info
located_in nuclear periphery	ISO Inferred from Sequence Orthology more info
located_in nuclear speck	IEA Inferred from Electronic Annotation 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	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
part_of transcription regulator complex	ISO Inferred from Sequence Orthology more info

General protein information

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

Names: activating transcription factor 4 (tax-responsive enhancer element B67); activating transcription factor ATF-4; cAMP-dependent transcription factor ATF-4; rATF-4

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_024403.2 → NP_077379.1 cyclic AMP-dependent transcription factor ATF-4

See identical proteins and their annotated locations for NP_077379.1

Status: VALIDATED

Source sequence(s)

BC158588, JAXUCZ010000007

UniProtKB/Swiss-Prot

Q9ES19

UniProtKB/TrEMBL

B0BMW3

Related

ENSRNOP00000060302.1, ENSRNOT00000065304.5

Conserved Domains (1) summary

cd14692
Location:275 → 337

bZIP_ATF4; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-4 (ATF-4) and similar proteins: a DNA-binding and dimerization 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_086025.1 Reference GRCr8

Range

113684681..113686739

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039079942.2 → XP_038935870.1 cyclic AMP-dependent transcription factor ATF-4 isoform X1

Conserved Domains (1) summary

cd14692
Location:229 → 291

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