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ATF4 activating transcription factor 4 [ Homo sapiens (human) ]

Gene ID: 468, updated on 9-Dec-2024

Summary

Official Symbol
ATF4provided by HGNC
Official Full Name
activating transcription factor 4provided by HGNC
Primary source
HGNC:HGNC:786
See related
Ensembl:ENSG00000128272 MIM:604064; AllianceGenome:HGNC:786
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CREB2; TXREB; CREB-2; TAXREB67
Summary
This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [provided by RefSeq, Sep 2011]
Expression
Ubiquitous expression in bone marrow (RPKM 183.9), fat (RPKM 87.6) and 25 other tissues See more
Orthologs
NEW
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Genomic context

See ATF4 in Genome Data Viewer
Location:
22q13.1
Exon count:
3
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (39520559..39522686)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (39985692..39993317)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (39916564..39918691)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373035 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:39898075-39898576 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:39898577-39899076 Neighboring gene mitochondrial elongation factor 1 Neighboring gene mitochondrial elongation factor 1 upstream open reading frame Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr22:39906581-39907106 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13758 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19058 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19059 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19060 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:39919051-39919552 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19061 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19062 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19063 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19064 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19065 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19066 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19067 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19068 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:39927967-39928482 Neighboring gene ribosomal protein S19 binding protein 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:39928483-39928998 Neighboring gene Sharpr-MPRA regulatory region 14739 Neighboring gene uncharacterized LOC124905120

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 infection-mediated upregulation of ATF4 enhances HIV replication by synergistic interaction with HIV Tat PubMed
tat ATF4 enhances HIV-1 LTR activation and induces HIV-1 reactivation in latently infected cells PubMed
Vpu vpu HIV-1 Vpu is a strong competitive inhibitor of beta-TrCP and impairs the degradation of SCF-beta-TrCP substrates such as IKBalpha, ATF4 and beta-catenin PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
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 factor activity IDA
Inferred from Direct Assay
more info
PubMed 
enables DNA-binding transcription factor activity TAS
Traceable Author Statement
more info
PubMed 
enables 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 ISA
Inferred from Sequence Alignment
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 IPI
Inferred from Physical Interaction
more info
PubMed 
enables cAMP response element binding protein binding ISS
Inferred from Sequence or Structural Similarity
more info
 
enables general transcription initiation factor binding IEA
Inferred from Electronic Annotation
more info
 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables leucine zipper domain binding IDA
Inferred from Direct Assay
more info
PubMed 
enables promoter-specific chromatin binding IDA
Inferred from Direct Assay
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein heterodimerization activity ISS
Inferred from Sequence or Structural Similarity
more info
 
enables protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
enables sequence-specific double-stranded DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to transcription cis-regulatory region binding IDA
Inferred from Direct Assay
more info
PubMed 
enables transcription cis-regulatory region binding IDA
Inferred from Direct Assay
more info
PubMed 
enables transcription cis-regulatory region binding TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
involved_in HRI-mediated signaling IDA
Inferred from Direct Assay
more info
PubMed 
involved_in L-asparagine metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in PERK-mediated unfolded protein response IDA
Inferred from Direct Assay
more info
PubMed 
involved_in PERK-mediated unfolded protein response ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in PERK-mediated unfolded protein response TAS
Traceable Author Statement
more info
PubMed 
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 ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in cellular response to glucose starvation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cellular response to hypoxia IEA
Inferred from Electronic Annotation
more info
 
involved_in cellular response to leucine starvation IDA
Inferred from Direct Assay
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 ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in circadian regulation of gene expression ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in embryonic hemopoiesis ISS
Inferred from Sequence or Structural Similarity
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 IEA
Inferred from Electronic Annotation
more info
 
involved_in gluconeogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in integrated stress response signaling IDA
Inferred from Direct Assay
more info
PubMed 
involved_in integrated stress response signaling NAS
Non-traceable Author Statement
more info
PubMed 
involved_in intracellular calcium ion homeostasis IEA
Inferred from Electronic Annotation
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 ISS
Inferred from Sequence or Structural Similarity
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 ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in negative regulation of potassium ion transport IEA
Inferred from Electronic Annotation
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 IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of DNA-templated transcription IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of DNA-templated transcription IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of DNA-templated transcription ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in positive regulation of DNA-templated transcription NAS
Non-traceable Author Statement
more info
PubMed 
involved_in positive regulation of apoptotic process TAS
Traceable Author Statement
more info
PubMed 
involved_in positive regulation of biomineral tissue development IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of neuron apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in positive regulation of sodium-dependent phosphate transport IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of transcription by RNA polymerase I IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in 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 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
 
involved_in positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in positive regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
PubMed 
involved_in positive regulation of vascular associated smooth muscle cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of vascular endothelial growth factor production IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in regulation of DNA-templated transcription ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in regulation of osteoblast differentiation IDA
Inferred from Direct Assay
more info
PubMed 
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
 
involved_in regulation of transcription by RNA polymerase II ISO
Inferred from Sequence Orthology
more info
 
involved_in regulation of transcription by RNA polymerase II NAS
Non-traceable Author Statement
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 manganese-induced endoplasmic reticulum stress IEA
Inferred from Electronic Annotation
more info
 
involved_in response to nutrient levels IDA
Inferred from Direct Assay
more info
PubMed 
involved_in response to toxic substance IEA
Inferred from Electronic Annotation
more info
 
involved_in transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
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 IDA
Inferred from Direct Assay
more info
PubMed 
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 CHOP-ATF4 complex IDA
Inferred from Direct Assay
more info
PubMed 
part_of CHOP-ATF4 complex IPI
Inferred from Physical Interaction
more info
PubMed 
part_of CHOP-ATF4 complex NAS
Non-traceable Author Statement
more info
PubMed 
located_in Lewy body core 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 IDA
Inferred from Direct Assay
more info
PubMed 
located_in chromatin ISA
Inferred from Sequence Alignment
more info
 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
located_in cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in cytosol TAS
Traceable Author Statement
more info
 
located_in dendrite membrane IEA
Inferred from Electronic Annotation
more info
 
located_in neuron projection IDA
Inferred from Direct Assay
more info
PubMed 
located_in nuclear periphery IDA
Inferred from Direct Assay
more info
PubMed 
located_in nuclear speck IEA
Inferred from Electronic Annotation
more info
 
located_in nucleoplasm IDA
Inferred from Direct Assay
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 ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in nucleus NAS
Non-traceable Author Statement
more info
PubMed 
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
cyclic AMP-dependent transcription factor ATF-4
Names
DNA-binding protein TAXREB67
cAMP response element-binding protein 2
cAMP-dependent transcription factor ATF-4
cAMP-responsive element-binding protein 2
cyclic AMP-responsive element-binding protein 2
tax-responsive enhancer element B67
tax-responsive enhancer element-binding protein 67

NCBI Reference Sequences (RefSeq)

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)

  1. NM_001675.4NP_001666.2  cyclic AMP-dependent transcription factor ATF-4

    See identical proteins and their annotated locations for NP_001666.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript. The protein translation of this variant is regulated by an internal ribosome entry site (PMID: 23665047). Both variants 1 and 2 encode the same protein.
    Source sequence(s)
    AL022312, BC011994, D90209
    Consensus CDS
    CCDS13996.1
    UniProtKB/Swiss-Prot
    P18848, Q96AQ3, Q9UH31
    UniProtKB/TrEMBL
    Q6ICP0
    Related
    ENSP00000336790.2, ENST00000337304.2
    Conserved Domains (1) summary
    cd14692
    Location:279341
    bZIP_ATF4; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-4 (ATF-4) and similar proteins: a DNA-binding and dimerization domain
  2. NM_182810.3NP_877962.1  cyclic AMP-dependent transcription factor ATF-4

    See identical proteins and their annotated locations for NP_877962.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an internal segment in the 5' UTR, compared to variant 1. The protein translation of this variant is regulated by two upstream open reading frames (PMID: 15277680). Both variants 1 and 2 encode the same protein.
    Source sequence(s)
    AL022312
    Consensus CDS
    CCDS13996.1
    UniProtKB/Swiss-Prot
    P18848, Q96AQ3, Q9UH31
    UniProtKB/TrEMBL
    Q6ICP0
    Related
    ENSP00000501863.1, ENST00000674920.3
    Conserved Domains (1) summary
    cd14692
    Location:279341
    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_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    39520559..39522686
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    39985692..39993317
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054325649.1XP_054181624.1  cyclic AMP-dependent transcription factor ATF-4 isoform X1

    UniProtKB/TrEMBL
    Q6ICP0
  2. XM_054325650.1XP_054181625.1  cyclic AMP-dependent transcription factor ATF-4 isoform X1

    UniProtKB/TrEMBL
    Q6ICP0