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

    Gene ID: 468, updated on 17-Jun-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
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See ATF4 in Genome Data Viewer
    Location:
    22q13.1
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (39520559..39522686)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (39985692..39993317)
    105.20220307 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 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 
    part_of 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_2023_10

    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