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    ATF3 activating transcription factor 3 [ Homo sapiens (human) ]

    Gene ID: 467, updated on 28-Oct-2024

    Summary

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    Official Symbol
    ATF3provided by HGNC
    Official Full Name
    activating transcription factor 3provided by HGNC
    Primary source
    HGNC:HGNC:785
    See related
    Ensembl:ENSG00000162772 MIM:603148; AllianceGenome:HGNC:785
    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
    Summary
    This gene encodes a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. This gene is induced by a variety of signals, including many of those encountered by cancer cells, and is involved in the complex process of cellular stress response. Multiple transcript variants encoding different isoforms have been found for this gene. It is possible that alternative splicing of this gene may be physiologically important in the regulation of target genes. [provided by RefSeq, Apr 2011]
    Expression
    Ubiquitous expression in gall bladder (RPKM 38.3), liver (RPKM 37.5) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ATF3 in Genome Data Viewer
    Location:
    1q32.3
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (212565407..212620777)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (211810345..211865712)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (212738749..212794119)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372908 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:212687383-212688110 Neighboring gene VISTA enhancer hs2089 Neighboring gene long intergenic non-protein coding RNA 1740 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:212731832-212732569 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2506 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2507 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2508 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_3744 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2509 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:212769225-212770424 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1797 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:212780771-212781728 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:212781729-212782686 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1800 Neighboring gene Sharpr-MPRA regulatory region 14805 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:212799247-212799747 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:212803852-212804383 Neighboring gene long intergenic non-protein coding RNA 2773 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1801 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:212810785-212811984 Neighboring gene golgi associated RAB2 interactor family member 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:212819605-212820114 Neighboring gene RFK pseudogene 5

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. Steroids and extracellular signal-regulated kinase 1/2 activity suppress activating transcription factor 3 expression in patients with severe asthma. Roussel L, et al. J Allergy Clin Immunol, 2011 Jun. PMID 21514952
    2. The utility of ATF3 in distinguishing cutaneous squamous cell carcinoma among other cutaneous epithelial neoplasms. Rose CL, et al. J Cutan Pathol, 2012 Aug. PMID 22764884
    3. Enhancement of cisplatin cytotoxicity by disulfiram involves activating transcription factor 3. O'Brien A, et al. Anticancer Res, 2012 Jul. PMID 22753726
    4. The stress response gene ATF3 is a direct target of the Wnt/β-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells. Inoue M, et al. PLoS One, 2018. PMID 29966001, Free PMC Article
    5. IL-1β/ATF3-mediated induction of Ski2 expression enhances hepatitis B virus x mRNA degradation. Shiromoto F, et al. Biochem Biophys Res Commun, 2018 Sep 10. PMID 30055801

    See all (324) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. LINC00894 inhibited neuron cellular apoptosis and regulated activating transcription factor 3 expression.
      Title: LINC00894 inhibited neuron cellular apoptosis and regulated activating transcription factor 3 expression.
    2. Deubiquitinating enzyme OTUD4 stabilizes RBM47 to induce ATF3 transcription: a novel mechanism underlying the restrained malignant properties of ccRCC cells.
      Title: Deubiquitinating enzyme OTUD4 stabilizes RBM47 to induce ATF3 transcription: a novel mechanism underlying the restrained malignant properties of ccRCC cells.
    3. Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.
      Title: Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.
    4. ATF3 characterizes aggressive drug-tolerant persister cells in HGSOC.
      Title: ATF3 characterizes aggressive drug-tolerant persister cells in HGSOC.
    5. Role of ATF3 triggering M2 macrophage polarization to protect against the inflammatory injury of sepsis through ILF3/NEAT1 axis.
      Title: Role of ATF3 triggering M2 macrophage polarization to protect against the inflammatory injury of sepsis through ILF3/NEAT1 axis.
    6. Altered expression of activating transcription factor 3 in the hippocampus of patients with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS).
      Title: Altered expression of activating transcription factor 3 in the hippocampus of patients with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS).
    7. CircEXOC5 Aggravates Sepsis-Induced Acute Lung Injury by Promoting Ferroptosis Through the IGF2BP2/ATF3 Axis.
      Title: CircEXOC5 Aggravates Sepsis-Induced Acute Lung Injury by Promoting Ferroptosis Through the IGF2BP2/ATF3 Axis.
    8. Activating transcription factor 3 is a new biomarker correlation with renal clear cell carcinoma progression.
      Title: Activating transcription factor 3 is a new biomarker correlation with renal clear cell carcinoma progression.
    9. Methylation-Mediated Silencing of ATF3 Promotes Thyroid Cancer Progression by Regulating Prognostic Genes in the MAPK and PI3K/AKT Pathways.
      Title: Methylation-Mediated Silencing of ATF3 Promotes Thyroid Cancer Progression by Regulating Prognostic Genes in the MAPK and PI3K/AKT Pathways.
    10. Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR-27a-3p.
      Title: Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR-27a-3p.
    Submit: New GeneRIF Correction See all GeneRIFs (232)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef Expression of activating transcription factor 3 (ATF-3) is upregulated by HIV-1 Nef in HeLa cells PubMed
    Tat tat HIV-1 and the viral protein Tat modulate the expression of activating transcription factor 3 (ATF3) in immature dendritic cells and monocyte-derived macrophages PubMed
    tat HIV-1 Tat upregulates ATF3 expression in Tat-infected Jurkat T cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ41705

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-binding transcription activator activity, RNA polymerase II-specific ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables DNA-binding transcription repressor activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein heterodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transcription cis-regulatory region binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular response to amino acid starvation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in endoplasmic reticulum unfolded protein response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in gluconeogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of ERK1 and ERK2 cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of TRAIL-activated apoptotic signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 skeletal muscle cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of CHOP-ATF3 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 
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in nucleolus IDA
    Inferred from Direct Assay
    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 NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cyclic AMP-dependent transcription factor ATF-3
    Names
    cAMP-dependent transcription factor ATF-3

    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.

    Genomic

    1. NG_029871.1 RefSeqGene

      Range
      48407..60421
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001030287.4 → NP_001025458.1  cyclic AMP-dependent transcription factor ATF-3 isoform 1

      See identical proteins and their annotated locations for NP_001025458.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Both variants 1 and 3 encode the same isoform (1), which represses rather than activates transcription from promoters with ATF-binding elements.
      Source sequence(s)
      AI949953, BC006322, CD638624, CD641946, CD742713
      Consensus CDS
      CCDS1506.1
      UniProtKB/Swiss-Prot
      P18847, Q5VTZ2, Q6ICQ9, Q7Z566, Q8WYM6
      UniProtKB/TrEMBL
      Q5VTZ4
      Related
      ENSP00000355954.2, ENST00000366987.6
      Conserved Domains (1) summary
      cd14722
      Location:96 → 149
      bZIP_ATF3; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-3 (ATF-3) and similar proteins: a DNA-binding and dimerization domain

    2. NM_001040619.3 → NP_001035709.1  cyclic AMP-dependent transcription factor ATF-3 isoform 2

      See identical proteins and their annotated locations for NP_001035709.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4, also known as deltaZip2a) contains an alternate terminal exon, and thus differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (2, also known as deltaZip2) has a distinct and shorter C-terminus, compared to isoform 1. Isoform 2 lacks the leucine zipper protein-dimerization motif and does not bind to DNA, and it stimulates transcription presumably by sequestering inhibitory co-factors away from the promoter.
      Source sequence(s)
      AB078026, AI949953, BC006322, CD742713, DB197400
      Consensus CDS
      CCDS41464.1
      UniProtKB/TrEMBL
      Q7Z567
      Related
      ENSP00000355950.1, ENST00000366983.5
      Conserved Domains (1) summary
      cl21462
      Location:96 → 116
      bZIP; Basic leucine zipper (bZIP) domain of bZIP transcription factors: a DNA-binding and dimerization domain

    3. NM_001206484.3 → NP_001193413.2  cyclic AMP-dependent transcription factor ATF-3 isoform 3

      See identical proteins and their annotated locations for NP_001193413.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (3) is shorter at the N-terminus, compared to isoform 1. Both variants 5 and 8 encode isoform 3.
      Source sequence(s)
      AB078026, AI949953, BC006322, CD742713, DA589280
      Consensus CDS
      CCDS58059.1
      UniProtKB/TrEMBL
      A0A0A0MRJ2
      Conserved Domains (1) summary
      cd14722
      Location:39 → 92
      bZIP_ATF3; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-3 (ATF-3) and similar proteins: a DNA-binding and dimerization domain

    4. NM_001206486.2 → NP_001193415.1  cyclic AMP-dependent transcription factor ATF-3 isoform 5

      See identical proteins and their annotated locations for NP_001193415.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR, lacks an in-frame segment of the 5' coding region, and contains an alternate terminal exon, thus differing in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (5, also known as deltaZip2c) has a distinct C-terminus and is shorter than isoform 1.
      Source sequence(s)
      AB078026, AI949953, AY313927, BC006322, CD742713
      Consensus CDS
      CCDS55688.1
      UniProtKB/Swiss-Prot
      P18847
      Related
      ENSP00000336908.4, ENST00000336937.8
      Conserved Domains (1) summary
      cl21462
      Location:67 → 87
      bZIP; Basic leucine zipper (bZIP) domain of bZIP transcription factors: a DNA-binding and dimerization domain

    5. NM_001206488.3 → NP_001193417.2  cyclic AMP-dependent transcription factor ATF-3 isoform 3

      See identical proteins and their annotated locations for NP_001193417.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (3) is shorter at the N-terminus, compared to isoform 1. Both variants 5 and 8 encode isoform 3.
      Source sequence(s)
      AI949953, AL560585, BC006322, BI524020, CD742713
      Consensus CDS
      CCDS58059.1
      UniProtKB/TrEMBL
      A0A0A0MRJ2
      Related
      ENSP00000480606.1, ENST00000613104.1
      Conserved Domains (1) summary
      cd14722
      Location:39 → 92
      bZIP_ATF3; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-3 (ATF-3) and similar proteins: a DNA-binding and dimerization domain

    6. NM_001674.4 → NP_001665.1  cyclic AMP-dependent transcription factor ATF-3 isoform 1

      See identical proteins and their annotated locations for NP_001665.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1), which represses rather than activates transcription from promoters with ATF-binding elements. Both variants 1 and 3 encode isoform 1.
      Source sequence(s)
      AI949953, AL560585, BC006322, CD742713
      Consensus CDS
      CCDS1506.1
      UniProtKB/Swiss-Prot
      P18847, Q5VTZ2, Q6ICQ9, Q7Z566, Q8WYM6
      UniProtKB/TrEMBL
      Q5VTZ4
      Related
      ENSP00000344352.4, ENST00000341491.9
      Conserved Domains (1) summary
      cd14722
      Location:96 → 149
      bZIP_ATF3; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-3 (ATF-3) 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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      212565407..212620777
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011509579.2 → XP_011507881.1  cyclic AMP-dependent transcription factor ATF-3 isoform X1

      See identical proteins and their annotated locations for XP_011507881.1

      UniProtKB/Swiss-Prot
      P18847, Q5VTZ2, Q6ICQ9, Q7Z566, Q8WYM6
      UniProtKB/TrEMBL
      Q5VTZ4
      Conserved Domains (1) summary
      cd14722
      Location:96 → 149
      bZIP_ATF3; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-3 (ATF-3) and similar proteins: a DNA-binding and dimerization domain

    2. XM_005273146.2 → XP_005273203.1  cyclic AMP-dependent transcription factor ATF-3 isoform X1

      See identical proteins and their annotated locations for XP_005273203.1

      UniProtKB/Swiss-Prot
      P18847, Q5VTZ2, Q6ICQ9, Q7Z566, Q8WYM6
      UniProtKB/TrEMBL
      Q5VTZ4
      Conserved Domains (1) summary
      cd14722
      Location:96 → 149
      bZIP_ATF3; Basic leucine zipper (bZIP) domain of Activating Transcription Factor-3 (ATF-3) and similar proteins: a DNA-binding and dimerization domain

    3. XM_047421211.1 → XP_047277167.1  cyclic AMP-dependent transcription factor ATF-3 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      211810345..211865712
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054336744.1 → XP_054192719.1  cyclic AMP-dependent transcription factor ATF-3 isoform X1

      UniProtKB/Swiss-Prot
      P18847, Q5VTZ2, Q6ICQ9, Q7Z566, Q8WYM6

    2. XM_054336743.1 → XP_054192718.1  cyclic AMP-dependent transcription factor ATF-3 isoform X1

      UniProtKB/Swiss-Prot
      P18847, Q5VTZ2, Q6ICQ9, Q7Z566, Q8WYM6

    3. XM_054336745.1 → XP_054192720.1  cyclic AMP-dependent transcription factor ATF-3 isoform X2

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001206485.1: Suppressed sequence

      Description
      NM_001206485.1: This RefSeq was permanently suppressed because the transcript is incompletely processed.

    2. NM_004024.4: Suppressed sequence

      Description
      NM_004024.4: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P18847.2 GenPept UniProtKB/Swiss-Prot:P18847

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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