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    ATF3 activating transcription factor 3 [ Homo sapiens ]

    Gene ID: 467, updated on 21-May-2012
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    Summary

    Official Symbol
    ATF3provided by HGNC
    Official Full Name
    activating transcription factor 3provided by HGNC
    Primary source
    HGNC:785
    Locus tag
    RP11-338C15.1
    See related
    Ensembl:ENSG00000162772; HPRD:04395; MIM:603148; Vega:OTTHUMG00000036747
    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
    FLJ41705
    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]
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    Genomic context

    Location :
    1q32.3
    Sequence :
    Chromosome: 1; NC_000001.10 (212738697..212794117)
    See ATF3 in Epigenomics, MapViewer

    Chromosome 1 - NC_000001.10Genomic Context describing neighboring genes Neighboring gene transmembrane protein 206 Neighboring gene neudesin neurotrophic factor Neighboring gene riboflavin kinase pseudogene Neighboring gene family with sequence similarity 71, member A

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. ROS-induced ATF3 causes susceptibility to secondary infections during sepsis-associated immunosuppression. Hoetzenecker W, et al. Nat Med, 2011 Dec 18. PMID 22179317.
    2. Systems analysis of ATF3 in stress response and cancer reveals opposing effects on pro-apoptotic genes in p53 pathway. Tanaka Y, et al. PLoS One, 2011. PMID 22046379.
    3. ATF3 inhibits PDX-1-stimulated transactivation. Kim WH, et al. Biochem Biophys Res Commun, 2011 Nov 4. PMID 21986529.
    4. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    5. Transcriptional activity of ATF3 in the stromal compartment of tumors promotes cancer progression. Buganim Y, et al. Carcinogenesis, 2011 Dec. PMID 21900211.

    See all (114) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. an extensive network of stress-inducible transcription factors and demonstrate that ATF3 has opposing, cell context-dependent effects on p53 target genes in DNA damage response and cancer development
      Title: Systems analysis of ATF3 in stress response and cancer reveals opposing effects on pro-apoptotic genes in p53 pathway.
    2. the loss of the major reactive oxygen species scavenger, glutathione, during SAIS directly correlates with an increase in the expression of activating transcription factor 3.
      Title: ROS-induced ATF3 causes susceptibility to secondary infections during sepsis-associated immunosuppression.
    3. found that the ability of stromal ATF3 to promote cancer progression is mediated by transcriptional repression of CLDN1 and induction of CXCL12 and RGS4
      Title: Transcriptional activity of ATF3 in the stromal compartment of tumors promotes cancer progression.
    4. ATF3 bound to the TREM-1 promoter.
      Title: TREM-1 and DAP12 expression in monocytes of patients with severe psychiatric disorders. EGR3, ATF3 and PU.1 as important transcription factors.
    5. these results demonstrate that ATF3 represses PDX-1 expression via binding to an ATF3-responsive element in its promoter, which plays an important role in suppression of pancreatic beta-cells function.
      Title: ATF3 represses PDX-1 expression in pancreatic β-cells.
    6. activating transcription factor 3 appears to play an oncogenic role in the development of squamous cell carcinomas and may be related to the biologic behavior of them.
      Title: Increased expression of activating transcription factor 3 is related to the biologic behavior of cutaneous squamous cell carcinomas.
    7. KAI1 gene is engaged in NDRG1 gene-mediated metastasis suppression through the ATF3-NFkappaB complex in human prostate cancer.
      Title: KAI1 gene is engaged in NDRG1 gene-mediated metastasis suppression through the ATF3-NFkappaB complex in human prostate cancer.
    8. MUC18 is involved in cell signaling regulating the expression of Id-1 and ATF-3, thus contributing to melanoma metastasis
      Title: Expression of Id-1 is regulated by MCAM/MUC18: a missing link in melanoma progression.
    9. ATF3 interacts with HTLV-I bZIP factor and promotes proliferation of ATL cells.
      Title: ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells.
    10. LDLR repression by organelle stress via ATF3
      Title: Organelle stress-induced activating transcription factor-3 downregulates low-density lipoprotein receptor expression in Sk-Hep1 human liver cells.
    Submit: New GeneRIF Correction See all (68)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    HIV-1 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

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_001665.1 NP_001665.1 ATF3    BIND  PubMed An unspecified isoform of ATF3 interacts with itself intermolecularly. This interaction was modeled on a demonstrated interaction between ATF3 from an unspecified species. 
    NP_001665.1 NP_000537.2 TP53    BIND  PubMed An unspecified isoform of ATF3 interacts with p53. 
    P18847 P18847 ATF3    HPRD  PubMed  
    P18847 Jun dimerization protein p21SNFT BATF3    HPRD  PubMed  
    P18847 P35638 DDIT3    HPRD  PubMed  
    P18847 P22607 FGFR3    HPRD  PubMed  
    P18847 Q96ID5 IGSF21    HPRD  PubMed  
    P18847 P05412 JUN    HPRD  PubMed  
    P18847 P17535 JUND    HPRD  PubMed  
    P18847 Q5T3J3 LRIF1    HPRD  PubMed  
    P18847 P19838 NFKB1    HPRD  PubMed  
    P18847 Q9BZD4 NUF2    HPRD  PubMed  
    P18847 P84022 SMAD3    HPRD  PubMed  
    P18847 P04637 TP53    HPRD  PubMed  
    BioGRID:106957 BioGRID:106575 ACTB    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106957 BioGRID:107776 ATF2    BioGRID  PubMed Two-hybrid 
    BioGRID:106957 BioGRID:106958 ATF4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106957 BioGRID:107480 CEBPB    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106957 BioGRID:107482 CEBPE    BioGRID  PubMed Co-localization 
    BioGRID:106957 BioGRID:107777 CREBBP    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106957 BioGRID:108016 DDIT3    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106957 BioGRID:108552 FGFR3    BioGRID  PubMed Two-hybrid 
    BioGRID:106957 BioGRID:109187 GSK3B    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106957 BioGRID:109315 HDAC1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106957 BioGRID:124396 IGSF21    BioGRID  PubMed Two-hybrid 
    BioGRID:106957 BioGRID:109928 JUN    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106957 BioGRID:109930 JUND    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106957 BioGRID:120905 LRIF1    BioGRID  PubMed Two-hybrid 
    BioGRID:106957 BioGRID:110358 MDM2    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Reconstituted Complex 
    BioGRID:106957 BioGRID:109860 PDX1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106957 BioGRID:107129 POLR3D    BioGRID  PubMed Two-hybrid 
    BioGRID:106957 BioGRID:111902 RELA    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106957 BioGRID:110262 SMAD2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106957 BioGRID:110263 SMAD3    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106957 BioGRID:112481 SMARCA4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106957 BioGRID:117505 SS18L1    BioGRID  PubMed Two-hybrid 
    BioGRID:106957 BioGRID:112649 STAT1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106957 BioGRID:112497 SUMO2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106957 BioGRID:113010 TP53    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:106957 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • ATF-2 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
      ATF-2 transcription factor network, organism-specific biosystem
      ATF-2 transcription factor network
    • Activation of Genes by ATF4, organism-specific biosystem (from REACTOME)
      Activation of Genes by ATF4, organism-specific biosystemATF4 is a transcription factor and activates expression of IL-8, MCP1, IGFBP-1, CHOP, HERP1 and ATF3.
    • Diabetes pathways, organism-specific biosystem (from REACTOME)
      Diabetes pathways, organism-specific biosystemThis module groups several normal processes that have key roles in the synthesis and function of insulin, insulin-like growth factors and ghrelin, and whose derangement is thus central to the pathoge...
    • Direct p53 effectors, organism-specific biosystem (from Pathway Interaction Database)
      Direct p53 effectors, organism-specific biosystem
      Direct p53 effectors
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • HTLV-I infection, organism-specific biosystem (from KEGG)
      HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • HTLV-I infection, conserved biosystem (from KEGG)
      HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • Hypertrophy Model, organism-specific biosystem (from WikiPathways)
      Hypertrophy Model, organism-specific biosystem
      Hypertrophy Model
    • Id Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Id Signaling Pathway, organism-specific biosystemInhibitor of DNA binding (ID) proteins are members of the helix-loop-helix (HLH) family of proteins which lack a DNA binding domain themselves but bind to other family members inhibiting their DNA bi...
    • Myometrial Relaxation and Contraction Pathways, organism-specific biosystem (from WikiPathways)
      Myometrial Relaxation and Contraction Pathways, organism-specific biosystemThis pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile ac...
    • PERK regulated gene expression, organism-specific biosystem (from REACTOME)
      PERK regulated gene expression, organism-specific biosystemPERK is a single-pass transmembrane protein located in the endoplasmic reticulum (ER) membrane such that the N-terminus of PERK is luminal and the C-terminus is cytosolic. PERK is maintained in an in...
    • Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
      Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem
      Regulation of nuclear SMAD2/3 signaling
    • TGF-beta Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TGF-beta Receptor Signaling Pathway, organism-specific biosystem"The TGF beta receptors TGFBR1 and TGFBR2 belong to a subfamily of membrane-bound serine/threonine kinases which are designated as Type I or II based on their structural and functional properties. Th...
    • Unfolded Protein Response, organism-specific biosystem (from REACTOME)
      Unfolded Protein Response, organism-specific biosystemThe Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER d...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein dimerization activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    sequence-specific DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    sequence-specific DNA binding transcription factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    transcription corepressor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    activation of signaling protein activity involved in unfolded protein response TAS
    Traceable Author Statement
    more info
    		  
    endoplasmic reticulum unfolded protein response TAS
    Traceable Author Statement
    more info
    		  
    gluconeogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of transcription, DNA-dependent IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of transcription, DNA-dependent TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    cyclic AMP-dependent transcription factor ATF-3
    Names
    cyclic AMP-dependent transcription factor ATF-3
    cAMP-dependent transcription factor ATF-3
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    NCBI Reference Sequences (RefSeq)

    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
      4980..60423
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001030287.3 → NP_001025458.1  cyclic AMP-dependent transcription factor ATF-3 isoform 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)
      AC092803, AI949953, BC006322, CD638624, CD641946, CD742713
      Consensus CDS
      CCDS1506.1
      UniProtKB/Swiss-Prot
      P18847
      Related
      ENSP00000355954, ENST00000366987
      Conserved Domains (1) summary
      cl02576
      Location:103 – 147
      Blast Score: 101
      bZIP_1; bZIP transcription factor

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

      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, AL560585, BC006322, CD742713, DB197400
      Consensus CDS
      CCDS41464.1
      UniProtKB/Swiss-Prot
      P18847
      Related
      ENSP00000355950, OTTHUMP00000034890, ENST00000366983, OTTHUMT00000089299

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

      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, AL560585, BC006322, CD742713, DA589280
      UniProtKB/Swiss-Prot
      P18847
      UniProtKB/TrEMBL
      Q5VTZ2
      Conserved Domains (1) summary
      cl02576
      Location:46 – 90
      Blast Score: 87
      bZIP_1; bZIP transcription factor

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

      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, OTTHUMP00000038593, ENST00000336937, OTTHUMT00000098523

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

      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
      UniProtKB/Swiss-Prot
      P18847
      UniProtKB/TrEMBL
      Q5VTZ2
      Conserved Domains (1) summary
      cl02576
      Location:46 – 90
      Blast Score: 87
      bZIP_1; bZIP transcription factor

    6. NM_001674.3 → NP_001665.1  cyclic AMP-dependent transcription factor ATF-3 isoform 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
      Related
      ENSP00000344352, OTTHUMP00000034887, ENST00000341491, OTTHUMT00000089296
      Conserved Domains (1) summary
      cl02576
      Location:103 – 147
      Blast Score: 101
      bZIP_1; bZIP transcription factor

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000001.10 Reference GRCh37.p5 Primary Assembly

      Range
      212738697..212794117
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000133.1 Alternate HuRef

      Range
      183415493..183470941
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    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.
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC092803.2 (184010..188344) None
    genomic AL590648.9 CAH72653.1
      CAH72654.1
      CAH72655.1
      CAH72656.1
      CAH72657.1
    genomic AL606913.8 (40983..44982) None
    genomic AY426987.1 AAQ93358.1
    genomic CH471100.2 EAW93383.1
      EAW93384.1
      EAW93385.1
      EAW93386.1
      EAW93387.1
      EAW93388.1
    mRNA AB066566.1 BAB84092.1
    mRNA AB078026.1 BAC00495.1
    mRNA AB078027.1 BAC00496.1
    mRNA AB078028.1 BAC05510.1
    mRNA AB209032.1 BAD92269.1
    mRNA AI492228.1 None
    mRNA AI949953.1 None
    mRNA AK123699.1 None
    mRNA AK125255.1 None
    mRNA AK294296.1 BAG57579.1
    mRNA AK312998.1 BAG35834.1
    mRNA AL560585.3 None
    mRNA AU135799.1 None
    mRNA AY313926.1 AAP93895.1
    mRNA AY313927.1 AAP93896.1
    mRNA BC006322.2 AAH06322.1
    mRNA BI524020.1 None
    mRNA BI819383.1 None
    mRNA BT006996.1 AAP35642.1
    mRNA CD638624.1 None
    mRNA CD641946.1 None
    mRNA CD742713.1 None
    mRNA CR450334.1 CAG29330.1
    mRNA DA589280.1 None
    mRNA DA691940.1 None
    mRNA DB197400.1 None
    mRNA L19871.1 AAA20506.1
    other-genetic DQ892723.2 ABM83649.1
    other-genetic DQ895972.2 ABM86898.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P18847.2 GenPept UniProtKB/Swiss-Prot:P18847
    Q59GS7 GenPept UniProtKB/TrEMBL:Q59GS7
    Q5VTZ2 GenPept UniProtKB/TrEMBL:Q5VTZ2
    Q5VTZ4 GenPept UniProtKB/TrEMBL:Q5VTZ4
    Q7Z567 GenPept UniProtKB/TrEMBL:Q7Z567
    Q8NG55 GenPept UniProtKB/TrEMBL:Q8NG55
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    Additional Links

    Gene LinkOut

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

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