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    ZBP1 Z-DNA binding protein 1 [ Homo sapiens ]

    Gene ID: 81030, updated on 13-May-2012
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    Summary

    Official Symbol
    ZBP1provided by HGNC
    Official Full Name
    Z-DNA binding protein 1provided by HGNC
    Primary source
    HGNC:16176
    Locus tag
    RP4-718J7.1
    See related
    Ensembl:ENSG00000124256; HPRD:09484; MIM:606750; Vega:OTTHUMG00000032824
    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
    DAI; DLM1; DLM-1; C20orf183
    Summary
    This gene encodes a Z-DNA binding protein. The encoded protein plays a role in the innate immune response by binding to foreign DNA and inducing type-I interferon production. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
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    Genomic context

    Location :
    20q13.31
    Sequence :
    Chromosome: 20; NC_000020.10 (56178902..56195632, complement)
    See ZBP1 in Epigenomics, MapViewer

    Chromosome 20 - NC_000020.10Genomic Context describing neighboring genes Neighboring gene CCCTC-binding factor (zinc finger protein)-like Neighboring gene phosphoenolpyruvate carboxykinase 1 (soluble) Neighboring gene prostate transmembrane protein, androgen induced 1 Neighboring gene microRNA 4532

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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. Transgenic expression of ZBP1 in neurons suppresses cocaine-associated conditioning. Lapidus KA, et al. Learn Mem, 2012 Feb. PMID 22240322.
    2. The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA. Sim S, et al. RNA, 2012 Jan. PMID 22114317.
    3. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Li S, et al. Immunity, 2011 Sep 23. PMID 21903422.
    4. Solution structure of the Zbeta domain of human DNA-dependent activator of IFN-regulatory factors and its binding modes to B- and Z-DNAs. Kim K, et al. Proc Natl Acad Sci U S A, 2011 Apr 26. PMID 21471454.
    5. The Zβ domain of human DAI binds to Z-DNA via a novel B-Z transition pathway. Kim HE, et al. FEBS Lett, 2011 Mar 9. PMID 21296080.

    See all (24) 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. The data of this study suggest that RNA-binding proteins can be used as a tool to identify the post-transcriptional regulation of gene expression in the establishment and function of neural circuits involved in addiction behaviors.
      Title: Transgenic expression of ZBP1 in neurons suppresses cocaine-associated conditioning.
    2. these data indicate that ZBP1 may function as an adapter to export the Ro/Y3 RNA complex from nuclei.
      Title: The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA.
    3. Solution structure of the Zbeta domain of human DNA-dependent activator of IFN-regulatory factors and its binding modes to B- and Z-DNAs.
      Title: Solution structure of the Zbeta domain of human DNA-dependent activator of IFN-regulatory factors and its binding modes to B- and Z-DNAs.
    4. hZbeta(DAI) binds to Z-DNA via an active-di B-Z transition mechanism.
      Title: The Zβ domain of human DAI binds to Z-DNA via a novel B-Z transition pathway.
    5. These results suggest that activation of DAI might contribute to augment HIV-1 replication through DAI- NF-kappaB pathway.
      Title: DNA-dependent activator of IFN-regulatory factors enhances the transcription of HIV-1 through NF-κB.
    6. Observational study of gene-disease association. (HuGE Navigator)
      Title: New genetic associations detected in a host response study to hepatitis B vaccine.
    7. identify ZBP1 as being essential for IRF3 activation and interferon beta expression triggered by HCMV, as well as being sufficient to enhance HCMV-stimulated beta interferon transcription and secretion.
      Title: Human cytomegalovirus induces the interferon response via the DNA sensor ZBP1.
    8. These data suggest that repression of ZBP1 by blocking beta-catenin binding at the ZBP1 promoter deregulates its associated mRNAs, leading to the phenotypic changes of breast cancers.
      Title: Blocking beta-catenin binding to the ZBP1 promoter represses ZBP1 expression, leading to increased proliferation and migration of metastatic breast-cancer cells.
    9. binding 2 DAIs to 1 dsDNA brings about dimerization of DAI that might facilitate DNA-mediated innate immune activation.
      Title: The crystal structure of the second Z-DNA binding domain of human DAI (ZBP1) in complex with Z-DNA reveals an unusual binding mode to Z-DNA.
    10. DAI binds to and colocalizes with endogenous adaptor receptor-interacting protein kinase (RIP)1 at characteristic cytoplasmic granules.
      Title: Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors.
    Submit: New GeneRIF Correction See all (13)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease.

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    BioGRID:123349 BioGRID:107869 CTBP1    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:123349 BioGRID:107870 CTBP2    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:123349 BioGRID:108619 FMR1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:123349 BioGRID:116667 KDM1A    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:123349 BioGRID:118028 KIAA1274    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:123349 BioGRID:117130 ORC3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:123349 BioGRID:124338 PLXDC2    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:123349 BioGRID:113039 TRAF3    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:123349 BioGRID:120855 VPS35    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:123349 BioGRID:115016 ZNF516    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Cytosolic DNA-sensing pathway, organism-specific biosystem (from KEGG)
      Cytosolic DNA-sensing pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified s...
    • Cytosolic DNA-sensing pathway, conserved biosystem (from KEGG)
      Cytosolic DNA-sensing pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified s...
    • Cytosolic sensors of pathogen-associated DNA, organism-specific biosystem (from REACTOME)
      Cytosolic sensors of pathogen-associated DNA, organism-specific biosystemPresence of pathogen-associated DNA in cytosol induces type I IFN production. Several intracellular receptors have been implicated to some degree. These include DNA-dependent activator of interferon ...
    • DAI mediated induction of type I IFNs, organism-specific biosystem (from REACTOME)
      DAI mediated induction of type I IFNs, organism-specific biosystemDNA-dependent activator of IFN-regulatory factors (DAI), also known as Z-DNA-binding protein-1 (ZBP-1), was reported to initiate innate immune responses in murine L929 cells upon stimulation by multi...
    • IRF3 mediated activation of type 1 IFN, organism-specific biosystem (from REACTOME)
      IRF3 mediated activation of type 1 IFN, organism-specific biosystemInterferon regulatory factors (IRF) IRF-3 and IRF-7 are the major modulators of IFN gene expression in response to pathogenic molecules. The relative contribution of IRF3 and IRF7 depends on the sign...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • RIP-mediated NFkB activation via DAI, organism-specific biosystem (from REACTOME)
      RIP-mediated NFkB activation via DAI, organism-specific biosystemOverexpression of human or murine DAI in human embryonic kidney 293T cells (HEK293T) activated NF-kB-dependent promoter in a dose-dependent manner. Two RHIM-contaning kinases RIP1 and RIP3 are implic...
    • TRIF mediated TLR3 signaling, organism-specific biosystem (from REACTOME)
      TRIF mediated TLR3 signaling, organism-specific biosystemTIR-domain-containing adaptor inducing interferon-beta (TRIF or TIKAM1) is known to be an essential and exclusive adaptor used by TLR3; all the poly(I:C)-induced pathways leading to NFkB and IRF3 act...
    • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
    • Toll Receptor Cascades, organism-specific biosystem (from REACTOME)
      Toll Receptor Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
    • Viral dsRNA:TLR3:TRIF Complex Activates RIP1, organism-specific biosystem (from REACTOME)
      Viral dsRNA:TLR3:TRIF Complex Activates RIP1, organism-specific biosystemReceptor-interacting protein 1 (RIP1) mediates the activation of interferon-alpha/beta via intermediate activation of IKK/TBK1 or NFkB pathways.

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    RNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    double-stranded RNA adenosine deaminase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    left-handed Z-DNA binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    biological_process ND
    No biological Data available
    more info
    		  
    innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    Z-DNA-binding protein 1
    Names
    Z-DNA-binding protein 1
    DNA-dependent activator of IRFs
    DNA-dependent activator of IFN-regulatory factors
    tumor stroma and activated macrophage protein DLM-1
    DNA-dependent activator of interferon regulatory factors
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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_031836.1 RefSeqGene

      Range
      5001..21731
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001160417.1 → NP_001153889.1  Z-DNA-binding protein 1 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the internal coding region compared to variant 1. This results in a shorter protein (isoform b) compared to isoform a.
      Source sequence(s)
      AJ300575, AK122761, AK314062, AL035541, DA674238, DB331848
      UniProtKB/TrEMBL
      B3KVA1
      UniProtKB/Swiss-Prot
      Q9H171
      Conserved Domains (1) summary
      cl02659
      Location:14 – 66
      Blast Score: 130
      z-alpha; Adenosine deaminase z-alpha domain

    2. NM_001160418.1 → NP_001153890.1  Z-DNA-binding protein 1 isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (c) is shorter than isoform a.
      Source sequence(s)
      AJ300575, AK122761, AL035541, DB331848
      Consensus CDS
      CCDS54477.1
      UniProtKB/TrEMBL
      A2A2F7
      UniProtKB/TrEMBL
      B3KVA1
      UniProtKB/Swiss-Prot
      Q9H171
      Related
      ENSP00000379167, OTTHUMP00000174290, ENST00000395822, OTTHUMT00000267828
      Conserved Domains (1) summary
      cl02659
      Location:35 – 78
      Blast Score: 94
      z-alpha; Adenosine deaminase z-alpha domain

    3. NM_001160419.2 → NP_001153891.1  Z-DNA-binding protein 1 isoform d

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (d) is shorter and has a distinct C-terminus compared to isoform a.
      Source sequence(s)
      AI659939, AI925506, AK122761, CT002036, DA676308
      Consensus CDS
      CCDS54478.1
      UniProtKB/TrEMBL
      B3KVA1
      UniProtKB/TrEMBL
      F5GYT1
      Related
      ENSP00000440552, OTTHUMP00000237854, ENST00000541799, OTTHUMT00000398022
      Conserved Domains (1) summary
      cl02659
      Location:14 – 66
      Blast Score: 125
      z-alpha; Adenosine deaminase z-alpha domain

    4. NM_030776.2 → NP_110403.2  Z-DNA-binding protein 1 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AJ300575, AK122761, AL035541, DB331848
      Consensus CDS
      CCDS13461.1
      UniProtKB/TrEMBL
      B3KVA1
      UniProtKB/Swiss-Prot
      Q9H171
      Related
      ENSP00000360215, OTTHUMP00000031373, ENST00000371173, OTTHUMT00000079849
      Conserved Domains (1) summary
      cl02659
      Location:14 – 66
      Blast Score: 130
      z-alpha; Adenosine deaminase z-alpha domain

    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_000020.10 Reference GRCh37.p5 Primary Assembly

      Range
      56178902..56195632, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000152.1 Alternate HuRef

      Range
      52960880..52977617, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL035541.15 CAI23107.1
      CAM28298.1
      CAM28299.1
    genomic AL035541.15 CAI23107.1
      CAM28298.1
      CAM28299.1
    genomic CH471077.2 EAW75509.1
      EAW75510.1
      EAW75511.1
      EAW75512.1
      EAW75513.1
    mRNA AI659939.1 None
    mRNA AI925506.1 None
    mRNA AJ300575.1 CAC18810.1
    mRNA AK122761.1 BAG53713.1
    mRNA AK128405.1 None
    mRNA AK290918.1 BAF83607.1
    mRNA AK314062.1 None
    mRNA AX775973.1 CAE11686.1
    mRNA AX775975.1 CAE11687.1
    mRNA BC028218.1 AAH28218.1
    mRNA BC131706.1 AAI31707.1
    mRNA BF511589.1 None
    mRNA CT002036.1 None
    mRNA DA674238.1 None
    mRNA DA676308.1 None
    mRNA DB331848.1 None
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H171.2 GenPept UniProtKB/Swiss-Prot:Q9H171
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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.

    Chemical Information
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    Research Materials
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