Description: Homo sapiens zinc finger CCCH-type, antiviral 1 (ZC3HAV1), transcript variant 1, mRNA. RefSeq Summary (NM_020119): This gene encodes a CCCH-type zinc finger protein that is thought to prevent infection by retroviruses. Studies of the rat homolog indicate that the protein may primarily function to inhibit viral gene expression and induce an innate immunity to viral infection. Alternative splicing occurs at this locus and two variants, each encoding distinct isoforms, are described. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr7:138,728,266-138,794,465 Size: 66,200 Total Exon Count: 13 Strand: - Coding Region Position: hg19 chr7:138,732,340-138,794,077 Size: 61,738 Coding Exon Count: 13
ID:ZCCHV_HUMAN DESCRIPTION: RecName: Full=Zinc finger CCCH-type antiviral protein 1; AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 13; Short=ARTD13; AltName: Full=Zinc finger CCCH domain-containing protein 2; AltName: Full=Zinc finger antiviral protein; Short=ZAP; FUNCTION: Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)- specific ribonuclease PARN to remove the poly(A) tail, and the 3'- 5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of DDX58/RIG-I signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Thermostable; SUBUNIT: Homodimer or homooligomer. Homooligomerization is essential for its antiviral activity. Interacts with EXOSC5 (By similarity). Interacts (via N-terminal domain) with DDX17 in an RNA-independent manner (By similarity). Interacts with EXOSC3, EXOSC7, DCP2 and DCP1A. Interacts with PARN in an RNA-independent manner. Interacts with XRN1 in an RNA-dependent manner. Isoform 2 interacts (via zinc-fingers) with DDX58/RIG-I in an RNA-dependent manner. Interacts (via N-terminal domain) with DHX30 (via N- terminus) in an RNA-independent manner. INTERACTION: O95786:DDX58; NbExp=3; IntAct=EBI-922540, EBI-995350; SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Nucleus. Note=Localizes in the cytoplasm at steady state, but shuttles between nucleus and cytoplasm in a XPO1-dependent manner (By similarity). SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. INDUCTION: By type I interferon (IFN) and viruses. Isoform 2 is up-regulated by 3'-PPP-RNA. DOMAIN: The N-terminal domain is sufficient to bind to viral RNAs and promote their degradation. The second and fourth zinc fingers are involved in binding to specific viral RNAs. PTM: Phosphorylation at Ser-275 is essential for sequential phosphorylation of Ser-271, Ser-267, Ser-263 and Ser-257 by GSK3- beta. Phosphorylation by GSK3-beta enhances its antiviral activity (By similarity). SIMILARITY: Contains 4 C3H1-type zinc fingers. SIMILARITY: Contains 1 PARP catalytic domain. SIMILARITY: Contains 1 WWE domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q7Z2W4
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002376 immune system process GO:0009615 response to virus GO:0032727 positive regulation of interferon-alpha production GO:0032728 positive regulation of interferon-beta production GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0045071 negative regulation of viral genome replication GO:0045087 innate immune response GO:0051607 defense response to virus GO:0061014 positive regulation of mRNA catabolic process GO:1900246 positive regulation of RIG-I signaling pathway GO:0070212 protein poly-ADP-ribosylation