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]
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 (HISLV1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLSLVrelated 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 HISLV1 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).
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.
Subcellular Location:
Cytoplasm. Nucleus. Localizes in the cytoplasm at steady state, but shuttles between nucleus and cytoplasm in a XPO1-dependent manner.
Post-translational modifications:
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
Similarity:
Contains 4 C3H1-type zinc fingers.
Contains 1 PARP catalytic domain.
Contains 1 WWE domain.
SWISS:
Q7Z2W4
Gene ID:
56829
Database links:
Entrez Gene: 56829 Human
Omim: 607312 Human
SwissProt: Q7Z2W4 Human
Unigene: 133512 Human
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