ZC3HAV1

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.

Full Name

zinc finger CCCH-type containing, antiviral 1

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 RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs).

Biological Process

Biological Process defense response to virus Source:UniProtKB-KW
Biological Process innate immune response Source:UniProtKB-KW
Biological Process negative regulation of viral genome replication Source:UniProtKB1 Publication
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signaling Source:UniProtKB
Biological Process positive regulation of interferon-alpha production Source:UniProtKB
Biological Process positive regulation of interferon-beta production Source:UniProtKB
Biological Process positive regulation of mRNA catabolic process Source:UniProtKB1 Publication
Biological Process positive regulation of RIG-I signaling pathway Source:UniProtKB
Biological Process positive regulation of type I interferon production Source:GO_Central1 Publication
Biological Process response to virus Source:UniProtKB1 Publication

Cellular Location

Isoform 1
Cytoplasm
Nucleus
Localizes in the cytoplasm at steady state, but shuttles between nucleus and cytoplasm in a XPO1-dependent manner.
Isoform 2
Cytoplasm

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).