| 2013 |
S-farnesylation of the long isoform of ZAP (ZAPL) is required for its targeting to endolysosomes and enhances its antiviral activity; bioorthogonal proteomics with alkyne-isoprenoid chemical reporters identified this isoform-specific lipid modification. |
Bioorthogonal proteomics (alkyne-isoprenoid chemical reporters), subcellular fractionation/imaging, functional antiviral assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
23776219
|
| 2014 |
PARP13/ZAP binds cellular mRNAs via its four CCCH-type zinc-finger domains and destabilizes the TRAILR4 transcript post-transcriptionally in an exosome-dependent manner by binding to a region in its 3' UTR, thereby repressing TRAILR4 expression and increasing cell sensitivity to TRAIL-mediated apoptosis. |
RNA immunoprecipitation, knockdown (siRNA), RNA stability assay, luciferase reporter assay, exosome inhibition |
Nature communications |
High |
25382312
|
| 2013 |
ZAP acts as a cytosolic RNA sensor that recruits viral (MLV) transcripts and exosome components to RNA granules, inducing viral RNA degradation by the exosome; this function requires the CCCH-type zinc-finger domains of ZAP. ZAP deficiency did not affect RIG-I-dependent type I IFN production in mouse cells. |
Genetic knockout (ZAP-deficient mice/cells), viral replication assay, co-localization microscopy, domain mutant analysis, RNA granule fractionation |
Proceedings of the National Academy of Sciences of the United States of America |
High |
23836649
|
| 2015 |
ZAP interacts with LINE-1 ORF1p in an RNA-dependent manner and inhibits retrotransposition of human L1, Alu, mouse L1, and zebrafish LINE-2 elements by reducing accumulation of full-length L1 RNA and L1-encoded proteins; ZAP co-localizes with L1 RNA and ORF1p in cytoplasmic stress granule foci. |
Co-immunoprecipitation with mass spectrometry, siRNA knockdown, retrotransposition assay (cell culture), fluorescence microscopy |
PLoS genetics |
High |
25951186 26001115
|
| 2015 |
ZAP (PARP13/ZC3HAV1) restricts L1 retrotransposition through loss of L1 RNA and ribonucleoprotein particle integrity; ZAP co-immunoprecipitates with ORF1p and co-localizes in cytoplasmic stress granules. Mass spectrometry of the ZAP interactome identified associated proteins including MOV10 RNA helicase, RNA degradation proteins, helicases, and chaperonin complex components. |
Co-immunoprecipitation, mass spectrometry (ZAP interactome), retrotransposition assay, fluorescence microscopy |
PLoS genetics |
High |
26001115
|
| 2012 |
Poly(ADP-ribose) (pADPr) functions are mediated in the cytoplasm through catalytically inactive PARP-13/ZC3HAV1 together with mono/poly(ADP-ribose)-synthesizing enzymes; PARP-13 participates in cytoplasmic stress granule assembly and modulation of microRNA activities. |
Biochemical fractionation, pADPr modification assay, stress granule assembly assay |
RNA biology |
Medium |
22531498
|
| 2021 |
ZAP/ZC3HAV1 directly binds SARS-CoV-2 RNA (identified by RNP capture) and functions as an antiviral RBP; knockdown experiments confirmed its antiviral role in coronavirus replication. |
RNP capture (ribonucleoprotein capture protocol), siRNA knockdown, transcriptome analysis |
Molecular cell |
Medium |
33989516
|
| 2021 |
ZAP (both ZAP-S and ZAP-L isoforms) restricts HCMV replication by destabilizing a distinct subset of viral mRNAs, particularly UL4 and UL5 transcripts from the UL4-UL6 locus; eCLIP-seq identified these as direct ZAP binding targets. ZAP preferentially recognizes CG-rich sequences and other cytosine-rich sequences. |
Enhanced cross-linking immunoprecipitation and sequencing (eCLIP-seq), SLAM-seq (metabolic RNA labeling + sequencing), transcriptome and proteome analysis, ZAP overexpression |
mBio |
High |
33947766
|
| 2019 |
ZAP suppresses HTLV-1 viral transcript levels in a dose-dependent manner; overexpression of ZAP reduced virus production and siRNA knockdown of endogenous ZAP increased virus production. HTLV-1's high CG dinucleotide content is associated with susceptibility to ZAP-mediated restriction. |
ZAP overexpression, siRNA knockdown, virus production assay (CAGE sequencing for transcript analysis) |
Retrovirology |
Medium |
31842935
|
| 2020 |
ZC3HAV1 is induced by IFN-β/IFNAR signaling during influenza A virus (IAV) and Sendai virus infection; knockdown of ZC3HAV1 enhanced IAV replication by impairing IFN-β and MxA production, while overexpression of ZC3HAV1 restricted IAV replication by increasing IFN-β expression and promoting TNF and IL-6 induction. |
siRNA knockdown, ectopic overexpression, viral replication assay, cytokine measurement, IFNAR deficiency (genetic) |
Frontiers in microbiology |
Medium |
32922375
|
| 2024 |
ZC3HAV1 (ZAP) potentiates STING activation by directly associating with STING protein to promote its oligomerization and translocation from the ER to the Golgi, facilitating downstream IRF3 and NF-κB pathway activation; Zc3hav1-deficient mice show reduced inflammation upon HSV-1 infection or DMXAA treatment in a STING-dependent manner. |
Co-immunoprecipitation, STING oligomerization assay, ER-to-Golgi translocation assay, genetic KO (Zc3hav1-deficient mice), in vivo infection model, IRF3/NF-κB pathway activation assay |
Communications biology |
High |
39478149
|
| 2024 |
ZAP/ZC3HAV1 interacts with NLRP3 and promotes NLRP3 oligomerization, thereby facilitating NLRP3 inflammasome activation in macrophages; the shorter isoform ZAPS shows greater activity than ZAPL in this context. Zap-deficient mice show reduced susceptibility to alum-induced peritonitis and LPS-induced sepsis. |
Co-immunoprecipitation, NLRP3 oligomerization assay, inflammasome activation assay, Zap-deficient mouse model (peritonitis and sepsis in vivo) |
International immunopharmacology |
High |
38663314
|
| 2023 |
ZC3HAV1 dampens and shortens cytokine (IFNG, TNF, IL2) production duration in human T cells by binding to their 3' UTRs; RNA aptamer-based capture assay identified ZC3HAV1 as one of >130 RBPs interacting with cytokine 3' UTRs, with its interaction showing plasticity upon T cell activation. |
RNA aptamer-based capture assay, RBP-RNA interaction mapping, T cell activation assay, cytokine production measurement |
Cell reports |
Medium |
37074914
|
| 2021 |
ZC3HAV1 was identified as an interaction partner of SARS-CoV-2 nucleocapsid (N) protein by affinity purification and mass spectrometry in HEK293T and Calu-3 cells. |
Affinity purification and mass spectrometry (AP-MS) |
Pathogens (Basel, Switzerland) |
Low |
34578187
|
| 2023 |
ZCCHC3 associates with ZC3HAV1/ZAP as demonstrated by co-immunoprecipitation; collectively, evidence from subcellular localization, Co-IP, and velocity gradient centrifugation links both proteins to the RNA exosome complex for retrotransposon control. |
Co-immunoprecipitation, velocity gradient centrifugation, co-localization microscopy |
PLoS genetics |
Medium |
37405998
|
| 2023 |
KHNYN's nuclear export signal (NES) in its CUBAN domain is required for its cytoplasmic localization and interaction with ZAP; deletion or mutation of the NES increased KHNYN nuclear localization and decreased its interaction with ZAP, reducing antiviral activity against retroviruses. |
Co-immunoprecipitation, subcellular localization assay, antiviral activity assay, CUBAN domain deletion and NES mutagenesis |
Journal of virology |
Medium |
36633408
|
| 2025 |
Porcine ZAP long isoform (pZAPL), encoded by ZC3HAV1, inhibits PCV2 replication by targeting ORF1, ORF2 and ORF3 mRNAs; dual luciferase and RNA immunoprecipitation analyses confirmed direct binding to these viral mRNAs and showed pZAPL overexpression impacts their mRNA stability. pZAPL shows stronger antiviral activity than pZAPS against PCV2. |
Dual luciferase reporter assay, RNA immunoprecipitation, mRNA stability assay, overexpression |
Veterinary microbiology |
Medium |
41076738
|
| 2021 |
ZC3HAV1 directly binds to KRAS by immunoprecipitation and positively regulates KRAS expression, activating the MAPK signaling pathway (increasing p-ERK levels); knockdown of KRAS attenuated ZC3HAV1-mediated promotion of proliferation and invasion in pancreatic cancer cells. |
Co-immunoprecipitation, siRNA knockdown (KRAS), overexpression, Western blot (p-ERK), cell proliferation and invasion assay |
Aging |
Low |
34319912
|