Gene Name | TRIM25 |
HF Protein Name | E3 ubiquitin/ISG15 ligase TRIM25 |
HF Function | Required for the antiviral activity of zinc finger against viruses |
Uniprot ID | Q14258 |
Protein Sequence | View Fasta Sequence |
NCBI Gene ID | 7706 |
Host Factor (HF) Name in Paper | TRIM25 |
Gene synonyms | EFP RNF147 ZNF147 |
Ensemble Gene ID | ENSG00000121060 |
Ensemble Transcript | ENST00000316881;ENST00000537230 |
KEGG ID | Go to KEGG Database |
Gene Ontology ID(s) | GO:0003700, GO:0003723, GO:0004842, GO:0005654, GO:0005829, GO:0006511, GO:0006513, GO:0008270, GO:0016032, GO:0016579, GO:0016604, GO:0016874, GO:0019985, GO:0032480, GO:0033280, GO:0036503, GO:0043123, GO:0043627, GO:0045087, GO:0045296, GO:0046596, GO:0046597, GO:0051091, GO:0051092, GO:0051607, GO:0060333, GO:1902186, GO:1902187, GO:1904264, GO:1990830, |
MINT ID | Q14258 |
STRING | Click to see interaction map |
GWAS Analysis | Click to see gwas analysis |
OMIM ID | 600453 |
PANTHER ID | N.A. |
PDB ID(s) | 4CFG, 4LTB, 5EYA, 5FER, |
pfam ID | PF13765, PF00622, PF13445, |
Drug Bank ID | N.A., |
ChEMBL ID | N.A. |
Organism | Homo sapiens (Human) |
Virus Name | Sindbis virus |
Virus Short Name | SINV |
Order | Unassigned |
Virus Family | Togaviridae |
Virus Subfamily | N.A. |
Genus | Alphavirus |
Species | Sindbis virus |
Host | Human, mammals,mosquitoes and birds |
Cell Tropism | N.A. |
Associated Disease | Sindbis fever |
Mode of Transmission | By infected mosquito |
VIPR DB link | https://www.viprbrc.org/brc/vipr_allSpecies_search.spg?method=SubmitForm&decorator=toga |
ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/275/togaviridae |
Virus Host DB link | N.A. |
Paper Title | TRIM25 Is required for the antiviral activity of Zinc finger antiviral protein |
Author's Name | Xiaojiao Zheng, Xinlu Wang, Fan Tu, Qin Wang, Zusen Fan, Guangxia Gao |
Journal Name | JOURNAL OF VIROLOGY |
Pubmed ID | 28202764 |
Abstract | Zinc finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by binding to viral mRNAs and repressing the translation and/or promoting the degradation of target mRNA. In addition, ZAP regulates the expression of certain cellular genes. Here, we report that tripartite motif-containing protein 25 (TRIM25), a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 abolished ZAPs antiviral activity. The E3 ligase activity of TRIM25 is required for this regulation. TRIM25 mediated ZAP ubiquitination, but the ubiquitination of ZAP itself did not seem to be required for its antiviral activity. Downregulation of endogenous ubiquitin or overexpression of the deubiquitinase OTUB1 impaired ZAPs activity. We provide evidence indicating that TRIM25 modulates the target RNA binding activity of ZAP. These results uncover a mechanism by which the antiviralactivity of ZAP is regulated.IMPORTANCE ZAP is a host antiviral factor that specifically inhibits the replication of certain viruses, including HIV-1, Sindbis virus, and Ebola virus. ZAP binds directly to target mRNA, and it represses the translation and promotes the degradation of target mRNA. While the mechanisms by which ZAP posttranscriptionally inhibits target RNA expression have been extensively studied, how its antiviral activity is regulated is not very clear. Here, we report that TRIM25, a ubiquitin E3 ligase, is requiredfor the antiviral activity of ZAP. Downregulation of endogenous TRIM25 remarkably abolished ZAPs activity. TRIM25 is required for ZAP optimal binding to target mRNA. These results help us to better understand how the antiviral activity of ZAP is regulated. |
Used Model | 293TRex-ZAP and 293TRex-NZAP-Zeo cells |
DOI | 10.1128/JVI.00088-17 |