9kbo

Structural highlights

Function

SHFL_HUMAN Inhibits programmed -1 ribosomal frameshifting (-1PRF) of a variety of mRNAs from viruses, such as HIV1, and cellular genes, such as PEG10. Interacts with the -1PRF signal of target mRNA and translating ribosomes and causes premature translation termination at the frameshifting site (PubMed:30682371). Regulates HIV1 GAG-POL expression by inhibiting -1PRF (PubMed:30682371). Exhibits antiviral activity against dengue virus (DENV) and can inhibit the replication of all DENV serotypes. May block the protein translation of DENV RNA via its association with cellular mRNA-binding proteins and viral RNA. Also interrupts Zika virus replication by promoting viral NS3 degradation via a lysosome-dependent pathway (PubMed:32150556). Can also limit the replication of hepatitis C virus (HCV) by restricting formation of viral replication organelle, West Nile virus (WNV), Chikungunya virus (CHIKV), herpes simplex virus type 1 (HHV-1), herpes virus type 8 (HHV-8) and human adenovirus (PubMed:26735137, PubMed:27974568, PubMed:30944177, PubMed:32294532). Binds nucleic acids with a higher affinity for ssRNA and ssDNA than for dsDNA (PubMed:27974568).^{[1] [2] [3] [4] [5] [6]} Isoform 4 does not inhibit programmed ribosomal frameshifting (-1PRF). Does not bind to ribosomes.^[7]

References

1. ↑ Suzuki Y, Chin WX, Han Q, Ichiyama K, Lee CH, Eyo ZW, Ebina H, Takahashi H, Takahashi C, Tan BH, Hishiki T, Ohba K, Matsuyama T, Koyanagi Y, Tan YJ, Sawasaki T, Chu JJ, Vasudevan SG, Sano K, Yamamoto N. Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication. PLoS Pathog. 2016 Jan 6;12(1):e1005357. PMID:26735137 doi:10.1371/journal.ppat.1005357
2. ↑ Balinsky CA, Schmeisser H, Wells AI, Ganesan S, Jin T, Singh K, Zoon KC. IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue Virus, Interacts with MOV10. J Virol. 2017 Feb 14;91(5):e01606-16. PMID:27974568 doi:10.1128/JVI.01606-16
3. ↑ Wang X, Xuan Y, Han Y, Ding X, Ye K, Yang F, Gao P, Goff SP, Gao G. Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting. Cell. 2019 Jan 24;176(3):625-635.e14. PMID:30682371 doi:10.1016/j.cell.2018.12.030
4. ↑ Rodriguez W, Srivastav K, Muller M. C19ORF66 Broadly Escapes Virus-Induced Endonuclease Cleavage and Restricts Kaposi's Sarcoma-Associated Herpesvirus. J Virol. 2019 May 29;93(12):e00373-19. PMID:30944177 doi:10.1128/JVI.00373-19
5. ↑ Wu Y, Yang X, Yao Z, Dong X, Zhang D, Hu Y, Zhang S, Lin J, Chen J, An S, Ye H, Zhang S, Qiu Z, He Z, Huang M, Wei G, Zhu X. C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. PLoS Negl Trop Dis. 2020 Mar 9;14(3):e0008083. PMID:32150556 doi:10.1371/journal.pntd.0008083
6. ↑ Kinast V, Plociennikowska A, Anggakusuma, Bracht T, Todt D, Brown RJP, Boldanova T, Zhang Y, Brüggemann Y, Friesland M, Engelmann M, Vieyres G, Broering R, Vondran FWR, Heim MH, Sitek B, Bartenschlager R, Pietschmann T, Steinmann E. C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle. J Hepatol. 2020 Sep;73(3):549-558. PMID:32294532 doi:10.1016/j.jhep.2020.03.047
7. ↑ Wang X, Xuan Y, Han Y, Ding X, Ye K, Yang F, Gao P, Goff SP, Gao G. Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting. Cell. 2019 Jan 24;176(3):625-635.e14. PMID:30682371 doi:10.1016/j.cell.2018.12.030