6jh1

Structural highlights

Function

[NS1_INBLE] Binds and inhibits the ubiquitin-like protein G1P2/ISG15, which is an early antiviral protein. Inhibits IRF-3 nuclear translocation and activation. Inhibits IFN-beta promoter activation; this inhibition is not dsRNA-binding dependent Prevents EIF2AK2/PKR activation, either by binding double strand RNA or by interacting directly with EIF2AK2/PKR. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells.^[1] [ISG15_BOVIN] Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Exhibits antiviral activity towards both DNA and RNA viruses. The secreted form of ISG15 can: induce natural killer cell proliferation, augment lymphokine-activated-killer (LAK) activity, induce dendritic cell maturation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity (By similarity). The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (By similarity). In response to IFN-tau secreted by the conceptus, may ligate to and regulate proteins involved in the release of prostaglandin F2-alpha (PGF), and thus prevent lysis of the corpus luteum and maintain the pregnancy (PubMed:9546718).[UniProtKB:P05161][UniProtKB:Q64339]^[2]

References

1. ↑ Donelan NR, Dauber B, Wang X, Basler CF, Wolff T, Garcia-Sastre A. The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation. J Virol. 2004 Nov;78(21):11574-82. PMID:15479798 doi:78/21/11574
2. ↑ Johnson GA, Austin KJ, Van Kirk EA, Hansen TR. Pregnancy and interferon-tau induce conjugation of bovine ubiquitin cross-reactive protein to cytosolic uterine proteins. Biol Reprod. 1998 Apr;58(4):898-904. PMID:9546718