Figure 7.

ORFV ANKR/F-box proteins—sequestering FIH to facilitate HIF signalling. (A) The overall percent amino acid identity between each of the ORFV ANKR/F-box proteins was determined using the EMBOSS Needle alignment tool using default settings. (B) Multiple ORFV ANKR/F-box proteins bind and are hydroxylated on asparagine (Asn) residues by the cellular enzyme factor-inhibiting HIF (FIH). Note: the ability of the different proteins to bind and be hydroxylated by FIH varies. The ORFV ANKR/F-box proteins are thought to activate HIF transcriptional activity by binding and sequestering FIH, perhaps in the nucleus. This prevents the asparaginyl hydroxylation of HIF-1α which would otherwise impair HIF-1α transcriptional activity by blocking the recruitment of the transcriptional coactivators p300/CBP.