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8.B.25 The Viral Glycoprotein N (GN; UL49.5) TAP Inhibitor (GN-I) Family

TAP translocates virus-derived peptides from the cytosol into the endoplasmic reticulum, where the peptides are loaded onto MHC class I molecules. This process is crucial for the detection of virus-infected cells by CTL that recognize the MHC class I-peptide complexes at the cell surface (Verweij et al. 2008). The varicellovirus bovine herpesvirus 1 encodes a protein, UL49.5 or GN-1, that acts as a potent inhibitor of TAP (TC# 3.A.1.209.1). UL49.5 acts in two ways: 1) by blocking conformational changes of TAP required for the translocation of peptides into the endoplasmic reticulum, and 2) by targeting TAP1 and TAP2 for proteasomal degradation. TAP is the target of UL49.5 within the peptide-loading complex. The presence of TAP1 and TAP2 is required for efficient interaction with UL49.5. The 6+6 trans-membrane core complex of TAP is sufficient for UL49.5 to interact with TAP and block its function.  However, UL49.5-induced inhibition of peptide transport was most efficient in cells expressing full-length TAP1 and TAP2. Inhibition by UL49.5 appeared to be independent of the presence of other peptide-loading complex components, including tapasin (Verweij et al. 2008).

References associated with 8.B.25 family:

Karska, N., M. Graul, E. Sikorska, I. Zhukov, M.J. Ślusarz, F. Kasprzykowski, A.D. Lipińska, and S. Rodziewicz-Motowidło. (2019). Structure determination of UL49.5 transmembrane protein from bovine herpesvirus 1 by NMR spectroscopy and molecular dynamics. Biochim. Biophys. Acta. Biomembr 1861: 926-938. 30772281
Verweij, M.C., D. Koppers-Lalic, S. Loch, F. Klauschies, H. de la Salle, E. Quinten, P.J. Lehner, A. Mulder, M.R. Knittler, R. Tampé, J. Koch, M.E. Ressing, and E.J. Wiertz. (2008). The varicellovirus UL49.5 protein blocks the transporter associated with antigen processing (TAP) by inhibiting essential conformational transitions in the 6+6 transmembrane TAP core complex. J Immunol 181: 4894-4907. 18802093