8.A.126.  The Nuclear Receptor Coactivator 7 (NCOA7) Family 

Interferons (IFNs) mediate cellular defence against viral pathogens by upregulation of IFN-stimulated genes whose products interact with viral components or alter cellular physiology to suppress viral replication. Among the IFN-stimulated genes that can inhibit influenza A virus are the myxovirus resistance 1 GTPase and IFN-induced transmembrane protein 3. (Doyle et al. 2018) demonstrated that the IFN-inducible 219-amino acid short isoform of the full length (942 aas) human nuclear receptor coactivator 7 (NCOA7; TC# 8.A.58.1.3) is an inhibitor of influenza A virus and other viruses that enter the cell by endocytosis.  NCOA7 interacts with the vacuolar H+-ATPase (V-ATPase), and its expression promotes cytoplasmic vesicle acidification, lysosomal protease activity and the degradation of endocytosed antigens. Step-wise dissection of the IAV entry pathway demonstrated that NCOA7 inhibits fusion of the viral and endosomal membranes and subsequent nuclear translocation of viral ribonucleoproteins (Doyle et al. 2018). Therefore, NCOA7 provides a mechanism for immune regulation of endolysosomal physiology that not only suppresses viral entry into the cytosol from this compartment but may also regulate other V-ATPase-associated cellular processes, such as physiological adjustments to nutritional status, or the maturation and function of antigen-presenting cells.

 


 

References:

Doyle, T., O. Moncorgé, B. Bonaventure, D. Pollpeter, M. Lussignol, M. Tauziet, L. Apolonia, M.T. Catanese, C. Goujon, and M.H. Malim. (2018). The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry. Nat Microbiol 3: 1369-1376.

Uytterhoeven, V., S. Kuenen, J. Kasprowicz, K. Miskiewicz, and P. Verstreken. (2011). Loss of skywalker reveals synaptic endosomes as sorting stations for synaptic vesicle proteins. Cell 145: 117-132.

Examples:

TC#NameOrganismal TypeExample
8.A.126.1.1

The human nuclear receptor coactivator 7 (NCOA7) of 942 aas.  It inhibits the V-type ATPase and therefore has multiple consequences, including inhibiting viral entry into vesicles; see family description (Doyle et al. 2018).

NOCOA7 of Homo sapiens

 
8.A.126.1.2

GTPase-activating protein (GAP), skywalker (Sky) of 587 aas, for Rab35 which regulates synaptic vesicle (SV) protein recycling and turnover at neuromuscular junctions (Uytterhoeven et al. 2011). The N-terminal domain of this protein show sequence similarity with family 8.A.87, but the C-terminal domain shows greater seqence similarity with 8.A.116.1.1.


GAP of Drosophila melanogaster (Fruit fly)

 
8.A.126.1.3

TBC1 domain family member 24 isoform X1 of 655 aas and 2 C-terminal TMSs.

TBC1 protein of Marmota flaviventris

 
8.A.126.1.4

Uncharacterized TLD family protein of 484 aas and 2 TMSs near the N-terminal domain.

UP of Trichomonas vaginalis