1.A.97 The Human Papillomavirus type 16 E5 Viroporin (HPV-E5) Family High-risk human papillomavirus type 16 (HPV16) is the primary causative agent of cervical cancer. Cellular transformation is mediated directly by the expression of viral oncogenes,one of which, E5, subverts cellular proliferation and immune recognition processes. HPV16 E5 is an oligomeric channel-forming protein, placing it within the virus-encoded 'viroporin' family (Wetherill et al. 2012). E5 forms oligomeric assemblies of a defined luminal diameter and stoichiometry in membranous environments, and such channels mediate H⁺ transport and fluorescent dye release from liposomes. Hexameric E5 channel stoichiometry was suggested by native PAGE studies. A specific small-molecule E5 inhibitor, capable of both abrogating channel activity in vitro and reducing E5-mediated effects on cell signaling pathways was identified (Wetherill et al. 2012).
References:
Mahato, D.R. and W.B. Fischer. (2016). Weak Selectivity Predicted for Modeled Bundles of Viral Channel-Forming Protein E5 of Human Papillomavirus-16. J Phys Chem B 120: 13076-13085.
Mahato, D.R. and W.B. Fischer. (2018). Specification of binding modes between a transmembrane peptide mimic of ATP6V0C and polytopic E5 of human papillomavirus-16. J Biomol Struct Dyn 36: 2618-2627.
Scott, C. and S. Griffin. (2015). Viroporins: structure, function and potential as antiviral targets. J Gen Virol 96: 2000-2027.
Wetherill, L.F., K.K. Holmes, M. Verow, M. Müller, G. Howell, M. Harris, C. Fishwick, N. Stonehouse, R. Foster, G.E. Blair, S. Griffin, and A. Macdonald. (2012). High-risk human papillomavirus E5 oncoprotein displays channel-forming activity sensitive to small-molecule inhibitors. J. Virol. 86: 5341-5351.
Examples:
TC#	Name	Organismal Type	Example
1.A.97.1.1	The E5 viroporin protein of 83 aas and 3 TMSs (Wetherill et al. 2012). It forms hexameric channels with TMS2 lining the pore, creating a water column through which ions and small molecules, including H⁺, can pass fairly non-specifically (Mahato and Fischer 2016). A "snapshot" structure of the putative open pore of the protein bundle suggested the proposed low channel selectivity (Mahato and Fischer 2016). The protein is involved in signalling and protein trafficking. Its gene may be an oncogene (Scott and Griffin 2015).The protein also interacts with the fourth TMS of the 16 kDa c subunit of the human vacuolar H⁺-ATPase (Mahato and Fischer 2018).		E5 protein of high-risk human papillomavirus (cervical cancer-causing) type 16 (HPV16)

1.A.97.1.2	Human papillomavirus type 82 E5 protein of 84 aas and 3 TMSs.		E5 of human papillomavirus type 82

1.A.97.1.3	Human papillomavirus type 39 E5 protein of 72 aas and 2 TMSs.		E5 protein of human papillomavirus type 39

1.A.97.1.4	Common chimpanzee papillomavirus 1 E5 protein of 94 aas and 3 TMSs		E5 protein of the common chimpanzee papillomavirus 1

1.A.97.1.5	Human papillomavirus type 6 E5a protein of 91 aas and 3 TMSs.		E5a protein of human papillomavirus type 6