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Hepatitis C Virus, HCV-P7, of 63 aas and 2 TMSs (Clarke et al., 2006).  It's mechanism and  function have been investigated in considerable detail (Gan et al. 2014).  Histidine-17, which faces the lumen of the pore when protonated, allows Cl- entry, but deprotonation also allows Ca2+ entry.  Imposition of voltage creates a Cl- current (Wang et al. 2014). The structure and dual pore/ion channel activity of p7 of different HCV genotypes have been reviewed (Madan and Bartenschlager 2015). It may transport protons (Scott and Griffin 2015); it's structure has been determined by NMR (Montserret et al. 2010) and by electron microscopy (Luik et al. 2009).  The p7 N-terminal helical region is critical for E2/p7 processing, protein-protein interactions, ion channel activity, and infectious HCV production (Scull et al. 2015). HCV p7 is released from the viral polyprotein through cleavage at E2-p7 and p7-NS2 junctions by signal peptidase, but also exists as an E2p7 precursor. The retarded E2p7 precursor cleavage is essential to regulate the intracellular and secreted levels of E2 through p7-mediated modulation of the cell secretory pathway (Denolly et al. 2017).  Chen et al. 2018 provided evidence that the oligomeric channel is a cation-selective hexamer. The his-9 in the hexameric model forms a first gate, acting as a selectivity filter for cations. while valines form a second gate, serving as a hydrophobic filter for dehydrated cations. The binding pocket for the channel blockers, amantadine and rimantadine, is composed of residues 20-26 in H2 helix and 52-60 in H3 helix (Ying et al. 2018). Two of the best inhibitors were ARD87 and ARD112 (Wei et al. 2021).

Accession Number:Q5QRI8
Protein Name:P7 aka Polyprotein
Molecular Weight:6778.00
Species:Hepatitis C virus subtype 1b [31647]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Secreted1
Substrate chloride, cation, calcium(2+), 17beta-hydroxy-5alpha-androstan-3-one

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References (1)

[1] “Hepatitis C Virus p7 membrane protein quasispecies variability in chronically infected patients treated with interferon and ribavirin, with or without amantadine.”  Castelain   17177298

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FASTA formatted sequence
61:	AYA