Recombinant Human papillomavirus type 16 Probable protein E5 (E5) Protein

Function

Acts to keep host cells in a proliferation-competent state upon differentiation. Enhances host epidermal growth factor receptor (EGFR) activation after stimulation by EGF by inhibiting EGFR internalization. Induces a redistribution of host caveolin-1 and glycosphingolipid (ganglioside GM1) components of lipid rafts to the plasma membrane. Since GM1s inhibit cytotoxic T-lymphocytes, block immune synapse formation, and enhance proliferative signaling by the EGFR, E5 may enhance immune evasion and cell proliferation via a common mechanism. E5 also alters endosomal pH by interacting with the vacuolar H+-ATPase, which is a proton pump responsible for acidifying cellular organelles. Additionally, E5 prevents transport of the major histocompatibility class I to the cell surface and retains the complex in the Golgi apparatus. Binds and prevents host ZNT1-TMC6-TMC8 complex-mediated inhibition of transcription factors induced by zinc and cytokines in keratinocytes (PubMed:18158319)

Subcellular Location

Host membrane (Multi-pass membrane protein); Host endoplasmic reticulum membrane; Host Golgi apparatus

Subunit

Homooligomer. Interacts with host BCAP31; this interaction seems to correlate with the ability of HPV-positive differentiated cells to remain competent for proliferation. Interacts with host ATP6V0C. Interacts (via N-terminus) with host HLA class I heavy chains A1, A2, A3 and B8; these interactions inhibit host immune response by sequestering MHC class I peptides to the host Golgi apparatus. Interacts with host TMC6, TMC8 and ZNT1; the interaction blocks their negative regulation (PubMed:18158319)

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• Rodriguez M.I. et al. Binding of human papillomavirus 16 E5 to the 16 kDa subunit c (proteolipid) of the vacuolar H+-ATPase can be dissociated from the E5-mediated epidermal growth factor receptor overactivation. — Oncogene (2000)
• Gieswein C.E. et al. Oligomerization of the E5 protein of human papillomavirus type 16 occurs through multiple hydrophobic regions. — Virology (2003)
• Disbrow G.L. et al. Endoplasmic reticulum-localized human papillomavirus type 16 E5 protein alters endosomal pH but not trans-Golgi pH. — J. Virol. (2005)
• Ashrafi G.H. et al. E5 protein of human papillomavirus 16 downregulates HLA class I and interacts with the heavy chain via its first hydrophobic domain. — Int. J. Cancer (2006)