Human papillomavirus type 6 E6 protein (HPV-6 E6)

Human papillomavirus type 6 E6 protein is a small zinc-binding protein of approximately 150 amino acids that forms two distinct zinc-finger domains[3]. It is classified as a low-risk HPV E6 protein, distinguishing it from high-risk variants found in HPV-16 and HPV-18 that are strongly associated with cancer. Unlike high-risk E6 proteins, HPV-6 E6 lacks a PDZ binding motif (PBM) at its carboxy-terminus[5]. This structural difference explains why low-risk E6 proteins cannot interact with PDZ domain-containing proteins that high-risk variants target. However, like high-risk E6 proteins, HPV-6 E6 can bind to E6-associated protein (E6AP)[5]. A significant function of HPV-6 E6 is its ability to degrade the PDZ-adapter protein NHERF1 through an E6AP-dependent mechanism, which activates the Wnt/β-catenin pathway[5]. This activity is conserved across both high and low-risk HPV types, suggesting its importance in viral function. HPV-6 E6 also interferes with host immune responses by inhibiting interferon signaling pathways, which contributes to persistent HPV infections[3]. Unlike high-risk E6 proteins, HPV-6 E6 does not interact with the tumor suppressor p53[5], which explains its lower oncogenic potential. The protein has a molecular weight of approximately 21 kDa[7] and contains structural elements that enable it to interact with various cellular factors, allowing it to manipulate normal cellular pathways to enhance viral replication within host cells[3].

Other names

Low-risk HPV E6 proteinHPV6 E6 protein

E6AP-dependent degradation of NHERF1