E6 early regulatory protein (IPR001334)

Short name: E6

Family relationships



The papillomavirus E6 oncoproteins are small zinc-binding proteins that share a conserved zinc-binding CXXC motif and do not have identified intrinsic enzymatic activity. E6 proteins are thought to act as adapter proteins, thereby altering the function of E6-associated cellular proteins. This model for E6 function is best supported by observations of human papillomavirus type 16 (HPV-16) E6 (16E6), which can alter the metabolism of the p53 tumor suppressor through association with a cellular E3 ubiquitin ligase called E6AP. HPV-16 E6 interacts with an 18-amino-acid sequence in E6AP, and in an as yet ill-defined fashion the E6AP-16E6 complex binds to p53, inducing the ubiquitin-dependent degradation of the trimolecular complex. 16E6 apparently functions as an adapter protein in the complex with p53, since E6AP does not interact with p53 in the absence of E6 and since the degradation of p53 requires both E6 and E6AP [PMID: 26789255, PMID: 15664194, PMID: 17023019].

Despite the similarity in structure of the E6 oncoproteins, studies have indicated surprising biochemical diversity among E6 oncoproteins of different papillomavirus types. E6 from the cancer-associated human papillomaviruses (HPVs) complex with a cellular protein termed E6-AP and together with E6-AP bind to the p53 tumor suppressor protein thereby degrading p53 through ubiquitin-mediated proteolysis. E6 from the non-cancer-associated HPV types do not bind E6-AP or degrade p53. Bovine papilloma virus E6 (BE6) binds E6-AP but fails either to complex with p53 or to degrade associated proteins, implying that BE6 might transform cells through a mechanism different from that of the HPVs. In addition to targeting p53, E6 of both cancer-associated HPVs and BPV-1 have been shown to associate with a cellular-calcium-binding protein localized to the endoplasmic reticulum [PMID: 10623743, PMID: 9151888].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

No terms assigned in this category.

Cellular Component

GO:0042025 host cell nucleus

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.