Reviewed
Homo Sapiens (Human) [TaxID: 9606]
E6
Protein E6
Human Papillomavirus Type 33
Viruses> DsDNA Viruses> No RNA Stage> Papillomaviridae> Alphapapillomavirus> Alphapapillomavirus 9> Human Papillomavirus Type 33
Not Available
Various pathway(s) in which protein is involved
Not Available
Not Available
MFQDTEEKPRTLHDLCQALETTIHNIELQCVECKKPLQRSEVYDFAFADLTVVYREGNPFGICKLCLRFLSKISEYRHYNYSVYGNTLEQTVKKPLNEIL
IRCIICQRPLCPQEKKRHVDLNKRFHNISGRWAGRCAACWRSRRRETAL
IRCIICQRPLCPQEKKRHVDLNKRFHNISGRWAGRCAACWRSRRRETAL
149
Not Available
Not Available
01-01-1988
Evidence at protein level
| Amino Acid | Count | % Frequency | Amino Acid | Count | % Frequency |
|---|---|---|---|---|---|
| Alanine (A) | Leucine (L) | ||||
| Arginine (R) | Lysine (K) | ||||
| Asparagine (N) | Methionine (M) | ||||
| Aspartic Acid (D) | Phenylalanine (F) | ||||
| Cysteine (C) | Proline (P) | ||||
| Glutamine (Q) | Serine (S) | ||||
| Glutamic Acid (E) | Threonine (T) | ||||
| Glycine (G) | Tryptophan (W) | ||||
| Histidine (H) | Tyrosine (Y) | ||||
| Isoleucine (I) | Valine (V) |
| % Number of Residues in Helices | % Number of Residues in Strands | % Number of Residues in Coils |
|---|---|---|
♦This protein may be involved in the oncogenic potential of this virus (cervical neoplasia-associated virus).
♦ Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates with host UBE3A/E6-AP ubiquitin-protein ligase, and inactivates tumor suppressors TP53 and TP73 by targeting them to the 26S proteasome for degradation. In turn, DNA damage and chromosomal instabilities increase and lead to cell proliferation and cancer development. The complex E6/E6AP targets several other substrates to degradation via the proteasome including host DLG1 or NFX1, a repressor of human telomerase reverse transcriptase (hTERT). The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. Other cellular targets including BAK1, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. E6 also inhibits immune response by interacting with host IRF3 and TYK2. These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway.
♦ Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates with host UBE3A/E6-AP ubiquitin-protein ligase, and inactivates tumor suppressors TP53 and TP73 by targeting them to the 26S proteasome for degradation. In turn, DNA damage and chromosomal instabilities increase and lead to cell proliferation and cancer development. The complex E6/E6AP targets several other substrates to degradation via the proteasome including host DLG1 or NFX1, a repressor of human telomerase reverse transcriptase (hTERT). The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. Other cellular targets including BAK1, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. E6 also inhibits immune response by interacting with host IRF3 and TYK2. These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway.
Not Available
GO:0003677 ; GO:0006351 ; GO:0006355 ; GO:0030430 ; GO:0039526 ;
GO:0039548 ; GO:0042025 ; GO:0046872
GO:0039548 ; GO:0042025 ; GO:0046872
Host cytoplasm . Host nucleus .
Not Available
MOTIF 147 149 PDZ-binding domain.
Predicted/Modelled
Not Available
Not Available
Protein couldn't be modeled using I-Tasser and Raptor X because of length constraints of the software.
Not Available
- Million Molecules
Best 20 Hit molecules
Not Available