20210801 20180803 20180328 20210801 IID90014 Protein E6 Human papillomavirus type 51 151 P26554 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. 0 0 0 0 E6 VE6_HPV51 MFEDKRERPRTLHELCEALNVSMHNIQVVCVYCKKELCRADVYNVAFTEIKIVYRDNNPYAVCKQCLLFYSKIREYRRYSRSVYGTTLEAITKKSLYDLSIRCHRCQRPLGPEEKQKLVDEKKRFHEIAGRWTGQCANCWQRTRQRNETQV 1 2m3mB 142 151 order 2 2 2m3lA 80 151 order 1 3 141 151 disorder 3 4 2m3lA 145 151 high_rmsd 1 1 2m3l NMR 23638119 A.MISCHO,O.OHLENSCHLAGER,P.HORTSCHANSKY,R.RAMACHANDRAN,M.GORLACH 2013 PLOS ONE 8 62584 nmr 2m3l A 80 151 100 0 1 2m3l_1 2633 Monomer monomer 2m3lA P26554 IID90014 2 2m3m NMR 23638119 A.MISCHO,O.OHLENSCHLAGER,P.HORTSCHANSKY,R.RAMACHANDRAN,M.GORLACH 2013 PLOS ONE 8 62584 nmr 2m3m B 142 151 100 0 1 2m3m_1 2634 Hetero dimer 2m3mB P26554 IID90014 2m3mA Q12959 IID00513 2m3mB-2m3mA 3 NMR 23638119 A.MISCHO,O.OHLENSCHLAGER,P.HORTSCHANSKY,R.RAMACHANDRAN,M.GORLACH 2013 PLOS ONE 8 62584 ProS 1 verified 1 141 151 3 141 151 1-141 142-151 6-146 1-5,147-151 147-151