Target Information
Target General Information | Top | |||||
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Target ID |
T53811
(Former ID: TTDI02206)
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Target Name |
Human papillomavirus protein E6 (HPV E6)
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Synonyms |
Protein E6; E6
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Gene Name |
HPV E6
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Cervical intraepithelial neoplasia [ICD-11: 2E66] | |||||
2 | Dysplasia [ICD-11: LB30-LD2F] | |||||
Function |
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 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/E6P targets several other substrates to degradation via the proteasome including host NFX1- 91, 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 Bak, 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.
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BioChemical Class |
Papillomaviridae E protein
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UniProt ID | ||||||
Sequence |
MHQKRTAMFQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQLLRREVYDFAFRDLCIV
YRDGNPYAVCDKCLKFYSKISEYRHYCYSLYGTTLEQQYNKPLCDLLIRCINCQKPLCPE EKQRHLDKKQRFHNIRGRWTGRCMSCCRSSRTRRETQL Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | VGX-3100 | Drug Info | Phase 3 | Cervical Intraepithelial neoplasia | [2] | |
2 | Tipapkinogene sovacivec | Drug Info | Phase 2 | Cervical Intraepithelial neoplasia | [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | VGX-3100 | Drug Info | [1] | |||
2 | Tipapkinogene sovacivec | Drug Info | [4], [5] |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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Chemical Structure based Activity Landscape of Target | Top |
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Target Affiliated Biological Pathways | Top | |||||
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PID Pathway | [+] 1 PID Pathways | + | ||||
1 | Regulation of Telomerase |
References | Top | |||||
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REF 1 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 3 | ClinicalTrials.gov (NCT01022346) A Study of RO5217790 (HPV Targeted Immunotherapy) in Patients With High Grade Cervical Intraepithelial Neoplasia Associated With High Risk HPV Infection. U.S. National Institutes of Health. | |||||
REF 4 | Immune therapy for human papillomaviruses-related cancers | |||||
REF 5 | Therapeutic peptides: new arsenal against drug resistant pathogens. Curr Pharm Des. 2014;20(5):771-92. |
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