Q9IZG6 · Q9IZG6_HPV58
- ProteinProtein E6
- GeneE6
- StatusUniProtKB unreviewed (TrEMBL)
- Organism
- Amino acids149 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
Function
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 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 NFX-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 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.
Miscellaneous
Belongs to the high risk human alphapapillomavirus family. The cancer-causing human papillomavirus E6 protein has a unique carboxy terminal PDZ domain containing substrate.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | host cell cytoplasm | |
Cellular Component | host cell nucleus | |
Molecular Function | DNA binding | |
Molecular Function | metal ion binding | |
Molecular Function | PDZ domain binding | |
Biological Process | DNA-templated transcription | |
Biological Process | regulation of DNA-templated transcription | |
Biological Process | symbiont-mediated perturbation of host apoptosis | |
Biological Process | symbiont-mediated perturbation of host ubiquitin-like protein modification | |
Biological Process | symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity | |
Biological Process | symbiont-mediated suppression of host type I interferon-mediated signaling pathway | |
Biological Process | virus-mediated perturbation of host defense response |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameProtein E6
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageViruses > Monodnaviria > Shotokuvirae > Cossaviricota > Papovaviricetes > Zurhausenvirales > Papillomaviridae > Firstpapillomavirinae > Alphapapillomavirus > Alphapapillomavirus 9
- Virus hosts
Accessions
- Primary accessionQ9IZG6
Proteomes
Subcellular Location
Expression
Keywords
- Developmental stage
Interaction
Subunit
Forms homodimers. Interacts with ubiquitin-protein ligase UBE3A/E6-AP and thus forms a complex with human TP53. Interacts with human NFX1 and MAGI3. Interacts with human IRF3; this interaction inhibits the establishment of antiviral state. Interacts with human TYK2; this interaction inhibits JAK-STAT activation by interferon alpha. Interacts with host DLG1; this interaction leads to the proteasomal degradation of DLG1.
Structure
Family & Domains
Sequence
- Sequence statusComplete
- Length149
- Mass (Da)17,780
- Last updated2000-10-01 v1
- MD5 Checksum2A51AA278EAC5430B7584DCC3039AAC2
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF234530 EMBL· GenBank· DDBJ | AAF60306.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF478152 EMBL· GenBank· DDBJ | AAL85397.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF478154 EMBL· GenBank· DDBJ | AAL85399.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF478163 EMBL· GenBank· DDBJ | AAL85408.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ385262 EMBL· GenBank· DDBJ | ACJ13457.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ385263 EMBL· GenBank· DDBJ | ACJ13465.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ385265 EMBL· GenBank· DDBJ | ACJ13481.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ385266 EMBL· GenBank· DDBJ | ACJ13489.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ385268 EMBL· GenBank· DDBJ | ACJ13505.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407193 EMBL· GenBank· DDBJ | ACK37631.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407194 EMBL· GenBank· DDBJ | ACK37636.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407195 EMBL· GenBank· DDBJ | ACK37646.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407199 EMBL· GenBank· DDBJ | ACK37664.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407201 EMBL· GenBank· DDBJ | ACK37678.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407203 EMBL· GenBank· DDBJ | ACK37686.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407209 EMBL· GenBank· DDBJ | ACK37736.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407212 EMBL· GenBank· DDBJ | ACK37756.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407214 EMBL· GenBank· DDBJ | ACK37770.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407215 EMBL· GenBank· DDBJ | ACK37780.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FJ407217 EMBL· GenBank· DDBJ | ACK37800.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
JX401164 EMBL· GenBank· DDBJ | AFO70366.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
JX401171 EMBL· GenBank· DDBJ | AFO70373.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
JX401172 EMBL· GenBank· DDBJ | AFO70374.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
JX401173 EMBL· GenBank· DDBJ | AFO70375.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
JX401175 EMBL· GenBank· DDBJ | AFO70377.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
JX401176 EMBL· GenBank· DDBJ | AFO70378.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
JX401182 EMBL· GenBank· DDBJ | AFO70384.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
JX401184 EMBL· GenBank· DDBJ | AFO70386.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
KC190276 EMBL· GenBank· DDBJ | AFY09735.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
KC860270 EMBL· GenBank· DDBJ | AGQ21857.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
KX354761 EMBL· GenBank· DDBJ | ANM72850.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
KX354762 EMBL· GenBank· DDBJ | ANM72852.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
KX354766 EMBL· GenBank· DDBJ | ANM72860.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
KX354767 EMBL· GenBank· DDBJ | ANM72862.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
KY225918 EMBL· GenBank· DDBJ | ASQ41702.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
KY225919 EMBL· GenBank· DDBJ | ASQ41710.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MF741323 EMBL· GenBank· DDBJ | AWA45981.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MF741327 EMBL· GenBank· DDBJ | AWA45989.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MF741331 EMBL· GenBank· DDBJ | AWA45997.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MH348919 EMBL· GenBank· DDBJ | AZC11041.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MH348922 EMBL· GenBank· DDBJ | AZC11047.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MH348927 EMBL· GenBank· DDBJ | AZC11057.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MH348929 EMBL· GenBank· DDBJ | AZC11061.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MH348932 EMBL· GenBank· DDBJ | AZC11067.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MH348933 EMBL· GenBank· DDBJ | AZC11069.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MK343263 EMBL· GenBank· DDBJ | QHI05744.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MK343264 EMBL· GenBank· DDBJ | QHI05745.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
MK343265 EMBL· GenBank· DDBJ | QHI05746.1 EMBL· GenBank· DDBJ | Genomic DNA |