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Protein

Protein E6

Gene

E6

Organism
Human papillomavirus type 18
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional transactivator. Binds double-stranded DNA (By similarity). Has transforming activity. Inactivates, with E6-AP ubiquitin-protein ligase, the human p53/TP53 tumor suppressor protein by targeting it to degradation. Binds and targets human MUPP1/MPDZ protein to degradation. Those two functions presumably contribute to transforming activity. Interaction with human FBLN1 protein also seems to be linked to cell transformation.By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri32 – 6837Sequence analysisAdd
BLAST
Zinc fingeri105 – 14137Sequence analysisAdd
BLAST

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • zinc ion binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host IRF3 by virus, Inhibition of host RLR pathway by virus, Inhibition of host TYK2 by virus, Modulation of host PP1 activity by virus, Transcription, Transcription regulation, Viral immunoevasion

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Protein E6
Gene namesi
Name:E6
OrganismiHuman papillomavirus type 18
Taxonomic identifieri333761 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stagePapillomaviridaeAlphapapillomavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000009109 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi156 – 1583TQV → DQA: Complete loss of binding to MPDZ protein. 1 Publication
Mutagenesisi158 – 1581V → A: Complete loss of binding to MPDZ protein. 1 Publication

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 158158Protein E6PRO_0000133338Add
BLAST

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Forms a complex with E6-AP ubiquitin-protein ligase which interacts with human P53. Binds to human FBLN1, MAGI3 and MPDZ.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DLG1Q129593EBI-1186926,EBI-357481From a different organism.
Dlg1Q811D02EBI-1186926,EBI-514290From a different organism.
MAGI1Q96QZ73EBI-1186926,EBI-924464From a different organism.
MCM7P339932EBI-1186926,EBI-355924From a different organism.
PTPN3P260454EBI-1186926,EBI-1047946From a different organism.
SCRIBQ141603EBI-1186926,EBI-357345From a different organism.
TP53P046372EBI-1186926,EBI-366083From a different organism.
UBE3AQ050863EBI-1186926,EBI-954357From a different organism.

Protein-protein interaction databases

DIPiDIP-44730N.
IntActiP06463. 15 interactions.
MINTiMINT-96616.

Structurei

Secondary structure

1
158
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi155 – 1584Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2I04X-ray2.15C/D152-158[»]
2I0IX-ray2.80D/E/F152-158[»]
2I0LX-ray2.31C/D152-158[»]
4JORX-ray1.34C/D149-158[»]
ProteinModelPortaliP06463.
SMRiP06463. Positions 82-146.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06463.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi155 – 1584PDZ-bindingBy similarity

Sequence similaritiesi

Belongs to the papillomaviridae E6 protein family.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri32 – 6837Sequence analysisAdd
BLAST
Zinc fingeri105 – 14137Sequence analysisAdd
BLAST

Keywords - Domaini

Zinc-finger

Family and domain databases

InterProiIPR001334. E6.
[Graphical view]
PfamiPF00518. E6. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P06463-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARFEDPTRR PYKLPDLCTE LNTSLQDIEI TCVYCKTVLE LTEVFEFAFK
60 70 80 90 100
DLFVVYRDSI PHAACHKCID FYSRIRELRH YSDSVYGDTL EKLTNTGLYN
110 120 130 140 150
LLIRCLRCQK PLNPAEKLRH LNEKRRFHNI AGHYRGQCHS CCNRARQERL

QRRRETQV
Length:158
Mass (Da):18,872
Last modified:January 1, 1988 - v1
Checksum:i5BCF13CF43D157FA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti22 – 221N → S in AAA46946 (PubMed:3023067).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04354 Genomic DNA. Translation: CAA27879.1.
X05015 Genomic DNA. Translation: CAA28664.1.
M20325 mRNA. Translation: AAA99514.1.
M26798 Genomic DNA. Translation: AAA46946.1.
X04773 Genomic DNA. Translation: CAA28466.1.
PIRiA26165. W6WL18.
RefSeqiNP_040310.1. NC_001357.1.

Genome annotation databases

GeneIDi1489088.
KEGGivg:1489088.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04354 Genomic DNA. Translation: CAA27879.1.
X05015 Genomic DNA. Translation: CAA28664.1.
M20325 mRNA. Translation: AAA99514.1.
M26798 Genomic DNA. Translation: AAA46946.1.
X04773 Genomic DNA. Translation: CAA28466.1.
PIRiA26165. W6WL18.
RefSeqiNP_040310.1. NC_001357.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2I04X-ray2.15C/D152-158[»]
2I0IX-ray2.80D/E/F152-158[»]
2I0LX-ray2.31C/D152-158[»]
4JORX-ray1.34C/D149-158[»]
ProteinModelPortaliP06463.
SMRiP06463. Positions 82-146.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-44730N.
IntActiP06463. 15 interactions.
MINTiMINT-96616.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1489088.
KEGGivg:1489088.

Miscellaneous databases

EvolutionaryTraceiP06463.

Family and domain databases

InterProiIPR001334. E6.
[Graphical view]
PfamiPF00518. E6. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Nucleotide sequence and comparative analysis of the human papillomavirus type 18 genome. Phylogeny of papillomaviruses and repeated structure of the E6 and E7 gene products."
    Cole S.T., Danos O.
    J. Mol. Biol. 193:599-608(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The expression of human papillomavirus type 18 E6 protein in bacteria and the production of anti-E6 antibodies."
    Matlashewski G., Banks L., Wu-Liao J., Spence P., Pim D., Crawford L.
    J. Gen. Virol. 67:1909-1916(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Nucleotide sequences of cDNAs for human papillomavirus type 18 transcripts in HeLa cells."
    Inagaki Y., Tsunokawa Y., Takebe N., Nawa H., Nakanishi S., Terada M., Sugimura T.
    J. Virol. 62:1640-1646(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes."
    Schneider-Gaedicke A., Schwarz E.
    EMBO J. 5:2285-2292(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "Identification of early proteins of the human papilloma viruses type 16 (HPV 16) and type 18 (HPV 18) in cervical carcinoma cells."
    Seedorf K., Oltersdorf T., Kraemer G., Roewekamp W.
    EMBO J. 6:139-144(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. "E6 protein of human papillomavirus type 18 binds zinc."
    Grossman S.R., Laimins L.A.
    Oncogene 4:1089-1093(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: ZINC-BINDING.
  7. "The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53."
    Scheffner M., Huibregtse J.M., Vierstra R.D., Howley P.M.
    Cell 75:495-505(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN TP53 PROTEIN.
  8. "Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins."
    Lee S.S., Glaunsinger B., Mantovani F., Banks L., Javier R.T.
    J. Virol. 74:9680-9693(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN MPDZ, MUTAGENESIS OF 156-THR--VAL-158 AND VAL-158.
  9. "Interaction of oncogenic papillomavirus E6 proteins with fibulin-1."
    Du M., Fan X., Hong E., Chen J.J.
    Biochem. Biophys. Res. Commun. 296:962-969(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN FBLN1, INHIBITION OF E6-MEDIATED TRANSFORMATION.
  10. "Oncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation."
    Thomas M., Laura R., Hepner K., Guccione E., Sawyers C., Lasky L., Banks L.
    Oncogene 21:5088-5096(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN MAGI3.
  11. "Role of the PDZ domain-binding motif of the oncoprotein E6 in the pathogenesis of human papillomavirus type 31."
    Lee C., Laimins L.A.
    J. Virol. 78:12366-12377(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN MAGI3.
  12. "HPV E6 specifically targets different cellular pools of its PDZ domain-containing tumour suppressor substrates for proteasome-mediated degradation."
    Massimi P., Gammoh N., Thomas M., Banks L.
    Oncogene 23:8033-8039(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN MAGI3.

Entry informationi

Entry nameiVE6_HPV18
AccessioniPrimary (citable) accession number: P06463
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: May 11, 2016
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.