VE5_HPV16
ID VE5_HPV16 Reviewed; 83 AA.
AC P06927; Q71BI2;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 2.
DT 23-FEB-2022, entry version 83.
DE RecName: Full=Probable protein E5;
GN Name=E5;
OS Human papillomavirus type 16.
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC Alphapapillomavirus.
OX NCBI_TaxID=333760;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2990099; DOI=10.1016/0042-6822(85)90214-4;
RA Seedorf K., Krammer G., Durst M., Suhai S., Rowekamp W.G.;
RT "Human papillomavirus type 16 DNA sequence.";
RL Virology 145:181-185(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2831662; DOI=10.1016/0042-6822(88)90259-0;
RA Bubb V., McCance D.J., Schlegel R.;
RT "DNA sequence of the HPV-16 E5 ORF and the structural conservation of its
RT encoded protein.";
RL Virology 163:243-246(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate European German 131;
RA Terai M., Fu L., Ma Z., Burk R.D.;
RT "Cloning and sequencing of non-European human papillomavirus (HPV) variant
RT complete genomes from cervicovaginal cells by an overlapping PCR method.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=7690419; DOI=10.1128/jvi.67.10.6170-6178.1993;
RA Conrad M., Bubb V.J., Schlegel R.;
RT "The human papillomavirus type 6 and 16 E5 proteins are membrane-associated
RT proteins which associate with the 16-kilodalton pore-forming protein.";
RL J. Virol. 67:6170-6178(1993).
RN [5]
RP INTERACTION WITH HOST ATP6V0C.
RX PubMed=10949926; DOI=10.1038/sj.onc.1203718;
RA Rodriguez M.I., Finbow M.E., Alonso A.;
RT "Binding of human papillomavirus 16 E5 to the 16 kDa subunit c
RT (proteolipid) of the vacuolar H+-ATPase can be dissociated from the E5-
RT mediated epidermal growth factor receptor overactivation.";
RL Oncogene 19:3727-3732(2000).
RN [6]
RP SUBUNIT.
RX PubMed=12954209; DOI=10.1016/s0042-6822(03)00296-4;
RA Gieswein C.E., Sharom F.J., Wildeman A.G.;
RT "Oligomerization of the E5 protein of human papillomavirus type 16 occurs
RT through multiple hydrophobic regions.";
RL Virology 313:415-426(2003).
RN [7]
RP FUNCTION.
RX PubMed=15827198; DOI=10.1128/jvi.79.9.5839-5846.2005;
RA Disbrow G.L., Hanover J.A., Schlegel R.;
RT "Endoplasmic reticulum-localized human papillomavirus type 16 E5 protein
RT alters endosomal pH but not trans-Golgi pH.";
RL J. Virol. 79:5839-5846(2005).
RN [8]
RP FUNCTION, AND INTERACTION WITH HOST HLA-A.
RX PubMed=16823848; DOI=10.1002/ijc.22089;
RA Ashrafi G.H., Haghshenas M., Marchetti B., Campo M.S.;
RT "E5 protein of human papillomavirus 16 downregulates HLA class I and
RT interacts with the heavy chain via its first hydrophobic domain.";
RL Int. J. Cancer 119:2105-2112(2006).
RN [9]
RP FUNCTION.
RX PubMed=17704805; DOI=10.1038/sj.onc.1210725;
RA Suprynowicz F.A., Disbrow G.L., Krawczyk E., Simic V., Lantzky K.,
RA Schlegel R.;
RT "HPV-16 E5 oncoprotein upregulates lipid raft components caveolin-1 and
RT ganglioside GM1 at the plasma membrane of cervical cells.";
RL Oncogene 27:1071-1078(2008).
RN [10]
RP INTERACTION WITH HOST BCAP31.
RX PubMed=18684816; DOI=10.1128/jvi.01240-08;
RA Regan J.A., Laimins L.A.;
RT "Bap31 is a novel target of the human papillomavirus E5 protein.";
RL J. Virol. 82:10042-10051(2008).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=19712955; DOI=10.1016/j.virol.2009.07.034;
RA Hu L., Ceresa B.P.;
RT "Characterization of the plasma membrane localization and orientation of
RT HPV16 E5 for cell-cell fusion.";
RL Virology 393:135-143(2009).
RN [12]
RP ROLE AS ANTIGEN IN HEAD AND NECK SQUAMOUS CELL CARCINOMA.
RX PubMed=34471285; DOI=10.1038/s41586-021-03862-z;
RA Eberhardt C.S., Kissick H.T., Patel M.R., Cardenas M.A., Prokhnevska N.,
RA Obeng R.C., Nasti T.H., Griffith C.C., Im S.J., Wang X., Shin D.M.,
RA Carrington M., Chen Z.G., Sidney J., Sette A., Saba N.F., Wieland A.,
RA Ahmed R.;
RT "Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck
RT cancer.";
RL Nature 597:279-284(2021).
CC -!- FUNCTION: Acts to keep host cells in a proliferation-competent state
CC upon differentiation. Enhances host epidermal growth factor receptor
CC (EGFR) activation after stimulation by EGF by inhibiting EGFR
CC internalization. Induces a redistribution of host caveolin-1 and
CC glycosphingolipid (ganglioside GM1) components of lipid rafts to the
CC plasma membrane. Since GM1s inhibit cytotoxic T-lymphocytes, block
CC immune synapse formation, and enhance proliferative signaling by the
CC EGFR, E5 may enhance immune evasion and cell proliferation via a common
CC mechanism. E5 also alters endosomal pH by interacting with the vacuolar
CC H+-ATPase, which is a proton pump responsible for acidifying cellular
CC organelles. Additionally, E5 prevents transport of the major
CC histocompatibility class I to the cell surface and retains the complex
CC in the Golgi apparatus. {ECO:0000269|PubMed:15827198,
CC ECO:0000269|PubMed:16823848, ECO:0000269|PubMed:17704805}.
CC -!- SUBUNIT: Homooligomer. Interacts with host BCAP31; this interaction
CC seems to correlate with the ability of HPV-positive differentiated
CC cells to remain competent for proliferation. Interacts with host
CC ATP6V0C. Interacts (via N-terminus) with host HLA class I heavy chains
CC A1, A2, A3 and B8; these interactions inhibit host immune response by
CC sequestring MHC class I peptides to the host Golgi apparatus.
CC {ECO:0000269|PubMed:10949926, ECO:0000269|PubMed:12954209,
CC ECO:0000269|PubMed:16823848, ECO:0000269|PubMed:18684816}.
CC -!- INTERACTION:
CC P06927; Q93050: ATP6V0A1; Xeno; NbExp=3; IntAct=EBI-8561748, EBI-2891238;
CC -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000269|PubMed:19712955};
CC Multi-pass membrane protein {ECO:0000269|PubMed:19712955}. Host
CC endoplasmic reticulum membrane {ECO:0000269|PubMed:7690419}. Host Golgi
CC apparatus {ECO:0000269|PubMed:7690419}.
CC -!- MISCELLANEOUS: HPV16, in comparison to HPV types 6 and 11, is more
CC often associated with malignant genital cancers in humans.
CC -!- MISCELLANEOUS: Part of the antigens expressed and presented within HPV-
CC positive head and neck tumors. {ECO:0000269|PubMed:34471285}.
CC -!- SIMILARITY: Belongs to the papillomaviridae E5 protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA46938.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; K02718; AAA46938.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AF536179; AAQ10717.1; -; Genomic_DNA.
DR PIR; A30016; W5WLHS.
DR RefSeq; NP_041330.2; NC_001526.4.
DR BioGRID; 4263556; 152.
DR IntAct; P06927; 153.
DR MINT; P06927; -.
DR TCDB; 1.A.97.1.1; the human papillomavirus type 16 e5 viroporin (hpv-e5) family.
DR PRIDE; P06927; -.
DR GeneID; 1489077; -.
DR KEGG; vg:1489077; -.
DR Proteomes; UP000009251; Genome.
DR Proteomes; UP000106302; Genome.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IDA:CACAO.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0019048; P:modulation by virus of host process; IDA:CACAO.
DR GO; GO:0033668; P:negative regulation by symbiont of host apoptotic process; IMP:CACAO.
DR GO; GO:0046776; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR InterPro; IPR004270; Papilloma_E5_alpha.
DR Pfam; PF03025; Papilloma_E5; 1.
PE 1: Evidence at protein level;
KW Early protein; Host endoplasmic reticulum; Host Golgi apparatus;
KW Host membrane; Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
KW Inhibition of host MHC class I molecule presentation by virus; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix;
KW Viral immunoevasion.
FT CHAIN 1..83
FT /note="Probable protein E5"
FT /id="PRO_0000133289"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 42..62
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CONFLICT 44
FT /note="I -> L (in Ref. 3; AAQ10717)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="V -> G (in Ref. 3; AAQ10717)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="V -> G (in Ref. 3; AAQ10717)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 83 AA; 9402 MW; 442C0ABF0D77CDCF CRC64;
MTNLDTASTT LLACFLLCFC VLLCVCLLIR PLLLSVSTYT SLIILVLLLW ITAASAFRCF
IVYIIFVYIP LFLIHTHARF LIT
