ID   GE_HHV1F                Reviewed;         552 AA.
AC   Q703F0; Q86624;
DT   07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 71.
DE   RecName: Full=Envelope glycoprotein E;
DE            Short=gE;
DE   AltName: Full=gE-1;
DE   Flags: Precursor;
GN   Name=gE; ORFNames=US8;
OS   Human herpesvirus 1 (strain F) (HHV-1) (Human herpes simplex virus 1).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Alphaherpesvirinae; Simplexvirus;
OC   Simplexvirus humanalpha1; Human herpesvirus 1.
OX   NCBI_TaxID=10304;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=15367642; DOI=10.1128/jvi.78.19.10755-10764.2004;
RA   Norberg P.R., Bergstroem T., Kekabdar E., Lindh M., Liljeqvist J.-A.;
RT   "Phylogenetic analysis of clinical herpes simplex virus type 1 isolates
RT   identified three genetic groups and recombinant viruses.";
RL   J. Virol. 78:10755-10764(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 440-552.
RX   PubMed=8389914; DOI=10.1128/jvi.67.7.3961-3968.1993;
RA   Georgopoulou U., Michaelidou A., Roizman B., Mavromara-Nazos P.;
RT   "Identification of a new transcriptional unit that yields a gene product
RT   within the unique sequences of the short component of the herpes simplex
RT   virus 1 genome.";
RL   J. Virol. 67:3961-3968(1993).
RN   [3]
RP   FUNCTION, AND INTERACTION WITH GLYCOPROTEIN I.
RX   PubMed=2831396; DOI=10.1128/jvi.62.4.1347-1354.1988;
RA   Johnson D.C., Frame M.C., Ligas M.W., Cross A.M., Stow N.D.;
RT   "Herpes simplex virus immunoglobulin G Fc receptor activity depends on a
RT   complex of two viral glycoproteins, gE and gI.";
RL   J. Virol. 62:1347-1354(1988).
RN   [4]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=11134295; DOI=10.1128/jvi.75.2.821-833.2001;
RA   Johnson D.C., Webb M., Wisner T.W., Brunetti C.;
RT   "Herpes simplex virus gE/gI sorts nascent virions to epithelial cell
RT   junctions, promoting virus spread.";
RL   J. Virol. 75:821-833(2001).
RN   [5]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=16537585; DOI=10.1128/jvi.80.7.3167-3179.2006;
RA   Farnsworth A., Johnson D.C.;
RT   "Herpes simplex virus gE/gI must accumulate in the trans-Golgi network at
RT   early times and then redistribute to cell junctions to promote cell-cell
RT   spread.";
RL   J. Virol. 80:3167-3179(2006).
RN   [6]
RP   FUNCTION.
RX   PubMed=18753205; DOI=10.1128/jvi.01241-08;
RA   Snyder A., Polcicova K., Johnson D.C.;
RT   "Herpes simplex virus gE/gI and US9 proteins promote transport of both
RT   capsids and virion glycoproteins in neuronal axons.";
RL   J. Virol. 82:10613-10624(2008).
RN   [7]
RP   SUBCELLULAR LOCATION.
RX   PubMed=18596102; DOI=10.1128/jvi.00904-08;
RA   Loret S., Guay G., Lippe R.;
RT   "Comprehensive characterization of extracellular herpes simplex virus type
RT   1 virions.";
RL   J. Virol. 82:8605-8618(2008).
CC   -!- FUNCTION: In epithelial cells, the heterodimer gE/gI is required for
CC       the cell-to-cell spread of the virus, by sorting nascent virions to
CC       cell junctions. Once the virus reaches the cell junctions, virus
CC       particles can spread to adjacent cells extremely rapidly through
CC       interactions with cellular receptors that accumulate at these
CC       junctions. Implicated in basolateral spread in polarized cells. In
CC       neuronal cells, gE/gI is essential for the anterograde spread of the
CC       infection throughout the host nervous system. Together with US9, the
CC       heterodimer gE/gI is involved in the sorting and transport of viral
CC       structural components toward axon tips. {ECO:0000269|PubMed:11134295,
CC       ECO:0000269|PubMed:16537585, ECO:0000269|PubMed:18753205,
CC       ECO:0000269|PubMed:2831396}.
CC   -!- FUNCTION: The heterodimer gE/gI serves as a receptor for the Fc part of
CC       host IgG. Dissociation of gE/gI from IgG occurs at acidic pH. May thus
CC       be involved in anti-HSV antibodies bipolar bridging, followed by
CC       intracellular endocytosis and degradation, thereby interfering with
CC       host IgG-mediated immune responses (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with gI; this interaction enhances the Fc receptor
CC       function of gE. The heterodimer gE/gI interacts with the Fc part of
CC       host IgG. Interacts (via C-terminus) with VP22 tegument protein; this
CC       interaction is necessary for the recruitment of VP22 to the Golgi and
CC       its packaging into virions. Interacts (via C-terminus) with UL11
CC       tegument protein (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000269|PubMed:18596102};
CC       Single-pass type I membrane protein {ECO:0000255}. Host cell membrane
CC       {ECO:0000269|PubMed:16537585}; Single-pass type I membrane protein
CC       {ECO:0000255}. Host cell junction {ECO:0000269|PubMed:11134295,
CC       ECO:0000269|PubMed:16537585}. Host Golgi apparatus, host trans-Golgi
CC       network {ECO:0000269|PubMed:16537585}. Note=During virion
CC       morphogenesis, this protein probably accumulates in host trans-Golgi
CC       where secondary envelopment occurs. The heterodimer gE/gI then
CC       redistributes to cell junctions to promote cell-cell spread later in
CC       the infection. {ECO:0000269|PubMed:11134295}.
CC   -!- PTM: Phosphorylated on serines within the acidic cluster.
CC       Phosphorylation determines whether endocytosed viral gE traffics to the
CC       trans-Golgi network or recycles to the cell membrane. {ECO:0000305}.
CC   -!- PTM: N-glycosylated, and sulfated. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the alphaherpesvirinae glycoprotein E family.
CC       {ECO:0000305}.
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DR   EMBL; AJ626469; CAF24756.1; -; Genomic_DNA.
DR   EMBL; S62895; AAB27080.1; -; Genomic_DNA.
DR   GlyCosmos; Q703F0; 2 sites, No reported glycans.
DR   GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0044156; C:host cell junction; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   InterPro; IPR046463; Herpes_gE_N.
DR   InterPro; IPR003404; Herpes_glycopE_Fc.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   Pfam; PF02480; Herpes_gE; 1.
DR   Pfam; PF20418; Herpes_gE_N; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
PE   1: Evidence at protein level;
KW   Disulfide bond; Glycoprotein; Host cell junction; Host cell membrane;
KW   Host Golgi apparatus; Host membrane; Host-virus interaction; Membrane;
KW   Phosphoprotein; Signal; Sulfation; Transmembrane; Transmembrane helix;
KW   Viral envelope protein; Viral immunoevasion; Virion.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..552
FT                   /note="Envelope glycoprotein E"
FT                   /id="PRO_0000038226"
FT   TOPO_DOM        21..421
FT                   /note="Virion surface"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        422..442
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        443..552
FT                   /note="Intravirion"
FT                   /evidence="ECO:0000255"
FT   REGION          63..88
FT                   /note="Interaction with gI"
FT                   /evidence="ECO:0000250"
FT   REGION          162..216
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          237..382
FT                   /note="Fc-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          393..418
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          472..497
FT                   /note="Interaction with VP22 and UL11"
FT                   /evidence="ECO:0000250"
FT   REGION          478..486
FT                   /note="Acidic"
FT                   /evidence="ECO:0000250"
FT   REGION          484..552
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           465..468
FT                   /note="Internalization motif"
FT                   /evidence="ECO:0000255"
FT   MOTIF           474..477
FT                   /note="Internalization motif"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        175..189
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        198..213
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        518..552
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         176
FT                   /note="Sulfotyrosine; by host"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         478
FT                   /note="Phosphoserine; by host CK2"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         479
FT                   /note="Phosphoserine; by host CK2"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         505
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        124
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        245
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        273..299
FT                   /evidence="ECO:0000250"
FT   DISULFID        282..291
FT                   /evidence="ECO:0000250"
FT   DISULFID        316..325
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   552 AA;  59313 MW;  8F689BF77BE07BB7 CRC64;
     MDRGAVVGFL LGVCVVSCLA GTPKTSWRRV SVGEDVSLLP APGPTGRGPT QKLLWAVEPL
     DGCGPLHPSW XSLMPPKQVP ETVVDAACMR APVPLAMAYA PPAPSATGGL RTDFVWQERA
     AVVNRSLVIY GVRETDSGLY TLSVGDIKDP ARQVASVVLV VQPAPVPTPP PTPADYDEDD
     NDEGEGEDES LAGTPASGTP RLPPPPAPPR SWPSAPEVSH VRGVTVRMET PEAILFSPGE
     AFSTNVSIHA IAHDDQTYTM DVVWLRFDVP TSCAEMRIYE SCLYHPQLPE CLSPADAPCA
     ASTWTSRLAV RSYAGCSRTN PPPRCSAEAH MEPVPGLAWQ AASVNLEFRD ASPQHSGLYL
     CVVYVNDHIH AWGHITISTA AXYRNAVVEQ PLPQRGADLA EPTHPHVGAP PHAPPTHGAL
     RLGAVMGAAL LLSVLGLSVW ACMTCWRRRA WRAVKSRASG KGPTYIRVAD SELYADWSSD
     SEGERDQVPW LAPPERPDSP STNGSGFEIL SPTAPSVYPR SDGHQSRRQL TTFGSGRPDR
     RYSQASDSSV FW
//