GE_HHV11
ID GE_HHV11 Reviewed; 550 AA.
AC P04488; B9VQK2; Q09I69;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 116.
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 17) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10299;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2984429; DOI=10.1016/0022-2836(85)90320-1;
RA McGeoch D.J., Dolan A., Donald S., Rixon F.J.;
RT "Sequence determination and genetic content of the short unique region in
RT the genome of herpes simplex virus type 1.";
RL J. Mol. Biol. 181:1-13(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Nonneuroinvasive mutant HF10;
RX PubMed=17218138; DOI=10.1016/j.micinf.2006.10.019;
RA Ushijima Y., Luo C., Goshima F., Yamauchi Y., Kimura H., Nishiyama Y.;
RT "Determination and analysis of the DNA sequence of highly attenuated herpes
RT simplex virus type 1 mutant HF10, a potential oncolytic virus.";
RL Microbes Infect. 9:142-149(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17 syn+;
RA Cunningham C., Davison A.J.;
RT "Herpes simplex virus type 1 bacterial artificial chromosome.";
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP GLYCOSYLATION, AND SULFATION.
RX PubMed=6310034; DOI=10.1099/0022-1317-64-9-1943;
RA Hope R.G., Marsden H.S.;
RT "Processing of glycoproteins induced by herpes simplex virus type 1:
RT sulphation and nature of the oligosaccharide linkages.";
RL J. Gen. Virol. 64:1943-1953(1983).
RN [5]
RP FUNCTION, AND INTERACTION WITH GLYCOPROTEIN I.
RC STRAIN=17 syn+, and F;
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 [6]
RP PHOSPHORYLATION AT SER-476 AND SER-477.
RX PubMed=10725429; DOI=10.1099/0022-1317-81-4-1027;
RA Miriagou V., Stevanato L., Manservigi R., Mavromara P.;
RT "The C-terminal cytoplasmic tail of herpes simplex virus type 1 gE protein
RT is phosphorylated in vivo and in vitro by cellular enzymes in the absence
RT of other viral proteins.";
RL J. Gen. Virol. 81:1027-1031(2000).
RN [7]
RP FUNCTION.
RC STRAIN=KOS;
RX PubMed=14734541; DOI=10.1074/jbc.m313281200;
RA Sprague E.R., Martin W.L., Bjorkman P.J.;
RT "pH dependence and stoichiometry of binding to the Fc region of IgG by the
RT herpes simplex virus Fc receptor gE-gI.";
RL J. Biol. Chem. 279:14184-14193(2004).
RN [8]
RP INTERACTION WITH VP22 AND UL11 TEGUMENT PROTEINS.
RC STRAIN=F;
RX PubMed=17035313; DOI=10.1128/jvi.01842-06;
RA Farnsworth A., Wisner T.W., Johnson D.C.;
RT "Cytoplasmic residues of herpes simplex virus glycoprotein gE required for
RT secondary envelopment and binding of tegument proteins VP22 and UL11 to gE
RT and gD.";
RL J. Virol. 81:319-331(2007).
RN [9]
RP INTERACTION WITH VP22 TEGUMENT PROTEIN.
RC STRAIN=17 syn+;
RX PubMed=16997344; DOI=10.1016/j.virol.2006.08.024;
RA O'Regan K.J., Bucks M.A., Murphy M.A., Wills J.W., Courtney R.J.;
RT "A conserved region of the herpes simplex virus type 1 tegument protein
RT VP22 facilitates interaction with the cytoplasmic tail of glycoprotein E
RT (gE).";
RL Virology 358:192-200(2007).
RN [10]
RP INTERACTION WITH VP22 TEGUMENT PROTEIN.
RX PubMed=19279114; DOI=10.1128/jvi.00069-09;
RA Stylianou J., Maringer K., Cook R., Bernard E., Elliott G.;
RT "Virion incorporation of the herpes simplex virus type 1 tegument protein
RT VP22 occurs via glycoprotein E-specific recruitment to the late secretory
RT pathway.";
RL J. Virol. 83:5204-5218(2009).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 213-390, X-RAY CRYSTALLOGRAPHY
RP (5.0 ANGSTROMS) OF 21-419 IN COMPLEX WITH HOST FC RECEPTOR, AND DISULFIDE
RP BONDS.
RX PubMed=16646632; DOI=10.1371/journal.pbio.0040148;
RA Sprague E.R., Wang C., Baker D., Bjorkman P.J.;
RT "Crystal structure of the HSV-1 Fc receptor bound to Fc reveals a mechanism
RT for antibody bipolar bridging.";
RL PLoS Biol. 4:E148-E148(2006).
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 (By
CC similarity). In neuronal cells, gE/gI is essential for the anterograde
CC spread of the infection throughout the host nervous system. Together
CC with US9, the heterodimer gE/gI is involved in the sorting and
CC transport of viral structural components toward axon tips.
CC {ECO:0000250, ECO:0000269|PubMed:14734541, 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.
CC -!- SUBUNIT: Interacts with gI; this interaction enhances the Fc receptor
CC function of gE (By similarity). The heterodimer gE/gI interacts with
CC the Fc part of host IgG. Interacts (via C-terminus) with VP22 tegument
CC protein; this interaction is necessary for the recruitment of VP22 to
CC the Golgi and its packaging into virions. Interacts (via C-terminus)
CC with UL11 tegument protein. {ECO:0000250, ECO:0000269|PubMed:16646632,
CC ECO:0000269|PubMed:16997344, ECO:0000269|PubMed:17035313,
CC ECO:0000269|PubMed:19279114, ECO:0000269|PubMed:2831396}.
CC -!- INTERACTION:
CC P04488; P04488: gE; NbExp=2; IntAct=EBI-15581257, EBI-15581257;
CC P04488; P01857: IGHG1; Xeno; NbExp=2; IntAct=EBI-15581257, EBI-356114;
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Host cell membrane {ECO:0000250};
CC Single-pass type I membrane protein {ECO:0000250}. Host cell junction.
CC Host Golgi apparatus membrane {ECO:0000250}; Single-pass membrane
CC protein {ECO:0000250}. Host endosome membrane {ECO:0000250}; Single-
CC pass membrane protein {ECO:0000250}. Note=During virion morphogenesis,
CC this protein probably accumulates in the endosomes and trans-Golgi
CC where secondary envelopment occurs. It is probably transported to the
CC cell surface from where it is endocytosed and directed to the trans-
CC Golgi network (TGN), maybe through an interaction with PACS-1 sorting
CC protein. The heterodimer gE/gI then redistributes to cell junctions to
CC promote cell-cell spread later in the infection.
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:0000269|PubMed:6310034}.
CC -!- SIMILARITY: Belongs to the alphaherpesvirinae glycoprotein E family.
CC {ECO:0000305}.
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DR EMBL; X14112; CAA32272.1; -; Genomic_DNA.
DR EMBL; X02138; CAA26062.1; -; Genomic_DNA.
DR EMBL; L00036; AAA96680.1; -; Genomic_DNA.
DR EMBL; DQ889502; ABI63526.1; -; Genomic_DNA.
DR EMBL; FJ593289; ACM62297.1; -; Genomic_DNA.
DR PIR; A03733; VGBE18.
DR RefSeq; YP_009137143.1; NC_001806.2.
DR PDB; 2GIY; X-ray; 1.78 A; A/B=213-390.
DR PDB; 2GJ7; X-ray; 5.00 A; E/F=21-419.
DR PDBsum; 2GIY; -.
DR PDBsum; 2GJ7; -.
DR SMR; P04488; -.
DR DIP; DIP-29186N; -.
DR IntAct; P04488; 1.
DR ChEMBL; CHEMBL2364696; -.
DR DrugCentral; P04488; -.
DR iPTMnet; P04488; -.
DR PRIDE; P04488; -.
DR ABCD; P04488; 1 sequenced antibody.
DR DNASU; 2703448; -.
DR GeneID; 2703448; -.
DR KEGG; vg:2703448; -.
DR EvolutionaryTrace; P04488; -.
DR PRO; PR:P04488; -.
DR Proteomes; UP000009294; Genome.
DR Proteomes; UP000180652; Genome.
DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044156; C:host cell junction; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of 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:0042802; F:identical protein binding; IPI:IntAct.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR003404; Herpes_glycopE.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF02480; Herpes_gE; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Host cell junction;
KW Host cell membrane; Host endosome; Host Golgi apparatus; Host membrane;
KW Host-virus interaction; Membrane; Phosphoprotein; Reference proteome;
KW Signal; Sulfation; Transmembrane; Transmembrane helix;
KW Viral envelope protein; Viral immunoevasion; Virion.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..550
FT /note="Envelope glycoprotein E"
FT /id="PRO_0000038225"
FT TOPO_DOM 21..419
FT /note="Virion surface"
FT /evidence="ECO:0000255"
FT TRANSMEM 420..440
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 441..550
FT /note="Intravirion"
FT /evidence="ECO:0000255"
FT REGION 63..88
FT /note="Interaction with gI"
FT /evidence="ECO:0000250"
FT REGION 162..214
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..380
FT /note="Fc-binding"
FT REGION 394..413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 470..495
FT /note="Interaction with VP22 and UL11"
FT /evidence="ECO:0000269|PubMed:17035313"
FT REGION 476..550
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..484
FT /note="Acidic"
FT MOTIF 463..466
FT /note="Internalization motif"
FT /evidence="ECO:0000255"
FT MOTIF 472..475
FT /note="Internalization motif"
FT /evidence="ECO:0000255"
FT COMPBIAS 196..211
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..550
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 476
FT /note="Phosphoserine; by host CK2"
FT /evidence="ECO:0000305|PubMed:10725429"
FT MOD_RES 477
FT /note="Phosphoserine; by host CK2"
FT /evidence="ECO:0000305|PubMed:10725429"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0000305"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 243
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 271..297
FT /evidence="ECO:0000269|PubMed:16646632"
FT DISULFID 280..289
FT /evidence="ECO:0000269|PubMed:16646632"
FT DISULFID 314..323
FT /evidence="ECO:0000269|PubMed:16646632"
FT VARIANT 120
FT /note="A -> T (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 130
FT /note="H -> Y (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 143
FT /note="S -> F (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 239
FT /note="T -> A (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 257
FT /note="S -> A (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 432
FT /note="A -> V (in strain: Nonneuroinvasive mutant HF10)"
FT STRAND 221..227
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 245..253
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 256..265
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 272..277
FT /evidence="ECO:0007829|PDB:2GIY"
FT HELIX 278..282
FT /evidence="ECO:0007829|PDB:2GIY"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:2GIY"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 306..315
FT /evidence="ECO:0007829|PDB:2GIY"
FT TURN 320..323
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 324..329
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:2GIY"
FT HELIX 351..353
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 355..363
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 366..376
FT /evidence="ECO:0007829|PDB:2GIY"
FT TURN 378..380
FT /evidence="ECO:0007829|PDB:2GIY"
FT STRAND 383..387
FT /evidence="ECO:0007829|PDB:2GIY"
SQ SEQUENCE 550 AA; 59094 MW; BE8271E5B7E34776 CRC64;
MDRGAVVGFL LGVCVVSCLA GTPKTSWRRV SVGEDVSLLP APGPTGRGPT QKLLWAVEPL
DGCGPLHPSW VSLMPPKQVP ETVVDAACMR APVPLAMAYA PPAPSATGGL RTDFVWQERA
AVVNRSLVIH GVRETDSGLY TLSVGDIKDP ARQVASVVLV VQPAPVPTPP PTPADYDEDD
NDEGEDESLA GTPASGTPRL PPPPAPPRSW PSAPEVSHVR GVTVRMETPE AILFSPGETF
STNVSIHAIA HDDQTYSMDV VWLRFDVPTS CAEMRIYESC LYHPQLPECL SPADAPCAAS
TWTSRLAVRS YAGCSRTNPP PRCSAEAHME PVPGLAWQAA SVNLEFRDAS PQHSGLYLCV
VYVNDHIHAW GHITISTAAQ YRNAVVEQPL PQRGADLAEP THPHVGAPPH APPTHGALRL
GAVMGAALLL SALGLSVWAC MTCWRRRAWR AVKSRASGKG PTYIRVADSE LYADWSSDSE
GERDQVPWLA PPERPDSPST NGSGFEILSP TAPSVYPRSD GHQSRRQLTT FGSGRPDRRY
SQASDSSVFW
