ID   GD_HHV1K                Reviewed;         394 AA.
AC   A1Z0Q5; Q05060; Q69081; Q69082;
DT   22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT   22-SEP-2009, sequence version 2.
DT   24-JAN-2024, entry version 62.
DE   RecName: Full=Envelope glycoprotein D;
DE            Short=gD;
DE   Flags: Precursor;
GN   Name=gD; ORFNames=US6;
OS   Human herpesvirus 1 (strain KOS) (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=10306;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Isolate KOSc, Isolate KOSc(AC3,AC6), and Isolate KOSc(AC4);
RX   PubMed=17604805; DOI=10.1016/j.virol.2007.05.040;
RA   Ekblad M., Adamiak B., Bergefall K., Nenonen H., Roth A., Bergstrom T.,
RA   Ferro V., Trybala E.;
RT   "Molecular basis for resistance of herpes simplex virus type 1 mutants to
RT   the sulfated oligosaccharide inhibitor PI-88.";
RL   Virology 367:244-252(2007).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=KOS, Mutant Rid1, and Mutant Rid2;
RX   PubMed=8116256; DOI=10.1006/viro.1994.1098;
RA   Dean H.J., Terhune S.S., Shieh M.-T., Spear P.G.;
RT   "Single amino acid substitutions in glycoprotein D of herpes simplex virus
RT   type 1 that confer resistance to gD-mediated interference also alter virus
RT   infectivity.";
RL   Virology 199:67-80(1994).
RN   [3]
RP   INTERACTION WITH HUMAN RECEPTORS NECTIN1 AND TNFRSF14.
RX   PubMed=9696799; DOI=10.1128/jvi.72.9.7064-7074.1998;
RA   Krummenacher C., Nicola A.V., Whitbeck J.C., Lou H., Hou W., Lambris J.D.,
RA   Geraghty R.J., Spear P.G., Cohen G.H., Eisenberg R.J.;
RT   "Herpes simplex virus glycoprotein D can bind to poliovirus receptor-
RT   related protein 1 or herpesvirus entry mediator, two structurally unrelated
RT   mediators of virus entry.";
RL   J. Virol. 72:7064-7074(1998).
RN   [4]
RP   BINDING TO 3-O-SULFATED HEPARAN SULFATE.
RX   PubMed=10520990; DOI=10.1016/s0092-8674(00)80058-6;
RA   Shukla D., Liu J., Blaiklock P., Shworak N.W., Bai X., Esko J.D.,
RA   Cohen G.H., Eisenberg R.J., Rosenberg R.D., Spear P.G.;
RT   "A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1
RT   entry.";
RL   Cell 99:13-22(1999).
RN   [5]
RP   INTERACTION OF MUTANT RID1 WITH HUMAN NECTIN2.
RC   STRAIN=Mutant Rid1;
RX   PubMed=11602758; DOI=10.1128/jvi.75.22.11185-11195.2001;
RA   Martinez W.M., Spear P.G.;
RT   "Structural features of nectin-2 (HveB) required for herpes simplex virus
RT   entry.";
RL   J. Virol. 75:11185-11195(2001).
CC   -!- FUNCTION: Envelope glycoprotein that binds to the potential host cell
CC       entry receptors TNFRSF14/HVEM, NECTIN1 and 3-O-sulfated heparan
CC       sulfate. May trigger fusion with host membrane, by recruiting the
CC       fusion machinery composed of gB and gH/gL (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Homodimer (By similarity). Interacts with host receptor
CC       TNFRSF14. Interacts with host receptor NECTIN1. Mutant Rid1 interacts
CC       with host receptor NECTIN2. Interacts (via profusion domain) with gB;
CC       this interaction occurs in the absence of gH/gL. Interacts (via
CC       profusion domain) with gH/gL heterodimer; this interaction occurs in
CC       the absence of gB. Associates with the gB-gH/gL-gD complex. Interacts
CC       (via C-terminus) with UL11 tegument protein. Interacts (via C-terminus)
CC       with VP22 tegument protein; this interaction might be very weak (By
CC       similarity). Interacts with host RSAD2 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}. Host Golgi apparatus
CC       {ECO:0000250|UniProtKB:Q69091}. Note=During virion morphogenesis, this
CC       protein probably accumulates in the endosomes and trans-Golgi where
CC       secondary envelopment occurs. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the herpesviridae glycoprotein D family.
CC       {ECO:0000305}.
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DR   EMBL; L09243; AAA19629.1; -; Unassigned_DNA.
DR   EMBL; L09244; AAA19631.1; -; Unassigned_DNA.
DR   EMBL; L09245; AAA19630.1; -; Unassigned_DNA.
DR   EMBL; EF157319; ABM52978.1; -; Genomic_DNA.
DR   EMBL; EF157320; ABM52979.1; -; Genomic_DNA.
DR   EMBL; EF157321; ABM52980.1; -; Genomic_DNA.
DR   BMRB; A1Z0Q5; -.
DR   SMR; A1Z0Q5; -.
DR   MINT; A1Z0Q5; -.
DR   GlyCosmos; A1Z0Q5; 3 sites, No reported glycans.
DR   GO; GO:0044177; C:host cell Golgi apparatus; 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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0098670; P:entry receptor-mediated virion attachment to host cell; IEA:UniProtKB-KW.
DR   GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR   CDD; cd12087; TM_EGFR-like; 1.
DR   Gene3D; 2.70.230.10; -; 1.
DR   InterPro; IPR002896; Herpes_glycop_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   Pfam; PF01537; Herpes_glycop_D; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
PE   1: Evidence at protein level;
KW   Disulfide bond; Glycoprotein; Host Golgi apparatus; Host-virus interaction;
KW   Membrane; Metal-binding; Signal; Transmembrane; Transmembrane helix;
KW   Viral attachment to host cell; Viral attachment to host entry receptor;
KW   Viral envelope protein; Virion; Virus entry into host cell; Zinc.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..394
FT                   /note="Envelope glycoprotein D"
FT                   /id="PRO_5000142086"
FT   TOPO_DOM        26..340
FT                   /note="Virion surface"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        341..361
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        362..394
FT                   /note="Intravirion"
FT                   /evidence="ECO:0000255"
FT   REGION          26..57
FT                   /note="Interaction with TNFRSF14"
FT                   /evidence="ECO:0000269|PubMed:9696799"
FT   REGION          261..305
FT                   /note="Profusion"
FT                   /evidence="ECO:0000250"
FT   REGION          275..301
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         64
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P57083"
FT   BINDING         240
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P57083"
FT   CARBOHYD        119
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        146
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        287
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        91..214
FT                   /evidence="ECO:0000250|UniProtKB:P57083"
FT   DISULFID        131..227
FT                   /evidence="ECO:0000250|UniProtKB:P57083"
FT   DISULFID        143..152
FT                   /evidence="ECO:0000250|UniProtKB:P57083"
FT   VARIANT         52
FT                   /note="Q -> P (in strain: Mutant rid1 and Isolate
FT                   KOSc(AC3,AC6); interference resistant)"
FT   VARIANT         52
FT                   /note="Q -> R (in strain: Mutant rid2; interference
FT                   resistant)"
FT   CONFLICT        30
FT                   /note="A -> V (in Ref. 1; AAA19630 and 2; ABM52980)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   394 AA;  43317 MW;  905A0F0F1953CB7F CRC64;
     MGGAAARLGA VILFVVIVGL HGVRGKYALA DASLKMADPN RFRGKDLPVL DQLTDPPGVR
     RVYHIQAGLP DPFQPPSLPI TVYYAVLERA CRSVLLNAPS EAPQIVRGAS EDVRKQPYNL
     TIAWFRMGGN CAIPITVMEY TECSYNKSLG ACPIRTQPRW NYYDSFSAVS EDNLGFLMHA
     PAFETAGTYL RLVKINDWTE ITQFILEHRA KGSCKYALPL RIPPSACLSP QAYQQGVTVD
     SIGMLPRFIP ENQRTVAVYS LKIAGWHGPK APYTSTLLPP ELSETPNATQ PELAPEDPED
     SALLEDPVGT VAPQIPPNWH IPSIQDAATP YHPPATPNNM GLIAGAVGGS LLAALVICGI
     VYWMHRRTRK APKRIRLPHI REDDQPSSHQ PLFY
//