GK_HHV11
ID GK_HHV11 Reviewed; 338 AA.
AC P68331; B9VQI2; P10237; Q09I81;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 09-NOV-2004, sequence version 1.
DT 23-FEB-2022, entry version 78.
DE RecName: Full=Envelope glycoprotein K;
DE AltName: Full=Syncytial protein;
DE Flags: Precursor;
GN Name=gK; ORFNames=UL53;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=2839594; DOI=10.1099/0022-1317-69-7-1531;
RA McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D.,
RA Perry L.J., Scott J.E., Taylor P.;
RT "The complete DNA sequence of the long unique region in the genome of
RT herpes simplex virus type 1.";
RL J. Gen. Virol. 69:1531-1574(1988).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-76.
RX PubMed=2826807; DOI=10.1128/jvi.62.2.444-453.1988;
RA McGeoch D.J., Dalrymple M.A., Dolan A., McNab D., Perry L.J., Taylor P.,
RA Challberg M.D.;
RT "Structures of herpes simplex virus type 1 genes required for replication
RT of virus DNA.";
RL J. Virol. 62:444-453(1988).
RN [5]
RP CHARACTERIZATION, AND IDENTIFICATION OF N-TERMINUS.
RX PubMed=1310186; DOI=10.1016/0042-6822(92)90024-j;
RA Ramaswamy R., Holland T.C.;
RT "In vitro characterization of the HSV-1 UL53 gene product.";
RL Virology 186:579-587(1992).
RN [6]
RP MUTAGENESIS OF PRO-33; ALA-40; LEU-86; ASP-99; ALA-111; THR-121; LEU-304
RP AND ARG-310.
RX PubMed=7966620; DOI=10.1128/jvi.68.12.8277-8281.1994;
RA Dolter K.E., Ramaswamy R., Holland T.C.;
RT "Syncytial mutations in the herpes simplex virus type 1 gK (UL53) gene
RT occur in two distinct domains.";
RL J. Virol. 68:8277-8281(1994).
RN [7]
RP TOPOLOGY.
RX PubMed=9407122; DOI=10.1074/jbc.272.52.33305;
RA Mo C., Holland T.C.;
RT "Determination of the transmembrane topology of herpes simplex virus type 1
RT glycoprotein K.";
RL J. Biol. Chem. 272:33305-33311(1997).
RN [8]
RP SUBCELLULAR LOCATION.
RC STRAIN=KOS;
RX PubMed=11711633; DOI=10.1128/jvi.75.24.12431-12438.2001;
RA Foster T.P., Rybachuk G.V., Kousoulas K.G.;
RT "Glycoprotein K specified by herpes simplex virus type 1 is expressed on
RT virions as a Golgi complex-dependent glycosylated species and functions in
RT virion entry.";
RL J. Virol. 75:12431-12438(2001).
RN [9]
RP SUBCELLULAR LOCATION, TOPOLOGY, AND MUTAGENESIS OF ALA-40.
RX PubMed=12477855; DOI=10.1128/jvi.77.1.499-510.2003;
RA Foster T.P., Alvarez X., Kousoulas K.G.;
RT "Plasma membrane topology of syncytial domains of herpes simplex virus type
RT 1 glycoprotein K (gK): the UL20 protein enables cell surface localization
RT of gK but not gK-mediated cell-to-cell fusion.";
RL J. Virol. 77:499-510(2003).
RN [10]
RP FUNCTION.
RX PubMed=15113914; DOI=10.1128/jvi.78.10.5347-5357.2004;
RA Foster T.P., Melancon J.M., Baines J.D., Kousoulas K.G.;
RT "The herpes simplex virus type 1 UL20 protein modulates membrane fusion
RT events during cytoplasmic virion morphogenesis and virus-induced cell
RT fusion.";
RL J. Virol. 78:5347-5357(2004).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=15542677; DOI=10.1128/jvi.78.23.13262-13277.2004;
RA Foster T.P., Melancon J.M., Olivier T.L., Kousoulas K.G.;
RT "Herpes simplex virus type 1 glycoprotein K and the UL20 protein are
RT interdependent for intracellular trafficking and trans-Golgi network
RT localization.";
RL J. Virol. 78:13262-13277(2004).
RN [12]
RP FUNCTION.
RX PubMed=15596825; DOI=10.1128/jvi.79.1.299-313.2005;
RA Melancon J.M., Luna R.E., Foster T.P., Kousoulas K.G.;
RT "Herpes simplex virus type 1 gK is required for gB-mediated virus-induced
RT cell fusion, while neither gB and gK nor gB and UL20p function redundantly
RT in virion de-envelopment.";
RL J. Virol. 79:299-313(2005).
RN [13]
RP INTERACTION WITH UL20.
RX PubMed=18434401; DOI=10.1128/jvi.00147-08;
RA Foster T.P., Chouljenko V.N., Kousoulas K.G.;
RT "Functional and physical interactions of the herpes simplex virus type 1
RT UL20 membrane protein with glycoprotein K.";
RL J. Virol. 82:6310-6323(2008).
RN [14]
RP SUBCELLULAR LOCATION.
RC STRAIN=F;
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: Glycoprotein that probably modulates membrane fusion events
CC during secondary envelopment of cytoplasmic capsids that bud into
CC specific trans-Golgi network (TGN)-derived membranes. Also plays a
CC role, together with gB, in virus-induced cell-to-cell fusion (syncytia
CC formation). Seems to block fusion of virions with infected-cell
CC membranes. {ECO:0000269|PubMed:15113914, ECO:0000269|PubMed:15596825}.
CC -!- SUBUNIT: Interacts (via UL20 interaction region) with protein UL20 (via
CC N-terminus); this interaction probably plays a role in the coordinate
CC transport of protein UL20 and gK to the trans-Golgi network (TGN), and
CC is required for the cell surface expression of gK.
CC {ECO:0000269|PubMed:18434401}.
CC -!- INTERACTION:
CC P68331; P10204: UL20; NbExp=5; IntAct=EBI-7906305, EBI-7906325;
CC -!- SUBCELLULAR LOCATION: Host cell membrane; Multi-pass membrane protein.
CC Host endosome membrane {ECO:0000250}; Multi-pass membrane protein
CC {ECO:0000250}. Host Golgi apparatus membrane; Multi-pass membrane
CC protein. Note=During virion morphogenesis, this protein probably
CC accumulates in the endosomes and trans-Golgi where secondary
CC envelopment occurs. It is probably transported with UL20 to the cell
CC surface from where it is endocytosed and directed to the trans-Golgi
CC network (TGN). Cell surface expression of gK is required for virus-
CC induced cell-to-cell fusion. Likely not present in extracellular
CC virions.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the alphaherpesvirinae glycoprotein K family.
CC {ECO:0000305}.
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DR EMBL; X14112; CAA32289.1; -; Genomic_DNA.
DR EMBL; DQ889502; ABI63514.1; -; Genomic_DNA.
DR EMBL; FJ593289; ACM62277.1; -; Genomic_DNA.
DR EMBL; M19122; AAA45827.1; -; Genomic_DNA.
DR PIR; A94358; MMBEK2.
DR RefSeq; YP_009137129.1; NC_001806.2.
DR SMR; P68331; -.
DR IntAct; P68331; 1.
DR MINT; P68331; -.
DR ChEMBL; CHEMBL2364696; -.
DR DrugCentral; P68331; -.
DR PRIDE; P68331; -.
DR DNASU; 2703425; -.
DR GeneID; 2703425; -.
DR KEGG; vg:2703425; -.
DR PRO; PR:P68331; -.
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:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0039700; P:fusion of viral membrane with host outer nuclear membrane; IEA:UniProtKB-KW.
DR GO; GO:0060141; P:positive regulation of syncytium formation by virus; IEA:UniProtKB-KW.
DR InterPro; IPR002567; GK.
DR Pfam; PF01621; Fusion_gly_K; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Host cell membrane; Host endosome; Host Golgi apparatus;
KW Host membrane; Membrane; Reference proteome; Signal;
KW Syncytium formation induced by viral infection; Transmembrane;
KW Transmembrane helix;
KW Viral primary envelope fusion with host outer nuclear membrane;
KW Viral release from host cell.
FT SIGNAL 1..30
FT CHAIN 31..338
FT /note="Envelope glycoprotein K"
FT /id="PRO_0000038298"
FT TOPO_DOM 31..121
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:12477855,
FT ECO:0000269|PubMed:9407122"
FT TRANSMEM 122..140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 141..212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..243
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 244..264
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 265..301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 323..338
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 31..121
FT /note="Involved in fusion"
FT /evidence="ECO:0000255"
FT REGION 265..301
FT /note="Interaction with UL20"
FT /evidence="ECO:0000255"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000305"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000305"
FT VARIANT 226
FT /note="F -> V (in strain: Nonneuroinvasive mutant HF10)"
FT MUTAGEN 33
FT /note="P->S: Induces cell-to-cell fusion capacity in cell
FT culture."
FT /evidence="ECO:0000269|PubMed:7966620"
FT MUTAGEN 40
FT /note="A->V: Induces cell-to-cell fusion capacity in cell
FT culture."
FT /evidence="ECO:0000269|PubMed:12477855,
FT ECO:0000269|PubMed:7966620"
FT MUTAGEN 86
FT /note="L->F: Induces cell-to-cell fusion capacity in cell
FT culture."
FT /evidence="ECO:0000269|PubMed:7966620"
FT MUTAGEN 99
FT /note="D->N: Induces cell-to-cell fusion capacity in cell
FT culture."
FT /evidence="ECO:0000269|PubMed:7966620"
FT MUTAGEN 111
FT /note="A->V: Induces cell-to-cell fusion capacity in cell
FT culture."
FT /evidence="ECO:0000269|PubMed:7966620"
FT MUTAGEN 121
FT /note="T->I: Induces cell-to-cell fusion capacity in cell
FT culture."
FT /evidence="ECO:0000269|PubMed:7966620"
FT MUTAGEN 304
FT /note="L->P: Induces cell-to-cell fusion capacity in cell
FT culture."
FT /evidence="ECO:0000269|PubMed:7966620"
FT MUTAGEN 310
FT /note="R->L: Induces cell-to-cell fusion capacity in cell
FT culture."
FT /evidence="ECO:0000269|PubMed:7966620"
SQ SEQUENCE 338 AA; 37573 MW; DC69FE77084E84A1 CRC64;
MLAVRSLQHL STVVLITAYG LVLVWYTVFG ASPLHRCIYA VRPTGTNNDT ALVWMKMNQT
LLFLGAPTHP PNGGWRNHAH ICYANLIAGR VVPFQVPPDA MNRRIMNVHE AVNCLETLWY
TRVRLVVVGW FLYLAFVALH QRRCMFGVVS PAHKMVAPAT YLLNYAGRIV SSVFLQYPYT
KITRLLCELS VQRQNLVQLF ETDPVTFLYH RPAIGVIVGC ELMLRFVAVG LIVGTAFISR
GACAITYPLF LTITTWCFVS TIGLTELYCI LRRGPAPKNA DKAAAPGRSK GLSGVCGRCC
SIILSGIAVR LCYIAVVAGV VLVALHYEQE IQRRLFDV
