VP22_HHV11
ID VP22_HHV11 Reviewed; 301 AA.
AC P10233; B9VQH7; Q09I85;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 23-FEB-2022, entry version 90.
DE RecName: Full=Tegument protein VP22;
GN ORFNames=UL49;
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 IDENTIFICATION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=1312128; DOI=10.1099/0022-1317-73-3-723;
RA Elliott G.D., Meredith D.M.;
RT "The herpes simplex virus type 1 tegument protein VP22 is encoded by gene
RT UL49.";
RL J. Gen. Virol. 73:723-726(1992).
RN [5]
RP SUBCELLULAR LOCATION.
RC STRAIN=Isolate 1802;
RX PubMed=8659129; DOI=10.1006/viro.1996.0286;
RA Leslie J., Rixon F.J., McLauchlan J.;
RT "Overexpression of the herpes simplex virus type 1 tegument protein VP22
RT increases its incorporation into virus particles.";
RL Virology 220:60-68(1996).
RN [6]
RP FUNCTION.
RX PubMed=9658087; DOI=10.1128/jvi.72.8.6448-6455.1998;
RA Elliott G., O'Hare P.;
RT "Herpes simplex virus type 1 tegument protein VP22 induces the
RT stabilization and hyperacetylation of microtubules.";
RL J. Virol. 72:6448-6455(1998).
RN [7]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=11967313; DOI=10.1128/jvi.76.10.4961-4970.2002;
RA Martin A., O'Hare P., McLauchlan J., Elliott G.;
RT "Herpes simplex virus tegument protein VP22 contains overlapping domains
RT for cytoplasmic localization, microtubule interaction, and chromatin
RT binding.";
RL J. Virol. 76:4961-4970(2002).
RN [8]
RP FUNCTION, AND INTERACTION WITH HOST SET.
RX PubMed=12917472; DOI=10.1099/vir.0.19326-0;
RA van Leeuwen H., Okuwaki M., Hong R., Chakravarti D., Nagata K., O'Hare P.;
RT "Herpes simplex virus type 1 tegument protein VP22 interacts with TAF-I
RT proteins and inhibits nucleosome assembly but not regulation of histone
RT acetylation by INHAT.";
RL J. Gen. Virol. 84:2501-2510(2003).
RN [9]
RP SUBCELLULAR LOCATION.
RC STRAIN=F;
RX PubMed=15795259; DOI=10.1128/jvi.79.8.4730-4743.2005;
RA Yedowitz J.C., Kotsakis A., Schlegel E.F., Blaho J.A.;
RT "Nuclear localizations of the herpes simplex virus type 1 tegument proteins
RT VP13/14, vhs, and VP16 precede VP22-dependent microtubule reorganization
RT and VP22 nuclear import.";
RL J. Virol. 79:4730-4743(2005).
RN [10]
RP INTERACTION WITH GD AND GE.
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 [11]
RP INTERACTION WITH GE.
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 [12]
RP SUBCELLULAR LOCATION.
RC STRAIN=F;
RX PubMed=18353954; DOI=10.1128/jvi.02681-07;
RA Sugimoto K., Uema M., Sagara H., Tanaka M., Sata T., Hashimoto Y.,
RA Kawaguchi Y.;
RT "Simultaneous tracking of capsid, tegument, and envelope protein
RT localization in living cells infected with triply fluorescent herpes
RT simplex virus 1.";
RL J. Virol. 82:5198-5211(2008).
RN [13]
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).
RN [14]
RP SUBCELLULAR LOCATION, INTERACTION WITH GE AND VP16, AND LACK OF INTERACTION
RP WITH GD.
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 [15]
RP FUNCTION, AND INTERACTION WITH GE AND GM.
RX PubMed=22993164; DOI=10.1128/jvi.01913-12;
RA Maringer K., Stylianou J., Elliott G.;
RT "A network of protein interactions around the herpes simplex virus tegument
RT protein VP22.";
RL J. Virol. 86:12971-12982(2012).
RN [16]
RP FUNCTION.
RX PubMed=22951838; DOI=10.1128/jvi.01975-12;
RA Mbong E.F., Woodley L., Dunkerley E., Schrimpf J.E., Morrison L.A.,
RA Duffy C.;
RT "Deletion of the herpes simplex virus 1 UL49 gene results in mRNA and
RT protein translation defects that are complemented by secondary mutations in
RT UL41.";
RL J. Virol. 86:12351-12361(2012).
RN [17]
RP FUNCTION, AND INTERACTION WITH UL16.
RX PubMed=24131716; DOI=10.1128/jvi.02555-13;
RA Starkey J.L., Han J., Chadha P., Marsh J.A., Wills J.W.;
RT "Elucidation of the block to herpes simplex virus egress in the absence of
RT tegument protein UL16 reveals a novel interaction with VP22.";
RL J. Virol. 88:110-119(2014).
RN [18]
RP FUNCTION, AND INTERACTION WITH HOST CGAS.
RX PubMed=29793952; DOI=10.1128/jvi.00841-18;
RA Huang J., You H., Su C., Li Y., Chen S., Zheng C.;
RT "Herpes simplex virus 1 tegument protein VP22 abrogates cGAS/STING-mediated
RT antiviral innate immunity.";
RL J. Virol. 92:0-0(2018).
RN [19]
RP FUNCTION, AND INTERACTION WITH HOST CGAS.
RX PubMed=34015248; DOI=10.1016/j.molcel.2021.05.002;
RA Xu G., Liu C., Zhou S., Li Q., Feng Y., Sun P., Feng H., Gao Y., Zhu J.,
RA Luo X., Zhan Q., Liu S., Zhu S., Deng H., Li D., Gao P.;
RT "Viral tegument proteins restrict cGAS-DNA phase separation to mediate
RT immune evasion.";
RL Mol. Cell 81:2823-2837(2021).
CC -!- FUNCTION: Tegument protein that plays different roles during the time
CC course of infection (PubMed:22993164, PubMed:24131716, PubMed:9658087,
CC PubMed:11967313). Participates in both the accumulation of viral mRNAs
CC and viral protein translation at late time of infection
CC (PubMed:22993164, PubMed:24131716, PubMed:9658087, PubMed:11967313).
CC Modulates the RNase activity of the virion host shutoff protein UL41
CC probably to ensure necessary levels of key cellular mRNAs and proteins
CC (PubMed:22951838). Plays a role in microtubule reorganization that
CC occurs after viral infection by stabilizing microtubule network
CC (PubMed:9658087, PubMed:11967313). Finally, may prevent nucleosomal
CC deposition onto the viral genome by interacting with and inhibiting
CC host SET (PubMed:12917472). Plays a role in the inhibition of host
CC innate immune system by targeting the CGAS enzymatic activity which is
CC the principal cytosolic DNA sensor that detects invading viral DNA
CC (PubMed:29793952, PubMed:34015248). Acts by mediating disruption of
CC liquid-like droplets in which CGAS is activated, thereby preventing
CC CGAS activity (PubMed:34015248). {ECO:0000269|PubMed:11967313,
CC ECO:0000269|PubMed:12917472, ECO:0000269|PubMed:22951838,
CC ECO:0000269|PubMed:22993164, ECO:0000269|PubMed:24131716,
CC ECO:0000269|PubMed:29793952, ECO:0000269|PubMed:34015248,
CC ECO:0000269|PubMed:9658087}.
CC -!- SUBUNIT: Interacts with gE (via C-terminus); this interaction is
CC necessary for the recruitment of VP22 to the Golgi and its packaging
CC into virions (PubMed:17035313, PubMed:16997344, PubMed:19279114,
CC PubMed:22993164). Interacts with gM (via C-terminus) (PubMed:22993164).
CC Interacts with VP16; this interaction allows the formation of a
CC tripartite complex composed of VP16, VP22 and UL41/VHS
CC (PubMed:19279114). According to a report interacts with gD (via C-
CC terminus) (PubMed:17035313). According another publication, does not
CC interact with gD (PubMed:19279114). Interacts with host CGAS
CC (PubMed:29793952, PubMed:34015248). Interacts with host SET; this
CC interaction may interfere with SET-mediated nucleosomal deposition onto
CC the viral genome (PubMed:12917472). Interacts with the capsid-binding
CC protein UL16 (PubMed:24131716). {ECO:0000269|PubMed:12917472,
CC ECO:0000269|PubMed:16997344, ECO:0000269|PubMed:17035313,
CC ECO:0000269|PubMed:19279114, ECO:0000269|PubMed:22993164,
CC ECO:0000269|PubMed:24131716, ECO:0000269|PubMed:29793952,
CC ECO:0000269|PubMed:34015248}.
CC -!- INTERACTION:
CC P10233; P06492: UL48; NbExp=2; IntAct=EBI-7490002, EBI-7489933;
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000269|PubMed:18596102,
CC ECO:0000269|PubMed:8659129}. Host cytoplasm
CC {ECO:0000269|PubMed:11967313, ECO:0000269|PubMed:1312128,
CC ECO:0000269|PubMed:18353954, ECO:0000269|PubMed:19279114}. Host nucleus
CC {ECO:0000269|PubMed:11967313, ECO:0000269|PubMed:15795259,
CC ECO:0000269|PubMed:18353954}. Host Golgi apparatus
CC {ECO:0000269|PubMed:19279114}. Note=One of the most abundant tegument
CC protein (about 2000 copies per virion). Localizes in the cytoplasm at 8
CC hours postinfection and in the nucleus at 16 hours postinfection.
CC During virion morphogenesis, this protein probably accumulates at the
CC trans-Golgi where secondary envelopment occurs.
CC -!- PTM: Highly phosphorylated in the host cell. Packaging is selective for
CC underphosphorylated forms. {ECO:0000305|PubMed:1312128}.
CC -!- SIMILARITY: Belongs to the alphaherpesvirinae VP22 tegument protein
CC family. {ECO:0000305}.
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DR EMBL; X14112; CAA32299.1; -; Genomic_DNA.
DR EMBL; DQ889502; ABI63510.1; -; Genomic_DNA.
DR EMBL; FJ593289; ACM62272.1; -; Genomic_DNA.
DR PIR; D30089; WMBEF9.
DR RefSeq; YP_009137124.1; NC_001806.2.
DR PDB; 4XAL; X-ray; 1.87 A; A=174-281.
DR PDBsum; 4XAL; -.
DR SMR; P10233; -.
DR BioGRID; 971444; 9.
DR DIP; DIP-57160N; -.
DR IntAct; P10233; 3.
DR MINT; P10233; -.
DR PRIDE; P10233; -.
DR GeneID; 2703417; -.
DR KEGG; vg:2703417; -.
DR Proteomes; UP000009294; Genome.
DR Proteomes; UP000180652; Genome.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019033; C:viral tegument; IEA:UniProtKB-SubCell.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IDA:UniProtKB.
DR InterPro; IPR006908; Herpes_UL49.
DR Pfam; PF04823; Herpes_UL49_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cytoplasm; Host Golgi apparatus; Host nucleus;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Phosphoprotein; Reference proteome; Viral immunoevasion; Virion;
KW Virion tegument.
FT CHAIN 1..301
FT /note="Tegument protein VP22"
FT /id="PRO_0000116093"
FT REGION 1..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 174..267
FT /note="Interaction with gE"
FT /evidence="ECO:0000269|PubMed:17035313"
FT REGION 269..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 163..166
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P30022"
FT MOTIF 232..244
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P30022"
FT COMPBIAS 28..44
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 45..59
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 20
FT /note="E -> G (in strain: 17 syn+)"
FT VARIANT 135
FT /note="P -> Q (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 141
FT /note="R -> C (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 220
FT /note="L -> I (in strain: 17 syn+)"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:4XAL"
FT HELIX 191..224
FT /evidence="ECO:0007829|PDB:4XAL"
FT HELIX 229..238
FT /evidence="ECO:0007829|PDB:4XAL"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:4XAL"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:4XAL"
FT HELIX 251..257
FT /evidence="ECO:0007829|PDB:4XAL"
SQ SEQUENCE 301 AA; 32254 MW; 6E9539C2AEE13E29 CRC64;
MTSRRSVKSG PREVPRDEYE DLYYTPSSGM ASPDSPPDTS RRGALQTRSR QRGEVRFVQY
DESDYALYGG SSSEDDEHPE VPRTRRPVSG AVLSGPGPAR APPPPAGSGG AGRTPTTAPR
APRTQRVATK APAAPAAETT RGRKSAQPES AALPDAPAST APTRSKTPAQ GLARKLHFST
APPNPDAPWT PRVAGFNKRV FCAAVGRLAA MHARMAAVQL WDMSRPRTDE DLNELLGITT
IRVTVCEGKN LLQRANELVN PDVVQDVDAA TATRGRSAAS RPTERPRAPA RSASRPRRPV
E
