TEG1_HHV11
ID TEG1_HHV11 Reviewed; 718 AA.
AC P10230; B9VQH4; O09799; Q09I88;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2003, sequence version 2.
DT 02-JUN-2021, entry version 87.
DE RecName: Full=Tegument protein UL46;
DE AltName: Full=Tegument protein VP11/12;
GN ORFNames=UL46;
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 SEQUENCE REVISION TO 170-182.
RX PubMed=9499055; DOI=10.1128/jvi.72.3.2010-2021.1998;
RA Dolan A., Jamieson F.E., Cunningham C., Barnett B.C., McGeoch D.J.;
RT "The genome sequence of herpes simplex virus type 2.";
RL J. Virol. 72:2010-2021(1998).
RN [3]
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 [4]
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 [5]
RP INTERACTION WITH PROTEIN VP16.
RX PubMed=16014918; DOI=10.1128/jvi.79.15.9566-9571.2005;
RA Vittone V., Diefenbach E., Triffett D., Douglas M.W., Cunningham A.L.,
RA Diefenbach R.J.;
RT "Determination of interactions between tegument proteins of herpes simplex
RT virus type 1.";
RL J. Virol. 79:9566-9571(2005).
RN [6]
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 [7]
RP PHOSPHORYLATION BY HOST LCK.
RX PubMed=18417566; DOI=10.1128/jvi.02121-07;
RA Zahariadis G., Wagner M.J., Doepker R.C., Maciejko J.M., Crider C.M.,
RA Jerome K.R., Smiley J.R.;
RT "Cell-type-specific tyrosine phosphorylation of the herpes simplex virus
RT tegument protein VP11/12 encoded by gene UL46.";
RL J. Virol. 82:6098-6108(2008).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=18452963; DOI=10.1016/j.virol.2008.03.018;
RA Murphy M.A., Bucks M.A., O'Regan K.J., Courtney R.J.;
RT "The HSV-1 tegument protein pUL46 associates with cellular membranes and
RT viral capsids.";
RL Virology 376:279-289(2008).
RN [9]
RP FUNCTION.
RX PubMed=19776125; DOI=10.1128/jvi.01364-09;
RA Wagner M.J., Smiley J.R.;
RT "Herpes simplex virus requires VP11/12 to induce phosphorylation of the
RT activation loop tyrosine (Y394) of the Src family kinase Lck in T
RT lymphocytes.";
RL J. Virol. 83:12452-12461(2009).
RN [10]
RP FUNCTION, AND INTERACTION WITH HOST PIK3R1.
RX PubMed=21228233; DOI=10.1128/jvi.01877-10;
RA Wagner M.J., Smiley J.R.;
RT "Herpes simplex virus requires VP11/12 to activate Src family kinase-
RT phosphoinositide 3-kinase-Akt signaling.";
RL J. Virol. 85:2803-2812(2011).
RN [11]
RP FUNCTION, AND INTERACTION WITH ICP0 AND HOST YWHAB.
RX PubMed=23938468; DOI=10.1074/mcp.m113.030866;
RA Lin A.E., Greco T.M., Dohner K., Sodeik B., Cristea I.M.;
RT "A proteomic perspective of inbuilt viral protein regulation: pUL46
RT tegument protein is targeted for degradation by ICP0 during herpes simplex
RT virus type 1 infection.";
RL Mol. Cell. Proteomics 12:3237-3252(2013).
RN [12]
RP FUNCTION, AND INTERACTION WITH HOST LCK; PIK3R1; SHC1 AND GRB2.
RX PubMed=23946459; DOI=10.1128/jvi.01702-13;
RA Strunk U., Saffran H.A., Wu F.W., Smiley J.R.;
RT "Role of herpes simplex virus VP11/12 tyrosine-based motifs in binding and
RT activation of the Src family kinase Lck and recruitment of p85, Grb2, and
RT Shc.";
RL J. Virol. 87:11276-11286(2013).
RN [13]
RP FUNCTION.
RX PubMed=24741093; DOI=10.1128/jvi.00712-14;
RA Eaton H.E., Saffran H.A., Wu F.W., Quach K., Smiley J.R.;
RT "Herpes simplex virus protein kinases US3 and UL13 modulate VP11/12
RT phosphorylation, virion packaging, and phosphatidylinositol 3-kinase/Akt
RT signaling activity.";
RL J. Virol. 88:7379-7388(2014).
RN [14]
RP FUNCTION, AND INTERACTION WITH HOST DOK2.
RX PubMed=28841444; DOI=10.1016/j.virol.2017.08.018;
RA Lahmidi S., Strunk U., Smiley J.R., Pearson A., Duplay P.;
RT "Herpes simplex virus 1 infection of T cells causes VP11/12-dependent
RT phosphorylation and degradation of the cellular protein Dok-2.";
RL Virology 511:66-73(2017).
RN [15]
RP FUNCTION, INTERACTION WITH HOST TMEM173 AND TBK1, AND SUBCELLULAR LOCATION.
RX PubMed=28592536; DOI=10.1128/jvi.00535-17;
RA Deschamps T., Kalamvoki M.;
RT "Evasion of the STING DNA-Sensing Pathway by VP11/12 of Herpes Simplex
RT Virus 1.";
RL J. Virol. 91:0-0(2017).
CC -!- FUNCTION: Plays a role in the activation of the host PI3K/AKT pathway
CC to promote cell survival. Interacts with and activates host LCK and
CC thereby recruits downstream partners SHC1, GRB2 and PI3KR1 in order to
CC activate the PI3K pathway by phosphorylating host AKT on its activating
CC residues. This mechanism is inhibited by the viral protein US3 that
CC instead promotes incorporation of UL46 into virions. Plays a role in
CC the inhibition of TMEM173/STING-mediated type I interferon production
CC (PubMed:28592536). Interacts with host DOK2 and induces its
CC degradation. This immune evasion mechanism to inactivate T-cells may
CC play an important role during pathogenesis (PubMed:28841444).
CC {ECO:0000269|PubMed:19776125, ECO:0000269|PubMed:21228233,
CC ECO:0000269|PubMed:23938468, ECO:0000269|PubMed:23946459,
CC ECO:0000269|PubMed:24741093, ECO:0000269|PubMed:28592536,
CC ECO:0000269|PubMed:28841444}.
CC -!- SUBUNIT: Interacts with VP16. Interacts with host LCK, PIK3R1, SHC1 AND
CC GRB2; these interactions promote the activation of the PI3K/AKT
CC pathway. Interacts with host YWHAB. Interacts with ICP0; this
CC interaction targets UL46 for degradation by the proteasome. Interacts
CC (via N-terminus) with host TMEM173 (PubMed:28592536). Interacts (via C-
CC terminus) with host TBK1 (PubMed:28592536). Interacts with host DOK2
CC (PubMed:28841444). {ECO:0000269|PubMed:16014918,
CC ECO:0000269|PubMed:21228233, ECO:0000269|PubMed:23938468,
CC ECO:0000269|PubMed:23946459, ECO:0000269|PubMed:28592536,
CC ECO:0000269|PubMed:28841444}.
CC -!- INTERACTION:
CC P10230; P06492: UL48; NbExp=2; IntAct=EBI-7694458, EBI-7489933;
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000269|PubMed:18596102}.
CC Host cytoplasm {ECO:0000269|PubMed:28592536}. Host cell membrane
CC {ECO:0000269|PubMed:18452963}; Peripheral membrane protein
CC {ECO:0000269|PubMed:18452963}.
CC -!- PTM: Phosphorylated by host LCK. The phosphorylation seems to be
CC lymphocyte-specific. {ECO:0000269|PubMed:18417566}.
CC -!- SIMILARITY: Belongs to the herpesviridae HHV-1 VP11/12 protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABI63507.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X14112; CAA32296.1; -; Genomic_DNA.
DR EMBL; DQ889502; ABI63507.1; ALT_FRAME; Genomic_DNA.
DR EMBL; FJ593289; ACM62269.1; -; Genomic_DNA.
DR PIR; A30089; TNBEF6.
DR RefSeq; YP_009137121.1; NC_001806.2.
DR BioGRID; 971441; 9.
DR IntAct; P10230; 1.
DR MINT; P10230; -.
DR PRIDE; P10230; -.
DR DNASU; 2703413; -.
DR GeneID; 2703413; -.
DR KEGG; vg:2703413; -.
DR Proteomes; UP000009294; Genome.
DR Proteomes; UP000180652; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0019033; C:viral tegument; IEA:UniProtKB-SubCell.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR InterPro; IPR005051; Herpes_UL46.
DR Pfam; PF03387; Herpes_UL46; 1.
PE 1: Evidence at protein level;
KW Activator; Host cell membrane; Host cytoplasm; Host membrane;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Membrane; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Viral immunoevasion; Virion; Virion tegument.
FT CHAIN 1..718
FT /note="Tegument protein UL46"
FT /id="PRO_0000115792"
FT REGION 433..510
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 581..611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 454..471
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..611
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 3
FT /note="R -> H (in strain: 17 syn+)"
FT VARIANT 411
FT /note="N -> S (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 510
FT /note="A -> V (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 513
FT /note="T -> A (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 631
FT /note="R -> W (in strain: Nonneuroinvasive mutant HF10)"
SQ SEQUENCE 718 AA; 78241 MW; 45AD4157451C72B0 CRC64;
MQRRTRGASS LRLARCLTPA NLIRGDNAGV PERRIFGGCL LPTPEGLLSA AVGALRQRSD
DAQPAFLTCT DRSVRLAARQ HNTVPESLIV DGLASDPHYE YIRHYASAAT QALGEVELPG
GQLSRAILTQ YWKYLQTVVP SGLDVPEDPV GDCDPSLHVL LRPTLAPKLL ARTPFKSGAV
AAKYAATVAG LRDALHRIQQ YMFFMRPADP SRPSTDTALR LNELLAYVSV LYRWASWMLW
TTDKHVCHRL SPSNRRFLPL GGSPEAPAET FARHLDRGPS GTTGSMQCMA LRAAVSDVLG
HLTRLANLWQ TGKRSGGTYG TVDTVVSTVE VLSIVHHHAQ YIINATLTGY GVWATDSLNN
EYLRAAVDSQ ERFCRTTAPL FPTMTAPSWA RMELSIKAWF GAALAADLLR NGAPSLHYES
ILRLVASRRT TWSAGPPPDD MASGPGGHRA GGGTCREKIQ RARRDNEPPP LPRPRLHSTP
ASTRRFRRRR ADGAGPPLPD ANDPVAEPPA AATQPATYYT HMGEVPPRLP ARNVAGPDRR
PPAATCPLLV RRASLGSLDR PRVWGPAPEG EPDQMEATYL TADDDDDDAR RKATHAASAR
ERHAPYEDDE SIYETVSEDG GRVYEEIPWM RVYENVCVNT ANAAPASPYI EAENPLYDWG
GSALFSPPGR TGPPPPPLSP SPVLARHRAN ALTNDGPTNV AALSALLTKL KREGRRSR
