ID   TEG1_HHV2H              Reviewed;         722 AA.
AC   P89466;
DT   22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   02-JUN-2021, entry version 73.
DE   RecName: Full=Tegument protein UL46;
DE   AltName: Full=Tegument protein VP11/12;
GN   ORFNames=UL46;
OS   Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX   NCBI_TaxID=10315;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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   [2]
RP   INTERACTION WITH VP16.
RC   STRAIN=186;
RX   PubMed=11087097; DOI=10.1007/s007050070045;
RA   Kato K., Daikoku T., Goshima F., Kume H., Yamaki K., Nishiyama Y.;
RT   "Synthesis, subcellular localization and VP16 interaction of the herpes
RT   simplex virus type 2 UL46 gene product.";
RL   Arch. Virol. 145:2149-2162(2000).
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.
CC       {ECO:0000250|UniProtKB:P10230}.
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.
CC       {ECO:0000250|UniProtKB:P10230, ECO:0000269|PubMed:11087097}.
CC   -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000250|UniProtKB:P10230}.
CC       Host cell membrane {ECO:0000250|UniProtKB:P10230}; Peripheral membrane
CC       protein {ECO:0000250|UniProtKB:P10230}.
CC   -!- PTM: Phosphorylated by host LCK. The phosphorylation seems to be
CC       lymphocyte-specific. {ECO:0000250|UniProtKB:P10230}.
CC   -!- SIMILARITY: Belongs to the herpesviridae HHV-1 VP11/12 protein family.
CC       {ECO:0000305}.
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DR   EMBL; Z86099; CAB06732.1; -; Genomic_DNA.
DR   PRIDE; P89466; -.
DR   Proteomes; UP000001874; Genome.
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   InterPro; IPR005051; Herpes_UL46.
DR   Pfam; PF03387; Herpes_UL46; 1.
PE   1: Evidence at protein level;
KW   Activator; Host cell membrane; Host membrane; Membrane; Reference proteome;
KW   Transcription; Transcription regulation; Virion; Virion tegument.
FT   CHAIN           1..722
FT                   /note="Tegument protein UL46"
FT                   /id="PRO_0000385462"
FT   REGION          423..534
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        470..487
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        510..524
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   722 AA;  77709 MW;  A2CFC2E04D8ABA11 CRC64;
     MQRRARGASS LRLARCLTPA NLIRGANAGV PERRIFAGCL LPTPEGLLSA AVGVLRQRAD
     DLQPAFLTGA DRSVRLAARH HNTVPESLIV DGLASDPHYD YIRHYASAAK QALGEVELSG
     GQLSRAILAQ YWKYLQTVVP SGLDIPDDPA GDCDPSLHVL LRPTLLPKLL VRAPFKSGAA
     AAKYAAAVAG LRDAAHRLQQ YMFFMRPADP SRPSTDTALR LSELLAYVSV LYHWASWMLW
     TADKYVCRRL GPADRRFVAL SGSLEAPAET FARHLDRGPS GTTGSMQCMA LRAAVSDVLG
     HLTRLAHLWE TGKRSGGTYG IVDAIVSTVE VLSIVHHHAQ YIINATLTGY VVWASDSLNN
     EYLTAAVDSQ ERFCRTAAPL FPTMTAPSWA RMELSIKSWF GAALAPDLLR SGTPSPHYES
     ILRLAASGPP GGRGAVGGSC RDKIQRTRRD NAPPPLPRAR PHSTPAAPRR CRRHREDLPE
     PPHVDAADRG PEPCAGRPAT YYTHMAGAPP RLPPRNPAPP EQRPAAAARP LAAQREAAGV
     YDAVRTWGPD AEAEPDQMEN TYLLPDDDAA MPAGVGLGAT PAADTTAAAA WPAESHAPRA
     PSEDADSIYE SVGEDGGRVY EEIPWVRVYE NICPRRRLAG GAALPGDAPD SPYIEAENPL
     YDWGGSALFS PRRATRAPDP GLSLSPMPAR PRTNALANDG PTNVAALSAL LTKLKRGRHQ
     SH