ID   VP16_HHV1F              Reviewed;         490 AA.
AC   P04486;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   22-SEP-2009, sequence version 2.
DT   02-JUN-2021, entry version 89.
DE   RecName: Full=Tegument protein VP16;
DE   AltName: Full=Alpha trans-inducing protein;
DE   AltName: Full=Alpha-TIF;
DE   AltName: Full=ICP25;
DE   AltName: Full=Vmw65;
GN   ORFNames=UL48;
OS   Human herpesvirus 1 (strain F) (HHV-1) (Human herpes simplex virus 1).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX   NCBI_TaxID=10304;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2994050; DOI=10.1073/pnas.82.17.5870;
RA   Pellett P.E., McKnight J.L.C., Jenkins F.J., Roizman B.;
RT   "Nucleotide sequence and predicted amino acid sequence of a protein encoded
RT   in a small herpes simplex virus DNA fragment capable of trans-inducing
RT   alpha genes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:5870-5874(1985).
RN   [2]
RP   FUNCTION, AND INTERACTION WITH HUMAN HCFC1.
RX   PubMed=15522876; DOI=10.1074/jbc.m410178200;
RA   Narayanan A., Nogueira M.L., Ruyechan W.T., Kristie T.M.;
RT   "Combinatorial transcription of herpes simplex virus and varicella zoster
RT   virus immediate early genes is strictly determined by the cellular
RT   coactivator HCF-1.";
RL   J. Biol. Chem. 280:1369-1375(2005).
RN   [3]
RP   SUBCELLULAR LOCATION.
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   [4]
RP   SUBCELLULAR LOCATION.
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   [5]
RP   STRUCTURE BY NMR OF 445-479 IN COMPLEX WITH THE TFB1 SUBUNIT OF TFIIH.
RX   PubMed=18630911; DOI=10.1021/ja800975h;
RA   Langlois C., Mas C., Di Lello P., Jenkins L.M., Legault P.,
RA   Omichinski J.G.;
RT   "NMR structure of the complex between the Tfb1 subunit of TFIIH and the
RT   activation domain of VP16: structural similarities between VP16 and p53.";
RL   J. Am. Chem. Soc. 130:10596-10604(2008).
CC   -!- FUNCTION: Transcriptional activator of immediate-early (IE) gene
CC       products (alpha genes). Acts as a key activator of lytic infection by
CC       initiating the lytic program through the assembly of the
CC       transcriptional regulatory VP16-induced complex composed of VP16 and
CC       two cellular factors, HCFC1 and POU2F 1. VP16-induced complex
CC       represents a regulatory switch: when it is on, it promotes IE-gene
CC       expression and thus lytic infection, and when it is off, it limits IE-
CC       gene transcription favoring latent infection (By similarity).
CC       {ECO:0000250, ECO:0000269|PubMed:15522876}.
CC   -!- FUNCTION: May play a role in the aggregation of tegument proteins
CC       around nucleocapsids during virus morphogenesis. {ECO:0000305}.
CC   -!- SUBUNIT: Interacts with VP22. Interacts with gH (via C-terminus).
CC       Interacts with the virion host shutoff protein (vhs). Interacts with
CC       VP11/12. Associates with the VP16-induced complex; binding to host
CC       HCFC1 activates VP16 for association with the octamer motif-binding
CC       host protein POU2F1, to form a multiprotein-DNA complex responsible for
CC       activating transcription of the viral immediate early genes (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000269|PubMed:15795259,
CC       ECO:0000269|PubMed:18596102}. Host nucleus
CC       {ECO:0000269|PubMed:15795259, ECO:0000269|PubMed:18596102}.
CC   -!- DOMAIN: The transcriptional activation region seems to target many
CC       proteins of the RNA polymerase II transcription machinery.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the herpesviridae tegument protein VP16 protein
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA45766.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; K03350; AAA45766.1; ALT_INIT; Genomic_DNA.
DR   PIR; A03727; IXBE1F.
DR   PDB; 2K2U; NMR; -; B=456-490.
DR   PDBsum; 2K2U; -.
DR   BMRB; P04486; -.
DR   SMR; P04486; -.
DR   EvolutionaryTrace; P04486; -.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0019033; C:viral tegument; IEA:UniProtKB-SubCell.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0039695; P:DNA-templated viral transcription; ISS:UniProtKB.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR   DisProt; DP02291; -.
DR   Gene3D; 1.10.1290.10; -; 1.
DR   IDEAL; IID90006; -.
DR   InterPro; IPR003174; Alpha_TIF.
DR   InterPro; IPR036538; Alpha_TIF_sf.
DR   InterPro; IPR021051; HSV_VP16_C.
DR   Pfam; PF02232; Alpha_TIF; 1.
DR   Pfam; PF12149; HSV_VP16_C; 1.
DR   SMART; SM00814; Alpha_TIF; 1.
DR   SUPFAM; SSF56548; SSF56548; 1.
PE   1: Evidence at protein level;
KW   3D-structure; DNA-binding; Host nucleus; Host-virus interaction;
KW   Phosphoprotein; Transcription; Transcription regulation; Virion;
KW   Virion tegument.
FT   CHAIN           1..490
FT                   /note="Tegument protein VP16"
FT                   /id="PRO_0000115799"
FT   REGION          12..37
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          411..490
FT                   /note="Transcriptional activation"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        17..31
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            442
FT                   /note="Critical role in activation"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         18
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         353
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         411
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         452
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250"
FT   HELIX           471..477
FT                   /evidence="ECO:0007829|PDB:2K2U"
SQ   SEQUENCE   490 AA;  54316 MW;  014372DE8FE6C417 CRC64;
     MDLLVDELFA DMDADGASPP PPRPAGGPKN TPAAPPLYAT GRLSQAQLMP SPPMPVPPAA
     LFNRLLDDLG FSAGPALCTM LDTWNEDLFS ALPTNADLYR ECKFLSTLPS DVVEWGDAYV
     PERAQIDIRA HGDVAFPTLP ATRDGLGLYY EALSRFFHAE LRAREESYRT VLANFCSALY
     RYLRASVRQL HRQAHMRGRD RDLGEMLRAT IADRYYRETA RLARVLFLHL YLFLTREILW
     AAYAEQMMRP DLFDCLCCDL ESWRQLAGLF QPFMFVNGAL TVRGVPIEAR RLRELNHIRE
     HLNLPLVRSA ATEEPGAPLT TPPTLHGNQA RASGYFMVLI RAKLDSYSSF TTSPSEAVMR
     EHAYSRARTK NNYGSTIEGL LDLPDDDAPE EAGLAAPRLS FLPAGHTRRL STAPPTDVSL
     GDELHLDGED VAMAHADALD DFDLDMLGDG DSPGPGFTPH DSAPYGALDM ADFEFEQMFT
     DALGIDEYGG