VP16_HHV11
ID VP16_HHV11 Reviewed; 490 AA.
AC P06492; B9VQH6; Q09I86;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 25-MAY-2022, entry version 141.
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 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 [GENOMIC DNA].
RX PubMed=2999707; DOI=10.1093/nar/13.21.7865;
RA Dalrymple M.A., McGeoch D.J., Davison A.J., Preston C.M.;
RT "DNA sequence of the herpes simplex virus type 1 gene whose product is
RT responsible for transcriptional activation of immediate early promoters.";
RL Nucleic Acids Res. 13:7865-7879(1985).
RN [2]
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 [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 DNA-BINDING.
RX PubMed=2676518; DOI=10.1002/j.1460-2075.1989.tb08361.x;
RA Cousens D.J., Greaves R.F., Goding C.R., O'Hare P.;
RT "The C-terminal 79 amino acids of the herpes simplex virus regulatory
RT protein, Vmw65, efficiently activate transcription in yeast and mammalian
RT cells in chimeric DNA-binding proteins.";
RL EMBO J. 8:2337-2342(1989).
RN [6]
RP INTERACTION WITH VIRION HOST SHUTOFF PROTEIN.
RC STRAIN=KOS;
RX PubMed=8139019; DOI=10.1128/jvi.68.4.2339-2346.1994;
RA Smibert C.A., Popova B., Xiao P., Capone J.P., Smiley J.R.;
RT "Herpes simplex virus VP16 forms a complex with the virion host shutoff
RT protein vhs.";
RL J. Virol. 68:2339-2346(1994).
RN [7]
RP INTERACTION WITH GH.
RC STRAIN=SC16;
RX PubMed=14675620; DOI=10.1016/j.virol.2003.08.023;
RA Gross S.T., Harley C.A., Wilson D.W.;
RT "The cytoplasmic tail of Herpes simplex virus glycoprotein H binds to the
RT tegument protein VP16 in vitro and in vivo.";
RL Virology 317:1-12(2003).
RN [8]
RP PHOSPHORYLATION AT SER-18; SER-353; SER-411 AND SER-452.
RX PubMed=16297954; DOI=10.1016/j.virol.2005.10.011;
RA Ottosen S., Herrera F.J., Doroghazi J.R., Hull A., Mittal S., Lane W.S.,
RA Triezenberg S.J.;
RT "Phosphorylation of the VP16 transcriptional activator protein during
RT herpes simplex virus infection and mutational analysis of putative
RT phosphorylation sites.";
RL Virology 345:468-481(2006).
RN [9]
RP INTERACTION WITH VP22.
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 [10]
RP REVIEW, AND IDENTIFICATION IN THE VP16-INDUCED COMPLEX.
RX PubMed=12826401; DOI=10.1016/s0968-0004(03)00088-4;
RA Wysocka J., Herr W.;
RT "The herpes simplex virus VP16-induced complex: the makings of a regulatory
RT switch.";
RL Trends Biochem. Sci. 28:294-304(2003).
RN [11]
RP STRUCTURE BY NMR OF 465-490.
RX PubMed=15654739; DOI=10.1021/bi0482912;
RA Jonker H.R., Wechselberger R.W., Boelens R., Folkers G.E., Kaptein R.;
RT "Structural properties of the promiscuous VP16 activation domain.";
RL Biochemistry 44:827-839(2005).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 49-412, AND INTERACTION WITH HUMAN
RP HCFC1 AND HUMAN POU2F1.
RX PubMed=10398682; DOI=10.1101/gad.13.13.1692;
RA Liu Y., Gong W., Huang C.C., Herr W., Cheng X.;
RT "Crystal structure of the conserved core of the herpes simplex virus
RT transcriptional regulatory protein VP16.";
RL Genes Dev. 13:1692-1703(1999).
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.
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.
CC {ECO:0000269|PubMed:10398682, ECO:0000269|PubMed:12826401,
CC ECO:0000269|PubMed:14675620, ECO:0000269|PubMed:19279114,
CC ECO:0000269|PubMed:8139019}.
CC -!- INTERACTION:
CC P06492; P10225: UL41; NbExp=3; IntAct=EBI-7489933, EBI-6148417;
CC P06492; P10230: UL46; NbExp=2; IntAct=EBI-7489933, EBI-7694458;
CC P06492; P10233: UL49; NbExp=2; IntAct=EBI-7489933, EBI-7490002;
CC P06492; Q7XYY2: MED25; Xeno; NbExp=2; IntAct=EBI-7489933, EBI-1386292;
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000250|UniProtKB:P04486}.
CC Host nucleus {ECO:0000250|UniProtKB:P04486}.
CC -!- DOMAIN: The transcriptional activation region seems to target many
CC proteins of the RNA polymerase II transcription machinery.
CC -!- SIMILARITY: Belongs to the herpesviridae tegument protein VP16 protein
CC family. {ECO:0000305}.
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DR EMBL; X14112; CAA32298.1; -; Genomic_DNA.
DR EMBL; X03141; CAA26913.1; -; Genomic_DNA.
DR EMBL; DQ889502; ABI63509.1; -; Genomic_DNA.
DR EMBL; FJ593289; ACM62271.1; -; Genomic_DNA.
DR PIR; A24118; IXBE17.
DR RefSeq; YP_009137123.1; NC_001806.2.
DR PDB; 16VP; X-ray; 2.10 A; A=47-412.
DR PDB; 2PHE; NMR; -; C=465-490.
DR PDB; 2PHG; NMR; -; B=465-490.
DR PDBsum; 16VP; -.
DR PDBsum; 2PHE; -.
DR PDBsum; 2PHG; -.
DR BMRB; P06492; -.
DR SMR; P06492; -.
DR BioGRID; 971443; 17.
DR DIP; DIP-41776N; -.
DR ELM; P06492; -.
DR IntAct; P06492; 9.
DR MINT; P06492; -.
DR BindingDB; P06492; -.
DR ChEMBL; CHEMBL4218; -.
DR iPTMnet; P06492; -.
DR PRIDE; P06492; -.
DR DNASU; 24271473; -.
DR GeneID; 24271473; -.
DR KEGG; vg:24271473; -.
DR EvolutionaryTrace; P06492; -.
DR PRO; PR:P06492; -.
DR Proteomes; UP000009294; Genome.
DR Proteomes; UP000180652; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:CAFA.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IDA:CAFA.
DR GO; GO:0042025; C:host cell nucleus; IDA:CAFA.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IDA:CAFA.
DR GO; GO:0046809; C:replication compartment; IDA:CAFA.
DR GO; GO:0005667; C:transcription regulator complex; IMP:UniProtKB.
DR GO; GO:0019033; C:viral tegument; IDA:CAFA.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IMP:CAFA.
DR GO; GO:0003677; F:DNA binding; IDA:CAFA.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:CAFA.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:CAFA.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:CAFA.
DR GO; GO:0039660; F:structural constituent of virion; IDA:CAFA.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:CAFA.
DR GO; GO:0051701; P:biological process involved in interaction with host; IDA:CAFA.
DR GO; GO:0039695; P:DNA-templated viral transcription; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:CAFA.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:CAFA.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:CAFA.
DR GO; GO:0046782; P:regulation of viral transcription; IMP:CAFA.
DR DisProt; DP01642; -.
DR Gene3D; 1.10.1290.10; -; 1.
DR IDEAL; IID90007; -.
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; Reference proteome; Transcription;
KW Transcription regulation; Virion; Virion tegument.
FT CHAIN 1..490
FT /note="Tegument protein VP16"
FT /id="PRO_0000115798"
FT REGION 12..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 411..490
FT /note="Transcriptional activation"
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 MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16297954"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16297954"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16297954"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16297954"
FT VARIANT 14
FT /note="A -> S (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 124
FT /note="T -> A (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 235
FT /note="T -> A (in strain: 17 syn+)"
FT VARIANT 390
FT /note="E -> K (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 413
FT /note="A -> P (in strain: Nonneuroinvasive mutant HF10)"
FT HELIX 58..69
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 74..83
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 96..99
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 109..118
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 146..196
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 203..247
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 250..253
FT /evidence="ECO:0007829|PDB:16VP"
FT STRAND 256..261
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 264..267
FT /evidence="ECO:0007829|PDB:16VP"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 289..301
FT /evidence="ECO:0007829|PDB:16VP"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:16VP"
FT HELIX 332..344
FT /evidence="ECO:0007829|PDB:16VP"
FT STRAND 398..401
FT /evidence="ECO:0007829|PDB:16VP"
FT TURN 466..469
FT /evidence="ECO:0007829|PDB:2PHE"
FT HELIX 470..473
FT /evidence="ECO:0007829|PDB:2PHE"
FT HELIX 475..479
FT /evidence="ECO:0007829|PDB:2PHE"
FT TURN 480..482
FT /evidence="ECO:0007829|PDB:2PHE"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:2PHE"
FT HELIX 486..488
FT /evidence="ECO:0007829|PDB:2PHE"
SQ SEQUENCE 490 AA; 54345 MW; 8DDDEDEDB2A699D3 CRC64;
MDLLVDELFA DMNADGASPP PPRPAGGPKN TPAAPPLYAT GRLSQAQLMP SPPMPVPPAA
LFNRLLDDLG FSAGPALCTM LDTWNEDLFS ALPTNADLYR ECKFLSTLPS DVVEWGDAYV
PERTQIDIRA 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
