ICP4_HHV11
ID ICP4_HHV11 Reviewed; 1298 AA.
AC P08392;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 02-JUN-2021, entry version 116.
DE RecName: Full=Major viral transcription factor ICP4;
DE AltName: Full=Alpha-4 protein;
DE AltName: Full=Infected cell protein 4;
DE AltName: Full=Transcriptional activator IE175;
GN Name=ICP4; Synonyms=IE175; ORFNames=RS1;
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=3005980; DOI=10.1093/nar/14.4.1727;
RA McGeoch D.J., Dolan A., Donald S., Brauer D.H.K.;
RT "Complete DNA sequence of the short repeat region in the genome of herpes
RT simplex virus type 1.";
RL Nucleic Acids Res. 14:1727-1745(1986).
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 HOMODIMERIZATION.
RX PubMed=2991559; DOI=10.1128/jvi.55.2.329-337.1985;
RA Metzler D.W., Wilcox K.W.;
RT "Isolation of herpes simplex virus regulatory protein ICP4 as a homodimeric
RT complex.";
RL J. Virol. 55:329-337(1985).
RN [4]
RP DNA-BINDING DOMAIN.
RX PubMed=2155403; DOI=10.1093/nar/18.3.531;
RA Wu C.-L., Wilcox K.W.;
RT "Codons 262 to 490 from the herpes simplex virus ICP4 gene are sufficient
RT to encode a sequence-specific DNA binding protein.";
RL Nucleic Acids Res. 18:531-538(1990).
RN [5]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=1846804; DOI=10.1002/j.1460-2075.1991.tb07961.x;
RA Papavassiliou A.G., Wilcox K.W., Silverstein S.J.;
RT "The interaction of ICP4 with cell/infected-cell factors and its state of
RT phosphorylation modulate differential recognition of leader sequences in
RT herpes simplex virus DNA.";
RL EMBO J. 10:397-406(1991).
RN [6]
RP FUNCTION, AND INTERACTION WITH HOST GTF2B.
RX PubMed=8392607; DOI=10.1128/jvi.67.8.4676-4687.1993;
RA Smith C.A., Bates P., Rivera-Gonzalez R., Gu B., DeLuca N.A.;
RT "ICP4, the major transcriptional regulatory protein of herpes simplex virus
RT type 1, forms a tripartite complex with TATA-binding protein and TFIIB.";
RL J. Virol. 67:4676-4687(1993).
RN [7]
RP FUNCTION, AND INTERACTION WITH HOST TBP AND TAF1.
RX PubMed=8649420; DOI=10.1128/mcb.16.6.3085;
RA Carrozza M.J., DeLuca N.A.;
RT "Interaction of the viral activator protein ICP4 with TFIID through
RT TAF250.";
RL Mol. Cell. Biol. 16:3085-3093(1996).
RN [8]
RP INTERACTION WITH ICP27.
RX PubMed=8995681; DOI=10.1128/jvi.71.2.1547-1557.1997;
RA Panagiotidis C.A., Lium E.K., Silverstein S.J.;
RT "Physical and functional interactions between herpes simplex virus
RT immediate-early proteins ICP4 and ICP27.";
RL J. Virol. 71:1547-1557(1997).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=17959681; DOI=10.1128/jvi.01588-07;
RA Sedlackova L., Rice S.A.;
RT "Herpes simplex virus type 1 immediate-early protein ICP27 is required for
RT efficient incorporation of ICP0 and ICP4 into virions.";
RL J. Virol. 82:268-277(2008).
RN [10]
RP FUNCTION.
RX PubMed=18094162; DOI=10.1128/jvi.02459-07;
RA Sampath P., Deluca N.A.;
RT "Binding of ICP4, TATA-binding protein, and RNA polymerase II to herpes
RT simplex virus type 1 immediate-early, early, and late promoters in virus-
RT infected cells.";
RL J. Virol. 82:2339-2349(2008).
RN [11]
RP FUNCTION.
RX PubMed=18216093; DOI=10.1128/jvi.02560-07;
RA Zabierowski S.E., Deluca N.A.;
RT "Stabilized binding of TBP to the TATA box of herpes simplex virus type 1
RT early (tk) and late (gC) promoters by TFIIA and ICP4.";
RL J. Virol. 82:3546-3554(2008).
RN [12]
RP FUNCTION, AND DOMAIN.
RX PubMed=22496239; DOI=10.1128/jvi.00651-12;
RA Wagner L.M., Lester J.T., Sivrich F.L., DeLuca N.A.;
RT "The N terminus and C terminus of herpes simplex virus 1 ICP4 cooperate to
RT activate viral gene expression.";
RL J. Virol. 86:6862-6874(2012).
RN [13]
RP FUNCTION.
RX PubMed=23135715; DOI=10.1128/jvi.02844-12;
RA Wagner L.M., Bayer A., Deluca N.A.;
RT "Requirement of the N-terminal activation domain of herpes simplex virus
RT ICP4 for viral gene expression.";
RL J. Virol. 87:1010-1018(2013).
RN [14]
RP FUNCTION.
RX PubMed=24147125; DOI=10.1371/journal.pone.0078242;
RA Wagner L.M., DeLuca N.A.;
RT "Temporal association of herpes simplex virus ICP4 with cellular complexes
RT functioning at multiple steps in PolII transcription.";
RL PLoS ONE 8:E78242-E78242(2013).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF 288-487, AND HOMODIMERIZATION.
RX PubMed=28505309; DOI=10.1093/nar/gkx419;
RA Tunnicliffe R.B., Lockhart-Cairns M.P., Levy C., Mould A.P., Jowitt T.A.,
RA Sito H., Baldock C., Sandri-Goldin R.M., Golovanov A.P.;
RT "The herpes viral transcription factor ICP4 forms a novel DNA recognition
RT complex.";
RL Nucleic Acids Res. 45:8064-8078(2017).
CC -!- FUNCTION: Plays an essential role in the regulation of viral gene
CC expression by both activating and repressing host RNA polymerase II-
CC mediated transcription. Binds with high affinity to the sequence 5'-
CC ATCGTC-3'. Activates transcription by recruiting a form of the host
CC TFIID to promoters and stabilizing the pre-initiation complex
CC formation. Negatively regulates its own transcription. This immediate
CC early (IE) protein is absolutely necessary for the transition from IE
CC transcription to later viral gene transcription.
CC {ECO:0000269|PubMed:18094162, ECO:0000269|PubMed:18216093,
CC ECO:0000269|PubMed:1846804, ECO:0000269|PubMed:22496239,
CC ECO:0000269|PubMed:23135715, ECO:0000269|PubMed:24147125,
CC ECO:0000269|PubMed:8649420}.
CC -!- SUBUNIT: Forms homodimers (PubMed:2991559, PubMed:28505309). Interacts
CC with transcriptional regulator ICP27; this interaction is required for
CC proper incorporation of ICP4 into virions (PubMed:8995681). Interacts
CC with host TBP and host TAF1; these interactions help the stabilization
CC of the pre-nitiation complex on specific promoters (PubMed:8649420).
CC Interacts with host GTF2B (PubMed:8392607).
CC {ECO:0000269|PubMed:28505309, ECO:0000269|PubMed:2991559,
CC ECO:0000269|PubMed:8392607, ECO:0000269|PubMed:8649420,
CC ECO:0000269|PubMed:8995681}.
CC -!- INTERACTION:
CC P08392; P10238: UL54; NbExp=5; IntAct=EBI-7185388, EBI-6883946;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:17959681}. Host
CC cytoplasm {ECO:0000269|PubMed:17959681}. Virion tegument
CC {ECO:0000269|PubMed:17959681}. Note=Localizes to the cytoplasm when
CC phosphorylated. {ECO:0000250}.
CC -!- DOMAIN: The N-terminal and C-terminal domains are required for the
CC transcriptional activation function of ICP4.
CC {ECO:0000269|PubMed:22496239}.
CC -!- PTM: ADP-ribosylated.
CC -!- PTM: The long stretch of Ser is a major site of phosphorylation. Only
CC the phosphorylated forms are capable of interacting with beta or gamma
CC genes. {ECO:0000269|PubMed:1846804}.
CC -!- SIMILARITY: Belongs to the herpesviridae ICP4 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X14112; CAA32286.1; -; Genomic_DNA.
DR EMBL; X14112; CAA32278.1; -; Genomic_DNA.
DR EMBL; X06461; CAA29763.1; -; Genomic_DNA.
DR EMBL; L00036; AAA96675.1; -; Genomic_DNA.
DR EMBL; L00036; AAA96688.1; -; Genomic_DNA.
DR PIR; A23510; EDBE75.
DR PDB; 5MHJ; X-ray; 2.12 A; A/B=288-487.
DR PDB; 5MHK; X-ray; 2.28 A; A/B/C/D=258-487, J=283-286.
DR PDBsum; 5MHJ; -.
DR PDBsum; 5MHK; -.
DR BMRB; P08392; -.
DR SASBDB; P08392; -.
DR SMR; P08392; -.
DR BioGRID; 971428; 1.
DR BioGRID; 971429; 10.
DR IntAct; P08392; 4.
DR MINT; P08392; -.
DR PRIDE; P08392; -.
DR Proteomes; UP000009294; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019033; C:viral tegument; IDA:CACAO.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0039695; P:DNA-templated viral transcription; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0034340; P:response to type I interferon; IDA:BHF-UCL.
DR DisProt; DP01305; -.
DR InterPro; IPR005205; Herpes_ICP4_C.
DR InterPro; IPR005206; Herpes_ICP4_N.
DR Pfam; PF03585; Herpes_ICP4_C; 1.
DR Pfam; PF03584; Herpes_ICP4_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; ADP-ribosylation; DNA-binding; Early protein;
KW Host cytoplasm; Host nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Virion; Virion tegument.
FT CHAIN 1..1298
FT /note="Major viral transcription factor ICP4"
FT /id="PRO_0000115815"
FT DNA_BIND 262..490
FT REGION 1..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 94..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..554
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 594..620
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 718..826
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 877..904
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 45..67
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..148
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..197
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 230..248
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 597..620
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 762..783
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT HELIX 295..298
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:5MHJ"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:5MHK"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:5MHJ"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 343..355
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 369..379
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 387..392
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 398..411
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 432..438
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 444..454
FT /evidence="ECO:0007829|PDB:5MHJ"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:5MHJ"
FT HELIX 460..484
FT /evidence="ECO:0007829|PDB:5MHJ"
SQ SEQUENCE 1298 AA; 132844 MW; 4F32E04C95CA9344 CRC64;
MASENKQRPG SPGPTDGPPP TPSPDRDERG ALGWGAETEE GGDDPDHDPD HPHDLDDARR
DGRAPAAGTD AGEDAGDAVS PRQLALLASM VEEAVRTIPT PDPAASPPRT PAFRADDDDG
DEYDDAADAA GDRAPARGRE REAPLRGAYP DPTDRLSPRP PAQPPRRRRH GRWRPSASST
SSDSGSSSSS SASSSSSSSD EDEDDDGNDA ADHAREARAV GRGPSSAAPA APGRTPPPPG
PPPLSEAAPK PRAAARTPAA SAGRIERRRA RAAVAGRDAT GRFTAGQPRR VELDADATSG
AFYARYRDGY VSGEPWPGAG PPPPGRVLYG GLGDSRPGLW GAPEAEEARR RFEASGAPAA
VWAPELGDAA QQYALITRLL YTPDAEAMGW LQNPRVVPGD VALDQACFRI SGAARNSSSF
ITGSVARAVP HLGYAMAAGR FGWGLAHAAA AVAMSRRYDR AQKGFLLTSL RRAYAPLLAR
ENAALTGAAG SPGAGADDEG VAAVAAAAPG ERAVPAGYGA AGILAALGRL SAAPASPAGG
DDPDAARHAD ADDDAGRRAQ AGRVAVECLA ACRGILEALA EGFDGDLAAV PGLAGARPAS
PPRPEGPAGP ASPPPPHADA PRLRAWLREL RFVRDALVLM RLRGDLRVAG GSEAAVAAVR
AVSLVAGALG PALPRDPRLP SSAAAAAADL LFDNQSLRPL LAAAASAPDA ADALAAAAAS
AAPREGRKRK SPGPARPPGG GGPRPPKTKK SGADAPGSDA RAPLPAPAPP STPPGPEPAP
AQPAAPRAAA AQARPRPVAV SRRPAEGPDP LGGWRRQPPG PSHTAAPAAA ALEAYCSPRA
VAELTDHPLF PVPWRPALMF DPRALASIAA RCAGPAPAAQ AACGGGDDDD NPHPHGAAGG
RLFGPLRASG PLRRMAAWMR QIPDPEDVRV VVLYSPLPGE DLAGGGASGG PPEWSAERGG
LSCLLAALAN RLCGPDTAAW AGNWTGAPDV SALGAQGVLL LSTRDLAFAG AVEFLGLLAS
AGDRRLIVVN TVRACDWPAD GPAVSRQHAY LACELLPAVQ CAVRWPAARD LRRTVLASGR
VFGPGVFARV EAAHARLYPD APPLRLCRGG NVRYRVRTRF GPDTPVPMSP REYRRAVLPA
LDGRAAASGT TDAMAPGAPD FCEEEAHSHA ACARWGLGAP LRPVYVALGR EAVRAGPARW
RGPRRDFCAR ALLEPDDDAP PLVLRGDDDG PGALPPAPPG IRWASATGRS GTVLAAAGAV
EVLGAEAGLA TPPRREVVDW EGAWDEDDGG AFEGDGVL
