ICP4_HHV2H
ID ICP4_HHV2H Reviewed; 1318 AA.
AC P90493; O12645; O12646;
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=Major viral transcription factor ICP4 homolog;
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 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 FUNCTION, AND INTERACTION WITH HOST TBP.
RX PubMed=30619292; DOI=10.3389/fimmu.2018.02932;
RA Zhang M., Deng X., Guan X., Geng L., Fu M., Zhang B., Chen R., Hu H.,
RA Hu K., Zhang D., Li M., Liu Y., Gong S., Hu Q.;
RT "Herpes Simplex Virus Type 2 Infection-Induced Expression of CXCR3 Ligands
RT Promotes CD4+ T Cell Migration and Is Regulated by the Viral Immediate-
RT Early Protein ICP4.";
RL Front. Immunol. 9:2932-2932(2018).
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 (PubMed:30619292). Binds with high affinity to
CC the sequence 5'-ATCGTC-3'. Activates transcription by recruiting a form
CC of the host TFIID to promoters and stabilizing the pre-initiation
CC complex formation. Negatively regulates its own transcription. This
CC immediate early (IE) protein is absolutely necessary for the transition
CC from IE transcription to later viral gene transcription (By
CC similarity). In addition, binds to the host promoters of CXCR3 ligands
CC including CXCL9, CXCL10, and CXCL11 and interacts with TBP to activate
CC their transcription. In turn, mediates CD4+ T-cell migration
CC (PubMed:30619292). {ECO:0000250|UniProtKB:P08392,
CC ECO:0000269|PubMed:30619292}.
CC -!- SUBUNIT: Homodimer. Interacts with transcriptional regulator ICP27;
CC this interaction is required for proper incorporation of ICP4 into
CC virions (By similarity). Interacts with host TBP; theis interaction
CC helps the stabilization of the pre-initiation complex on specific
CC promoters (PubMed:30619292). Interacts with host GTF2B.
CC {ECO:0000250|UniProtKB:P08392, ECO:0000269|PubMed:30619292}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:P08392}. Host
CC cytoplasm {ECO:0000250|UniProtKB:P08392}. Virion tegument
CC {ECO:0000250|UniProtKB:P08392}. 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:0000250|UniProtKB:P08392}.
CC -!- PTM: ADP-ribosylated. {ECO:0000250|UniProtKB:P08392}.
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:0000250|UniProtKB:P08392}.
CC -!- SIMILARITY: Belongs to the herpesviridae ICP4 family. {ECO:0000305}.
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DR EMBL; Z86099; CAB06701.1; -; Genomic_DNA.
DR EMBL; Z86099; CAB06707.1; -; Genomic_DNA.
DR SMR; P90493; -.
DR PRIDE; P90493; -.
DR Proteomes; UP000001874; 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; 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:0045893; P:positive regulation of transcription, DNA-templated; IEA:InterPro.
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 Activator; ADP-ribosylation; DNA-binding; Early protein; Host cytoplasm;
KW Host nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Virion; Virion tegument.
FT CHAIN 1..1318
FT /note="Major viral transcription factor ICP4 homolog"
FT /id="PRO_0000385460"
FT DNA_BIND 319..547
FT /evidence="ECO:0000250"
FT REGION 1..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 123..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 542..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 606..630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 780..873
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1291..1318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 45..60
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..173
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 205..224
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 228..256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 297..311
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 550..564
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 823..847
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1318 AA; 135104 MW; 9C0EEAF76897D7B2 CRC64;
MSAEQRKKKK TTTTTQGRGA EVAMADEDGG RLRAAAETTG GPGSPDPADG PPPTPNPDRR
PAARPGFGWH GGPEENEDEA DDAAADADAD EAAPASGEAV DEPAADGVVS PRQLALLASM
VDEAVRTIPS PPPERDGAQE EAARSPSPPR TPSMRADYGE ENDDDDDDDD DDDRDAGRWV
RGPETTSAVR GAYPDPMASL SPRPPAPRRH HHHHHHRRRR APRRRSAASD SSKSGSSSSA
SSASSSASSS SSASASSSDD DDDDDAARAP ASAADHAAGG TLGADDEEAG VPARAPGAAP
RPSPPRAEPA PARTPAATAG RLERRRARAA VAGRDATGRF TAGRPRRVEL DADAASGAFY
ARYRDGYVSG EPWPGAGPPP PGRVLYGGLG DSRPGLWGAP EAEEARARFE ASGAPAPVWA
PELGDAAQQY ALITRLLYTP DAEAMGWLQN PRVAPGDVAL DQACFRISGA ARNSSSFISG
SVARAVPHLG YAMAAGRFGW GLAHVAAAVA MSRRYDRAQK GFLLTSLRRA YAPLLARENA
ALTGARTPDD GGDANRHDGD DARGKPAAAA APLPSAAASP ADERAVPAGY GAAGVLAALG
RLSAAPASAP AGADDDDDDD GAGGGGGGRR AEAGRVAVEC LAACRGILEA LAEGFDGDLA
AVPGLAGARP AAPPRPGPAG AAAPPHADAP RLRAWLRELR FVRDALVLMR LRGDLRVAGG
SEAAVAAVRA VSLVAGALGP ALPRSPRLLS SAAAAAADLL FQNQSLRPLL ADTVAAADSL
AAPASAPREA RKRKSPAPAR APPGGAPRPP KKSRADAPRP AAAPPAGAAP PAPPTPPPRP
PRPAALTRRP AEGPDPQGGW RRQPPGPSHT PAPSAAALEA YCAPRAVAEL TDHPLFPAPW
RPALMFDPRA LASLAARCAA PPPGGAPAAF GPLRASGPLR RAAAWMRQVP DPEDVRVVIL
YSPLPGEDLA AGRAGGGPPP EWSAERGGLS CLLAALGNRL CGPATAAWAG NWTGAPDVSA
LGAQGVLLLS TRDLAFAGAV EFLGLLAGAC DRRLIVVNAV RAADWPADGP VVSRQHAYLA
CEVLPAVQCA VRWPAARDLR RTVLASGRVF GPGVFARVEA AHARLYPDAP PLRLCRGANV
RYRVRTRFGP DTLVPMSPRE YRRAVLPALD GRAAASGAGD AMAPGAPDFC EDEAHSHRAC
ARWGLGAPLR PVYVALGRDA VRGGPAELRG PRREFCARAL LEPDGDAPPL VLRDDADAGP
PPQIRWASAA GRAGTVLAAA GGGVEVVGTA AGLATPPRRE PVDMDAELED DDDGLFGE