ICP27_HHV2H
ID ICP27_HHV2H Reviewed; 512 AA.
AC P28276;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=mRNA export factor;
DE AltName: Full=Immediate-early protein IE63;
DE AltName: Full=Infected cell protein 27;
DE Short=ICP27;
DE AltName: Full=VMW63;
GN ORFNames=UL54;
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 [GENOMIC DNA].
RX PubMed=1662697; DOI=10.1099/0022-1317-72-12-3057;
RA McGeoch D.J., Cunningham C., McIntyre G., Dolan A.;
RT "Comparative sequence analysis of the long repeat regions and adjoining
RT parts of the long unique regions in the genomes of herpes simplex viruses
RT types 1 and 2.";
RL J. Gen. Virol. 72:3057-3075(1991).
RN [2]
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 [3]
RP FUNCTION.
RX PubMed=19729513; DOI=10.1093/nar/gkp633;
RA Nojima T., Oshiro-Ideue T., Nakanoya H., Kawamura H., Morimoto T.,
RA Kawaguchi Y., Kataoka N., Hagiwara M.;
RT "Herpesvirus protein ICP27 switches PML isoform by altering mRNA
RT splicing.";
RL Nucleic Acids Res. 37:6515-6527(2009).
RN [4]
RP FUNCTION.
RX PubMed=23487469; DOI=10.1128/jvi.03500-12;
RA Tang S., Guo N., Patel A., Krause P.R.;
RT "Herpes simplex virus 2 expresses a novel form of ICP34.5, a major viral
RT neurovirulence factor, through regulated alternative splicing.";
RL J. Virol. 87:5820-5830(2013).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=HG52;
RX PubMed=25540385; DOI=10.1128/jvi.02994-14;
RA Park D., Lalli J., Sedlackova-Slavikova L., Rice S.A.;
RT "Functional comparison of herpes simplex virus 1 (HSV-1) and HSV-2 ICP27
RT homologs reveals a role for ICP27 in virion release.";
RL J. Virol. 89:2892-2905(2015).
RN [6]
RP FUNCTION, INTERACTION WITH HOST IRF3, AND DOMAIN.
RX PubMed=30863402; DOI=10.3389/fimmu.2019.00290;
RA Guan X., Zhang M., Fu M., Luo S., Hu Q.;
RT "Herpes Simplex Virus Type 2 Immediate Early Protein ICP27 Inhibits IFN-
RT beta Production in Mucosal Epithelial Cells by Antagonizing IRF3
RT Activation.";
RL Front. Immunol. 10:290-290(2019).
CC -!- FUNCTION: Multifunctional regulator of the expression of viral genes
CC that contributes to the shutoff of host protein synthesis and mediates
CC nuclear export of viral intronless mRNAs. Also stimulates translation
CC of viral transcripts (PubMed:25540385). Independently, plays a role in
CC the regulation of virion release (PubMed:25540385). Also plays a role
CC in the inhibition of host innate immune response by targeting host IRF3
CC and therby preventing production of beta-interferon (PubMed:30863402).
CC Silences the 3' splice site of the host promyelocytic leukemia (PML)
CC intron 7a, thereby switching PML isoforms from PML-II to PML-V. This
CC could be linked to the accelerated mRNA export induced by ICP27 which
CC might not provide sufficient time for PML pre-mRNA to be spliced in the
CC nucleus (PubMed:19729513). Suppresses also splicing of the viral
CC ICP34.5 mRNA, allowing the virus to express a variant form of ICP34.5
CC (PubMed:23487469). {ECO:0000269|PubMed:19729513,
CC ECO:0000269|PubMed:23487469, ECO:0000269|PubMed:25540385,
CC ECO:0000269|PubMed:30863402}.
CC -!- SUBUNIT: Interacts with host RBP1; this interaction facilitates the RNA
CC polymerase recruitment to viral transcription sites. Interacts (via the
CC RGG box) with host ALYREF/THOC4; this interaction recruits ALYREF to
CC viral replication compartments and probably directs viral mRNA to the
CC TAP/NFX1 pathway. Interacts (via the RGG box) with host SRPK1; this
CC interaction relocalizes SRPK1 to the nucleus and seems to alter its
CC activity. Interacts with ICP4; this interaction modulates ICP4 DNA-
CC binding activity. Interacts with host NXF1; this interaction allows
CC efficient export of HSV-1 early and late transcripts (By similarity).
CC Interacts with host IRF3; this interaction inhibits IRF3
CC phosphorylation and nuclear translocation. {ECO:0000250,
CC ECO:0000269|PubMed:30863402}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:25540385}.
CC Host nucleus {ECO:0000269|PubMed:25540385}. Note=Shuttles between the
CC nucleus and the cytoplasm. {ECO:0000269|PubMed:25540385}.
CC -!- DOMAIN: Binds viral intronless RNAs through the RGG region.
CC {ECO:0000250}.
CC -!- DOMAIN: The N-terminal domain is mainly responsible for the inhibition
CC of IFN-beta induction. {ECO:0000269|PubMed:30863402}.
CC -!- PTM: Methylated within the RGG box possibly by host PRMT1. When
CC hypomethylated, ICP27 is exported to the cytoplasm earlier and more
CC rapidly (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the HHV-1 ICP27 protein family. {ECO:0000305}.
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DR EMBL; D10471; BAA01269.1; -; Genomic_DNA.
DR EMBL; Z86099; CAB06702.1; -; Genomic_DNA.
DR PIR; JQ1498; WMBEXA.
DR SMR; P28276; -.
DR PRIDE; P28276; -.
DR Proteomes; UP000001874; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0035891; P:exit from host cell; IDA:UniProtKB.
DR GO; GO:0039652; P:induction by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039524; P:suppression by virus of host mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IDA:UniProtKB.
DR InterPro; IPR031752; HHV-1_REF-bd.
DR InterPro; IPR008648; ICP27-like.
DR Pfam; PF05459; Herpes_UL69; 1.
DR Pfam; PF16852; HHV-1_VABD; 1.
PE 1: Evidence at protein level;
KW Activation of host NF-kappa-B by virus; Activator; Early protein;
KW Eukaryotic host gene expression shutoff by virus;
KW G1/S host cell cycle checkpoint dysregulation by virus; Host cytoplasm;
KW Host gene expression shutoff by virus; Host mRNA suppression by virus;
KW Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host IRF3 by virus;
KW Inhibition of host pre-mRNA processing by virus;
KW Inhibition of host RLR pathway by virus; Metal-binding; Methylation;
KW Modulation of host cell cycle by virus; Phosphoprotein; Reference proteome;
KW RNA-binding; Transcription; Transcription regulation; Viral immunoevasion;
KW Zinc; Zinc-finger.
FT CHAIN 1..512
FT /note="mRNA export factor"
FT /id="PRO_0000115825"
FT ZN_FING 400..488
FT /note="CHC2-type"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT REGION 1..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 104..112
FT /note="Interaction with host ALYREF"
FT /evidence="ECO:0000250"
FT REGION 138..152
FT /note="RGG-box"
FT MOTIF 5..17
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 110..138
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 26..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..57
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 400
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT BINDING 479
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT BINDING 483
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT BINDING 488
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT MOD_RES 16
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 18
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 113
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 138
FT /note="Dimethylated arginine; by host"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT MOD_RES 148
FT /note="Omega-N-methylarginine; by host"
FT /evidence="ECO:0000250|UniProtKB:P10238"
FT MOD_RES 150
FT /note="Dimethylated arginine; by host"
FT /evidence="ECO:0000250|UniProtKB:P10238"
SQ SEQUENCE 512 AA; 54959 MW; 459651470A503BA7 CRC64;
MATDIDMLID LGLDLSDSEL EEDALERDEE GRRDDPESDS SGECSSSDED MEDPCGDGGA
EAIDAAIPKG PPARPEDAGT PEASTPRPAA RRGADDPPPA TTGVWSRLGT RRSASPREPH
GGKVARIQPP STKAPHPRGG RRGRRRGRGR YGPGGADSTP KPRRRVSRNA HNQGGRHPAS
ARTDGPGATH GEARRGGEQL DVSGGPRPRG TRQAPPPLMA LSLTPPHADG RAPVPERKAP
SADTIDPAVR AVLRSISERA AVERISESFG RSALVMQDPF GGMPFPAANS PWAPVLATQA
GGFDAETRRV SWETLVAHGP SLYRTFAANP RAASTAKAMR DCVLRQENLI EALASADETL
AWCKMCIHHN LPLRPQDPII GTAAAVLENL ATRLRPFLQC YLKARGLCGL DDLCSRRRLS
DIKDIASFVL VILARLANRV ERGVSEIDYT TVGVGAGETM HFYIPGACMA GLIEILDTHR
QECSSRVCEL TASHTIAPLY VHGKYFYCNS LF
