ICP27_HHV11
ID ICP27_HHV11 Reviewed; 512 AA.
AC P10238; B9VQI3; Q09I80;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 116.
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 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=2846760; DOI=10.1099/0022-1317-69-11-2831;
RA Perry L.J., McGeoch D.J.;
RT "The DNA sequences of the long repeat region and adjoining parts of the
RT long unique region in the genome of herpes simplex virus type 1.";
RL J. Gen. Virol. 69:2831-2846(1988).
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 INTERACTION WITH ICP4.
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=9501050; DOI=10.1006/viro.1997.9006;
RA Mears W.E., Rice S.A.;
RT "The herpes simplex virus immediate-early protein ICP27 shuttles between
RT nucleus and cytoplasm.";
RL Virology 242:128-137(1998).
RN [7]
RP FUNCTION.
RX PubMed=9512520; DOI=10.1101/gad.12.6.868;
RA Sandri-Goldin R.M.;
RT "ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear
RT export signal and binding viral intronless RNAs through an RGG motif.";
RL Genes Dev. 12:868-879(1998).
RN [8]
RP PHOSPHORYLATION AT SER-16; SER-18 AND SER-114.
RX PubMed=10074178; DOI=10.1128/jvi.73.4.3246-3257.1999;
RA Zhi Y., Sandri-Goldin R.M.;
RT "Analysis of the phosphorylation sites of herpes simplex virus type 1
RT regulatory protein ICP27.";
RL J. Virol. 73:3246-3257(1999).
RN [9]
RP FUNCTION.
RX PubMed=11287586; DOI=10.1128/jvi.75.9.4376-4385.2001;
RA Bryant H.E., Wadd S.E., Lamond A.I., Silverstein S.J., Clements J.B.;
RT "Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-
RT associated protein 145 and inhibits splicing prior to the first catalytic
RT step.";
RL J. Virol. 75:4376-4385(2001).
RN [10]
RP INTERACTION WITH HOST ALYREF/THOC4.
RX PubMed=12438613; DOI=10.1128/jvi.76.24.12877-12889.2002;
RA Chen I.-H.B., Sciabica K.S., Sandri-Goldin R.M.;
RT "ICP27 interacts with the RNA export factor Aly/REF to direct herpes
RT simplex virus type 1 intronless mRNAs to the TAP export pathway.";
RL J. Virol. 76:12877-12889(2002).
RN [11]
RP FUNCTION, AND INTERACTION WITH HOST SRPK1.
RX PubMed=12660167; DOI=10.1093/emboj/cdg166;
RA Sciabica K.S., Dai Q.J., Sandri-Goldin R.M.;
RT "ICP27 interacts with SRPK1 to mediate HSV splicing inhibition by altering
RT SR protein phosphorylation.";
RL EMBO J. 22:1608-1619(2003).
RN [12]
RP FUNCTION.
RX PubMed=16537625; DOI=10.1128/jvi.80.7.3567-3581.2006;
RA Dai-Ju J.Q., Li L., Johnson L.A., Sandri-Goldin R.M.;
RT "ICP27 interacts with the C-terminal domain of RNA polymerase II and
RT facilitates its recruitment to herpes simplex virus 1 transcription sites,
RT where it undergoes proteasomal degradation during infection.";
RL J. Virol. 80:3567-3581(2006).
RN [13]
RP REVIEW.
RX PubMed=18508584; DOI=10.2741/3078;
RA Sandri-Goldin R.M.;
RT "The many roles of the regulatory protein ICP27 during herpes simplex virus
RT infection.";
RL Front. Biosci. 13:5241-5256(2008).
RN [14]
RP METHYLATION AT ARG-138; ARG-148 AND ARG-150.
RX PubMed=19321610; DOI=10.1128/jvi.00238-09;
RA Souki S.K., Gershon P.D., Sandri-Goldin R.M.;
RT "Arginine methylation of the ICP27 RGG box regulates ICP27 export and is
RT required for efficient herpes simplex virus 1 replication.";
RL J. Virol. 83:5309-5320(2009).
RN [15]
RP INTERACTION WITH HOST SRPK1, AND FUNCTION.
RX PubMed=19553338; DOI=10.1128/jvi.00801-09;
RA Souki S.K., Sandri-Goldin R.M.;
RT "Arginine methylation of the ICP27 RGG box regulates the functional
RT interactions of ICP27 with SRPK1 and Aly/REF during herpes simplex virus 1
RT infection.";
RL J. Virol. 83:8970-8975(2009).
RN [16]
RP INTERACTION WITH HOST NXF1, AND FUNCTION.
RX PubMed=19369354; DOI=10.1128/jvi.00375-09;
RA Johnson L.A., Li L., Sandri-Goldin R.M.;
RT "The cellular RNA export receptor TAP/NXF1 is required for ICP27-mediated
RT export of herpes simplex virus 1 RNA, but the TREX complex adaptor protein
RT Aly/REF appears to be dispensable.";
RL J. Virol. 83:6335-6346(2009).
RN [17]
RP INTERACTION WITH HOST NUP62, AND FUNCTION.
RX PubMed=22334672; DOI=10.1074/jbc.m111.331777;
RA Malik P., Tabarraei A., Kehlenbach R.H., Korfali N., Iwasawa R.,
RA Graham S.V., Schirmer E.C.;
RT "Herpes simplex virus ICP27 protein directly interacts with the nuclear
RT pore complex through Nup62, inhibiting host nucleocytoplasmic transport
RT pathways.";
RL J. Biol. Chem. 287:12277-12292(2012).
RN [18]
RP STRUCTURE BY NMR OF 103-138 IN COMPLEX WITH ALYREF2, AND INTERACTION WITH
RP HOST ALYREF AND ALYREF2.
RX PubMed=21253573; DOI=10.1371/journal.ppat.1001244;
RA Tunnicliffe R.B., Hautbergue G.M., Kalra P., Jackson B.R., Whitehouse A.,
RA Wilson S.A., Golovanov A.P.;
RT "Structural basis for the recognition of cellular mRNA export factor REF by
RT herpes viral proteins HSV-1 ICP27 and HVS ORF57.";
RL PLoS Pathog. 7:E1001244-E1001244(2011).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 190-512 IN COMPLEX WITH ZINC IONS,
RP SUBUNIT, AND DOMAIN.
RX PubMed=26085142; DOI=10.1128/jvi.00441-15;
RA Patel V., Dahlroth S.L., Rajakannan V., Ho H.T., Cornvik T., Nordlund P.;
RT "Structure of C-Terminal Domain of the Multifunctional ICP27 Protein from
RT Herpes Simplex Virus-1.";
RL J. Virol. 89:8828-8839(2015).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 241-512 IN COMPLEX WITH ZINC
RP IONS, SUBUNIT, DOMAIN, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 500-TYR--PHE-512.
RX PubMed=26062451; DOI=10.1038/srep11234;
RA Tunnicliffe R.B., Schacht M., Levy C., Jowitt T.A., Sandri-Goldin R.M.,
RA Golovanov A.P.;
RT "The structure of the folded domain from the signature multifunctional
RT protein ICP27 from herpes simplex virus-1 reveals an intertwined dimer.";
RL Sci. Rep. 5:11234-11234(2015).
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. Early in infection, this
CC immediate early (EI) protein mediates the inhibition of cellular
CC splicing. This results in the accumulation of unprocessed 3'end pre-
CC mRNAs which can't be exported from the nucleus. Cellular protein
CC synthesis is thereby shut off early after virus infection. Later in the
CC infection, it helps recruit cellular RNA polymerase II to viral
CC replication sites and promotes the nuclear export of viral intronless
CC mRNAs by interacting with mRNAs and host NXF1/TAP. ICP27 binds to NUP62
CC which may provide facilitated viral mRNA export and may indirectly
CC compete with some host cell transport receptors for binding and inhibit
CC cellular nucleocytoplasmic transport pathways (PubMed:22334672). Also
CC stimulates translation of viral transcripts. Repression of host gene
CC expression blocks the cell cycle at the G1 phase and prevents
CC apoptosis. Seems to silence the 3' splice site of the promyelocytic
CC leukemia (PML) intron 7a, thereby switching PML isoforms from PML-II to
CC PML-V. This could be linked to the accelerated mRNA export induced by
CC ICP27 which might not provide sufficient time for PML pre-mRNA to be
CC spliced in the nucleus. {ECO:0000269|PubMed:11287586,
CC ECO:0000269|PubMed:12660167, ECO:0000269|PubMed:16537625,
CC ECO:0000269|PubMed:19369354, ECO:0000269|PubMed:19553338,
CC ECO:0000269|PubMed:22334672, ECO:0000269|PubMed:9512520}.
CC -!- SUBUNIT: Homodimer (PubMed:26085142, PubMed:26062451). Interacts with
CC host RBP1; this interaction facilitates the RNA polymerase recruitment
CC to viral transcription sites. Interacts (via the RGG box) with host
CC ALYREF/THOC4; this interaction recruits ALYREF to viral replication
CC compartments and probably directs viral mRNA to the TAP/NFX1 pathway
CC (PubMed:12438613). Interacts with host ALYREF2 (PubMed:21253573).
CC Interacts (via the RGG box) with host SRPK1; this interaction
CC relocalizes SRPK1 to the nucleus and seems to alter its activity
CC (PubMed:12660167, PubMed:19553338). Interacts with ICP4; this
CC interaction modulates ICP4 DNA-binding activity (PubMed:8995681).
CC Interacts with host NXF1; this interaction allows efficient export of
CC HHV-1 early and late transcripts (PubMed:19369354).
CC {ECO:0000269|PubMed:12438613, ECO:0000269|PubMed:12660167,
CC ECO:0000269|PubMed:19369354, ECO:0000269|PubMed:19553338,
CC ECO:0000269|PubMed:21253573, ECO:0000269|PubMed:22334672,
CC ECO:0000269|PubMed:26062451, ECO:0000269|PubMed:26085142,
CC ECO:0000269|PubMed:8995681}.
CC -!- INTERACTION:
CC P10238; P08392: ICP4; NbExp=5; IntAct=EBI-6883946, EBI-7185388;
CC P10238; P37198: NUP62; Xeno; NbExp=3; IntAct=EBI-6883946, EBI-347978;
CC P10238; Q9UBU9: NXF1; Xeno; NbExp=4; IntAct=EBI-6883946, EBI-398874;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:9501050}. Host
CC nucleus {ECO:0000269|PubMed:26062451, ECO:0000269|PubMed:9501050}.
CC Note=Shuttles between the nucleus and the cytoplasm.
CC {ECO:0000269|PubMed:9501050}.
CC -!- DOMAIN: Binds viral intronless RNAs through the RGG region.
CC -!- DOMAIN: The C-terminus is essential for homodimerization.
CC {ECO:0000269|PubMed:26062451, ECO:0000269|PubMed:26085142}.
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. {ECO:0000269|PubMed:19321610}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:10074178}.
CC -!- SIMILARITY: Belongs to the HHV-1 ICP27 protein family. {ECO:0000305}.
CC -!- CAUTION: A role in degradation of host polymerase has been suggested in
CC PubMed 16537625, but this could be a consequence of binding to immature
CC mRNAs simultaneously to transcription by the polymerase. {ECO:0000305}.
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DR EMBL; X14112; CAA32290.1; -; Genomic_DNA.
DR EMBL; DQ889502; ABI63515.1; -; Genomic_DNA.
DR EMBL; FJ593289; ACM62278.1; -; Genomic_DNA.
DR PIR; I30089; WMBEY4.
DR RefSeq; YP_009137130.1; NC_001806.2.
DR PDB; 2KT5; NMR; -; B=103-138.
DR PDB; 4YXP; X-ray; 1.92 A; A/B=241-512.
DR PDB; 5BQK; X-ray; 2.00 A; A/B/C=242-512.
DR PDBsum; 2KT5; -.
DR PDBsum; 4YXP; -.
DR PDBsum; 5BQK; -.
DR BMRB; P10238; -.
DR SMR; P10238; -.
DR BioGRID; 971451; 7.
DR DIP; DIP-57688N; -.
DR IntAct; P10238; 5.
DR MINT; P10238; -.
DR iPTMnet; P10238; -.
DR PRIDE; P10238; -.
DR GeneID; 24271474; -.
DR KEGG; vg:24271474; -.
DR Proteomes; UP000009294; Genome.
DR Proteomes; UP000180652; 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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
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 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 3D-structure; Activation of host NF-kappa-B by virus; Activator;
KW Early protein; 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 pre-mRNA processing by virus; Metal-binding;
KW Methylation; Modulation of host cell cycle by virus; Phosphoprotein;
KW Reference proteome; RNA-binding; Transcription; Transcription regulation;
KW Zinc; Zinc-finger.
FT CHAIN 1..512
FT /note="mRNA export factor"
FT /id="PRO_0000115823"
FT ZN_FING 400..488
FT /note="CHC2-type"
FT /evidence="ECO:0000269|PubMed:26062451,
FT ECO:0000269|PubMed:26085142"
FT REGION 1..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 104..112
FT /note="Interaction with host ALYREF"
FT REGION 138..152
FT /note="RGG-box"
FT REGION 500..512
FT /note="Important for homodimerization"
FT /evidence="ECO:0000269|PubMed:26062451"
FT MOTIF 5..17
FT /note="Nuclear export signal"
FT MOTIF 110..138
FT /note="Nuclear localization signal"
FT COMPBIAS 25..39
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..55
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..234
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 400
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26062451,
FT ECO:0000269|PubMed:26085142"
FT BINDING 479
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26062451,
FT ECO:0000269|PubMed:26085142"
FT BINDING 483
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26062451,
FT ECO:0000269|PubMed:26085142"
FT BINDING 488
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26062451,
FT ECO:0000269|PubMed:26085142"
FT MOD_RES 16
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000305|PubMed:10074178"
FT MOD_RES 18
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000305|PubMed:10074178"
FT MOD_RES 114
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000305|PubMed:10074178"
FT MOD_RES 138
FT /note="Dimethylated arginine; by host"
FT /evidence="ECO:0000305|PubMed:19321610"
FT MOD_RES 148
FT /note="Omega-N-methylarginine; by host"
FT /evidence="ECO:0000305|PubMed:19321610"
FT MOD_RES 150
FT /note="Dimethylated arginine; by host"
FT /evidence="ECO:0000305|PubMed:19321610"
FT VARIANT 137
FT /note="A -> V (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 206
FT /note="Q -> P (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 383
FT /note="T -> A (in strain: Nonneuroinvasive mutant HF10 and
FT 17 syn+)"
FT MUTAGEN 500..512
FT /note="Missing: Impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:26062451"
FT HELIX 247..254
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 262..275
FT /evidence="ECO:0007829|PDB:4YXP"
FT TURN 279..282
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:4YXP"
FT TURN 305..308
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 312..328
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 330..346
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 349..368
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 378..381
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 383..405
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 410..416
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 425..442
FT /evidence="ECO:0007829|PDB:4YXP"
FT STRAND 445..447
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 449..452
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 467..478
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 479..481
FT /evidence="ECO:0007829|PDB:4YXP"
FT HELIX 486..496
FT /evidence="ECO:0007829|PDB:4YXP"
SQ SEQUENCE 512 AA; 55253 MW; 97DF74A2B7E63A85 CRC64;
MATDIDMLID LGLDLSDSDL DEDPPEPAES RRDDLESDSS GECSSSDEDM EDPHGEDGPE
PILDAARPAV RPSRPEDPGV PSTQTPRPTE RQGPNDPQPA PHSVWSRLGA RRPSCSPEQH
GGKVARLQPP PTKAQPARGG RRGRRRGRGR GGPGAADGLS DPRRRAPRTN RNPGGPRPGA
GWTDGPGAPH GEAWRGSEQP DPPGGQRTRG VRQAPPPLMT LAIAPPPADP RAPAPERKAP
AADTIDATTR LVLRSISERA AVDRISESFG RSAQVMHDPF GGQPFPAANS PWAPVLAGQG
GPFDAETRRV SWETLVAHGP SLYRTFAGNP RAASTAKAMR DCVLRQENFI EALASADETL
AWCKMCIHHN LPLRPQDPII GTTAAVLDNL ATRLRPFLQC YLKARGLCGL DELCSRRRLA
DIKDIASFVF VILARLANRV ERGVAEIDYA TLGVGVGEKM HFYLPGACMA GLIEILDTHR
QECSSRVCEL TASHIVAPPY VHGKYFYCNS LF
