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 24-JAN-2024, entry version 121. 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; Orthoherpesviridae; Alphaherpesvirinae; Simplexvirus; OC Simplexvirus humanalpha1; Human herpesvirus 1. 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}. 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; 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 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:perturbation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of DNA-templated transcription; 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 //