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P10238

- ICP27_HHV11

UniProt

P10238 - ICP27_HHV11

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Protein

mRNA export factor

Gene

UL54

Organism
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Multifunctional regulator of the expression of viral genes that contributes to the shutoff of host protein synthesis and mediates nuclear export of viral intronless mRNAs. Early in infection, this immediate early (EI) protein mediates the inhibition of cellular splicing. This results in the accumulation of unprocessed 3'end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off early after virus infection. Later in the infection, it helps recruit cellular RNA polymerase II to viral replication sites and promotes the nuclear export of viral intronless mRNAs by interacting with mRNAs and host NXF1/TAP. ICP27 binds to NUP62 which may provide facilitated viral mRNA export and may indirectly compete with some host cell transport receptors for binding and inhibit cellular nucleocytoplasmic transport pathways. Also stimulates translation of viral transcripts. Repression of host gene expression blocks the cell cycle at the G1 phase and prevents apoptosis. Seems to silence the 3' splice site of the promyelocytic leukemia (PML) intron 7a, thereby switching PML isoforms from PML-II to PML-V. This could be linked to the accelerated mRNA export induced by ICP27 which might not provide sufficient time for PML pre-mRNA to be spliced in the nucleus.7 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri468 – 51245Sequence AnalysisAdd
BLAST

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. RNA binding Source: UniProtKB-KW

GO - Biological processi

  1. activation by virus of host NF-kappaB transcription factor activity Source: UniProtKB-KW
  2. modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
  3. suppression by virus of host mRNA processing Source: UniProtKB-KW
  4. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Activation of host NF-kappa-B by virus, Eukaryotic host gene expression shutoff by virus, G1/S host cell cycle checkpoint dysregulation by virus, Host gene expression shutoff by virus, Host mRNA suppression by virus, Host-virus interaction, Inhibition of host pre-mRNA processing by virus, Modulation of host cell cycle by virus, Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, RNA-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
mRNA export factor
Alternative name(s):
Immediate-early protein IE63
Infected cell protein 27
Short name:
ICP27
VMW63
Gene namesi
ORF Names:UL54
OrganismiHuman herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
Taxonomic identifieri10299 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000009294: Genome

Subcellular locationi

Host cytoplasm 1 Publication. Host nucleus 1 Publication
Note: Shuttles between the nucleus and the cytoplasm.

GO - Cellular componenti

  1. host cell cytoplasm Source: UniProtKB-KW
  2. host cell nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 512512mRNA export factorPRO_0000115823Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei16 – 161Phosphoserine; by host1 Publication
Modified residuei18 – 181Phosphoserine; by host1 Publication
Modified residuei114 – 1141Phosphoserine; by host1 Publication
Modified residuei138 – 1381Omega-N-methylated arginine; by host1 Publication
Modified residuei148 – 1481Omega-N-methylated arginine; by host1 Publication
Modified residuei150 – 1501Omega-N-methylated arginine; by host1 Publication

Post-translational modificationi

Methylated within the RGG box possibly by host PRMT1. When hypomethylated, ICP27 is exported to the cytoplasm earlier and more rapidly.1 Publication
Phosphorylated.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Interacts with host RBP1; this interaction facilitates the RNA polymerase recruitment to viral transcription sites. Interacts (via the RGG box) with host ALYREF/THOC4; this interaction recruits ALYREF to viral replication compartments and probably directs viral mRNA to the TAP/NFX1 pathway. Interacts (via the RGG box) with host SRPK1; this interaction relocalizes SRPK1 to the nucleus and seems to alter its activity. Interacts with ICP4; this interaction modulates ICP4 DNA-binding activity. Interacts with host NXF1; this interaction allows efficient export of HHV-1 early and late transcripts.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ICP4P083925EBI-6883946,EBI-7185388
NUP62P371983EBI-6883946,EBI-347978From a different organism.
NXF1Q9UBU94EBI-6883946,EBI-398874From a different organism.

Protein-protein interaction databases

BioGridi971451. 1 interaction.
IntActiP10238. 4 interactions.
MINTiMINT-6732574.

Structurei

3D structure databases

ProteinModelPortaliP10238.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni5 – 1713Nuclear export signalAdd
BLAST
Regioni104 – 1129Interaction with host ALYREF
Regioni110 – 13829Nuclear localization signalAdd
BLAST
Regioni138 – 15215RGG-boxAdd
BLAST

Domaini

Binds viral intronless RNAs through the RGG region.

Sequence similaritiesi

Belongs to the HHV-1 ICP27 protein family.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri468 – 51245Sequence AnalysisAdd
BLAST

Keywords - Domaini

Zinc-finger

Family and domain databases

InterProiIPR008648. Herpes_UL69.
[Graphical view]
PfamiPF05459. Herpes_UL69. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P10238-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MATDIDMLID LGLDLSDSDL DEDPPEPAES RRDDLESDSS GECSSSDEDM
60 70 80 90 100
EDPHGEDGPE PILDAARPAV RPSRPEDPGV PSTQTPRPTE RQGPNDPQPA
110 120 130 140 150
PHSVWSRLGA RRPSCSPEQH GGKVARLQPP PTKAQPARGG RRGRRRGRGR
160 170 180 190 200
GGPGAADGLS DPRRRAPRTN RNPGGPRPGA GWTDGPGAPH GEAWRGSEQP
210 220 230 240 250
DPPGGQRTRG VRQAPPPLMT LAIAPPPADP RAPAPERKAP AADTIDATTR
260 270 280 290 300
LVLRSISERA AVDRISESFG RSAQVMHDPF GGQPFPAANS PWAPVLAGQG
310 320 330 340 350
GPFDAETRRV SWETLVAHGP SLYRTFAGNP RAASTAKAMR DCVLRQENFI
360 370 380 390 400
EALASADETL AWCKMCIHHN LPLRPQDPII GTTAAVLDNL ATRLRPFLQC
410 420 430 440 450
YLKARGLCGL DELCSRRRLA DIKDIASFVF VILARLANRV ERGVAEIDYA
460 470 480 490 500
TLGVGVGEKM HFYLPGACMA GLIEILDTHR QECSSRVCEL TASHIVAPPY
510
VHGKYFYCNS LF
Length:512
Mass (Da):55,253
Last modified:July 1, 1989 - v1
Checksum:i97DF74A2B7E63A85
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti137 – 1371A → V in strain: Nonneuroinvasive mutant HF10.
Natural varianti206 – 2061Q → P in strain: Nonneuroinvasive mutant HF10.
Natural varianti383 – 3831T → A in strain: Nonneuroinvasive mutant HF10 and 17 syn+.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X14112 Genomic DNA. Translation: CAA32290.1.
DQ889502 Genomic DNA. Translation: ABI63515.1.
FJ593289 Genomic DNA. Translation: ACM62278.1.
PIRiI30089. WMBEY4.
RefSeqiNP_044657.1. NC_001806.1.

Genome annotation databases

GeneIDi2703426.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X14112 Genomic DNA. Translation: CAA32290.1 .
DQ889502 Genomic DNA. Translation: ABI63515.1 .
FJ593289 Genomic DNA. Translation: ACM62278.1 .
PIRi I30089. WMBEY4.
RefSeqi NP_044657.1. NC_001806.1.

3D structure databases

ProteinModelPortali P10238.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 971451. 1 interaction.
IntActi P10238. 4 interactions.
MINTi MINT-6732574.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 2703426.

Family and domain databases

InterProi IPR008648. Herpes_UL69.
[Graphical view ]
Pfami PF05459. Herpes_UL69. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequences of the long repeat region and adjoining parts of the long unique region in the genome of herpes simplex virus type 1."
    Perry L.J., McGeoch D.J.
    J. Gen. Virol. 69:2831-2846(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1."
    McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D., Perry L.J., Scott J.E., Taylor P.
    J. Gen. Virol. 69:1531-1574(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Determination and analysis of the DNA sequence of highly attenuated herpes simplex virus type 1 mutant HF10, a potential oncolytic virus."
    Ushijima Y., Luo C., Goshima F., Yamauchi Y., Kimura H., Nishiyama Y.
    Microbes Infect. 9:142-149(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Nonneuroinvasive mutant HF10.
  4. "Herpes simplex virus type 1 bacterial artificial chromosome."
    Cunningham C., Davison A.J.
    Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: 17 syn+.
  5. "Physical and functional interactions between herpes simplex virus immediate-early proteins ICP4 and ICP27."
    Panagiotidis C.A., Lium E.K., Silverstein S.J.
    J. Virol. 71:1547-1557(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ICP4.
  6. "The herpes simplex virus immediate-early protein ICP27 shuttles between nucleus and cytoplasm."
    Mears W.E., Rice S.A.
    Virology 242:128-137(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  7. "ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif."
    Sandri-Goldin R.M.
    Genes Dev. 12:868-879(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Analysis of the phosphorylation sites of herpes simplex virus type 1 regulatory protein ICP27."
    Zhi Y., Sandri-Goldin R.M.
    J. Virol. 73:3246-3257(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-16; SER-18 AND SER-114.
  9. "Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated protein 145 and inhibits splicing prior to the first catalytic step."
    Bryant H.E., Wadd S.E., Lamond A.I., Silverstein S.J., Clements J.B.
    J. Virol. 75:4376-4385(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "ICP27 interacts with the RNA export factor Aly/REF to direct herpes simplex virus type 1 intronless mRNAs to the TAP export pathway."
    Chen I.-H.B., Sciabica K.S., Sandri-Goldin R.M.
    J. Virol. 76:12877-12889(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST ALYREF/THOC4.
  11. "ICP27 interacts with SRPK1 to mediate HSV splicing inhibition by altering SR protein phosphorylation."
    Sciabica K.S., Dai Q.J., Sandri-Goldin R.M.
    EMBO J. 22:1608-1619(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HOST SRPK1.
  12. "ICP27 interacts with the C-terminal domain of RNA polymerase II and facilitates its recruitment to herpes simplex virus 1 transcription sites, where it undergoes proteasomal degradation during infection."
    Dai-Ju J.Q., Li L., Johnson L.A., Sandri-Goldin R.M.
    J. Virol. 80:3567-3581(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "The many roles of the regulatory protein ICP27 during herpes simplex virus infection."
    Sandri-Goldin R.M.
    Front. Biosci. 13:5241-5256(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  14. "Arginine methylation of the ICP27 RGG box regulates ICP27 export and is required for efficient herpes simplex virus 1 replication."
    Souki S.K., Gershon P.D., Sandri-Goldin R.M.
    J. Virol. 83:5309-5320(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: METHYLATION AT ARG-138; ARG-148 AND ARG-150.
  15. "Arginine methylation of the ICP27 RGG box regulates the functional interactions of ICP27 with SRPK1 and Aly/REF during herpes simplex virus 1 infection."
    Souki S.K., Sandri-Goldin R.M.
    J. Virol. 83:8970-8975(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST SRPK1, FUNCTION.
  16. "The cellular RNA export receptor TAP/NXF1 is required for ICP27-mediated export of herpes simplex virus 1 RNA, but the TREX complex adaptor protein Aly/REF appears to be dispensable."
    Johnson L.A., Li L., Sandri-Goldin R.M.
    J. Virol. 83:6335-6346(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST NXF1, FUNCTION.
  17. "Structural basis for the recognition of cellular mRNA export factor REF by herpes viral proteins HSV-1 ICP27 and HVS ORF57."
    Tunnicliffe R.B., Hautbergue G.M., Kalra P., Jackson B.R., Whitehouse A., Wilson S.A., Golovanov A.P.
    PLoS Pathog. 7:E1001244-E1001244(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST ALYREF.
  18. "Herpes simplex virus ICP27 protein directly interacts with the nuclear pore complex through Nup62, inhibiting host nucleocytoplasmic transport pathways."
    Malik P., Tabarraei A., Kehlenbach R.H., Korfali N., Iwasawa R., Graham S.V., Schirmer E.C.
    J. Biol. Chem. 287:12277-12292(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST NUP62, FUNCTION.

Entry informationi

Entry nameiICP27_HHV11
AccessioniPrimary (citable) accession number: P10238
Secondary accession number(s): B9VQI3, Q09I80
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: October 29, 2014
This is version 82 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Caution

A role in degradation of host polymerase has been suggested in PubMed 16537625, but this could be a consequence of binding to immature mRNAs simultaneously to transcription by the polymerase.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3