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P10238

- ICP27_HHV11

UniProt

P10238 - ICP27_HHV11

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
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    • History
      Entry version 81 (01 Oct 2014)
      Sequence version 1 (01 Jul 1989)
      Previous versions | rss
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    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. protein binding Source: IntAct
    3. 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

    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-SubCell
    2. host cell nucleus Source: UniProtKB-SubCell

    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

    MATDIDMLID LGLDLSDSDL DEDPPEPAES RRDDLESDSS GECSSSDEDM    50
    EDPHGEDGPE PILDAARPAV RPSRPEDPGV PSTQTPRPTE RQGPNDPQPA 100
    PHSVWSRLGA RRPSCSPEQH GGKVARLQPP PTKAQPARGG RRGRRRGRGR 150
    GGPGAADGLS DPRRRAPRTN RNPGGPRPGA GWTDGPGAPH GEAWRGSEQP 200
    DPPGGQRTRG VRQAPPPLMT LAIAPPPADP RAPAPERKAP AADTIDATTR 250
    LVLRSISERA AVDRISESFG RSAQVMHDPF GGQPFPAANS PWAPVLAGQG 300
    GPFDAETRRV SWETLVAHGP SLYRTFAGNP RAASTAKAMR DCVLRQENFI 350
    EALASADETL AWCKMCIHHN LPLRPQDPII GTTAAVLDNL ATRLRPFLQC 400
    YLKARGLCGL DELCSRRRLA DIKDIASFVF VILARLANRV ERGVAEIDYA 450
    TLGVGVGEKM HFYLPGACMA GLIEILDTHR QECSSRVCEL TASHIVAPPY 500
    VHGKYFYCNS LF 512
    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

    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 1, 2014
    This is version 81 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