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P08393

- ICP0_HHV11

UniProt

P08393 - ICP0_HHV11

Protein

E3 ubiquitin-protein ligase ICP0

Gene

ICP0

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 103 (01 Oct 2014)
      Sequence version 1 (01 Aug 1988)
      Previous versions | rss
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    Functioni

    Evades nuclear antiviral defenses triggered by dsDNA viruses. Acts during the initial stages of lytic infection and the reactivation of latent viral genome. Prevents the antiviral effect of nuclear bodies by degrading host PML and SP100. Prevents antiviral response to viral DNA induced by IFI16 by degrading it. Additionally, inhibits host IRF3 nuclear signaling to prevent interferon production by the infected cells. Interestingly, the E3 ubiquitin ligase activity associated with the RING finger domain does not seem to be directly required to inhibit the activation of IRF3 but instead plays a critical role in modulating the cellular localization of ICP0. Upon reactivation of latent genome, suppresses the silencing of viral DNA by dissociating either HDAC1 or HDAC2 from the HDAC-RCOR1-REST-KDM1A complex localized at the ND10 structures and causes their dispersal. Two cellular histone ubiquitin ligases RNF8 and RNF168 are also targeted by ICP0 for degradation, leading to a loss of ubiquitinated forms of H2A, a relief of transcriptional repression, and the activation of latent viral genomes. Enhances the localization of host CCND3 to ND10 bodies that serve as precursors of replication compartments to enable efficient viral replication. Like many RING-finger E3 ubiquitin ligases, ICP0 can induce its own ubiquitination, an activity that promotes its instability due to its targeting to the 26S proteasome for degradation. ICP0 restricts this process by recruiting the cellular ubiquitin-specific protease USP7 that cleaves the anchored ubiquitin chains from ICP0, thereby promoting its stabilization.7 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri116 – 15742RING-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. ligase activity Source: UniProtKB-KW
    3. protein binding Source: IntAct
    4. ubiquitin-protein transferase activity Source: AgBase
    5. zinc ion binding Source: InterPro

    GO - Biological processi

    1. disruption by symbiont of host cell PML body Source: UniProtKB
    2. modulation by virus of host protein ubiquitination Source: UniProtKB-KW
    3. positive regulation of protein catabolic process Source: AgBase
    4. protein polyubiquitination Source: AgBase
    5. release from viral latency Source: AgBase
    6. response to type I interferon Source: BHF-UCL
    7. suppression by virus of host exit from mitosis Source: UniProtKB-KW
    8. suppression by virus of host IRF3 activity Source: UniProtKB
    9. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Ligase

    Keywords - Biological processi

    Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host IRF3 by virus, Inhibition of host mitotic exit by virus, Inhibition of host RLR pathway by virus, Modulation of host cell cycle by virus, Modulation of host ubiquitin pathway by viral E3 ligase, Modulation of host ubiquitin pathway by virus, Transcription, Transcription regulation, Ubl conjugation pathway, Viral immunoevasion

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase ICP0 (EC:6.3.2.-)
    Alternative name(s):
    Alpha-0 protein
    Immediate-early protein IE110
    Trans-acting transcriptional protein ICP0
    VMW110
    Gene namesi
    Name:ICP0
    Synonyms:IE110
    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

    GO - Cellular componenti

    1. host cell cytoplasm Source: UniProtKB-SubCell
    2. host cell nucleus Source: UniProtKB
    3. viral tegument Source: CACAO

    Keywords - Cellular componenti

    Host cytoplasm, Host nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi67 – 671T → A: Abolishes interaction host RNF8. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 775775E3 ubiquitin-protein ligase ICP0PRO_0000056352Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei67 – 671Phosphothreonine; by host; by CK11 Publication

    Post-translational modificationi

    Phosphorylated at Thr-67, leading to promote interaction with host RNF8.1 Publication
    Auto-ubiquitinated. Deubiquitinated by host USP7; leading to stabilize it.2 Publications

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Expressioni

    Keywords - Developmental stagei

    Early protein

    Interactioni

    Subunit structurei

    Interacts directly with human RCOR1/CoREST protein, leading to the disruption of the human BHC corepressor complex. Interacts with human CENPA, leading to its degradation. Interacts with human USP7; this interaction modulates ICP0 stability. Interacts with human CDC34. Interacts (when phosphorylated) with human RNF8 (via FHA domain).6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CCND3P302813EBI-6148881,EBI-375013From a different organism.
    HDAC3O153793EBI-6148881,EBI-607682From a different organism.
    HDAC4P565243EBI-6148881,EBI-308629From a different organism.
    HDAC5Q9UQL63EBI-6148881,EBI-715576From a different organism.
    HDAC7Q8WUI43EBI-6148881,EBI-1048378From a different organism.

    Protein-protein interaction databases

    DIPiDIP-42446N.
    IntActiP08393. 12 interactions.
    MINTiMINT-1345075.

    Structurei

    3D structure databases

    ProteinModelPortaliP08393.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi233 – 24311Poly-AspAdd
    BLAST
    Compositional biasi305 – 3084Poly-Gly
    Compositional biasi558 – 56811Poly-SerAdd
    BLAST

    Sequence similaritiesi

    Belongs to the simplexviruses ICp0 family.Curated
    Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri116 – 15742RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Family and domain databases

    Gene3Di3.30.40.10. 1 hit.
    InterProiIPR018957. Znf_C3HC4_RING-type.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    IPR017907. Znf_RING_CS.
    [Graphical view]
    PfamiPF00097. zf-C3HC4. 1 hit.
    [Graphical view]
    SMARTiSM00184. RING. 1 hit.
    [Graphical view]
    PROSITEiPS00518. ZF_RING_1. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P08393-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEPRPGASTR RPEGRPQREP APDVWVFPCD RDLPDSSDSE AETEVGGRGD    50
    ADHHDDDSAS EADSTDTELF ETGLLGPQGV DGGAVSGGSP PREEDPGSCG 100
    GAPPREDGGS DEGDVCAVCT DEIAPHLRCD TFPCMHRFCI PCMKTWMQLR 150
    NTCPLCNAKL VYLIVGVTPS GSFSTIPIVN DPQTRMEAEE AVRAGTAVDF 200
    IWTGNQRFAP RYLTLGGHTV RALSPTHPEP TTDEDDDDLD DADYVPPAPR 250
    RTPRAPPRRG AAAPPVTGGA SHAAPQPAAA RTAPPSAPIG PHGSSNTNTT 300
    TNSSGGGGSR QSRAAAPRGA SGPSGGVGVG VGVVEAEAGR PRGRTGPLVN 350
    RPAPLANNRD PIVISDSPPA SPHRPPAAPM PGSAPRPGPP ASAAASGPAR 400
    PRAAVAPCVR APPPGPGPRA PAPGAEPAAR PADARRVPQS HSSLAQAANQ 450
    EQSLCRARAT VARGSGGPGV EGGHGPSRGA APSGAAPLPS AASVEQEAAV 500
    RPRKRRGSGQ ENPSPQSTRP PLAPAGAKRA ATHPPSDSGP GGRGQGGPGT 550
    PLTSSAASAS SSSASSSSAP TPAGAASSAA GAASSSASAS SGGAVGALGG 600
    RQEETSLGPR AASGPRGPRK CARKTRHAET SGAVPAGGLT RYLPISGVSS 650
    VVALSPYVNK TITGDCLPIL DMETGNIGAY VVLVDQTGNM ATRLRAAVPG 700
    WSRRTLLPET AGNHVMPPEY PTAPASEWNS LWMTPVGNML FDQGTLVGAL 750
    DFRSLRSRHP WSGEQGASTR DEGKQ 775
    Length:775
    Mass (Da):78,457
    Last modified:August 1, 1988 - v1
    Checksum:iDF38A1C539DAB15C
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14112 Genomic DNA. Translation: CAA32336.1.
    X14112 Genomic DNA. Translation: CAA32293.1.
    X04614 Genomic DNA. Translation: CAA28285.1.
    PIRiA29152. EDBE11.
    RefSeqiNP_044601.1. NC_001806.1.
    NP_044660.1. NC_001806.1.

    Genome annotation databases

    GeneIDi2703389.
    2703390.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14112 Genomic DNA. Translation: CAA32336.1 .
    X14112 Genomic DNA. Translation: CAA32293.1 .
    X04614 Genomic DNA. Translation: CAA28285.1 .
    PIRi A29152. EDBE11.
    RefSeqi NP_044601.1. NC_001806.1.
    NP_044660.1. NC_001806.1.

    3D structure databases

    ProteinModelPortali P08393.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-42446N.
    IntActi P08393. 12 interactions.
    MINTi MINT-1345075.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 2703389.
    2703390.

    Family and domain databases

    Gene3Di 3.30.40.10. 1 hit.
    InterProi IPR018957. Znf_C3HC4_RING-type.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    IPR017907. Znf_RING_CS.
    [Graphical view ]
    Pfami PF00097. zf-C3HC4. 1 hit.
    [Graphical view ]
    SMARTi SM00184. RING. 1 hit.
    [Graphical view ]
    PROSITEi PS00518. ZF_RING_1. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "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 [GENOMIC DNA].
    2. "Characterization of the IE110 gene of herpes simplex virus type 1."
      Perry L.J., Rixon F.J., Everett R.D., Frame M.C., McGeoch D.J.
      J. Gen. Virol. 67:2365-2380(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "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].
    4. "Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0."
      Lomonte P., Sullivan K.F., Everett R.D.
      J. Biol. Chem. 276:5829-5835(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN CENPA.
    5. "The infected cell protein 0 of herpes simplex virus 1 dynamically interacts with proteasomes, binds and activates the cdc34 E2 ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin ligase activity."
      Van Sant C., Hagglund R., Lopez P., Roizman B.
      Proc. Natl. Acad. Sci. U.S.A. 98:8815-8820(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN CDC34.
    6. "Protein interaction domains of the ubiquitin-specific protease, USP7/HAUSP."
      Holowaty M.N., Sheng Y., Nguyen T., Arrowsmith C., Frappier L.
      J. Biol. Chem. 278:47753-47761(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN USP7.
    7. "A RING finger ubiquitin ligase is protected from autocatalyzed ubiquitination and degradation by binding to ubiquitin-specific protease USP7."
      Canning M., Boutell C., Parkinson J., Everett R.D.
      J. Biol. Chem. 279:38160-38168(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: AUTOUBIQUITINATION.
    8. "Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells."
      Gu H., Liang Y., Mandel G., Roizman B.
      Proc. Natl. Acad. Sci. U.S.A. 102:7571-7576(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH HUMAN RCOR1.
    9. "Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease USP7."
      Boutell C., Canning M., Orr A., Everett R.D.
      J. Virol. 79:12342-12354(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Identification of a novel higher molecular weight isoform of USP7/HAUSP that interacts with the Herpes simplex virus type-1 immediate early protein ICP0."
      Antrobus R., Boutell C.
      Virus Res. 137:64-71(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN USP7, DEUBIQUITINATION BY HUMAN USP7.
    11. "A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses."
      Lilley C.E., Chaurushiya M.S., Boutell C., Landry S., Suh J., Panier S., Everett R.D., Stewart G.S., Durocher D., Weitzman M.D.
      EMBO J. 29:943-955(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Cellular localization of the herpes simplex virus ICP0 protein dictates its ability to block IRF3-mediated innate immune responses."
      Paladino P., Collins S.E., Mossman K.L.
      PLoS ONE 5:E10428-E10428(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    13. "Comparison of the biological and biochemical activities of several members of the alphaherpesvirus ICP0 family of proteins."
      Everett R.D., Boutell C., McNair C., Grant L., Orr A.
      J. Virol. 84:3476-3487(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    14. "Viral E3 ubiquitin ligase-mediated degradation of a cellular E3: viral mimicry of a cellular phosphorylation mark targets the RNF8 FHA domain."
      Chaurushiya M.S., Lilley C.E., Aslanian A., Meisenhelder J., Scott D.C., Landry S., Ticau S., Boutell C., Yates J.R. III, Schulman B.A., Hunter T., Weitzman M.D.
      Mol. Cell 46:79-90(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH HUMAN RNF8, PHOSPHORYLATION AT THR-67, MUTAGENESIS OF THR-67.
    15. "Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein."
      Orzalli M.H., DeLuca N.A., Knipe D.M.
      Proc. Natl. Acad. Sci. U.S.A. 109:E3008-E3017(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiICP0_HHV11
    AccessioniPrimary (citable) accession number: P08393
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: August 1, 1988
    Last modified: October 1, 2014
    This is version 103 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3