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P08393 (ICP0_HHV11) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ICP0
Synonyms:IE110
OrganismHuman herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) [Reference proteome]
Taxonomic identifier10299 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length775 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15

Subunit structure

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). Ref.4 Ref.5 Ref.6 Ref.8 Ref.10 Ref.14

Subcellular location

Host cytoplasm. Host nucleus Ref.12.

Post-translational modification

Phosphorylated at Thr-67, leading to promote interaction with host RNF8. Ref.14

Auto-ubiquitinated. Deubiquitinated by host USP7; leading to stabilize it.

Sequence similarities

Belongs to the simplexviruses ICp0 family.

Contains 1 RING-type zinc finger.

Ontologies

Keywords
   Biological processHost-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
   Cellular componentHost cytoplasm
Host nucleus
   Developmental stageEarly protein
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Ligase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdisruption by symbiont of host cell PML body

Inferred from direct assay Ref.13. Source: UniProtKB

modulation by virus of host protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of protein catabolic process

Traceable author statement Ref.7. Source: AgBase

protein polyubiquitination

Inferred from direct assay Ref.7. Source: AgBase

release from viral latency

Traceable author statement Ref.7. Source: AgBase

response to type I interferon

Inferred from direct assay PubMed 16873258. Source: BHF-UCL

suppression by virus of host IRF3 activity

Inferred from direct assay PubMed 14747533. Source: UniProtKB

suppression by virus of host exit from mitosis

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell nucleus

Non-traceable author statement Ref.7. Source: UniProtKB

viral tegument

Inferred from direct assay PubMed 23408623. Source: CACAO

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 15194749PubMed 9311810. Source: IntAct

ubiquitin-protein transferase activity

Inferred from direct assay Ref.7. Source: AgBase

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 775775E3 ubiquitin-protein ligase ICP0
PRO_0000056352

Regions

Zinc finger116 – 15742RING-type
Compositional bias233 – 24311Poly-Asp
Compositional bias305 – 3084Poly-Gly
Compositional bias558 – 56811Poly-Ser

Amino acid modifications

Modified residue671Phosphothreonine; by host; by CK1 Ref.14

Experimental info

Mutagenesis671T → A: Abolishes interaction host RNF8. Ref.14

Sequences

Sequence LengthMass (Da)Tools
P08393 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: DF38A1C539DAB15C

FASTA77578,457
        10         20         30         40         50         60 
MEPRPGASTR RPEGRPQREP APDVWVFPCD RDLPDSSDSE AETEVGGRGD ADHHDDDSAS 

        70         80         90        100        110        120 
EADSTDTELF ETGLLGPQGV DGGAVSGGSP PREEDPGSCG GAPPREDGGS DEGDVCAVCT 

       130        140        150        160        170        180 
DEIAPHLRCD TFPCMHRFCI PCMKTWMQLR NTCPLCNAKL VYLIVGVTPS GSFSTIPIVN 

       190        200        210        220        230        240 
DPQTRMEAEE AVRAGTAVDF IWTGNQRFAP RYLTLGGHTV RALSPTHPEP TTDEDDDDLD 

       250        260        270        280        290        300 
DADYVPPAPR RTPRAPPRRG AAAPPVTGGA SHAAPQPAAA RTAPPSAPIG PHGSSNTNTT 

       310        320        330        340        350        360 
TNSSGGGGSR QSRAAAPRGA SGPSGGVGVG VGVVEAEAGR PRGRTGPLVN RPAPLANNRD 

       370        380        390        400        410        420 
PIVISDSPPA SPHRPPAAPM PGSAPRPGPP ASAAASGPAR PRAAVAPCVR APPPGPGPRA 

       430        440        450        460        470        480 
PAPGAEPAAR PADARRVPQS HSSLAQAANQ EQSLCRARAT VARGSGGPGV EGGHGPSRGA 

       490        500        510        520        530        540 
APSGAAPLPS AASVEQEAAV RPRKRRGSGQ ENPSPQSTRP PLAPAGAKRA ATHPPSDSGP 

       550        560        570        580        590        600 
GGRGQGGPGT PLTSSAASAS SSSASSSSAP TPAGAASSAA GAASSSASAS SGGAVGALGG 

       610        620        630        640        650        660 
RQEETSLGPR AASGPRGPRK CARKTRHAET SGAVPAGGLT RYLPISGVSS VVALSPYVNK 

       670        680        690        700        710        720 
TITGDCLPIL DMETGNIGAY VVLVDQTGNM ATRLRAAVPG WSRRTLLPET AGNHVMPPEY 

       730        740        750        760        770 
PTAPASEWNS LWMTPVGNML FDQGTLVGAL DFRSLRSRHP WSGEQGASTR DEGKQ 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14112 Genomic DNA. Translation: CAA32336.1.
X14112 Genomic DNA. Translation: CAA32293.1.
X04614 Genomic DNA. Translation: CAA28285.1.
PIREDBE11. A29152.
RefSeqNP_044601.1. NC_001806.1.
NP_044660.1. NC_001806.1.

3D structure databases

ProteinModelPortalP08393.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP08393. 12 interactions.
MINTMINT-1345075.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID2703389.
2703390.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamPF00097. zf-C3HC4. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
PROSITEPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameICP0_HHV11
AccessionPrimary (citable) accession number: P08393
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: June 11, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families