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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: -Experimental evidence at protein leveli

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

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri116 – 157RING-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • ubiquitin-protein transferase activity Source: AgBase

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Transferase
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, Viral latency, Viral reactivation from latency
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ICP0 (EC:2.3.2.27)
Alternative name(s):
Alpha-0 protein
Immediate-early protein IE110
RING-type E3 ubiquitin transferase ICP0Curated
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]
Proteomesi
  • UP000009294 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

  • host cell cytoplasm Source: UniProtKB-SubCell
  • host cell nucleus Source: UniProtKB
  • viral tegument Source: CACAO

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi67T → A: Abolishes interaction host RNF8. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000563521 – 775E3 ubiquitin-protein ligase ICP0Add BLAST775

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei67Phosphothreonine; by host; by CK11 Publication1

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

Proteomic databases

PRIDEiP08393

PTM databases

iPTMnetiP08393

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). Interacts with human TRIM27.7 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi971426, 5 interactors
971427, 24 interactors
DIPiDIP-42446N
IntActiP08393, 21 interactors
MINTiP08393

Structurei

3D structure databases

ProteinModelPortaliP08393
SMRiP08393
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi233 – 243Poly-AspAdd BLAST11
Compositional biasi305 – 308Poly-Gly4
Compositional biasi558 – 568Poly-SerAdd BLAST11

Sequence similaritiesi

Belongs to the simplexviruses ICp0 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri116 – 157RING-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Zinc-finger

Phylogenomic databases

KOiK19436
OrthoDBiVOG09000091

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR018957 Znf_C3HC4_RING-type
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PfamiView protein in Pfam
PF00097 zf-C3HC4, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequencei

Sequence statusi: Complete.

P08393-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEPRPGASTR RPEGRPQREP APDVWVFPCD RDLPDSSDSE AETEVGGRGD
60 70 80 90 100
ADHHDDDSAS EADSTDTELF ETGLLGPQGV DGGAVSGGSP PREEDPGSCG
110 120 130 140 150
GAPPREDGGS DEGDVCAVCT DEIAPHLRCD TFPCMHRFCI PCMKTWMQLR
160 170 180 190 200
NTCPLCNAKL VYLIVGVTPS GSFSTIPIVN DPQTRMEAEE AVRAGTAVDF
210 220 230 240 250
IWTGNQRFAP RYLTLGGHTV RALSPTHPEP TTDEDDDDLD DADYVPPAPR
260 270 280 290 300
RTPRAPPRRG AAAPPVTGGA SHAAPQPAAA RTAPPSAPIG PHGSSNTNTT
310 320 330 340 350
TNSSGGGGSR QSRAAAPRGA SGPSGGVGVG VGVVEAEAGR PRGRTGPLVN
360 370 380 390 400
RPAPLANNRD PIVISDSPPA SPHRPPAAPM PGSAPRPGPP ASAAASGPAR
410 420 430 440 450
PRAAVAPCVR APPPGPGPRA PAPGAEPAAR PADARRVPQS HSSLAQAANQ
460 470 480 490 500
EQSLCRARAT VARGSGGPGV EGGHGPSRGA APSGAAPLPS AASVEQEAAV
510 520 530 540 550
RPRKRRGSGQ ENPSPQSTRP PLAPAGAKRA ATHPPSDSGP GGRGQGGPGT
560 570 580 590 600
PLTSSAASAS SSSASSSSAP TPAGAASSAA GAASSSASAS SGGAVGALGG
610 620 630 640 650
RQEETSLGPR AASGPRGPRK CARKTRHAET SGAVPAGGLT RYLPISGVSS
660 670 680 690 700
VVALSPYVNK TITGDCLPIL DMETGNIGAY VVLVDQTGNM ATRLRAAVPG
710 720 730 740 750
WSRRTLLPET AGNHVMPPEY PTAPASEWNS LWMTPVGNML FDQGTLVGAL
760 770
DFRSLRSRHP WSGEQGASTR DEGKQ
Length:775
Mass (Da):78,457
Last modified:August 1, 1988 - v1
Checksum:iDF38A1C539DAB15C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14112 Genomic DNA Translation: CAA32336.1
X14112 Genomic DNA Translation: CAA32293.1
X04614 Genomic DNA Translation: CAA28285.1
PIRiA29152 EDBE11
RefSeqiYP_009137074.1, NC_001806.2
YP_009137133.1, NC_001806.2

Genome annotation databases

GeneIDi2703389
2703390
KEGGivg:2703389
vg:2703390

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14112 Genomic DNA Translation: CAA32336.1
X14112 Genomic DNA Translation: CAA32293.1
X04614 Genomic DNA Translation: CAA28285.1
PIRiA29152 EDBE11
RefSeqiYP_009137074.1, NC_001806.2
YP_009137133.1, NC_001806.2

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WPHX-ray2.92C/D617-627[»]
4WPIX-ray3.40C/D617-627[»]
5C56X-ray2.69B613-633[»]
ProteinModelPortaliP08393
SMRiP08393
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi971426, 5 interactors
971427, 24 interactors
DIPiDIP-42446N
IntActiP08393, 21 interactors
MINTiP08393

PTM databases

iPTMnetiP08393

Proteomic databases

PRIDEiP08393

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi2703389
2703390
KEGGivg:2703389
vg:2703390

Phylogenomic databases

KOiK19436
OrthoDBiVOG09000091

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR018957 Znf_C3HC4_RING-type
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PfamiView protein in Pfam
PF00097 zf-C3HC4, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiICP0_HHV11
AccessioniPrimary (citable) accession number: P08393
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: November 7, 2018
This is version 134 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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