ID   ICP22_HHV2H             Reviewed;         413 AA.
AC   P89474;
DT   22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   23-FEB-2022, entry version 75.
DE   RecName: Full=E3 ubiquitin ligase ICP22;
DE   AltName: Full=Immediate-early protein IE68;
DE   AltName: Full=Infected cell protein 22;
DE            Short=ICP22;
GN   ORFNames=US1;
OS   Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX   NCBI_TaxID=10315;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=9499055; DOI=10.1128/jvi.72.3.2010-2021.1998;
RA   Dolan A., Jamieson F.E., Cunningham C., Barnett B.C., McGeoch D.J.;
RT   "The genome sequence of herpes simplex virus type 2.";
RL   J. Virol. 72:2010-2021(1998).
RN   [2]
RP   FUNCTION.
RX   PubMed=32699158; DOI=10.4049/jimmunol.2000418;
RA   Zhang M., Fu M., Li M., Hu H., Gong S., Hu Q.;
RT   "Herpes Simplex Virus Type 2 Inhibits Type I IFN Signaling Mediated by the
RT   Novel E3 Ubiquitin Protein Ligase Activity of Viral Protein ICP22.";
RL   J. Immunol. 205:1281-1292(2020).
CC   -!- FUNCTION: Functions as a E3 ubiquitin ligase and plays a role in the
CC       inhibition of innate immunity by preventing IFN-mediated signaling.
CC       Induces the ubiquitination and degradation of host STAT1, STAT2 and
CC       IRF9, resulting in the blockade of ISGF3 nuclear translocation.
CC       {ECO:0000269|PubMed:32699158}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:P04485}.
CC       Note=Localizes in small nuclear bodies early in infection then moves to
CC       a more diffuse distribution in viral compartments as infection
CC       progresses.
CC   -!- PTM: Tyrosine phosphorylated. {ECO:0000250|UniProtKB:P04485}.
CC   -!- MISCELLANEOUS: ICP22 and protein US1.5 mRNAs are transcribed from two
CC       different promoters on the US1 gene.
CC   -!- SIMILARITY: Belongs to the herpesviridae ICP22 family. {ECO:0000305}.
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DR   EMBL; Z86099; CAB06708.1; -; Genomic_DNA.
DR   PRIDE; P89474; -.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000001874; Genome.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR   GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IDA:UniProtKB.
DR   GO; GO:0039564; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT2 activity; IDA:UniProtKB.
DR   GO; GO:0039523; P:suppression by virus of host mRNA transcription via inhibition of RNA polymerase II activity; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   InterPro; IPR003403; IE68.
DR   Pfam; PF02479; Herpes_IE68; 1.
PE   3: Inferred from homology;
KW   Early protein; Eukaryotic host gene expression shutoff by virus;
KW   Eukaryotic host transcription shutoff by virus;
KW   Host gene expression shutoff by virus; Host nucleus;
KW   Host-virus interaction; Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host RNA polymerase II by virus;
KW   Inhibition of host STAT1 by virus; Inhibition of host STAT2 by virus;
KW   Phosphoprotein; Reference proteome; Transcription;
KW   Transcription regulation; Ubl conjugation pathway; Viral immunoevasion.
FT   CHAIN           1..413
FT                   /note="E3 ubiquitin ligase ICP22"
FT                   /id="PRO_0000385458"
FT   REGION          1..124
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          289..334
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          370..390
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..30
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        33..51
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        58..76
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         189
FT                   /note="Phosphotyrosine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P04485"
SQ   SEQUENCE   413 AA;  44739 MW;  AF828B79CEDDF4A5 CRC64;
     MADIPPDPPA LNTTPANHAP PSPPPGSRKR RRPVLPSSSE SEGKPDTESE SSSTESSEDE
     AGDLRGGRRR SPRELGGRYF LDLSAESTTG TESEGTGPSD DDDDDASDGW LVDTPPRKSK
     RPRINLRLTS SPDRRAGVVF PEVWRSDRPI RAAQPQAPAS LPGIAHAHRR SARQAQMRSG
     AAWTLDLHYI RQCVNQLFRI LRAAPNPPGS ANRLRHLVRD CYLMGYCRTR LGPRTWGRLL
     QISGGTWDVR LRNAIREVEA HFEPAAEPVC ELPCLNARRY GPECDVGNLE TNGGSTSDDE
     ISDATDSDDT LASHSDTEGG PSPAGRENPE SASGGAIAAR LECEFGTFDW TSEEGSQPWL
     SAVVADTSSA ERSGLPAPGA CRATEAPERE DGCRKMRFPA ACPYPCGHTF LRP