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PP65_HCMVM
ID   PP65_HCMVM              Reviewed;         561 AA.
AC   Q6SW59; D2K3P1;
DT   11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   23-FEB-2022, entry version 64.
DE   RecName: Full=65 kDa phosphoprotein;
DE            Short=pp65;
DE   AltName: Full=65 kDa matrix phosphoprotein;
DE   AltName: Full=Phosphoprotein UL83;
DE   AltName: Full=Tegument protein UL83;
GN   Name=UL83;
OS   Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX   NCBI_TaxID=295027;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15105547; DOI=10.1099/vir.0.79888-0;
RA   Dolan A., Cunningham C., Hector R.D., Hassan-Walker A.F., Lee L.,
RA   Addison C., Dargan D.J., McGeoch D.J., Gatherer D., Emery V.C.,
RA   Griffiths P.D., Sinzger C., McSharry B.P., Wilkinson G.W.G., Davison A.J.;
RT   "Genetic content of wild-type human cytomegalovirus.";
RL   J. Gen. Virol. 85:1301-1312(2004).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 495-503.
RA   Reiser J.-B., Le Gorrec M., Chouquet A., Debeaupuis E., Echasserieau K.,
RA   Saulquin X., Bonneville M., Housset D.;
RT   "Crystal Structure of MHC class I HLA-A2 molecule complexed with short
RT   peptide.";
RL   Submitted (APR-2010) to the PDB data bank.
CC   -!- FUNCTION: Counteracts the host antiviral immune response when activated
CC       and phosphorylated, by preventing host IRF3 from entering the nucleus.
CC       Inhibits also the type I interferon production by inactivating the
CC       enzymatic activity of DNA sensor CGAS without affecting STING1.
CC       Participates in the transactivation of viral major immediate-early
CC       genes by the recruitment of host IFI16 to the promoters pf these genes.
CC       {ECO:0000250|UniProtKB:P06725}.
CC   -!- SUBUNIT: Interacts with host NCL/nucleolin. Interacts with host IFI16.
CC       Interacts with host CGAS; this interaction inhibits CGAS enzymatic
CC       activity. {ECO:0000250|UniProtKB:P06725}.
CC   -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000250|UniProtKB:P06725}.
CC       Host nucleus {ECO:0000250|UniProtKB:P06725}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:P06725}. Note=As part of the incoming virion,
CC       pp65 is targeted to the nucleus immediately after infection. The newly
CC       synthesized pp65 is observed in the nucleus until some time after 48
CC       hours postinfection. Thereafter, pp65 is probably exported and
CC       accumulates in the cytoplasm. Also found in dense bodies.
CC       {ECO:0000250|UniProtKB:P06725}.
CC   -!- PTM: Phosphorylation may play a role in the localization of the
CC       protein. {ECO:0000250|UniProtKB:P06725}.
CC   -!- SIMILARITY: Belongs to the herpesviridae pp65 family. {ECO:0000305}.
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DR   EMBL; AY446894; AAR31635.1; -; Genomic_DNA.
DR   RefSeq; YP_081531.1; NC_006273.2.
DR   PDB; 3MR9; X-ray; 1.93 A; P=495-503.
DR   PDB; 3MRB; X-ray; 1.40 A; P=495-503.
DR   PDB; 3MRC; X-ray; 1.80 A; P=495-503.
DR   PDB; 3MRD; X-ray; 1.70 A; P=495-503.
DR   PDB; 3VCL; X-ray; 1.70 A; C=265-275.
DR   PDBsum; 3MR9; -.
DR   PDBsum; 3MRB; -.
DR   PDBsum; 3MRC; -.
DR   PDBsum; 3MRD; -.
DR   PDBsum; 3VCL; -.
DR   SMR; Q6SW59; -.
DR   BioGRID; 1678132; 1.
DR   PRIDE; Q6SW59; -.
DR   GeneID; 3077579; -.
DR   KEGG; vg:3077579; -.
DR   Reactome; R-HSA-9609690; HCMV Early Events.
DR   Reactome; R-HSA-9610379; HCMV Late Events.
DR   EvolutionaryTrace; Q6SW59; -.
DR   Proteomes; UP000000938; Genome.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0072517; C:host cell viral assembly compartment; TAS:Reactome.
DR   GO; GO:0019033; C:viral tegument; TAS:Reactome.
DR   GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036157; dUTPase-like_sf.
DR   InterPro; IPR008649; Herpes_UL82/UL83.
DR   Pfam; PF05784; Herpes_UL82_83; 1.
DR   SUPFAM; SSF51283; SSF51283; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Host cytoplasm; Host nucleus; Host-virus interaction;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host IRF3 by virus; Inhibition of host RLR pathway by virus;
KW   Phosphoprotein; Reference proteome; Viral immunoevasion; Virion;
KW   Virion tegument.
FT   CHAIN           1..561
FT                   /note="65 kDa phosphoprotein"
FT                   /id="PRO_0000418238"
FT   REGION          389..475
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          534..561
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           537..560
FT                   /note="Bipartite nuclear localization signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        424..448
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         472
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250"
FT   STRAND          269..272
FT                   /evidence="ECO:0007829|PDB:3VCL"
SQ   SEQUENCE   561 AA;  62912 MW;  134FD1500DE40B32 CRC64;
     MESRGRRCPE MISVLGPISG HVLKAVFSRG DTPVLPHETR LLQTGIHVRV SQPSLILVSQ
     YTPDSTPCHR GDNQLQVQHT YFTGSEVENV SVNVHNPTGR SICPSQEPMS IYVYALPLKM
     LNIPSINVHH YPSAAERKHR HLPVADAVIH ASGKQMWQAR LTVSGLAWTR QQNQWKEPDV
     YYTSAFVFPT KDVALRHVVC AHELVCSMEN TRATKMQVIG DQYVKVYLES FCEDVPSGKL
     FMHVTLGSDV EEDLTMTRNP QPFMRPHERN GFTVLCPKNM IIKPGKISHI MLDVAFTSHE
     HFGLLCPKSI PGLSISGNLL MNGQQIFLEV QAIRETVELR QYDPVAALFF FDIDLLLQRG
     PQYSEHPTFT SQYRIQGKLE YRHTWDRHDE GAAQGDDDVW TSGSDSDEEL VTTERKTPRV
     TGGGAMASAS TSAGRKRKSA SSATACTAGV MTRGRLKAES TVAPEEDTDE DSDNEIHNPA
     VFTWPPWQAG ILARNLVPMV ATVQGQNLKY QEFFWDANDI YRIFAELEGV WQPAAQPKRR
     RHRQDALPGP CIASTPKKHR G
 
 
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