PP65_HCMVA
ID PP65_HCMVA Reviewed; 561 AA.
AC P06725; Q7M6K8;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 23-FEB-2022, entry version 94.
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 AD169) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=10360;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3027374; DOI=10.1128/jvi.61.2.446-453.1987;
RA Rueger B., Klages S., Walla B., Albrecht J.-C., Fleckenstein B.,
RA Tomlinson P., Barrell B.G.;
RT "Primary structure and transcription of the genes coding for the two virion
RT phosphoproteins pp65 and pp71 of human cytomegalovirus.";
RL J. Virol. 61:446-453(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=2161319; DOI=10.1007/978-3-642-74980-3_6;
RA Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R.,
RA Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A.,
RA Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G.;
RT "Analysis of the protein-coding content of the sequence of human
RT cytomegalovirus strain AD169.";
RL Curr. Top. Microbiol. Immunol. 154:125-169(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 495-538.
RX PubMed=6087357; DOI=10.1073/pnas.81.15.4965;
RA Pande H., Baak S.W., Riggs A.D., Clark B.R., Shively J.E., Zaia J.A.;
RT "Cloning and physical mapping of a gene fragment coding for a 64-kilodalton
RT major late antigen of human cytomegalovirus.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4965-4969(1984).
RN [4]
RP GENOME REANNOTATION.
RX PubMed=12533697; DOI=10.1099/vir.0.18606-0;
RA Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA McGeoch D.J., Hayward G.S.;
RT "The human cytomegalovirus genome revisited: comparison with the chimpanzee
RT cytomegalovirus genome.";
RL J. Gen. Virol. 84:17-28(2003).
RN [5]
RP ERRATUM OF PUBMED:12533697.
RA Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA McGeoch D.J., Hayward G.S.;
RL J. Gen. Virol. 84:1053-1053(2003).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=7815485; DOI=10.1128/jvi.69.2.1071-1078.1995;
RA Schmolke S., Drescher P., Jahn G., Plachter B.;
RT "Nuclear targeting of the tegument protein pp65 (UL83) of human
RT cytomegalovirus: an unusual bipartite nuclear localization signal functions
RT with other portions of the protein to mediate its efficient nuclear
RT transport.";
RL J. Virol. 69:1071-1078(1995).
RN [7]
RP IDENTIFICATION.
RX PubMed=15452216; DOI=10.1128/jvi.78.20.10960-10966.2004;
RA Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
RA Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
RA Shenk T., Smith R.D., Nelson J.A.;
RT "Identification of proteins in human cytomegalovirus (HCMV) particles: the
RT HCMV proteome.";
RL J. Virol. 78:10960-10966(2004).
RN [8]
RP ERRATUM OF PUBMED:15452216.
RA Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
RA Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
RA Shenk T., Smith R.D., Nelson J.A.;
RL J. Virol. 78:13395-13395(2004).
RN [9]
RP FUNCTION.
RX PubMed=15452220; DOI=10.1128/jvi.78.20.10995-11006.2004;
RA Abate D.A., Watanabe S., Mocarski E.S.;
RT "Major human cytomegalovirus structural protein pp65 (ppUL83) prevents
RT interferon response factor 3 activation in the interferon response.";
RL J. Virol. 78:10995-11006(2004).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=17715235; DOI=10.1128/jvi.02760-06;
RA Sanchez V., Mahr J.A., Orazio N.I., Spector D.H.;
RT "Nuclear export of the human cytomegalovirus tegument protein pp65 requires
RT cyclin-dependent kinase activity and the Crm1 exporter.";
RL J. Virol. 81:11730-11736(2007).
RN [11]
RP FUNCTION, AND INTERACTION WITH HOST IFI16.
RX PubMed=20504932; DOI=10.1128/jvi.00139-10;
RA Cristea I.M., Moorman N.J., Terhune S.S., Cuevas C.D., O'Keefe E.S.,
RA Rout M.P., Chait B.T., Shenk T.;
RT "Human cytomegalovirus pUL83 stimulates activity of the viral immediate-
RT early promoter through its interaction with the cellular IFI16 protein.";
RL J. Virol. 84:7803-7814(2010).
RN [12]
RP INTERACTION WITH HOST NCL.
RX PubMed=21053310; DOI=10.1002/jcb.22928;
RA Arcangeletti M.C., Rodighiero I., Mirandola P., De Conto F., Covan S.,
RA Germini D., Razin S., Dettori G., Chezzi C.;
RT "Cell-cycle-dependent localization of human cytomegalovirus UL83
RT phosphoprotein in the nucleolus and modulation of viral gene expression in
RT human embryo fibroblasts in vitro.";
RL J. Cell. Biochem. 112:307-317(2011).
RN [13]
RP FUNCTION, INTERACTION WITH HOST CGAS, AND SUBCELLULAR LOCATION.
RX PubMed=29263269; DOI=10.1128/jvi.01774-17;
RA Biolatti M., Dell'Oste V., Pautasso S., Gugliesi F., von Einem J.,
RA Krapp C., Jakobsen M.R., Borgogna C., Gariglio M., De Andrea M.,
RA Landolfo S.;
RT "Human Cytomegalovirus Tegument Protein pp65 (pUL83) Dampens Type I
RT Interferon Production by Inactivating the DNA Sensor cGAS without Affecting
RT STING.";
RL J. Virol. 92:0-0(2018).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 495-503.
RX PubMed=19655750; DOI=10.1021/ja9037559;
RA Celie P.H., Toebes M., Rodenko B., Ovaa H., Perrakis A., Schumacher T.N.;
RT "UV-induced ligand exchange in MHC class I protein crystals.";
RL J. Am. Chem. Soc. 131:12298-12304(2009).
CC -!- FUNCTION: Counteracts the host antiviral immune response when activated
CC and phosphorylated, by preventing host IRF3 from entering the nucleus
CC (PubMed:15452220). Inhibits also the type I interferon production by
CC inactivating the enzymatic activity of DNA sensor CGAS without
CC affecting STING1 (PubMed:29263269). Participates in the transactivation
CC of viral major immediate-early genes by the recruitment of host IFI16
CC to the promoters pf these genes (PubMed:20504932).
CC {ECO:0000269|PubMed:15452220, ECO:0000269|PubMed:20504932,
CC ECO:0000269|PubMed:29263269}.
CC -!- SUBUNIT: Interacts with host NCL/nucleolin (PubMed:21053310). Interacts
CC with host IFI16 (PubMed:20504932). Interacts with host CGAS; this
CC interaction inhibits CGAS enzymatic activity (PubMed:29263269).
CC {ECO:0000269|PubMed:20504932, ECO:0000269|PubMed:21053310,
CC ECO:0000269|PubMed:29263269}.
CC -!- INTERACTION:
CC P06725; O96017: CHEK2; Xeno; NbExp=2; IntAct=EBI-9545359, EBI-1180783;
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000305}. Host nucleus
CC {ECO:0000269|PubMed:17715235, ECO:0000269|PubMed:29263269,
CC ECO:0000269|PubMed:7815485}. Host cytoplasm
CC {ECO:0000269|PubMed:17715235}. Note=As part of the incoming virion,
CC pp65 is targeted to the nucleus immediately after infection
CC (PubMed:7815485). The newly synthesized pp65 is observed in the nucleus
CC until some time after 48 hours postinfection (PubMed:17715235).
CC Thereafter, pp65 is probably exported and accumulates in the cytoplasm
CC (PubMed:17715235). Also found in dense bodies (PubMed:7815485).
CC -!- PTM: Phosphorylation may play a role in the localization of the
CC protein.
CC -!- SIMILARITY: Belongs to the herpesviridae pp65 family. {ECO:0000305}.
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DR EMBL; M15120; AAA45996.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X17403; CAA35357.1; -; Genomic_DNA.
DR EMBL; K02531; AAA45983.1; -; Genomic_DNA.
DR EMBL; BK000394; DAA00180.1; -; Genomic_DNA.
DR PIR; A26793; WMBE65.
DR PDB; 2X4R; X-ray; 2.30 A; C/F=495-503.
DR PDB; 2X4T; X-ray; 2.30 A; C/F=495-503.
DR PDB; 3GSO; X-ray; 1.60 A; P=495-503.
DR PDBsum; 2X4R; -.
DR PDBsum; 2X4T; -.
DR PDBsum; 3GSO; -.
DR SMR; P06725; -.
DR DIP; DIP-61111N; -.
DR IntAct; P06725; 4.
DR ABCD; P06725; 8 sequenced antibodies.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR EvolutionaryTrace; P06725; -.
DR Proteomes; UP000008991; Genome.
DR Proteomes; UP000008992; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
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_0000116292"
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:0000305"
FT COMPBIAS 434..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 472
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT CONFLICT 94..106
FT /note="Missing (in Ref. 2; AAA45996)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 561 AA; 62898 MW; 37422EA149E88F30 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
TGGGAMAGAS TSAGRKRKSA SSATACTSGV MTRGRLKAES TVAPEEDTDE DSDNEIHNPA
VFTWPPWQAG ILARNLVPMV ATVQGQNLKY QEFFWDANDI YRIFAELEGV WQPAAQPKRR
RHRQDALPGP CIASTPKKHR G
