PP71_HCMVA
ID PP71_HCMVA Reviewed; 559 AA.
AC P06726; Q7M6K9;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 23-FEB-2022, entry version 85.
DE RecName: Full=Protein pp71;
DE Short=pp71;
DE AltName: Full=71 kDa upper matrix phosphoprotein;
DE AltName: Full=Phosphoprotein UL82;
DE Short=ppUL82;
DE AltName: Full=Tegument protein UL82;
GN Name=UL82;
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 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 [4]
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 [5]
RP SUBCELLULAR LOCATION.
RX PubMed=9000101; DOI=10.1099/0022-1317-77-12-3087;
RA Hensel G.M., Meyer H.H., Buchmann I., Pommerehne D., Schmolke S.,
RA Plachter B., Radsak K., Kern H.F.;
RT "Intracellular localization and expression of the human cytomegalovirus
RT matrix phosphoprotein pp71 (ppUL82): evidence for its translocation into
RT the nucleus.";
RL J. Gen. Virol. 77:3087-3097(1996).
RN [6]
RP FUNCTION.
RX PubMed=12610120; DOI=10.1128/jvi.77.6.3451-3459.2003;
RA Kalejta R.F., Shenk T.;
RT "The human cytomegalovirus UL82 gene product (pp71) accelerates progression
RT through the G1 phase of the cell cycle.";
RL J. Virol. 77:3451-3459(2003).
RN [7]
RP FUNCTION, AND INTERACTION WITH HOST RB1.
RX PubMed=12626766; DOI=10.1073/pnas.0538058100;
RA Kalejta R.F., Shenk T.;
RT "Proteasome-dependent, ubiquitin-independent degradation of the Rb family
RT of tumor suppressors by the human cytomegalovirus pp71 protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:3263-3268(2003).
RN [8]
RP INTERACTION WITH UL35.
RX PubMed=15308743; DOI=10.1128/jvi.78.17.9512-9523.2004;
RA Schierling K., Stamminger T., Mertens T., Winkler M.;
RT "Human cytomegalovirus tegument proteins ppUL82 (pp71) and ppUL35 interact
RT and cooperatively activate the major immediate-early enhancer.";
RL J. Virol. 78:9512-9523(2004).
RN [9]
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 [10]
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 [11]
RP FUNCTION, AND INTERACTION WITH HUMAN DAXX.
RX PubMed=18922870; DOI=10.1128/jvi.01215-08;
RA Lukashchuk V., McFarlane S., Everett R.D., Preston C.M.;
RT "Human cytomegalovirus protein pp71 displaces the chromatin-associated
RT factor ATRX from nuclear domain 10 at early stages of infection.";
RL J. Virol. 82:12543-12554(2008).
RN [12]
RP FUNCTION, INTERACTION WITH HOST DAXX, AND SUBCELLULAR LOCATION.
RX PubMed=19369322; DOI=10.1128/jvi.02639-08;
RA Hwang J., Kalejta R.F.;
RT "Human cytomegalovirus protein pp71 induces Daxx SUMOylation.";
RL J. Virol. 83:6591-6598(2009).
RN [13]
RP PHOSPHORYLATION AT THR-223, FUNCTION, INTERACTION WITH HOST TMEM173, AND
RP SUBCELLULAR LOCATION.
RX PubMed=28132838; DOI=10.1016/j.chom.2017.01.001;
RA Fu Y.Z., Su S., Gao Y.Q., Wang P.P., Huang Z.F., Hu M.M., Luo W.W., Li S.,
RA Luo M.H., Wang Y.Y., Shu H.B.;
RT "Human cytomegalovirus tegument Protein UL82 inhibits STING-mediated
RT signaling to evade antiviral immunity.";
RL Cell Host Microbe 21:231-243(2017).
RN [14]
RP FUNCTION, S-NITROSYLATION AT CYS-218, INTERACTION WITH HOST STING1, AND
RP MUTAGENESIS OF CYS-218.
RX PubMed=32581105; DOI=10.1128/jvi.00033-20;
RA Nukui M., Roche K.L., Jia J., Fox P.L., Murphy E.A.;
RT "Protein S-Nitrosylation of Human Cytomegalovirus pp71 Inhibits Its Ability
RT To Limit STING Antiviral Responses.";
RL J. Virol. 94:0-0(2020).
CC -!- FUNCTION: Stimulates viral immediate-early (IE) transcription. Plays a
CC role in the inhibition of the host innate repsonse by targeting STING1
CC and thus the cGAS-STING pathway (PubMed:28132838, PubMed:32581105).
CC Counteracts also host DAXX-mediated repression of viral transcription.
CC Displaces a DAXX-binding protein, ATRX, from nuclear domain 10 sites
CC (ND10) shortly after infection (PubMed:18922870). Increases the basal
CC level of SUMOylated DAXX in infected cells (PubMed:19369322).
CC Stimulates quiescent cells to re-enter the cell cycle, proceed through
CC G1 and enter the S phase (PubMed:12610120). Interacts with
CC hypophosphorylated forms of RB1 and induces their degradation by the
CC proteasome without involving ubiquitin conjugation (PubMed:12626766).
CC {ECO:0000269|PubMed:12610120, ECO:0000269|PubMed:12626766,
CC ECO:0000269|PubMed:18922870, ECO:0000269|PubMed:19369322,
CC ECO:0000269|PubMed:28132838, ECO:0000269|PubMed:32581105}.
CC -!- SUBUNIT: Interacts with the host protein DAXX; this interaction takes
CC place at ND10 and induces the reversal of DAXX-mediated repression of
CC viral transcription (PubMed:18922870, PubMed:19369322). Interacts with
CC UL35 (PubMed:15308743). Interacts with host TMEM173/STING1; this
CC interaction inhibits the cGAS/STING pathway (PubMed:28132838,
CC PubMed:32581105). Interacts with host RB1; this interaction mediates
CC RB1 proteasomal degradation (PubMed:12626766).
CC {ECO:0000269|PubMed:12626766, ECO:0000269|PubMed:15308743,
CC ECO:0000269|PubMed:18922870, ECO:0000269|PubMed:19369322,
CC ECO:0000269|PubMed:28132838, ECO:0000269|PubMed:32581105}.
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000305}. Host nucleus
CC {ECO:0000269|PubMed:19369322, ECO:0000269|PubMed:9000101}. Host
CC endoplasmic reticulum {ECO:0000269|PubMed:28132838}. Note=Present in
CC the nucleus shortly after infection as well as during the late phase of
CC viral morphogenesis. Detected at nuclear domain 10 (ND10).
CC -!- PTM: S-nitrosylation limits ability to undermine the cGAS/STING
CC antiviral pathway. {ECO:0000269|PubMed:32581105}.
CC -!- SIMILARITY: Belongs to the herpesviridae pp71 family. {ECO:0000305}.
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DR EMBL; M15120; AAA45997.1; -; Genomic_DNA.
DR EMBL; X17403; CAA35356.1; -; Genomic_DNA.
DR EMBL; BK000394; DAA00179.1; -; Genomic_DNA.
DR PIR; B26793; WMBES1.
DR DIP; DIP-61112N; -.
DR ELM; P06726; -.
DR IntAct; P06726; 1.
DR iPTMnet; P06726; -.
DR Proteomes; UP000008991; Genome.
DR Proteomes; UP000008992; Genome.
DR GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0019033; C:viral tegument; IEA:UniProtKB-SubCell.
DR GO; GO:0039695; P:DNA-templated viral transcription; IDA:UniProtKB.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR InterPro; IPR008649; Herpes_UL82/UL83.
DR Pfam; PF05784; Herpes_UL82_83; 1.
PE 1: Evidence at protein level;
KW Activator; G1/S host cell cycle checkpoint dysregulation by virus;
KW Host endoplasmic reticulum; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Modulation of host cell cycle by virus; Phosphoprotein; Reference proteome;
KW S-nitrosylation; Viral immunoevasion; Virion; Virion tegument.
FT CHAIN 1..559
FT /note="Protein pp71"
FT /id="PRO_0000116290"
FT REGION 404..440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 530..559
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..431
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 218
FT /note="S-nitrosocysteine; by host"
FT /evidence="ECO:0000269|PubMed:32581105"
FT MOD_RES 223
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:28132838"
FT MUTAGEN 218
FT /note="C->S: Increased inhibition of STING1-mediated
FT antiviral response."
FT /evidence="ECO:0000269|PubMed:32581105"
SQ SEQUENCE 559 AA; 61949 MW; F2F73FE652654659 CRC64;
MSQASSSPGE GPSSEAAAIS EAEAASGSFG RLHCQVLRLI TNVEGGSLEA GRLRLLDLRT
NIEVSRPSVL CCFQENKSPH DTVDLTDLNI KGRCVVGEQD RLLVDLNNFG PRRLTPGSEN
NTVSVLAFAL PLDRVPVSGL HLFQSQRRGG EENRPRMEAR AIIRRTAHHW AVRLTVTPNW
RRRTDSSLEA GQIFVSQFAF RAGAIPLTLV DALEQLACSD PNTYIHKTET DERGQWIMLF
LHHDSPHPPT SVFLHFSVYT HRAEVVARHN PYPHLRRLPD NGFQLLIPKS FTLTRIHPEY
IVQIQNAFET NQTHDTIFFP ENIPGVSIEA GPLPDRVRIT LRVTLTGDQA VHLEHRQPLG
RIHFFRRGFW TLTPGKPDKI KRPQVQLRAG LFPRSNVMRG AVSEFLPQSP GLPPTEEEEE
EEEEDDEDDL SSTPTPTPLS EAMFAGFEEA SGDEDSDTQA GLSPALILTG QRRRSGNNGA
LTLVIPSWHV FASLDDLVPL TVSVQHAALR PTSYLRSDMD GDVRTAADIS STLRSVPAPR
PSPISTASTS STPRSRPRI
