UL35_HCMVA
ID UL35_HCMVA Reviewed; 640 AA.
AC P16766; Q7M6P8;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Protein UL35;
GN Name=UL35;
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 [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 [2]
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 [3]
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 [4]
RP ISOFORM UL35A, AND SUBCELLULAR LOCATION.
RX PubMed=11836424; DOI=10.1128/jvi.76.5.2460-2468.2002;
RA Liu Y., Biegalke B.J.;
RT "The human cytomegalovirus UL35 gene encodes two proteins with different
RT functions.";
RL J. Virol. 76:2460-2468(2002).
RN [5]
RP IDENTIFICATION, AND SUBCELLULAR LOCATION.
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 [6]
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 [7]
RP INTERACTION WITH UL82.
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 [8]
RP FUNCTION.
RX PubMed=15709028; DOI=10.1128/jvi.79.5.3084-3096.2005;
RA Schierling K., Buser C., Mertens T., Winkler M.;
RT "Human cytomegalovirus tegument protein ppUL35 is important for viral
RT replication and particle formation.";
RL J. Virol. 79:3084-3096(2005).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21489587; DOI=10.1016/j.virol.2011.03.013;
RA Salsman J., Wang X., Frappier L.;
RT "Nuclear body formation and PML body remodeling by the human
RT cytomegalovirus protein UL35.";
RL Virology 414:119-129(2011).
RN [10]
RP FUNCTION, INTERACTION WITH HOST UBP7 AND DCAF1 (ISOFORM UL35), INTERACTION
RP WITH HOST UBP7 (ISOFORM UL35A), AND SUBCELLULAR LOCATION.
RX PubMed=22072767; DOI=10.1128/jvi.05442-11;
RA Salsman J., Jagannathan M., Paladino P., Chan P.K., Dellaire G., Raught B.,
RA Frappier L.;
RT "Proteomic profiling of the human cytomegalovirus UL35 gene products
RT reveals a role for UL35 in the DNA repair response.";
RL J. Virol. 86:806-820(2012).
RN [11]
RP FUNCTION (ISOFORM UL35), FUNCTION (ISOFORM UL35A), INTERACTION WITH HOST
RP SNX5 (ISOFORM UL35), AND INTERACTION WITH HOST SNX5 (ISOFORM UL35A).
RX PubMed=29444945; DOI=10.1128/jvi.00013-18;
RA Maschkowitz G., Gaertner S., Hofmann-Winkler H., Fickenscher H.,
RA Winkler M.;
RT "Interaction of Human Cytomegalovirus Tegument Proteins ppUL35 and ppUL35A
RT with Sorting Nexin 5 Regulates Glycoprotein B (gpUL55) Localization.";
RL J. Virol. 92:0-0(2018).
RN [12]
RP FUNCTION (ISOFORM UL35), INTERACTION WITH HOST TBK1 (ISOFORM UL35), AND
RP SUBCELLULAR LOCATION (ISOFORM UL35).
RX PubMed=32466380; DOI=10.3390/microorganisms8060790;
RA Fabits M., Goncalves Magalhaes V., Chan B., Girault V., Elbasani E.,
RA Rossetti E., Saeland E., Messerle M., Pichlmair A., Lisnic V.J.,
RA Brinkmann M.M.;
RT "The Cytomegalovirus Tegument Protein UL35 Antagonizes Pattern Recognition
RT Receptor-Mediated Type I IFN Transcription.";
RL Microorganisms 8:0-0(2020).
CC -!- FUNCTION: [Isoform UL35]: Plays important role in immediate-early gene
CC expression through interaction with UL82. Forms nuclear bodies in host
CC nucleus, independently of PML. In turn, UL35 nuclear bodies associate
CC with and remodel PML bodies (PubMed:22072767, PubMed:21489587). Through
CC interaction with host DCAF1, causes cells to accumulate in the G2 phase
CC of the cell cycle by inducing a DNA damage response (PubMed:22072767).
CC Regulates viral assembly by controlling the localization of the
CC essential gB through regulation of a retrograde transport pathway. This
CC modulation occurs via binding and inhibition of host sorting nexin
CC 5/SNX5 (PubMed:29444945). Also plays a role in the inhibition of
CC pattern recognition receptor-mediated type I interferon signaling at
CC the level of TBK1 (PubMed:32466380). {ECO:0000269|PubMed:21489587,
CC ECO:0000269|PubMed:22072767, ECO:0000269|PubMed:29444945,
CC ECO:0000269|PubMed:32466380}.
CC -!- FUNCTION: [Isoform UL35A]: Promotes cytoplasmic UL82 accumulation and
CC inhibits UL35-containing nuclear bodies formation (PubMed:21489587).
CC Regulates viral assembly by controlling the localization of the
CC essential gB through regulation of a retrograde transport pathway. This
CC modulation occurs via binding and inhibition of host sorting nexin
CC 5/SNX5 (PubMed:29444945). {ECO:0000269|PubMed:21489587,
CC ECO:0000269|PubMed:29444945}.
CC -!- SUBUNIT: [Protein UL35]: Interacts with UL82 (PubMed:15308743).
CC Interacts with isoform UL35A. Interacts with host UBP7; this
CC interaction significantly inhibits the ability of USP7 to form nuclear
CC bodies (PubMed:22072767). Interacts with host DCAF1 (via C-
CC terminus)(PubMed:22072767). Interacts with host SNX5; this interaction
CC allows proper gB localization during viral assembly (PubMed:29444945).
CC Interacts wth host TBK1; this interaction prevents type I interferon
CC production (PubMed:32466380). {ECO:0000269|PubMed:15308743,
CC ECO:0000269|PubMed:22072767, ECO:0000269|PubMed:29444945,
CC ECO:0000269|PubMed:32466380}.
CC -!- SUBUNIT: [Isoform UL35A]: Interacts with UL82. Interacts with isoform
CC UL35. Interacts with host UBP7; this interaction significantly inhibits
CC the ability of USP7 to form nuclear bodies (PubMed:22072767). Interacts
CC with host SNX5; this interaction allows proper gB localization during
CC viral assembly (PubMed:29444945). {ECO:0000269|PubMed:15308743,
CC ECO:0000269|PubMed:22072767, ECO:0000269|PubMed:29444945}.
CC -!- SUBCELLULAR LOCATION: [Isoform UL35]: Virion tegument
CC {ECO:0000269|PubMed:15452216}. Host nucleus
CC {ECO:0000269|PubMed:11836424, ECO:0000269|PubMed:21489587,
CC ECO:0000269|PubMed:22072767, ECO:0000269|PubMed:32466380}. Host
CC cytoplasm {ECO:0000269|PubMed:21489587, ECO:0000269|PubMed:32466380}.
CC Note=Found in nuclear bodies. {ECO:0000269|PubMed:21489587}.
CC -!- SUBCELLULAR LOCATION: [Isoform UL35A]: Host nucleus
CC {ECO:0000269|PubMed:11836424, ECO:0000269|PubMed:21489587}. Host
CC cytoplasm {ECO:0000269|PubMed:21489587}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=UL35;
CC IsoId=P16766-1; Sequence=Displayed;
CC Name=UL35A;
CC IsoId=P16766-2; Sequence=VSP_044013;
CC -!- SIMILARITY: Belongs to the herpesviridae pp85 family. {ECO:0000305}.
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DR EMBL; X17403; CAA35394.1; -; Genomic_DNA.
DR EMBL; BK000394; DAA00140.1; -; Genomic_DNA.
DR PIR; S09798; QQBEU2.
DR SMR; P16766; -.
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; 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:0039722; P:suppression by virus of host toll-like receptor signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039723; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity; IEA:UniProtKB-KW.
DR InterPro; IPR006731; Herpes_pp85.
DR Pfam; PF04637; Herpes_pp85; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Host cytoplasm; Host nucleus;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Inhibition of host TBK1 by virus; Inhibition of host TLR pathway by virus;
KW Reference proteome; Viral immunoevasion; Virion; Virion tegument.
FT CHAIN 1..640
FT /note="Protein UL35"
FT /id="PRO_0000115318"
FT REGION 353..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..571
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 586..640
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..563
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 587..601
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 625..640
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..447
FT /note="Missing (in isoform UL35A)"
FT /evidence="ECO:0000305"
FT /id="VSP_044013"
SQ SEQUENCE 640 AA; 72529 MW; 8FCCFA3C9F631C1C CRC64;
MAQGSRAPSG PPLPVLPVDD WLNFRVDLFG DEHRRLLLEM LTQGCSNFVG LLNFGVPSPV
YALEALVDFQ VRNAFMKVKP VAQEIIRICI LANHYRNSRD VLRDLRTQLD VLYSDPLKTR
LLRGLIRLCR AAQTGVKPED ISVHLGADDV TFGVLKRALV RLHRVRDALG LRASPEAEAR
YPRLTTYNLL FHPPPFTTVE AVDLCAENLS DVTQRRNRPL RCLTSIKRPG SRTLEDALND
MYLLLTLRHL QLRHALELQM MQDWVVERCN RLCDALYFCY TQAPETRQTF VTLVRGLELA
RQHSSPAFQP MLYNLLQLLT QLHEANVYLC PGYLHFSAYK LLKKIQSVSD ARERGEFGDE
DEEQENDGEP REAQLDLEAD PTAREGELFF FSKNLYGNGE VFRVPEQPSR YLRRRMFVER
PETLQIFYNF HEGKITTETY HLQRIYSMMI EGASRQTGLT PKRFMELLDR APLGQESEPE
ITEHRDLFAD VFRRPVTDAA SSSSASSSSS SASPNSVSLP SARSSSTRTT TPASTYTSAG
TSSTTGLLLS SSLSGSHGIS SADLEQPPRQ RRRMVSVTLF SPYSVAYSHH RRHRRRRSPP
PAPRGPAHTR FQGPDSMPST SYGSDVEDPR DDLAENLRHL
