CEP2_HCMVA
ID CEP2_HCMVA Reviewed; 345 AA.
AC P16800; Q7M6J7;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Cytoplasmic envelopment protein 2 {ECO:0000255|HAMAP-Rule:MF_04039};
GN Name=UL94;
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 FUNCTION.
RX PubMed=8648663; DOI=10.1128/jvi.70.6.3339-3345.1996;
RA Wing B.A., Lee G.C., Huang E.S.;
RT "The human cytomegalovirus UL94 open reading frame encodes a conserved
RT herpesvirus capsid/tegument-associated virion protein that is expressed
RT with true late kinetics.";
RL J. Virol. 70:3339-3345(1996).
RN [5]
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 [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 FUNCTION, INTERACTION WITH UL99, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=19345970; DOI=10.1016/j.virol.2009.03.007;
RA Liu Y., Cui Z., Zhang Z., Wei H., Zhou Y., Wang M., Zhang X.E.;
RT "The tegument protein UL94 of human cytomegalovirus as a binding partner
RT for tegument protein pp28 identified by intracellular imaging.";
RL Virology 388:68-77(2009).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22171267; DOI=10.1128/jvi.06548-11;
RA Phillips S.L., Bresnahan W.A.;
RT "The human cytomegalovirus (HCMV) tegument protein UL94 is essential for
RT secondary envelopment of HCMV virions.";
RL J. Virol. 86:2523-2532(2012).
RN [9]
RP INTERACTION WITH CYTOPLASMIC ENVELOPMENT PROTEIN 3, AND FUNCTION.
RX PubMed=22761384; DOI=10.1128/jvi.01078-12;
RA Phillips S.L., Cygnar D., Thomas A., Bresnahan W.A.;
RT "Interaction between the human cytomegalovirus tegument proteins UL94 and
RT UL99 is essential for virus replication.";
RL J. Virol. 86:9995-10005(2012).
RN [10]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-61; LEU-63 AND LEU-343.
RX PubMed=22414299; DOI=10.1016/j.virusres.2012.02.023;
RA Liu Y., Zhang Z., Zhao X., Wei H., Deng J., Cui Z., Zhang X.E.;
RT "Human cytomegalovirus UL94 is a nucleocytoplasmic shuttling protein
RT containing two NLSs and one NES.";
RL Virus Res. 166:31-42(2012).
RN [11]
RP FUNCTION.
RX PubMed=24899189; DOI=10.1128/jvi.01141-14;
RA Das S., Ortiz D.A., Gurczynski S.J., Khan F., Pellett P.E.;
RT "Identification of human cytomegalovirus genes important for biogenesis of
RT the cytoplasmic virion assembly complex.";
RL J. Virol. 88:9086-9099(2014).
RN [12]
RP FUNCTION, AND INTERACTION WITH HOST STING1.
RX PubMed=32238587; DOI=10.1128/jvi.00022-20;
RA Zou H.M., Huang Z.F., Yang Y., Luo W.W., Wang S.Y., Luo M.H., Fu Y.Z.,
RA Wang Y.Y.;
RT "Human Cytomegalovirus Protein UL94 Targets MITA to Evade the Antiviral
RT Immune Response.";
RL J. Virol. 94:0-0(2020).
CC -!- FUNCTION: Plays a critical role in cytoplasmic virus egress.
CC Participates in the final step of tegumentation and envelope
CC acquisition within the host cytoplasm by directly interacting with the
CC capsid. Upon virion binding to target cell, a signaling cascade is
CC triggered to disrupt the interaction with the capsid, thereby preparing
CC capsid uncoating (By similarity). Additionally, antagonizes the viral
CC DNA-triggered antiviral immune response by targeting host STING1 and
CC preventing its dimerization and trafficking (PubMed:32238587).
CC {ECO:0000255|HAMAP-Rule:MF_04039, ECO:0000269|PubMed:19345970,
CC ECO:0000269|PubMed:22171267, ECO:0000269|PubMed:22761384,
CC ECO:0000269|PubMed:24899189, ECO:0000269|PubMed:32238587,
CC ECO:0000269|PubMed:8648663}.
CC -!- SUBUNIT: Interacts with cytoplasmic envelopment protein 3 and with the
CC capsid (By similarity). Interacts with host STING1; this interaction
CC prevents viral DNA-triggered antiviral immune response
CC (PubMed:32238587). {ECO:0000255|HAMAP-Rule:MF_04039,
CC ECO:0000269|PubMed:19345970, ECO:0000269|PubMed:22761384,
CC ECO:0000269|PubMed:32238587}.
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000255|HAMAP-Rule:MF_04039,
CC ECO:0000269|PubMed:19345970}. Host cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_04039, ECO:0000269|PubMed:22414299}. Host nucleus
CC {ECO:0000255|HAMAP-Rule:MF_04039, ECO:0000269|PubMed:22414299}.
CC Note=Localizes in the host nucleus up to 18 hours postinfection, but at
CC later times localizes to punctate, cytoplasmic structures.
CC {ECO:0000255|HAMAP-Rule:MF_04039, ECO:0000269|PubMed:22414299}.
CC -!- DISRUPTION PHENOTYPE: UL94 deficiency mediates HCMV-induced
CC transcription of type I IFNs and downstream antiviral effectors leading
CC to impaired viral replication. {ECO:0000269|PubMed:32238587}.
CC -!- SIMILARITY: Belongs to the herpesviridae cytoplasmic envelopment
CC protein 2 family. {ECO:0000255|HAMAP-Rule:MF_04039}.
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DR EMBL; X17403; CAA35368.1; -; Genomic_DNA.
DR EMBL; BK000394; DAA00191.1; -; Genomic_DNA.
DR PIR; S09858; S09858.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR HAMAP; MF_04039; HSV_CEP2; 1.
DR InterPro; IPR004286; Herpes_UL16/UL94.
DR Pfam; PF03044; Herpes_UL16; 1.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus; Late protein;
KW Reference proteome; Viral immunoevasion; Virion; Virion tegument.
FT CHAIN 1..345
FT /note="Cytoplasmic envelopment protein 2"
FT /id="PRO_0000115957"
FT REGION 26..35
FT /note="Nuclear localization signal 1"
FT /evidence="ECO:0000269|PubMed:22414299"
FT REGION 55..63
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:22414299"
FT REGION 90..94
FT /note="Nuclear localization signal 2"
FT /evidence="ECO:0000269|PubMed:22414299"
FT MUTAGEN 61
FT /note="L->A: Almost complete loss of cytoplasmic
FT localization."
FT /evidence="ECO:0000269|PubMed:22414299"
FT MUTAGEN 63
FT /note="L->A: Almost complete of cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:22414299"
FT MUTAGEN 343
FT /note="L->A: Complete loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:22414299"
SQ SEQUENCE 345 AA; 38381 MW; 96A276F1C658F3F8 CRC64;
MAWRSGLCET DSRTLKQFLQ EECMWKLVGK SRKHREYRAV ACRSTIFSPE DDSSCILCQL
LLLYRDGEWI ICFCCNGRYQ GHYGVNHVHR RRRRICHLPT LYQLSFGGPL GPASIDFLPS
FSQVTSSMTC DGITPDVIYE VCMLVPQDEA KRILVKGHGA MDLTCQKAVT LGGAGAWLLP
RPEGYTLFFY ILCYDLFTSC GNRCDIPSMT RLMAAATACG QAGCSFCTDH EGHVDPTGNY
VGCTPDMGRC LCYVPCGPMT QSLIHNEEPA TFFCESDDAK YLCAVGSKTA AQVTLGDGLD
YHIGVKDSEG RWLPVKTDVW DLVKVEEPVS RMIVCSCPVL KNLVH
