EBNA2_EBVB9
ID EBNA2_EBVB9 Reviewed; 487 AA.
AC P12978; Q69023; Q777H1;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 02-JUN-2021, entry version 124.
DE RecName: Full=Epstein-Barr nuclear antigen 2;
DE Short=EBNA-2;
DE Short=EBV nuclear antigen 2;
GN Name=EBNA2; ORFNames=BYRF1;
OS Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Lymphocryptovirus.
OX NCBI_TaxID=10377;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6209719; DOI=10.1073/pnas.81.23.7632;
RA Dambaugh T., Hennessy K., Chamnankit L., Kieff E.;
RT "U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear
RT antigen 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:7632-7636(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=6087149; DOI=10.1038/310207a0;
RA Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J.,
RA Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C.,
RA Tuffnell P.S., Barrell B.G.;
RT "DNA sequence and expression of the B95-8 Epstein-Barr virus genome.";
RL Nature 310:207-211(1984).
RN [3]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=2161150; DOI=10.1016/0042-6822(90)90027-o;
RA Petti L., Sample C., Kieff E.;
RT "Subnuclear localization and phosphorylation of Epstein-Barr virus latent
RT infection nuclear proteins.";
RL Virology 176:563-574(1990).
RN [4]
RP DOMAINS.
RX PubMed=1850028; DOI=10.1128/jvi.65.5.2545-2554.1991;
RA Cohen J.I., Wang F., Kieff E.;
RT "Epstein-Barr virus nuclear protein 2 mutations define essential domains
RT for transformation and transactivation.";
RL J. Virol. 65:2545-2554(1991).
RN [5]
RP INTERACTION WITH HUMAN CBF1.
RX PubMed=8016657; DOI=10.1126/science.8016657;
RA Henkel T., Ling P.D., Hayward S.D., Peterson M.G.;
RT "Mediation of Epstein-Barr virus EBNA2 transactivation by recombination
RT signal-binding protein J kappa.";
RL Science 265:92-95(1994).
RN [6]
RP INTERACTION WITH HUMAN ERCC2 AND ERCC3.
RX PubMed=7724549; DOI=10.1073/pnas.92.8.3259;
RA Tong X., Drapkin R., Reinberg D., Kieff E.;
RT "The 62- and 80-kDa subunits of transcription factor IIH mediate the
RT interaction with Epstein-Barr virus nuclear protein 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3259-3263(1995).
RN [7]
RP INTERACTION WITH HUMAN GTF2B.
RX PubMed=7983760; DOI=10.1128/jvi.69.1.585-588.1995;
RA Tong X., Wang F., Thut C.J., Kieff E.;
RT "The Epstein-Barr virus nuclear protein 2 acidic domain can interact with
RT TFIIB, TAF40, and RPA70 but not with TATA-binding protein.";
RL J. Virol. 69:585-588(1995).
RN [8]
RP INTERACTION WITH HUMAN SMARCB1/INI1.
RX PubMed=8709224; DOI=10.1128/jvi.70.9.6020-6028.1996;
RA Wu D.Y., Kalpana G.V., Goff S.P., Schubach W.H.;
RT "Epstein-Barr virus nuclear protein 2 (EBNA2) binds to a component of the
RT human SNF-SWI complex, hSNF5/Ini1.";
RL J. Virol. 70:6020-6028(1996).
RN [9]
RP INTERACTION WITH HUMAN ZMYND11/BS69, AND MUTAGENESIS OF LEU-385 AND
RP LEU-439.
RX PubMed=11733528; DOI=10.1074/jbc.m110078200;
RA Ansieau S., Leutz A.;
RT "The conserved Mynd domain of BS69 binds cellular and oncoviral proteins
RT through a common PXLXP motif.";
RL J. Biol. Chem. 277:4906-4910(2002).
RN [10]
RP INTERACTION WITH HUMAN WAPL.
RX PubMed=15383329; DOI=10.1016/j.yexcr.2004.06.028;
RA Kwiatkowski B.A., Ragoczy T., Ehly J., Schubach W.H.;
RT "Identification and cloning of a novel chromatin-associated protein partner
RT of Epstein-Barr nuclear protein 2.";
RL Exp. Cell Res. 300:223-233(2004).
RN [11]
RP FUNCTION.
RX PubMed=19126642; DOI=10.1093/carcin/bgn291;
RA Pan S.H., Tai C.C., Lin C.S., Hsu W.B., Chou S.F., Lai C.C., Chen J.Y.,
RA Tien H.F., Lee F.Y., Wang W.B.;
RT "Epstein-Barr virus nuclear antigen 2 disrupts mitotic checkpoint and
RT causes chromosomal instability.";
RL Carcinogenesis 30:366-375(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH HOST EBF1.
RX PubMed=28968461; DOI=10.1371/journal.ppat.1006664;
RA Glaser L.V., Rieger S., Thumann S., Beer S., Kuklik-Roos C., Martin D.E.,
RA Maier K.C., Harth-Hertle M.L., Gruening B., Backofen R., Krebs S., Blum H.,
RA Zimmer R., Erhard F., Kempkes B.;
RT "EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes
RT in B cells.";
RL PLoS Pathog. 13:e1006664-e1006664(2017).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 381-389, INTERACTION WITH HUMAN
RP ZMYND11/BS69, AND FUNCTION.
RX PubMed=26845565; DOI=10.1371/journal.ppat.1005414;
RA Harter M.R., Liu C.D., Shen C.L., Gonzalez-Hurtado E., Zhang Z.M., Xu M.,
RA Martinez E., Peng C.W., Song J.;
RT "BS69/ZMYND11 C-Terminal Domains Bind and Inhibit EBNA2.";
RL PLoS Pathog. 12:1005414-1005414(2016).
CC -!- FUNCTION: Plays a key role in the activation of the host resting B-cell
CC and stimulation of B-cell proliferation. Acts by up-regulating the
CC expression of viral EBNA1-6, LMP1, LMP2A and LMP2B genes, as well as
CC several host genes including CD21, CD23 and MYC. Activates
CC transcription by acting as an adapter molecule that binds to cellular
CC sequence-specific DNA-binding proteins such as host CBF1, SMARCB1 and
CC SPI1. Once EBNA2 is near promoter sites, its acidic activating domain
CC recruits basal and activation-associated transcription factors TFIIB,
CC TAF40, TFIIH components ERCC2 and ERCC3, and CBP in order to promote
CC transcription. Alternatively, EBNA2 can affect activities of cell cycle
CC regulators and retard cell cycle progression at G2/M phase. It also
CC induces chromosomal instability, by disrupting mitotic checkpoints,
CC multi-nucleation and formation of micronuclei in infected cells.
CC {ECO:0000269|PubMed:19126642, ECO:0000269|PubMed:26845565,
CC ECO:0000269|PubMed:28968461}.
CC -!- SUBUNIT: Interacts with human SMARCB1/INI1, presumably generating an
CC open chromatin conformation at the EBNA2-responsive target genes
CC (PubMed:8709224). Interacts with human WAPL (PubMed:15383329).
CC Interacts with host CBF1; this interaction allows transcriptional
CC activation by EBNA2 (PubMed:8016657). Interacts with host general
CC transcription factors GTF2B, ERCC2 and ERCC3 (PubMed:7983760,
CC PubMed:7724549). Interacts (via PXLXP motif) with host ZMYND11/BS69
CC (via MYND-type zinc finger) (PubMed:11733528, PubMed:26845565).
CC Interacts with host EBF1 (PubMed:28968461).
CC {ECO:0000269|PubMed:11733528, ECO:0000269|PubMed:15383329,
CC ECO:0000269|PubMed:26845565, ECO:0000269|PubMed:28968461,
CC ECO:0000269|PubMed:7724549, ECO:0000269|PubMed:7983760,
CC ECO:0000269|PubMed:8016657, ECO:0000269|PubMed:8709224}.
CC -!- INTERACTION:
CC P12978; Q06330: RBPJ; Xeno; NbExp=2; IntAct=EBI-8052923, EBI-632552;
CC P12978; Q15326: ZMYND11; Xeno; NbExp=2; IntAct=EBI-8052923, EBI-2623509;
CC -!- SUBCELLULAR LOCATION: Host nucleus matrix {ECO:0000269|PubMed:2161150}.
CC Note=Associated with the nuclear matrix.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:2161150}.
CC -!- SIMILARITY: Belongs to the herpesviridae EBNA2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA24877.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; K03333; AAA45903.1; -; Genomic_DNA.
DR EMBL; V01555; CAA24877.1; ALT_INIT; Genomic_DNA.
DR EMBL; AJ507799; CAD53395.1; -; Genomic_DNA.
DR PIR; S42442; S42442.
DR RefSeq; YP_401644.1; NC_007605.1.
DR PDB; 2MKR; NMR; -; B=453-465.
DR PDB; 2N2J; NMR; -; A/B=1-58.
DR PDB; 5HDA; X-ray; 2.39 A; B/D=381-389.
DR PDBsum; 2MKR; -.
DR PDBsum; 2N2J; -.
DR PDBsum; 5HDA; -.
DR BMRB; P12978; -.
DR SASBDB; P12978; -.
DR SMR; P12978; -.
DR BioGRID; 971803; 5.
DR DIP; DIP-41174N; -.
DR ELM; P12978; -.
DR IntAct; P12978; 5.
DR MINT; P12978; -.
DR PRIDE; P12978; -.
DR DNASU; 3783761; -.
DR GeneID; 3783761; -.
DR KEGG; vg:3783761; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0044204; C:host cell nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0039695; P:DNA-templated viral transcription; IDA:UniProtKB.
DR GO; GO:0060153; P:modulation by virus of host cell cycle; IDA:UniProtKB.
DR GO; GO:0039586; P:modulation by virus of host PP1 activity; IEA:UniProtKB-KW.
DR GO; GO:0019056; P:modulation by virus of host transcription; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR IDEAL; IID90021; -.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Modulation of host cell cycle by virus;
KW Modulation of host PP1 activity by virus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Viral immunoevasion.
FT CHAIN 1..487
FT /note="Epstein-Barr nuclear antigen 2"
FT /id="PRO_0000116176"
FT REPEAT 345..346
FT /note="1"
FT REPEAT 347..348
FT /note="2"
FT REPEAT 349..350
FT /note="3"
FT REPEAT 351..352
FT /note="4"
FT REPEAT 353..354
FT /note="5"
FT REPEAT 355..356
FT /note="6"
FT REPEAT 357..358
FT /note="7"
FT REGION 1..210
FT /note="SMARCB1/INI1 binding"
FT REGION 52..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 258..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 345..358
FT /note="6.5 X 2 AA tandem repeats of R-G"
FT MOTIF 383..387
FT /note="PXLXP motif, interaction with host ZMYND11"
FT MOTIF 437..441
FT /note="PXLXP motif, interaction with host ZMYND11"
FT COMPBIAS 57..105
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..305
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..362
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 399..428
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 385
FT /note="L->A: Complete loss of interaction with host
FT ZMYND11."
FT /evidence="ECO:0000269|PubMed:11733528"
FT MUTAGEN 439
FT /note="L->A: Complete loss of interaction with host
FT ZMYND11."
FT /evidence="ECO:0000269|PubMed:11733528"
FT CONFLICT 88
FT /note="P -> PPPP (in Ref. 1; AAA45903)"
FT /evidence="ECO:0000305"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:2N2J"
FT STRAND 12..20
FT /evidence="ECO:0007829|PDB:2N2J"
FT STRAND 26..34
FT /evidence="ECO:0007829|PDB:2N2J"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:2N2J"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:2N2J"
FT HELIX 455..463
FT /evidence="ECO:0007829|PDB:2MKR"
SQ SEQUENCE 487 AA; 52545 MW; DEF40D7F8ED61D1A CRC64;
MPTFYLALHG GQTYHLIVDT DSLGNPSLSV IPSNPYQEQL SDTPLIPLTI FVGENTGVPP
PLPPPPPPPP PPPPPPPPPP PPPPPPPPSP PPPPPPPPPP QRRDAWTQEP SPLDRDPLGY
DVGHGPLASA MRMLWMANYI VRQSRGDRGL ILPQGPQTAP QARLVQPHVP PLRPTAPTIL
SPLSQPRLTP PQPLMMPPRP TPPTPLPPAT LTVPPRPTRP TTLPPTPLLT VLQRPTELQP
TPSPPRMHLP VLHVPDQSMH PLTHQSTPND PDSPEPRSPT VFYNIPPMPL PPSQLPPPAA
PAQPPPGVIN DQQLHHLPSG PPWWPPICDP PQPSKTQGQS RGQSRGRGRG RGRGRGKGKS
RDKQRKPGGP WRPEPNTSSP SMPELSPVLG LHQGQGAGDS PTPGPSNAAP VCRNSHTATP
NVSPIHEPES HNSPEAPILF PDDWYPPSID PADLDESWDY IFETTESPSS DEDYVEGPSK
RPRPSIQ
