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 27-MAR-2024, entry version 131. 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; Orthoherpesviridae; Gammaherpesvirinae; Lymphocryptovirus; OC Lymphocryptovirus humangamma4; Epstein-Barr virus (strain GD1). 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 7. DR DIP; DIP-41174N; -. DR ELM; P12978; -. DR IntAct; P12978; 5. DR MINT; P12978; -. DR DNASU; 3783761; -. DR GeneID; 3783761; -. DR KEGG; vg:3783761; -. DR Proteomes; UP000153037; Segment. 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:0004865; F:protein serine/threonine phosphatase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0039695; P:DNA-templated viral transcription; IDA:UniProtKB. DR GO; GO:0019056; P:modulation by virus of host transcription; IDA:UniProtKB. DR GO; GO:0060153; P:perturbation by virus of host cell cycle progression; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0039606; P:suppression by virus of host translation initiation; IEA:UniProtKB-KW. DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW. DR IDEAL; IID90021; -. DR PRINTS; PR01217; PRICHEXTENSN. 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 Interferon antiviral system evasion; 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 //