EBNA1_EBVB9
ID EBNA1_EBVB9 Reviewed; 641 AA.
AC P03211; Q777E1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 25-MAY-2022, entry version 164.
DE RecName: Full=Epstein-Barr nuclear antigen 1;
DE Short=EBNA-1;
DE Short=EBV nuclear antigen 1;
GN Name=EBNA1; ORFNames=BKRF1;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26.
RX PubMed=3460083; DOI=10.1073/pnas.83.14.5096;
RA Sample J., Hummel M., Braun D., Birkenbach M., Kieff E.;
RT "Nucleotide sequences of mRNAs encoding Epstein-Barr virus nuclear
RT proteins: a probable transcriptional initiation site.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:5096-5100(1986).
RN [3]
RP SUBCELLULAR LOCATION.
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 INTERACTION WITH HUMAN EBP2.
RX PubMed=10074103; DOI=10.1128/jvi.73.4.2587-2595.1999;
RA Shire K., Ceccarelli D.F.J., Avolio-Hunter T.M., Frappier L.;
RT "EBP2, a human protein that interacts with sequences of the Epstein-Barr
RT virus nuclear antigen 1 important for plasmid maintenance.";
RL J. Virol. 73:2587-2595(1999).
RN [5]
RP INTERACTION WITH HUMAN USP7.
RX PubMed=14506283; DOI=10.1074/jbc.m307200200;
RA Holowaty M.N., Sheng Y., Nguyen T., Arrowsmith C., Frappier L.;
RT "Protein interaction domains of the ubiquitin-specific protease,
RT USP7/HAUSP.";
RL J. Biol. Chem. 278:47753-47761(2003).
RN [6]
RP INTERACTION WITH BGLF4.
RX PubMed=19244323; DOI=10.1128/jvi.02378-08;
RA Zhu J., Liao G., Shan L., Zhang J., Chen M.R., Hayward G.S., Hayward S.D.,
RA Desai P., Zhu H.;
RT "Protein array identification of substrates of the epstein-barr virus
RT protein kinase BGLF4.";
RL J. Virol. 83:5219-5231(2009).
RN [7]
RP FUNCTION, INTERACTION WITH HUMAN PAX5, AND SUBCELLULAR LOCATION.
RX PubMed=31941781; DOI=10.1128/jvi.02028-19;
RA Liu C.D., Lee H.L., Peng C.W.;
RT "B Cell-Specific Transcription Activator PAX5 Recruits p300 To Support
RT EBNA1-Driven Transcription.";
RL J. Virol. 94:0-0(2020).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 469-607.
RX PubMed=7553871; DOI=10.1016/0092-8674(95)90232-5;
RA Bochkarev A., Barwell J.A., Pfuetzner R.A., Furey W.F. Jr., Edwards A.M.,
RA Frappier L.;
RT "Crystal structure of the DNA-binding domain of the Epstein-Barr virus
RT origin-binding protein EBNA 1.";
RL Cell 83:39-46(1995).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 441-450 IN COMPLEX WITH USP7,
RP FUNCTION, INTERACTION WITH HUMAN USP7, AND MUTAGENESIS OF GLU-444 AND
RP SER-447.
RX PubMed=15808506; DOI=10.1016/j.molcel.2005.02.029;
RA Saridakis V., Sheng Y., Sarkari F., Holowaty M.N., Shire K., Nguyen T.,
RA Zhang R.G., Liao J., Lee W., Edwards A.M., Arrowsmith C.H., Frappier L.;
RT "Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr
RT nuclear antigen 1 implications for EBV-mediated immortalization.";
RL Mol. Cell 18:25-36(2005).
CC -!- FUNCTION: Plays an essential role in replication and partitioning of
CC viral genomic DNA during latent viral infection. During this phase, the
CC circular double-stranded viral DNA undergoes replication once per cell
CC cycle and is efficiently partitioned to the daughter cells. EBNA1
CC activates the initiation of viral DNA replication through binding to
CC specific sites in the viral latent origin of replication, oriP.
CC Additionally, it governs the segregation of viral episomes by mediating
CC their attachment to host cell metaphase chromosomes. Also activates the
CC transcription of several viral latency genes. Finally, it can
CC counteract the stabilization of host p53/TP53 by host USP7, thereby
CC decreasing apoptosis and increasing host cell survival.
CC {ECO:0000269|PubMed:15808506, ECO:0000269|PubMed:31941781}.
CC -!- SUBUNIT: Interacts with human USP7. Interacts with human EBP2; this
CC interaction is important for the stable segregation of EBV episomes
CC during cell division but not for the replication of the episomes.
CC Interacts with BGLF4; this interaction facilitates the switch from
CC latent to lytic DNA replication by down-regulating EBNA1 replication
CC function. Interacts with human PAX5; this interaction promotes EBNA1-
CC dependent transcription. {ECO:0000269|PubMed:10074103,
CC ECO:0000269|PubMed:14506283, ECO:0000269|PubMed:15808506,
CC ECO:0000269|PubMed:19244323, ECO:0000269|PubMed:31941781}.
CC -!- INTERACTION:
CC P03211; Q13415: ORC1; Xeno; NbExp=2; IntAct=EBI-996522, EBI-374847;
CC P03211; Q13416: ORC2; Xeno; NbExp=6; IntAct=EBI-996522, EBI-374957;
CC P03211; Q15554: TERF2; Xeno; NbExp=3; IntAct=EBI-996522, EBI-706637;
CC P03211; Q93009: USP7; Xeno; NbExp=5; IntAct=EBI-996522, EBI-302474;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:2161150,
CC ECO:0000269|PubMed:31941781}.
CC -!- SIMILARITY: Belongs to the herpesviridae EBNA1 family. {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; V01555; CAA24816.1; -; Genomic_DNA.
DR EMBL; M13941; AAA45889.1; -; Genomic_DNA.
DR EMBL; AJ507799; CAD53427.1; -; Genomic_DNA.
DR PIR; C43043; QQBE31.
DR RefSeq; YP_401677.1; NC_007605.1.
DR PDB; 1B3T; X-ray; 2.20 A; A/B=461-607.
DR PDB; 1VHI; X-ray; 2.50 A; A/B=466-607.
DR PDB; 1YY6; X-ray; 1.70 A; B=441-450.
DR PDB; 2FYY; X-ray; 1.50 A; C=407-417.
DR PDB; 2FZ3; X-ray; 1.90 A; C=407-417.
DR PDB; 3MV7; X-ray; 2.00 A; C=407-417.
DR PDB; 3MV8; X-ray; 2.10 A; C=407-417.
DR PDB; 3MV9; X-ray; 2.70 A; C=407-417.
DR PDB; 4PRA; X-ray; 1.85 A; C=407-417.
DR PDB; 4PRE; X-ray; 1.65 A; C=407-417.
DR PDB; 4PRI; X-ray; 2.40 A; C=407-417.
DR PDB; 4PRP; X-ray; 2.50 A; C=407-417.
DR PDB; 5WMF; X-ray; 1.90 A; A/B/C/D/E/F=470-619.
DR PDB; 5WUM; X-ray; 2.00 A; B/C=378-386.
DR PDB; 5WUN; X-ray; 2.20 A; B/C=378-386.
DR PDB; 6NPI; X-ray; 1.50 A; A/B=471-607.
DR PDB; 6NPM; X-ray; 1.60 A; A/B=471-607.
DR PDB; 6NPP; X-ray; 1.35 A; A=471-607.
DR PDB; 6PW2; X-ray; 3.01 A; A/B/C/D/I/J/K/L=461-607.
DR PDB; 6VH6; X-ray; 1.30 A; A/B=470-607.
DR PDB; 7KE3; X-ray; 2.20 A; A/B/C/D/E/F/G/H/I/J/K/L=407-417.
DR PDB; 7KE5; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I/J/K/L=406-417.
DR PDBsum; 1B3T; -.
DR PDBsum; 1VHI; -.
DR PDBsum; 1YY6; -.
DR PDBsum; 2FYY; -.
DR PDBsum; 2FZ3; -.
DR PDBsum; 3MV7; -.
DR PDBsum; 3MV8; -.
DR PDBsum; 3MV9; -.
DR PDBsum; 4PRA; -.
DR PDBsum; 4PRE; -.
DR PDBsum; 4PRI; -.
DR PDBsum; 4PRP; -.
DR PDBsum; 5WMF; -.
DR PDBsum; 5WUM; -.
DR PDBsum; 5WUN; -.
DR PDBsum; 6NPI; -.
DR PDBsum; 6NPM; -.
DR PDBsum; 6NPP; -.
DR PDBsum; 6PW2; -.
DR PDBsum; 6VH6; -.
DR PDBsum; 7KE3; -.
DR PDBsum; 7KE5; -.
DR SMR; P03211; -.
DR BioGRID; 971751; 205.
DR DIP; DIP-29054N; -.
DR ELM; P03211; -.
DR IntAct; P03211; 44.
DR MINT; P03211; -.
DR BindingDB; P03211; -.
DR ChEMBL; CHEMBL1293281; -.
DR PRIDE; P03211; -.
DR ABCD; P03211; 2 sequenced antibodies.
DR GeneID; 3783709; -.
DR GeneID; 3783774; -.
DR KEGG; vg:3783774; -.
DR SIGNOR; P03211; -.
DR EvolutionaryTrace; P03211; -.
DR PRO; PR:P03211; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0006275; P:regulation of DNA replication; IEA:InterPro.
DR GO; GO:0039588; P:suppression by virus of host antigen processing and presentation; IEA:UniProtKB-KW.
DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR GO; GO:0019042; P:viral latency; IEA:UniProtKB-KW.
DR Gene3D; 3.30.70.390; -; 1.
DR IDEAL; IID90004; -.
DR InterPro; IPR035975; E2/EBNA1_C_sf.
DR InterPro; IPR004186; EBNA1_DNA-bd.
DR InterPro; IPR037007; EBNA1_DNA-bd_sf.
DR Pfam; PF02905; EBV-NA1; 1.
DR SUPFAM; SSF54957; SSF54957; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Host nucleus; Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
KW Inhibition of host NF-kappa-B by virus;
KW Inhibition of host proteasome antigen processing by virus;
KW Reference proteome; Transcription; Transcription regulation;
KW Viral immunoevasion; Viral latency;
KW Viral latency initiation and maintenance.
FT CHAIN 1..641
FT /note="Epstein-Barr nuclear antigen 1"
FT /id="PRO_0000116175"
FT REGION 1..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 224..478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 436..450
FT /note="Interaction with USP7"
FT REGION 612..641
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..381
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 619..641
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 444
FT /note="E->A: Slight decrease in binding to USP7. Major
FT decrease in binding to USP7; when associated with A-447."
FT /evidence="ECO:0000269|PubMed:15808506"
FT MUTAGEN 447
FT /note="S->A: Loss of binding to USP7. Major decrease in
FT binding to USP7; when associated with A-444."
FT /evidence="ECO:0000269|PubMed:15808506"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:4PRE"
FT HELIX 477..489
FT /evidence="ECO:0007829|PDB:6VH6"
FT STRAND 503..512
FT /evidence="ECO:0007829|PDB:6VH6"
FT HELIX 514..527
FT /evidence="ECO:0007829|PDB:6VH6"
FT STRAND 531..533
FT /evidence="ECO:0007829|PDB:6PW2"
FT STRAND 537..540
FT /evidence="ECO:0007829|PDB:6VH6"
FT STRAND 542..544
FT /evidence="ECO:0007829|PDB:6VH6"
FT STRAND 545..547
FT /evidence="ECO:0007829|PDB:6NPP"
FT HELIX 552..554
FT /evidence="ECO:0007829|PDB:6VH6"
FT STRAND 556..567
FT /evidence="ECO:0007829|PDB:6VH6"
FT HELIX 569..583
FT /evidence="ECO:0007829|PDB:6VH6"
FT HELIX 590..592
FT /evidence="ECO:0007829|PDB:6VH6"
FT STRAND 593..604
FT /evidence="ECO:0007829|PDB:6VH6"
SQ SEQUENCE 641 AA; 56427 MW; 4D161653E16FC341 CRC64;
MSDEGPGTGP GNGLGEKGDT SGPEGSGGSG PQRRGGDNHG RGRGRGRGRG GGRPGAPGGS
GSGPRHRDGV RRPQKRPSCI GCKGTHGGTG AGAGAGGAGA GGAGAGGGAG AGGGAGGAGG
AGGAGAGGGA GAGGGAGGAG GAGAGGGAGA GGGAGGAGAG GGAGGAGGAG AGGGAGAGGG
AGGAGAGGGA GGAGGAGAGG GAGAGGAGGA GGAGAGGAGA GGGAGGAGGA GAGGAGAGGA
GAGGAGAGGA GGAGAGGAGG AGAGGAGGAG AGGGAGGAGA GGGAGGAGAG GAGGAGAGGA
GGAGAGGAGG AGAGGGAGAG GAGAGGGGRG RGGSGGRGRG GSGGRGRGGS GGRRGRGRER
ARGGSRERAR GRGRGRGEKR PRSPSSQSSS SGSPPRRPPP GRRPFFHPVG EADYFEYHQE
GGPDGEPDVP PGAIEQGPAD DPGEGPSTGP RGQGDGGRRK KGGWFGKHRG QGGSNPKFEN
IAEGLRALLA RSHVERTTDE GTWVAGVFVY GGSKTSLYNL RRGTALAIPQ CRLTPLSRLP
FGMAPGPGPQ PGPLRESIVC YFMVFLQTHI FAEVLKDAIK DLVMTKPAPT CNIRVTVCSF
DDGVDLPPWF PPMVEGAAAE GDDGDDGDEG GDGDEGEEGQ E
