EBNA6_EBVB9
ID EBNA6_EBVB9 Reviewed; 992 AA.
AC P03204; Q777E7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 23-FEB-2022, entry version 117.
DE RecName: Full=Epstein-Barr nuclear antigen 6;
DE Short=EBNA-6;
DE Short=EBV nuclear antigen 6;
DE AltName: Full=Epstein-Barr nuclear antigen 3C;
DE Short=EBNA-3C;
DE Short=EBV nuclear antigen 3C;
DE AltName: Full=Epstein-Barr nuclear antigen 4B;
DE Short=EBNA-4B;
DE Short=EBV nuclear antigen 4B;
GN Name=EBNA6; ORFNames=BERF3-BERF4;
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 CHARACTERIZATION.
RX PubMed=2831394; DOI=10.1128/jvi.62.4.1330-1338.1988;
RA Petti L., Sample J., Wang F., Kieff E.;
RT "A fifth Epstein-Barr virus nuclear protein (EBNA3C) is expressed in
RT latently infected growth-transformed lymphocytes.";
RL J. Virol. 62:1330-1338(1988).
RN [3]
RP INTERACTION WITH HUMAN RBPJ.
RX PubMed=8627785; DOI=10.1128/jvi.70.5.3068-3074.1996;
RA Robertson E.S., Lin J., Kieff E.;
RT "The amino-terminal domains of Epstein-Barr virus nuclear proteins 3A, 3B,
RT and 3C interact with RBPJ(kappa).";
RL J. Virol. 70:3068-3074(1996).
RN [4]
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 [5]
RP INTERACTION WITH HUMAN CTBP1.
RX PubMed=11462050; DOI=10.1128/jvi.75.16.7749-7755.2001;
RA Touitou R., Hickabottom M., Parker G., Crook T., Allday M.J.;
RT "Physical and functional interactions between the corepressor CtBP and the
RT Epstein-Barr virus nuclear antigen EBNA3C.";
RL J. Virol. 75:7749-7755(2001).
RN [6]
RP FUNCTION.
RX PubMed=16352731; DOI=10.1073/pnas.0503886102;
RA Knight J.S., Sharma N., Robertson E.S.;
RT "Epstein-Barr virus latent antigen 3C can mediate the degradation of the
RT retinoblastoma protein through an SCF cellular ubiquitin ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:18562-18566(2005).
RN [7]
RP INTERACTION WITH HUMAN MYC.
RX PubMed=18256156; DOI=10.1128/jvi.02500-07;
RA Bajaj B.G., Murakami M., Cai Q., Verma S.C., Lan K., Robertson E.S.;
RT "Epstein-Barr virus nuclear antigen 3C interacts with and enhances the
RT stability of the c-Myc oncoprotein.";
RL J. Virol. 82:4082-4090(2008).
RN [8]
RP INTERACTION WITH HOST HISTONE H2AX, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=24429368; DOI=10.1128/jvi.03568-13;
RA Jha H.C., Aj M.P., Saha A., Banerjee S., Lu J., Robertson E.S.;
RT "Epstein-Barr virus essential antigen EBNA3C attenuates H2AX expression.";
RL J. Virol. 88:3776-3788(2014).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25121590; DOI=10.1371/journal.ppat.1004304;
RA Banerjee S., Lu J., Cai Q., Sun Z., Jha H.C., Robertson E.S.;
RT "EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to
RT promote B-cell proliferation.";
RL PLoS Pathog. 10:E1004304-E1004304(2014).
RN [10]
RP INTERACTION WITH HOST TP73, AND SUBCELLULAR LOCATION.
RX PubMed=24314664; DOI=10.1016/j.virol.2013.10.023;
RA Sahu S.K., Mohanty S., Kumar A., Kundu C.N., Verma S.C., Choudhuri T.;
RT "Epstein-Barr virus nuclear antigen 3C interact with p73: Interplay between
RT a viral oncoprotein and cellular tumor suppressor.";
RL Virology 448:333-343(2014).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 258-266.
RX PubMed=15657948; DOI=10.1002/eji.200425724;
RA Stewart-Jones G.B., di Gleria K., Kollnberger S., McMichael A.J.,
RA Jones E.Y., Bowness P.;
RT "Crystal structures and KIR3DL1 recognition of three immunodominant viral
RT peptides complexed to HLA-B*2705.";
RL Eur. J. Immunol. 35:341-351(2005).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 281-290.
RX PubMed=19139173; DOI=10.1084/jem.20082136;
RA Archbold J.K., Macdonald W.A., Gras S., Ely L.K., Miles J.J., Bell M.J.,
RA Brennan R.M., Beddoe T., Wilce M.C., Clements C.S., Purcell A.W.,
RA McCluskey J., Burrows S.R., Rossjohn J.;
RT "Natural micropolymorphism in human leukocyte antigens provides a basis for
RT genetic control of antigen recognition.";
RL J. Exp. Med. 206:209-219(2009).
CC -!- FUNCTION: Plays an essential role for the activation and
CC immortalization of human B-cells. Represses transcription of viral
CC promoters TP1 and Cp through interaction with host RBPJ, and inhibits
CC EBNA2-mediated activation of these promoters. Since Cp is the promoter
CC for all EBNA mRNAs, EBNA6 probably contributes to a negative
CC autoregulatory control loop. Alternatively, EBNA6 also regulates the
CC transcription of the EBV oncogene LMP1 in a cell cycle-dependent
CC manner. Modulates the activity of several host proteins involved in
CC cell cycle regulation including host cyclin A, MYC, RB, p21 and p27
CC mainly through binding to the host SCF(SKP2) complex. Inhibits the
CC promoter of host H2AX and targets H2AX to proteasomal degradation in
CC order to promote latency and cell proliferation.
CC {ECO:0000269|PubMed:16352731, ECO:0000269|PubMed:24429368,
CC ECO:0000269|PubMed:25121590}.
CC -!- SUBUNIT: Interacts with host CTPB1; this interaction seems important
CC for EBNA6-mediated transcriptional repression. Interacts with host MYC;
CC this interaction enhances MYC stability. Interacts (via N-terminus)
CC with host RBPJ. Interacts (via N-terminus) with host histone H2AX; this
CC interaction facilitates H2AX proteasomal degradation. Interacts with
CC host TP73; this interaction inhibits TP73-mediated apoptotic pathway.
CC {ECO:0000269|PubMed:11462050, ECO:0000269|PubMed:18256156,
CC ECO:0000269|PubMed:24314664, ECO:0000269|PubMed:24429368,
CC ECO:0000269|PubMed:8627785}.
CC -!- INTERACTION:
CC P03204; Q9Y676: MRPS18B; Xeno; NbExp=6; IntAct=EBI-9255985, EBI-750085;
CC P03204; P01106: MYC; Xeno; NbExp=11; IntAct=EBI-9255985, EBI-447544;
CC P03204; Q06330: RBPJ; Xeno; NbExp=3; IntAct=EBI-9255985, EBI-632552;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:24314664,
CC ECO:0000269|PubMed:24429368, ECO:0000269|PubMed:25121590}. Host nucleus
CC matrix {ECO:0000269|PubMed:2161150}. Note=Associated with the nuclear
CC matrix.
CC -!- SIMILARITY: Belongs to the herpesviridae EBNA-6 family. {ECO:0000305}.
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DR EMBL; V01555; CAA24859.1; -; Genomic_DNA.
DR EMBL; AJ507799; CAD53421.1; -; Genomic_DNA.
DR RefSeq; YP_401671.1; NC_007605.1.
DR PDB; 1CG9; X-ray; 2.70 A; C=98-106.
DR PDB; 2BSR; X-ray; 2.30 A; C=258-266.
DR PDB; 3DX6; X-ray; 1.70 A; C=281-290.
DR PDB; 3DX7; X-ray; 1.60 A; C=281-290.
DR PDB; 3DX8; X-ray; 2.10 A; C=281-290.
DR PDB; 3DXA; X-ray; 3.50 A; C/H/M=281-290.
DR PDBsum; 1CG9; -.
DR PDBsum; 2BSR; -.
DR PDBsum; 3DX6; -.
DR PDBsum; 3DX7; -.
DR PDBsum; 3DX8; -.
DR PDBsum; 3DXA; -.
DR SMR; P03204; -.
DR BioGRID; 3509134; 3.
DR DIP; DIP-29893N; -.
DR ELM; P03204; -.
DR IntAct; P03204; 7.
DR MINT; P03204; -.
DR PRIDE; P03204; -.
DR GeneID; 3783763; -.
DR KEGG; vg:3783763; -.
DR EvolutionaryTrace; P03204; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0044204; C:host cell nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0019042; P:viral latency; IEA:UniProtKB-KW.
DR InterPro; IPR007706; EBNA-3/4/6.
DR Pfam; PF05009; EBV-NA3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; G1/S host cell cycle checkpoint dysregulation by virus;
KW Host nucleus; Host-virus interaction;
KW Modulation of host cell apoptosis by virus;
KW Modulation of host cell cycle by virus; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Viral latency;
KW Viral latency initiation and maintenance.
FT CHAIN 1..992
FT /note="Epstein-Barr nuclear antigen 6"
FT /id="PRO_0000116179"
FT REPEAT 551..555
FT /note="1-1; approximate"
FT REPEAT 556..560
FT /note="2-1; approximate"
FT REPEAT 561..565
FT /note="3-1; approximate"
FT REPEAT 566..570
FT /note="4-1"
FT REPEAT 571..575
FT /note="5-1"
FT REPEAT 576..580
FT /note="6-1"
FT REPEAT 581..585
FT /note="7-1"
FT REPEAT 586..590
FT /note="8-1"
FT REPEAT 591..595
FT /note="9-1"
FT REPEAT 596..600
FT /note="10-1; approximate"
FT REPEAT 601..605
FT /note="11-1; approximate"
FT REPEAT 606..610
FT /note="12-1"
FT REPEAT 741..753
FT /note="1-2"
FT REPEAT 754..766
FT /note="2-2"
FT REPEAT 767..779
FT /note="3-2"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 355..905
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 551..610
FT /note="12 X 5 AA approximate tandem repeats of P-P-A-A-G"
FT REGION 741..779
FT /note="3 X 13 AA tandem repeats of P-[AP]-P-Q-A-P-Y-Q-G-Y-
FT Q-E-P"
FT REGION 931..954
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 967..992
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 11..25
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 365..383
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 431..446
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 474..495
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 555..594
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 659..683
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 700..716
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 747..775
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 780..794
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 841..880
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 881..901
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 992 AA; 109129 MW; 39BEAB9BC515BD84 CRC64;
MESFEGQGDS RQSPDNERGD NVQTTGEHDQ DPGPGPPSSG ASERLVPEES YSRDQQPWGQ
SRGDENRGWM QRIRRRRRRR AALSGHLLDT EDNVPPWLPP HDITPYTARN IRDAACRAVK
QSHLQALSNL ILDSGLDTQH ILCFVMAARQ RLQDIRRGPL VAEGGVGWRH WLLTSPSQSW
PMGYRTATLR TLTPVPNRVG ADSIMLTATF GCQNAARTLN TFSATVWTPP HAGPREQERY
AREAEVRFLR GKWQRRYRRI YDLIELCGSL HHIWQNLLQT EENLLDFVRF MGVMSSCNNP
AVNYWFHKTI GNFKPYYPWN APPNENPYHA RRGIKEHVIQ NAFRKAQIQG LSMLATGGEP
RGDATSETSS DEDTGRQGSD VELESSDDEL PYIDPNMEPV QQRPVMFVSR VPAKKPRKLP
WPTPKTHPVK RTNVKTSDRS DKAEAQSTPE RPGPSEQSSV TVEPAHPTPV EMPMVILHQP
PPVPKPVPVK PTPPPSRRRR GACVVYDDDV IEVIDVETTE DSSSVSQPNK PHRKHQDGFQ
RSGRRQKRAA PPTVSPSDTG PPAVGPPAAG PPAAGPPAAG PPAAGPPAAG PPAAGPRILA
PLSAGPPAAG PHIVTPPSAR PRIMAPPVVR MFMRERQLPQ STGRKPQCFW EMRAGREITQ
MQQEPSSHLQ SATQPTTPRP SWAPSVCALS VMDAGKAQPI ESSHLSSMSP TQPISHEEQP
RYEDPDAPLD LSLHPDVAAQ PAPQAPYQGY QEPPAPQAPY QGYQEPPPPQ APYQGYQEPP
AHGLQSSSYP GYAGPWTPRS QHPCYRHPWA PWSQDPVHGH TQGPWDPRAP HLPPQWDGSA
GHGQDQVSQF PHLQSETGPP RLQLSLVPLV SSSAPSWSSP QPRAPIRPIP TRFPPPPMPL
QDSMAVGCDS SGTACPSMPF ASDYSQGAFT PLDINATTPK RPRVEESSHG PARCSQATAE
AQEILSDNSE ISVFPKDAKQ TDYDASTESE LD
