EAR_EBVB9
ID EAR_EBVB9 Reviewed; 191 AA.
AC P03182; Q777H0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 25-MAY-2022, entry version 129.
DE RecName: Full=Apoptosis regulator BHRF1;
DE AltName: Full=Early antigen protein R;
DE Short=EA-R;
DE AltName: Full=Nuclear antigen;
GN ORFNames=BHRF1;
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].
RX PubMed=3039177; DOI=10.1128/jvi.61.9.2902-2909.1987;
RA Pfitzner A.J., Tsai E.C., Strominger J.L., Speck S.H.;
RT "Isolation and characterization of cDNA clones corresponding to transcripts
RT from the BamHI H and F regions of the Epstein-Barr virus genome.";
RL J. Virol. 61:2902-2909(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Akata;
RX PubMed=17626073; DOI=10.1128/jvi.02244-06;
RA Xing L., Kieff E.;
RT "Epstein-Barr virus BHRF1 micro- and stable RNAs during latency III and
RT after induction of replication.";
RL J. Virol. 81:9967-9975(2007).
RN [4]
RP CHARACTERIZATION.
RX PubMed=2820125; DOI=10.1016/0042-6822(87)90055-9;
RA Pearson G.R., Luka J., Petti L., Sample J., Birkenbach M., Braun D.,
RA Kieff E.;
RT "Identification of an Epstein-Barr virus early gene encoding a second
RT component of the restricted early antigen complex.";
RL Virology 160:151-161(1987).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=9367386; DOI=10.1099/0022-1317-78-11-2987;
RA Khanim F., Dawson C., Meseda C.A., Dawson J., Mackett M., Young L.S.;
RT "BHRF1, a viral homologue of the Bcl-2 oncogene, is conserved at both the
RT sequence and functional level in different Epstein-Barr virus isolates.";
RL J. Gen. Virol. 78:2987-2999(1997).
RN [6]
RP INTERACTION WITH HUMAN PRA1.
RX PubMed=11373297; DOI=10.1074/jbc.m103821200;
RA Li L.Y., Shih H.M., Liu M.Y., Chen J.Y.;
RT "The cellular protein PRA1 modulates the anti-apoptotic activity of
RT Epstein-Barr virus BHRF1, a homologue of Bcl-2, through direct
RT interaction.";
RL J. Biol. Chem. 276:27354-27362(2001).
RN [7]
RP FUNCTION, INTERACTION WITH BALF1, AND SUBCELLULAR LOCATION.
RX PubMed=11836425; DOI=10.1128/jvi.76.5.2469-2479.2002;
RA Bellows D.S., Howell M., Pearson C., Hazlewood S.A., Hardwick J.M.;
RT "Epstein-Barr virus BALF1 is a BCL-2-like antagonist of the herpesvirus
RT antiapoptotic BCL-2 proteins.";
RL J. Virol. 76:2469-2479(2002).
RN [8]
RP INTERACTION WITH HUMAN VRK2.
RX PubMed=16963744; DOI=10.1099/vir.0.81953-0;
RA Li L.Y., Liu M.Y., Shih H.M., Tsai C.H., Chen J.Y.;
RT "Human cellular protein VRK2 interacts specifically with Epstein-Barr virus
RT BHRF1, a homologue of Bcl-2, and enhances cell survival.";
RL J. Gen. Virol. 87:2869-2878(2006).
RN [9]
RP INTERACTION WITH HUMAN BCL2L11.
RX PubMed=18084238; DOI=10.1038/sj.cdd.4402292;
RA Flanagan A.M., Letai A.;
RT "BH3 domains define selective inhibitory interactions with BHRF-1 and KSHV
RT BCL-2.";
RL Cell Death Differ. 15:580-588(2008).
RN [10]
RP FUNCTION, AND INTERACTION WITH HOST BCL2L11.
RX PubMed=19293378; DOI=10.1073/pnas.0901036106;
RA Desbien A.L., Kappler J.W., Marrack P.;
RT "The Epstein-Barr virus Bcl-2 homolog, BHRF1, blocks apoptosis by binding
RT to a limited amount of Bim.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:5663-5668(2009).
RN [11]
RP STRUCTURE BY NMR OF 1-160.
RX PubMed=14499614; DOI=10.1016/j.jmb.2003.08.007;
RA Huang Q., Petros A.M., Virgin H.W., Fesik S.W., Olejniczak E.T.;
RT "Solution structure of the BHRF1 protein from Epstein-Barr virus, a homolog
RT of human Bcl-2.";
RL J. Mol. Biol. 332:1123-1130(2003).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 1-160, FUNCTION, AND INTERACTION
RP WITH HOST BCL2L11; BAD AND BBC3.
RX PubMed=21203485; DOI=10.1371/journal.ppat.1001236;
RA Kvansakul M., Wei A.H., Fletcher J.I., Willis S.N., Chen L., Roberts A.W.,
RA Huang D.C., Colman P.M.;
RT "Structural basis for apoptosis inhibition by Epstein-Barr virus BHRF1.";
RL PLoS Pathog. 6:E1001236-E1001236(2010).
CC -!- FUNCTION: Prevents premature death of the host cell during virus
CC production, which would otherwise reduce the amount of progeny virus.
CC Acts as a host B-cell leukemia/lymphoma 2 (Bcl-2) homolog, and
CC interacts with pro-apoptotic proteins to prevent mitochondria
CC permeabilization, release of cytochrome c and subsequent apoptosis of
CC the host cell. {ECO:0000269|PubMed:19293378,
CC ECO:0000269|PubMed:21203485}.
CC -!- SUBUNIT: Interacts with isoform 1 of host VRK2; this interaction is
CC involved in protecting cells from apoptosis (PubMed:16963744).
CC Interacts with host PRA1; this interaction seems to modulate BHRF1
CC anti-apoptotic activity (PubMed:11373297). Interacts with host BCL2L11
CC (PubMed:18084238, PubMed:19293378, PubMed:21203485). Interacts with
CC host BAD and BBC3 (PubMed:21203485). Interacts with BALF1; BALF1 acting
CC as a negative regulator of the survival function of BHRF1
CC (PubMed:11836425). {ECO:0000269|PubMed:11373297,
CC ECO:0000269|PubMed:11836425, ECO:0000269|PubMed:16963744,
CC ECO:0000269|PubMed:18084238, ECO:0000269|PubMed:19293378,
CC ECO:0000269|PubMed:21203485}.
CC -!- INTERACTION:
CC P03182; O54918: Bcl2l11; Xeno; NbExp=3; IntAct=EBI-1207659, EBI-526067;
CC P03182; Q86Y07: VRK2; Xeno; NbExp=7; IntAct=EBI-1207659, EBI-1207615;
CC -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}. Host mitochondrion {ECO:0000269|PubMed:11836425,
CC ECO:0000269|PubMed:9367386}. Note=also observed in the perinuclear
CC region of the cell.
CC -!- MISCELLANEOUS: EA-R is part of the restricted EA-complex.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; M17416; AAA45873.1; -; Genomic_DNA.
DR EMBL; V01555; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M17293; AAA45875.1; -; Genomic_DNA.
DR EMBL; AJ507799; CAD53396.1; -; Genomic_DNA.
DR EMBL; EF192979; ABM92330.1; -; Genomic_DNA.
DR PIR; C93065; QQBE4.
DR RefSeq; YP_401646.1; NC_007605.1.
DR PDB; 1Q59; NMR; -; A=1-160.
DR PDB; 2XPX; X-ray; 2.05 A; A=1-160.
DR PDBsum; 1Q59; -.
DR PDBsum; 2XPX; -.
DR BMRB; P03182; -.
DR SMR; P03182; -.
DR DIP; DIP-39168N; -.
DR IntAct; P03182; 149.
DR MINT; P03182; -.
DR PRIDE; P03182; -.
DR DNASU; 3783706; -.
DR GeneID; 3783706; -.
DR KEGG; vg:3783706; -.
DR EvolutionaryTrace; P03182; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0033668; P:negative regulation by symbiont of host apoptotic process; IDA:CACAO.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:CACAO.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR Pfam; PF00452; Bcl-2; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01258; BH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Early protein; Glycoprotein; Host membrane;
KW Host mitochondrion; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..191
FT /note="Apoptosis regulator BHRF1"
FT /id="PRO_0000143091"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..18
FT /note="Interaction with host VRK2"
FT REGION 89..142
FT /note="Interaction with host VRK2"
FT MOTIF 89..109
FT /note="BH1"
FT MOTIF 142..157
FT /note="BH2"
FT CARBOHYD 22
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT HELIX 5..20
FT /evidence="ECO:0007829|PDB:2XPX"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:1Q59"
FT HELIX 27..35
FT /evidence="ECO:0007829|PDB:2XPX"
FT HELIX 45..60
FT /evidence="ECO:0007829|PDB:2XPX"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:2XPX"
FT HELIX 79..91
FT /evidence="ECO:0007829|PDB:2XPX"
FT HELIX 98..117
FT /evidence="ECO:0007829|PDB:2XPX"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:1Q59"
FT HELIX 123..137
FT /evidence="ECO:0007829|PDB:2XPX"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:2XPX"
FT HELIX 141..146
FT /evidence="ECO:0007829|PDB:2XPX"
FT HELIX 150..155
FT /evidence="ECO:0007829|PDB:2XPX"
SQ SEQUENCE 191 AA; 21893 MW; 8108BCB94F81DC8B CRC64;
MAYSTREILL ALCIRDSRVH GNGTLHPVLE LAARETPLRL SPEDTVVLRY HVLLEEIIER
NSETFTETWN RFITHTEHVD LDFNSVFLEI FHRGDPSLGR ALAWMAWCMH ACRTLCCNQS
TPYYVVDLSV RGMLEASEGL DGWIHQQGGW STLIEDNIPG SRRFSWTLFL AGLTLSLLVI
CSYLFISRGR H
