ARBH_MHV68
ID ARBH_MHV68 Reviewed; 171 AA.
AC P89884;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 29-SEP-2021, entry version 98.
DE RecName: Full=Apoptosis regulator Bcl-2 homolog;
DE Short=vBcl-2;
DE AltName: Full=Protein M11;
GN Name=vBCL2;
OS Murid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=33708;
OH NCBI_TaxID=10129; Apodemus sylvaticus (European woodmouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=8083987; DOI=10.1128/jvi.68.10.6496-6504.1994;
RA Stewart J.P., Janjua N.J., Sunil-Chandra N.P., Nash A.A., Arrand J.R.;
RT "Characterization of murine gammaherpesvirus 68 glycoprotein B (gB)
RT homolog: similarity to Epstein-Barr virus gB (gp110).";
RL J. Virol. 68:6496-6504(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=8648686; DOI=10.1128/jvi.70.6.3528-3535.1996;
RA Stewart J.P., Janjua N.J., Pepper S.D., Bennion G., Mackett M., Allen T.,
RA Nash A.A., Arrand J.R.;
RT "Identification and characterization of murine gammaherpesvirus 68 gp150: a
RT virion membrane glycoprotein.";
RL J. Virol. 70:3528-3535(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=8638414; DOI=10.1006/viro.1996.0274;
RA Pepper S.D., Stewart J.P., Arrand J.R., Mackett M.;
RT "Murine gammaherpesvirus-68 encodes homologues of thymidine kinase and
RT glycoprotein H: sequence, expression, and characterization of pyrimidine
RT kinase activity.";
RL Virology 219:475-479(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=G2.4;
RX PubMed=9191940; DOI=10.1099/0022-1317-78-6-1425;
RA Mackett M., Stewart J.P., de V Pepper S., Chee M., Efstathiou S.,
RA Nash A.A., Arrand J.R.;
RT "Genetic content and preliminary transcriptional analysis of a
RT representative region of murine gammaherpesvirus 68.";
RL J. Gen. Virol. 78:1425-1433(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=9225045; DOI=10.1099/0022-1317-78-7-1675;
RA Bowden R.J., Simas J.P., Davis A.J., Efstathiou S.;
RT "Murine gammaherpesvirus 68 encodes tRNA-like sequences which are expressed
RT during latency.";
RL J. Gen. Virol. 78:1675-1687(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=G2.4;
RX PubMed=9223479; DOI=10.1128/jvi.71.8.5894-5904.1997;
RA Virgin H.W., Latreille P., Wamsley P., Hallsworth K., Weck K.E.,
RA Dal Canto A.J., Speck S.H.;
RT "Complete sequence and genomic analysis of murine gammaherpesvirus 68.";
RL J. Virol. 71:5894-5904(1997).
RN [7]
RP FUNCTION.
RX PubMed=10573168; DOI=10.1099/0022-1317-80-10-2737;
RA Wang G.H., Garvey T.L., Cohen J.I.;
RT "The murine gammaherpesvirus-68 M11 protein inhibits Fas- and TNF-induced
RT apoptosis.";
RL J. Gen. Virol. 80:2737-2740(1999).
RN [8]
RP FUNCTION.
RX PubMed=11205127; DOI=10.1007/s007050070030;
RA Roy D.J., Ebrahimi B.C., Dutia B.M., Nash A.A., Stewart J.P.;
RT "Murine gammaherpesvirus M11 gene product inhibits apoptosis and is
RT expressed during virus persistence.";
RL Arch. Virol. 145:2411-2420(2000).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15604429; DOI=10.1099/vir.0.80480-0;
RA de Lima B.D., May J.S., Marques S., Simas J.P., Stevenson P.G.;
RT "Murine gammaherpesvirus 68 bcl-2 homologue contributes to latency
RT establishment in vivo.";
RL J. Gen. Virol. 86:31-40(2005).
RN [10]
RP STRUCTURE BY NMR OF 1-136.
RX PubMed=16201011; DOI=10.1371/journal.ppat.0010010;
RA Loh J., Huang Q., Petros A.M., Nettesheim D., van Dyk L.F., Labrada L.,
RA Speck S.H., Levine B., Olejniczak E.T., Virgin H.W.;
RT "A surface groove essential for viral Bcl-2 function during chronic
RT infection in vivo.";
RL PLoS Pathog. 1:E10-E10(2005).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-136, INTERACTION WITH HOST
RP BECN1, FUNCTION, SUBCELLULAR LOCATION, AND DISULFIDE BOND.
RX PubMed=18797192; DOI=10.4161/auto.6803;
RA Sinha S., Colbert C.L., Becker N., Wei Y., Levine B.;
RT "Molecular basis of the regulation of Beclin 1-dependent autophagy by the
RT gamma-herpesvirus 68 Bcl-2 homolog M11.";
RL Autophagy 4:989-997(2008).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 5-135, FUNCTION, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH BECN1; BAX AND BAK.
RX PubMed=18248095; DOI=10.1371/journal.ppat.0040025;
RA Ku B., Woo J.S., Liang C., Lee K.H., Hong H.S., E X., Kim K.S., Jung J.U.,
RA Oh B.H.;
RT "Structural and biochemical bases for the inhibition of autophagy and
RT apoptosis by viral BCL-2 of murine gamma-herpesvirus 68.";
RL PLoS Pathog. 4:E25-E25(2008).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 2-136, AND DISULFIDE BONDS.
RX PubMed=24443581; DOI=10.1074/jbc.m113.515361;
RA Su M., Mei Y., Sanishvili R., Levine B., Colbert C.L., Sinha S.;
RT "Targeting gamma-herpesvirus 68 Bcl-2-mediated down-regulation of
RT autophagy.";
RL J. Biol. Chem. 289:8029-8040(2014).
CC -!- FUNCTION: Plays a role in the protection against apoptosis mediated by
CC cytotoxic cells during the immune response to acute and persistent
CC viral infection. Contributes therefore to latency establishment. Plays
CC also a role in the inhibition of host starvation-induced autophagy
CC which ultimately contributes to the viral chronic infection.
CC {ECO:0000269|PubMed:10573168, ECO:0000269|PubMed:11205127,
CC ECO:0000269|PubMed:15604429, ECO:0000269|PubMed:18248095,
CC ECO:0000269|PubMed:18797192}.
CC -!- SUBUNIT: Interacts with host BECN1; this interaction inhibits host
CC autophagy. Interacts with host BAK1 and BAX.
CC {ECO:0000269|PubMed:18248095, ECO:0000269|PubMed:18797192}.
CC -!- INTERACTION:
CC P89884; Q14457: BECN1; Xeno; NbExp=4; IntAct=EBI-8849581, EBI-949378;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:15604429,
CC ECO:0000269|PubMed:18248095, ECO:0000269|PubMed:18797192}.
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DR EMBL; U91858; AAB50016.1; -; Genomic_DNA.
DR EMBL; U97553; AAB66423.1; -; Genomic_DNA.
DR EMBL; AF105037; AAF19336.1; -; Genomic_DNA.
DR EMBL; GQ421301; ACV65512.1; -; Genomic_DNA.
DR RefSeq; NP_044912.1; NC_001826.2.
DR PDB; 2ABO; NMR; -; A=1-136.
DR PDB; 3BL2; X-ray; 2.30 A; A/B=5-135.
DR PDB; 3DVU; X-ray; 2.50 A; A/B=2-136.
DR PDB; 4MI8; X-ray; 2.10 A; A/B=2-136.
DR PDBsum; 2ABO; -.
DR PDBsum; 3BL2; -.
DR PDBsum; 3DVU; -.
DR PDBsum; 4MI8; -.
DR SMR; P89884; -.
DR DIP; DIP-47218N; -.
DR IntAct; P89884; 13.
DR MINT; P89884; -.
DR GeneID; 1497180; -.
DR KEGG; vg:1497180; -.
DR EvolutionaryTrace; P89884; -.
DR Proteomes; UP000099649; Genome.
DR Proteomes; UP000175018; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019050; P:suppression by virus of host apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0039521; P:suppression by virus of host autophagy; IEA:UniProtKB-KW.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR029450; Apo_reg_M11.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR Pfam; PF15286; Bcl-2_3; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Host cytoplasm; Host-virus interaction;
KW Inhibition of host apoptosis by viral BCL2-like protein;
KW Inhibition of host autophagy by virus;
KW Modulation of host cell apoptosis by virus; Reference proteome.
FT CHAIN 1..171
FT /note="Apoptosis regulator Bcl-2 homolog"
FT /id="PRO_0000443226"
FT DISULFID 29
FT /note="Interchain (with C-104)"
FT DISULFID 104
FT /note="Interchain (with C-29)"
FT HELIX 7..22
FT /evidence="ECO:0007829|PDB:4MI8"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:4MI8"
FT HELIX 32..55
FT /evidence="ECO:0007829|PDB:4MI8"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:4MI8"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:4MI8"
FT HELIX 67..80
FT /evidence="ECO:0007829|PDB:4MI8"
FT HELIX 85..101
FT /evidence="ECO:0007829|PDB:4MI8"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:2ABO"
FT HELIX 110..125
FT /evidence="ECO:0007829|PDB:4MI8"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:4MI8"
SQ SEQUENCE 171 AA; 19743 MW; 43937262635E3446 CRC64;
MSHKKSGTYW ATLITAFLKT VSKVEELDCV DSAVLVDVSK IITLTQEFRR HYDSVYRADY
GPALKNWKRD LSKLFTSLFV DVINSGRIVG FFDVGRYVCE EVLCPGSWTE DHELLNDCMT
HFFIENNLMN HFPLEDIFLA QRKFQTTGFT FLLHALAKVL PRIYSGNVIY V