BILF1_EBVB9
ID BILF1_EBVB9 Reviewed; 312 AA.
AC P03208; A0A1C9ZVS3; Q777B2;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=G-protein coupled receptor BILF1;
DE Short=GPCR BILF1 {ECO:0000303|PubMed:34216564};
GN ORFNames=BILF1;
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 [GENOMIC DNA].
RX PubMed=6092825;
RA Bankier A.T., Deininger P.L., Farrell P.J., Barrell B.G.;
RT "Sequence analysis of the 17,166 base-pair EcoRI fragment C of B95-8
RT Epstein-Barr virus.";
RL Mol. Biol. Med. 1:21-45(1983).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=HNNPC1 {ECO:0000312|EMBL:BAV60102.1};
RA Ploux O.;
RL Submitted (MAR-2016) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=HNNPC1 {ECO:0000312|EMBL:BAV60102.1},
RC HNNPC2 {ECO:0000312|EMBL:BAX36603.1}, HNNPC3 {ECO:0000312|EMBL:BAX36651.1},
RC HNNPC4 {ECO:0000312|EMBL:BAX36697.1}, HNNPC5 {ECO:0000312|EMBL:BAX36744.1},
RC HNNPC6 {ECO:0000312|EMBL:BAX36790.1}, HNNPC7 {ECO:0000312|EMBL:BAX36838.1},
RC and HNNPC8 {ECO:0000312|EMBL:BAX36885.1};
RA Xiong W., Li G.Y., Zeng C.Y., Tu C.F.;
RT "Whole-genome sequencing identification of genomic alterations in
RT nasopharyngeal carcinoma and NPC-derived Epstein-Barr virus.";
RL Submitted (MAY-2016) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=HNNPC4 {ECO:0000312|EMBL:BAX36697.1};
RA Lavstsen T., Jespersen J.S.;
RL Submitted (MAY-2016) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15596846; DOI=10.1128/jvi.79.1.536-546.2005;
RA Paulsen S.J., Rosenkilde M.M., Eugen-Olsen J., Kledal T.N.;
RT "Epstein-Barr virus-encoded BILF1 is a constitutively active G protein-
RT coupled receptor.";
RL J. Virol. 79:536-546(2005).
RN [7]
RP FUNCTION.
RX PubMed=15596837; DOI=10.1128/jvi.79.1.441-449.2005;
RA Beisser P.S., Verzijl D., Gruijthuijsen Y.K., Beuken E., Smit M.J.,
RA Leurs R., Bruggeman C.A., Vink C.;
RT "The Epstein-Barr virus BILF1 gene encodes a G protein-coupled receptor
RT that inhibits phosphorylation of RNA-dependent protein kinase.";
RL J. Virol. 79:441-449(2005).
RN [8]
RP FUNCTION.
RX PubMed=19119421; DOI=10.1371/journal.ppat.1000255;
RA Zuo J., Currin A., Griffin B.D., Shannon-Lowe C., Thomas W.A.,
RA Ressing M.E., Wiertz E.J., Rowe M.;
RT "The Epstein-Barr virus G-protein-coupled receptor contributes to immune
RT evasion by targeting MHC class I molecules for degradation.";
RL PLoS Pathog. 5:E1000255-E1000255(2009).
RN [9]
RP FUNCTION, AND INTERACTION WITH HOST CXCR4.
RX PubMed=20622011; DOI=10.1074/jbc.m110.115618;
RA Nijmeijer S., Leurs R., Smit M.J., Vischer H.F.;
RT "The Epstein-Barr virus-encoded G protein-coupled receptor BILF1 hetero-
RT oligomerizes with human CXCR4, scavenges Galphai proteins, and
RT constitutively impairs CXCR4 functioning.";
RL J. Biol. Chem. 285:29632-29641(2010).
RN [10]
RP FUNCTION.
RX PubMed=20543866; DOI=10.1038/onc.2010.173;
RA Lyngaa R., Noerregaard K., Kristensen M., Kubale V., Rosenkilde M.M.,
RA Kledal T.N.;
RT "Cell transformation mediated by the Epstein-Barr virus G protein-coupled
RT receptor BILF1 is dependent on constitutive signaling.";
RL Oncogene 29:4388-4398(2010).
RN [11]
RP FUNCTION.
RX PubMed=21123379; DOI=10.1128/jvi.01608-10;
RA Zuo J., Quinn L.L., Tamblyn J., Thomas W.A., Feederle R., Delecluse H.J.,
RA Hislop A.D., Rowe M.;
RT "The Epstein-Barr virus-encoded BILF1 protein modulates immune recognition
RT of endogenously processed antigen by targeting major histocompatibility
RT complex class I molecules trafficking on both the exocytic and endocytic
RT pathways.";
RL J. Virol. 85:1604-1614(2011).
RN [12]
RP FUNCTION, INDUCTION, AND DOMAIN.
RX PubMed=23315076; DOI=10.4049/jimmunol.1102462;
RA Griffin B.D., Gram A.M., Mulder A., Van Leeuwen D., Claas F.H., Wang F.,
RA Ressing M.E., Wiertz E.;
RT "EBV BILF1 evolved to downregulate cell surface display of a wide range of
RT HLA class I molecules through their cytoplasmic tail.";
RL J. Immunol. 190:1672-1684(2013).
RN [13]
RP DOMAIN, FUNCTION, AND MUTAGENESIS OF CYS-28; CYS-97; CYS-174 AND CYS-258.
RX PubMed=30647152; DOI=10.1128/mbio.01707-18;
RA Fares S., Spiess K., Olesen E.T.B., Zuo J., Jackson S., Kledal T.N.,
RA Wills M.R., Rosenkilde M.M.;
RT "Distinct Roles of Extracellular Domains in the Epstein-Barr Virus-Encoded
RT BILF1 Receptor for Signaling and Major Histocompatibility Complex Class I
RT Downregulation.";
RL MBio 10:0-0(2019).
RN [14]
RP REVIEW.
RX PubMed=33692148; DOI=10.1124/pharmrev.120.000186;
RA De Groof T.W.M., Elder E.G., Siderius M., Heukers R., Sinclair J.H.,
RA Smit M.J.;
RT "Viral G Protein-Coupled Receptors: Attractive Targets for Herpesvirus-
RT Associated Diseases.";
RL Pharmacol. Rev. 73:828-846(2021).
RN [15]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) OF 1-312 IN COMPLEX WITH
RP HOST GI HETEROTRIMER, INTERACTION WITH HOST GI HETEROTRIMER, AND
RP MUTAGENESIS OF LEU-75; HIS-115; GLU-121; LYS-122; ALA-125; MET-240;
RP LEU-241; ALA-271; TYR-282 AND HIS-288.
RX PubMed=34216564; DOI=10.1016/j.immuni.2021.06.001;
RA Tsutsumi N., Qu Q., Mavri M., Baggesen M.S., Maeda S., Waghray D., Berg C.,
RA Kobilka B.K., Rosenkilde M.M., Skiniotis G., Garcia K.C.;
RT "Structural basis for the constitutive activity and immunomodulatory
RT properties of the Epstein-Barr virus-encoded G protein-coupled receptor
RT BILF1.";
RL Immunity 54:1405-1416.e7(2021).
CC -!- FUNCTION: Constitutively active, ligand-independent G protein-coupled
CC receptor that has immunoevasive and oncogenic activities
CC (PubMed:34216564, PubMed:15596846, PubMed:15596837, PubMed:30647152).
CC Couples with the host inhibitory G protein (Gi) in order to disrupt the
CC host chemokine signaling (PubMed:34216564). As a consequence of its
CC constitutive activity, mediates host CXCR4 inhibition
CC (PubMed:20622011). Enhances degradation of host major
CC histocompatibility complex class I antigens via lysosomes, thereby
CC modulating the antigen presentation to cytotoxic T cells
CC (PubMed:19119421, PubMed:21123379, PubMed:23315076). Targets
CC selectively HLA-A, HLA-Band HLA-E molecules (PubMed:23315076). Targets
CC also newly synthesized MHC-I/peptide complexes en route to the host
CC cell surface (PubMed:21123379). Inhibits the host EIF2AK2/PKR
CC phosphorylation (PubMed:15596837). Displays tranforming activity
CC (PubMed:20543866). {ECO:0000269|PubMed:15596837,
CC ECO:0000269|PubMed:15596846, ECO:0000269|PubMed:19119421,
CC ECO:0000269|PubMed:20543866, ECO:0000269|PubMed:20622011,
CC ECO:0000269|PubMed:21123379, ECO:0000269|PubMed:23315076,
CC ECO:0000269|PubMed:30647152, ECO:0000269|PubMed:34216564}.
CC -!- SUBUNIT: Interacts with host CXCR4 to form higher-order heterooligomers
CC (PubMed:20622011). Interacts with host Gi heterotrimer
CC (PubMed:34216564). {ECO:0000269|PubMed:20622011,
CC ECO:0000269|PubMed:34216564}.
CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000269|PubMed:15596846};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- INDUCTION: Expressed early in the viral lytic cycle.
CC {ECO:0000269|PubMed:23315076}.
CC -!- DOMAIN: The extracellular N-terminus and third extracellular loop are
CC involved in host MHC-I down-regulation (PubMed:30647152). The
CC cytoplasmic C-terminus is also required for host MHC-I down-regulation
CC (PubMed:23315076). {ECO:0000269|PubMed:23315076,
CC ECO:0000269|PubMed:30647152}.
CC -!- SIMILARITY: Belongs to the Epstein-Barr virus BILF1 protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAV60102.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAX36603.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAX36651.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAX36697.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAX36744.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAX36790.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAX36838.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAX36885.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; V01555; CAA24804.1; -; Genomic_DNA.
DR EMBL; AJ507799; CAD53461.1; -; Genomic_DNA.
DR EMBL; LC137018; BAV60102.1; ALT_INIT; Genomic_DNA.
DR EMBL; LC149491; BAX36603.1; ALT_INIT; Genomic_DNA.
DR EMBL; LC150327; BAX36651.1; ALT_INIT; Genomic_DNA.
DR EMBL; LC150337; BAX36697.1; ALT_INIT; Genomic_DNA.
DR EMBL; LC150338; BAX36744.1; ALT_INIT; Genomic_DNA.
DR EMBL; LC150741; BAX36790.1; ALT_INIT; Genomic_DNA.
DR EMBL; LC150742; BAX36838.1; ALT_INIT; Genomic_DNA.
DR EMBL; LC150743; BAX36885.1; ALT_INIT; Genomic_DNA.
DR PIR; A03770; QQBE3L.
DR RefSeq; YP_401711.1; NC_007605.1.
DR PDB; 7JHJ; EM; 3.20 A; E=1-312.
DR PDBsum; 7JHJ; -.
DR SMR; P03208; -.
DR IntAct; P03208; 9.
DR PRIDE; P03208; -.
DR DNASU; 3783707; -.
DR GeneID; 3783707; -.
DR KEGG; vg:3783707; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0046776; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I; IDA:UniProtKB.
DR GO; GO:0039580; P:suppression by virus of host PKR signaling; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Early protein; Host cell membrane;
KW Host membrane; Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host MHC class I molecule presentation by virus;
KW Inhibition of host PKR by virus; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Viral immunoevasion.
FT CHAIN 1..312
FT /note="G-protein coupled receptor BILF1"
FT /id="PRO_0000116187"
FT TOPO_DOM 1..40
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:23315076"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 62..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:23315076"
FT TRANSMEM 68..88
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..95
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:23315076"
FT TRANSMEM 96..116
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 117..138
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:23315076"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..192
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:23315076"
FT TRANSMEM 193..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:23315076"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..269
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:23315076"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 291..312
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:23315076"
FT DISULFID 28..258
FT /evidence="ECO:0000269|PubMed:34216564"
FT DISULFID 97..174
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 28
FT /note="C->A: Reduced surface expression but no effect on
FT retained Gi signaling activity."
FT /evidence="ECO:0000269|PubMed:30647152"
FT MUTAGEN 75
FT /note="L->A: About 50% loss of constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 97
FT /note="C->A: Reduced surface expression and complete loss
FT of Gi signaling activity."
FT /evidence="ECO:0000269|PubMed:30647152"
FT MUTAGEN 115
FT /note="H->A: About 40% loss of constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 121
FT /note="E->A: About 50% loss of constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 122
FT /note="K->A: About 80% loss of constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 125
FT /note="A->F: About 25% loss of constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 174
FT /note="C->A: Reduced surface expression and complete loss
FT of Gi signaling activity."
FT /evidence="ECO:0000269|PubMed:30647152"
FT MUTAGEN 240
FT /note="M->F: Slight increase in constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 241
FT /note="L->F: About 10% loss of constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 258
FT /note="C->A: Reduced surface expression but no effect on
FT retained Gi signaling activity."
FT /evidence="ECO:0000269|PubMed:30647152"
FT MUTAGEN 271
FT /note="A->F: About 15% loss of constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 282
FT /note="Y->A: About 60% loss of constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT MUTAGEN 288
FT /note="H->A: No effect on constitutive Gi signaling."
FT /evidence="ECO:0000269|PubMed:34216564"
FT HELIX 34..59
FT /evidence="ECO:0007829|PDB:7JHJ"
FT HELIX 67..91
FT /evidence="ECO:0007829|PDB:7JHJ"
FT HELIX 97..126
FT /evidence="ECO:0007829|PDB:7JHJ"
FT HELIX 140..160
FT /evidence="ECO:0007829|PDB:7JHJ"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:7JHJ"
FT HELIX 182..211
FT /evidence="ECO:0007829|PDB:7JHJ"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:7JHJ"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:7JHJ"
FT HELIX 222..239
FT /evidence="ECO:0007829|PDB:7JHJ"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:7JHJ"
FT TURN 253..256
FT /evidence="ECO:0007829|PDB:7JHJ"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:7JHJ"
FT HELIX 268..284
FT /evidence="ECO:0007829|PDB:7JHJ"
FT HELIX 287..300
FT /evidence="ECO:0007829|PDB:7JHJ"
SQ SEQUENCE 312 AA; 34519 MW; 4AB7C717EF680EAD CRC64;
MLSTMAPGST VGTLVANMTS VNATEDACTK SYSAFLSGMT SLLLVLLILL TLAGILFIIF
VRKLVHRMDV WLIALLIELL LWVLGKMIQE FSSTGLCLLT QNMMFLGLMC SVWTHLGMAL
EKTLALFSRT PKRTSHRNVC LYLMGVFCLV LLLIIILLIT MGPDANLNRG PNMCREGPTK
GMHTAVQGLK AGCYLLAAVL IVLLTVIIIW KLLRTKFGRK PRLICNVTFT GLICAFSWFM
LSLPLLFLGE AGSLGFDCTE SLVARYYPGP AACLALLLII LYAWSFSHFM DSLKNQVTVT
ARYFRRVPSQ ST
