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Database: UniProt
Entry: LMP1_EBVB9
LinkDB: LMP1_EBVB9
Original site: LMP1_EBVB9 
ID   LMP1_EBVB9              Reviewed;         386 AA.
AC   P03230; Q777A4;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   17-JUN-2020, entry version 114.
DE   RecName: Full=Latent membrane protein 1;
DE            Short=LMP-1;
DE   AltName: Full=Protein p63;
DE   Contains:
DE     RecName: Full=Protein p25;
GN   Name=LMP1; ORFNames=BNLF1;
OS   Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4).
OC   Viruses; Herpesvirales; Herpesviridae; Gammaherpesvirinae;
OC   Lymphocryptovirus.
OX   NCBI_TaxID=10377;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6086953;
RA   Fennewald S., van Santen V., Kieff E.;
RT   "Nucleotide sequence of an mRNA transcribed in latent growth-transforming
RT   virus infection indicates that it may encode a membrane protein.";
RL   J. Virol. 51:411-419(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2982035;
RA   Hudson G.S., Farrell P.J., Barrell B.G.;
RT   "Two related but differentially expressed potential membrane proteins
RT   encoded by the EcoRI Dhet region of Epstein-Barr virus B95-8.";
RL   J. Virol. 53:528-535(1985).
RN   [3]
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   [4]
RP   CHARACTERIZATION.
RX   PubMed=3027413;
RA   Baichwal V.R., Sudgen B.;
RT   "Posttranslational processing of an Epstein-Barr virus-encoded membrane
RT   protein expressed in cells transformed by Epstein-Barr virus.";
RL   J. Virol. 61:866-875(1987).
RN   [5]
RP   TRANSFORMING PROPERTIES.
RX   PubMed=2836780;
RA   Baichwal V.R., Sudgen B.;
RT   "Transformation of Balb 3T3 cells by the BNLF-1 gene of Epstein-Barr
RT   virus.";
RL   Oncogene 2:461-467(1988).
RN   [6]
RP   PROTEOLYTIC PROCESSING.
RX   PubMed=2153246;
RA   Moorthy R., Thorley-Lawson D.A.;
RT   "Processing of the Epstein-Barr virus-encoded latent membrane protein
RT   p63/LMP.";
RL   J. Virol. 64:829-837(1990).
RN   [7]
RP   DOMAIN CTAR1 AND CTAR2.
RX   PubMed=7845680;
RA   Huen D.S., Henderson S.A., Croom-Carter D., Rowe M.;
RT   "The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates
RT   activation of NF-kappa B and cell surface phenotype via two effector
RT   regions in its carboxy-terminal cytoplasmic domain.";
RL   Oncogene 10:549-560(1995).
RN   [8]
RP   SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-330, AND UBIQUITINATION.
RX   PubMed=10807912; DOI=10.1074/jbc.m002052200;
RA   Aviel S., Winberg G., Massucci M., Ciechanover A.;
RT   "Degradation of the epstein-barr virus latent membrane protein 1 (LMP1) by
RT   the ubiquitin-proteasome pathway. Targeting via ubiquitination of the N-
RT   terminal residue.";
RL   J. Biol. Chem. 275:23491-23499(2000).
RN   [9]
RP   INTERACTION WITH HOST PROTEIN ZMYND11.
RX   PubMed=16382137; DOI=10.1128/mcb.26.2.448-456.2006;
RA   Wan J., Zhang W., Wu L., Bai T., Zhang M., Lo K.W., Chui Y.L., Cui Y.,
RA   Tao Q., Yamamoto M., Akira S., Wu Z.;
RT   "BS69, a specific adaptor in the latent membrane protein 1-mediated c-Jun
RT   N-terminal kinase pathway.";
RL   Mol. Cell. Biol. 26:448-456(2006).
RN   [10]
RP   FUNCTION, AND INTERACTION WITH HOST IRF7.
RX   PubMed=19017798; DOI=10.1073/pnas.0809933105;
RA   Song Y.J., Izumi K.M., Shinners N.P., Gewurz B.E., Kieff E.;
RT   "IRF7 activation by Epstein-Barr virus latent membrane protein 1 requires
RT   localization at activation sites and TRAF6, but not TRAF2 or TRAF3.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:18448-18453(2008).
RN   [11]
RP   INTERACTION WITH HOST PROTEIN ZMYND11.
RX   PubMed=19379743; DOI=10.1016/j.febslet.2009.04.022;
RA   Ikeda O., Sekine Y., Mizushima A., Oritani K., Yasui T., Fujimuro M.,
RA   Muromoto R., Nanbo A., Matsuda T.;
RT   "BS69 negatively regulates the canonical NF-kappaB activation induced by
RT   Epstein-Barr virus-derived LMP1.";
RL   FEBS Lett. 583:1567-1574(2009).
RN   [12]
RP   INTERACTION WITH HOST PROTEIN ZMYND11.
RX   PubMed=20138174; DOI=10.1016/j.febslet.2010.01.060;
RA   Ikeda O., Miyasaka Y., Yoshida R., Mizushima A., Oritani K., Sekine Y.,
RA   Kuroda M., Yasui T., Fujimuro M., Muromoto R., Nanbo A., Matsuda T.;
RT   "BS69 cooperates with TRAF3 in the regulation of Epstein-Barr virus-derived
RT   LMP1/CTAR1-induced NF-kappaB activation.";
RL   FEBS Lett. 584:865-872(2010).
RN   [13]
RP   FUNCTION, AND INTERACTION WITH HOST UBE2I.
RX   PubMed=21795333; DOI=10.1128/jvi.05035-11;
RA   Bentz G.L., Whitehurst C.B., Pagano J.S.;
RT   "Epstein-Barr virus latent membrane protein 1 (LMP1) C-terminal-activating
RT   region 3 contributes to LMP1-mediated cellular migration via its
RT   interaction with Ubc9.";
RL   J. Virol. 85:10144-10153(2011).
RN   [14]
RP   FUNCTION.
RX   PubMed=22951831; DOI=10.1128/jvi.01407-12;
RA   Bentz G.L., Shackelford J., Pagano J.S.;
RT   "Epstein-Barr virus latent membrane protein 1 regulates the function of
RT   interferon regulatory factor 7 by inducing its sumoylation.";
RL   J. Virol. 86:12251-12261(2012).
RN   [15]
RP   REVIEW ON FUNCTION.
RX   PubMed=23793113; DOI=10.3390/v5061587;
RA   Ersing I., Bernhardt K., Gewurz B.E.;
RT   "NF-kappaB and IRF7 pathway activation by Epstein-Barr virus Latent
RT   Membrane Protein 1.";
RL   Viruses 5:1587-1606(2013).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 204-210.
RX   PubMed=11880627; DOI=10.1073/pnas.052706099;
RA   Richardson J.S., Richardson D.C.;
RT   "Natural beta-sheet proteins use negative design to avoid edge-to-edge
RT   aggregation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:2754-2759(2002).
CC   -!- FUNCTION: Acts as a CD40 functional homolog to prevent apoptosis of
CC       infected B-lymphocytes and drive their proliferation. Functions as a
CC       constitutively active tumor necrosis factor receptor that induces the
CC       activation of several signaling pathways, including those of the NF-
CC       kappa-B family. LMP1 signaling leads to up-regulation of antiapoptotic
CC       proteins and provide growth signals in latently infected cells.
CC       Interacts with host UBE2I and subsequently affects the sumoylation
CC       state of several cellular proteins. For example, induces the
CC       sumoylation of host IRF7 thereby limiting its transcriptional activity
CC       and modulating the activation of innate immune responses.
CC       {ECO:0000269|PubMed:19017798, ECO:0000269|PubMed:21795333,
CC       ECO:0000269|PubMed:22951831}.
CC   -!- SUBUNIT: Interacts (via PXQXT motif) with host tumor necrosis factor
CC       receptor-associated factor (TRAF) proteins TRAF1, TRAF2, TRAF3 and
CC       TRAF5. Interacts with human protein ZMYND11; leading to negatively
CC       regulate NF-kappa-B activation. Interacts with host UBE2I; this
CC       interaction induces the sumoylation of various cellular proteins.
CC       Interacts with host IRF7. {ECO:0000269|PubMed:16382137,
CC       ECO:0000269|PubMed:19017798, ECO:0000269|PubMed:19379743,
CC       ECO:0000269|PubMed:20138174, ECO:0000269|PubMed:21795333}.
CC   -!- INTERACTION:
CC       P03230; O14920: IKBKB; Xeno; NbExp=2; IntAct=EBI-6973030, EBI-81266;
CC       P03230; Q92985-1: IRF7; Xeno; NbExp=5; IntAct=EBI-6973030, EBI-8850881;
CC       P03230; Q9UI14: RABAC1; Xeno; NbExp=9; IntAct=EBI-6973030, EBI-712367;
CC       P03230; Q9UKE5: TNIK; Xeno; NbExp=7; IntAct=EBI-6973030, EBI-1051794;
CC       P03230; Q15628: TRADD; Xeno; NbExp=4; IntAct=EBI-6973030, EBI-359215;
CC       P03230; P63279: UBE2I; Xeno; NbExp=5; IntAct=EBI-6973030, EBI-80168;
CC       P03230; Q15326: ZMYND11; Xeno; NbExp=3; IntAct=EBI-6973030, EBI-2623509;
CC   -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000269|PubMed:10807912};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:10807912}.
CC   -!- DOMAIN: Two regions, C-terminal-activating region 1 (CTAR1) and CTAR2,
CC       have been identified within the cytoplasmic carboxy terminal domain
CC       that activates NF-kappa-B. {ECO:0000269|PubMed:7845680}.
CC   -!- PTM: Ubiquitinated on the N-terminus. {ECO:0000269|PubMed:10807912}.
CC   -!- SIMILARITY: Belongs to the herpesviridae LMP-1 family. {ECO:0000305}.
DR   EMBL; X01995; CAA26023.1; -; Genomic_DNA.
DR   EMBL; K02165; AAA45888.1; -; Genomic_DNA.
DR   EMBL; V01555; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AJ507799; CAD53472.1; -; Genomic_DNA.
DR   PIR; D43045; QQBE50.
DR   RefSeq; YP_401722.1; NC_007605.1.
DR   PDB; 1CZY; X-ray; 2.00 A; D/E=204-210.
DR   PDBsum; 1CZY; -.
DR   SMR; P03230; -.
DR   BioGRID; 971792; 12.
DR   DIP; DIP-29603N; -.
DR   DIP; DIP-43767N; -.
DR   ELM; P03230; -.
DR   IntAct; P03230; 14.
DR   MINT; P03230; -.
DR   ChEMBL; CHEMBL1795089; -.
DR   SwissPalm; P03230; -.
DR   ABCD; P03230; 11 sequenced antibodies.
DR   GeneID; 3783750; -.
DR   KEGG; vg:3783750; -.
DR   KO; K19459; -.
DR   EvolutionaryTrace; P03230; -.
DR   PRO; PR:P03230; -.
DR   Proteomes; UP000153037; Genome.
DR   GO; GO:0033644; C:host cell membrane; IDA:CACAO.
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:0039652; P:activation by virus of host NF-kappaB transcription factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0039547; P:suppression by virus of host TRAF activity; IEA:UniProtKB-KW.
DR   GO; GO:0039574; P:suppression by virus of host TYK2 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0019087; P:transformation of host cell by virus; IEA:InterPro.
DR   InterPro; IPR007961; Herpes_LMP1.
DR   Pfam; PF05297; Herpes_LMP1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activation of host NF-kappa-B by virus; Host cell membrane;
KW   Host membrane; Host-virus interaction;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host RLR pathway by virus; Inhibition of host TRAFs by virus;
KW   Inhibition of host TYK2 by virus; Membrane; Oncogene; Phosphoprotein;
KW   Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation;
KW   Viral immunoevasion.
FT   CHAIN           1..386
FT                   /note="Latent membrane protein 1"
FT                   /id="PRO_0000038310"
FT   CHAIN           242..386
FT                   /note="Protein p25"
FT                   /id="PRO_0000038311"
FT   TOPO_DOM        1..23
FT                   /note="Cytoplasmic"
FT   TRANSMEM        24..44
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        45..51
FT                   /note="Extracellular"
FT   TRANSMEM        52..72
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        73..75
FT                   /note="Cytoplasmic"
FT   TRANSMEM        76..96
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        97..106
FT                   /note="Extracellular"
FT   TRANSMEM        107..127
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        128..139
FT                   /note="Cytoplasmic"
FT   TRANSMEM        140..160
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        161..163
FT                   /note="Extracellular"
FT   TRANSMEM        164..184
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        185..386
FT                   /note="Cytoplasmic"
FT   REGION          194..232
FT                   /note="CTAR1"
FT   REGION          351..386
FT                   /note="CTAR2"
FT   MOTIF           204..208
FT                   /note="Interaction with host TRAF proteins"
FT   MUTAGEN         330
FT                   /note="K->R: No effect on ubiquitination and proteasomal
FT                   degradation."
FT                   /evidence="ECO:0000269|PubMed:10807912"
SQ   SEQUENCE   386 AA;  41982 MW;  1E19446E857DB8A3 CRC64;
     MEHDLERGPP GPRRPPRGPP LSSSLGLALL LLLLALLFWL YIVMSDWTGG ALLVLYSFAL
     MLIIIILIIF IFRRDLLCPL GALCILLLMI TLLLIALWNL HGQALFLGIV LFIFGCLLVL
     GIWIYLLEML WRLGATIWQL LAFFLAFFLD LILLIIALYL QQNWWTLLVD LLWLLLFLAI
     LIWMYYHGQR HSDEHHHDDS LPHPQQATDD SGHESDSNSN EGRHHLLVSG AGDGPPLCSQ
     NLGAPGGGPD NGPQDPDNTD DNGPQDPDNT DDNGPHDPLP QDPDNTDDNG PQDPDNTDDN
     GPHDPLPHSP SDSAGNDGGP PQLTEEVENK GGDQGPPLMT DGGGGHSHDS GHGGGDPHLP
     TLLLGSSGSG GDDDDPHGPV QLSYYD
//
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