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 18-JUN-2025, entry version 134.
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; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Orthoherpesviridae; Gammaherpesvirinae; Lymphocryptovirus;
OC Lymphocryptovirus humangamma4; Epstein-Barr virus (strain GD1).
OX NCBI_TaxID=10377;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6086953; DOI=10.1128/jvi.51.2.411-419.1984;
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; DOI=10.1128/jvi.53.2.528-535.1985;
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 GENOME REANNOTATION.
RX PubMed=12771413; DOI=10.1099/vir.0.19054-0;
RA de Jesus O., Smith P.R., Spender L.C., Elgueta Karstegl C., Niller H.H.,
RA Huang D., Farrell P.J.;
RT "Updated Epstein-Barr virus (EBV) DNA sequence and analysis of a promoter
RT for the BART (CST, BARF0) RNAs of EBV.";
RL Virology 84:1443-1450(2003).
RN [5]
RP CHARACTERIZATION.
RX PubMed=3027413; DOI=10.1128/jvi.61.3.866-875.1987;
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 [6]
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 [7]
RP PROTEOLYTIC PROCESSING.
RX PubMed=2153246; DOI=10.1128/jvi.64.2.829-837.1990;
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 [8]
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 [9]
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 [10]
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 [11]
RP FUNCTION, AND INTERACTION WITH HOST TYK2.
RX PubMed=16987978; DOI=10.1128/jvi.01570-06;
RA Geiger T.R., Martin J.M.;
RT "The Epstein-Barr virus-encoded LMP-1 oncoprotein negatively affects Tyk2
RT phosphorylation and interferon signaling in human B cells.";
RL J. Virol. 80:11638-11650(2006).
RN [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
RP FUNCTION.
RX PubMed=30659232; DOI=10.1038/s41598-018-36312-4;
RA Salahuddin S., Fath E.K., Biel N., Ray A., Moss C.R., Patel A., Patel S.,
RA Hilding L., Varn M., Ross T., Cramblet W.T., Lowrey A., Pagano J.S.,
RA Shackelford J., Bentz G.L.;
RT "Epstein-Barr Virus Latent Membrane Protein-1 Induces the Expression of
RT SUMO-1 and SUMO-2/3 in LMP1-positive Lymphomas and Cells.";
RL Sci. Rep. 9:208-208(2019).
RN [19]
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. Also inhibits
CC host IFN-alpha-stimulated STAT2 nuclear translocation and interferon-
CC stimulated response element transcriptional activity by interacting
CC with and inhibiting host TYK2. Induces SUMO expression during viral
CC latency thereby dysregulating the host sumoylation processes
CC (PubMed:30659232). {ECO:0000269|PubMed:16987978,
CC ECO:0000269|PubMed:19017798, ECO:0000269|PubMed:21795333,
CC ECO:0000269|PubMed:22951831, ECO:0000269|PubMed:30659232}.
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 (PubMed:21795333). Interacts with host IRF7. Interacts with host TYK2.
CC {ECO:0000269|PubMed:16382137, ECO:0000269|PubMed:16987978,
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}.
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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 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; 15.
DR MINT; P03230; -.
DR BindingDB; P03230; -.
DR ChEMBL; CHEMBL1795089; -.
DR TCDB; 9.B.387.1.1; the viral latent membrane protein (vlmp) family.
DR SwissPalm; P03230; -.
DR ABCD; P03230; 11 sequenced antibodies.
DR DNASU; 3783750; -.
DR KEGG; vg:3783750; -.
DR SIGNOR; P03230; -.
DR EvolutionaryTrace; P03230; -.
DR PRO; PR:P03230; -.
DR Proteomes; UP000153037; Segment.
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:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0085033; P:symbiont-mediated activation of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR GO; GO:0039574; P:symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039527; P:symbiont-mediated suppression of host TRAF-mediated signal transduction; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:symbiont-mediated suppression of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0019087; P:symbiont-mediated transformation of host cell; 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; Interferon antiviral system evasion;
KW Membrane; Oncogene; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Ubl conjugation; 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..386
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 COMPBIAS 210..224
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 251..267
FT /note="Low complexity"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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
//
