LMP2_EBVA8
ID LMP2_EBVA8 Reviewed; 497 AA.
AC Q1HVJ2; Q1HVJ1;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 1.
DT 02-JUN-2021, entry version 48.
DE RecName: Full=Latent membrane protein 2;
DE AltName: Full=Terminal protein;
GN Name=LMP2;
OS Epstein-Barr virus (strain AG876) (HHV-4) (Human herpesvirus 4).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Lymphocryptovirus.
OX NCBI_TaxID=82830;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS LMP2A AND LMP2B).
RX PubMed=16490228; DOI=10.1016/j.virol.2006.01.015;
RA Dolan A., Addison C., Gatherer D., Davison A.J., McGeoch D.J.;
RT "The genome of Epstein-Barr virus type 2 strain AG876.";
RL Virology 350:164-170(2006).
CC -!- FUNCTION: Isoform LMP2A maintains EBV latent infection of B-lymphocyte,
CC by preventing lytic reactivation of the virus in response to surface
CC immunoglobulin (sIg) cross-linking. Acts like a dominant negative
CC inhibitor of the sIg-associated protein tyrosine kinases, LYN and SYK.
CC Also blocks translocation of the B-cell antigen receptor (BCR) into
CC lipid rafts, preventing the subsequent signaling and accelerated
CC internalization of the BCR upon BCR cross-linking. Serves as a
CC molecular scaffold to recruit SYK, LYN and E3 protein-ubiquitin
CC ligases, such as ITCH and NEDD4L, leading to ubiquitination and
CC potential degradation of both tyrosines kinases. Possesses a
CC constitutive signaling activity in non-transformed cells, inducing
CC bypass of normal B lymphocyte developmental checkpoints allowing
CC immunoglobulin-negative cells to colonize peripheral lymphoid organs
CC (By similarity). {ECO:0000250}.
CC -!- FUNCTION: Isoform LMP2B may be a negative regulator of isoform LMP2A.
CC {ECO:0000250}.
CC -!- SUBUNIT: Isoform LMP2A cytoplasmic N-terminal domain interacts with
CC human SRC family protein tyrosine kinases SYK and LYN. Binds human
CC ITCH, WWP2 and NEDD4L (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform LMP2A]: Host cell membrane; Multi-pass
CC membrane protein. Note=Isoform LMP2A is localized in plasma membrane
CC lipid rafts. {ECO:0000250|UniProtKB:P13285}.
CC -!- SUBCELLULAR LOCATION: [Isoform LMP2B]: Host endomembrane system; Multi-
CC pass membrane protein. Host cytoplasm, host perinuclear region.
CC Note=Isoform LMP2B localizes to perinuclear regions.
CC {ECO:0000250|UniProtKB:P13285}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=LMP2A; Synonyms=TP1;
CC IsoId=Q1HVJ2-1; Sequence=Displayed;
CC Name=LMP2B; Synonyms=TP2;
CC IsoId=Q1HVJ2-2; Sequence=VSP_037376;
CC -!- PTM: Isoform LMP2A is phosphorylated on cytoplasmic N-terminal tyrosine
CC residues, possibly by human LYN. {ECO:0000250}.
CC -!- PTM: Can be ubiquitinated by human ITCH and WWP2 on the N-terminus in a
CC lysine-independent manner. {ECO:0000250}.
CC -!- MISCELLANEOUS: In healthy individuals, EBV typically establishes a
CC persistent latent infection in which the virus can be detected in
CC resting, nonproliferating peripheral B-lymphocytes. These latently
CC infected cells express only 2 virally encoded genes, LMP2A and EBNA1.
CC -!- SIMILARITY: Belongs to the herpesviridae LMP-2 family. {ECO:0000305}.
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DR EMBL; DQ279927; ABB89217.1; ALT_SEQ; Genomic_DNA.
DR EMBL; DQ279927; ABB89219.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; YP_001129436.1; NC_009334.1.
DR BMRB; Q1HVJ2; -.
DR GeneID; 5176182; -.
DR KEGG; vg:5176182; -.
DR Proteomes; UP000007639; Genome.
DR GO; GO:0033645; C:host cell endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
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:0039648; P:modulation by virus of host protein ubiquitination; IEA:UniProtKB-KW.
DR GO; GO:0039649; P:modulation by virus of host ubiquitin-protein ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0019042; P:viral latency; IEA:InterPro.
DR InterPro; IPR010881; Herpes_LMP2.
DR Pfam; PF07415; Herpes_LMP2; 1.
PE 3: Inferred from homology;
KW Alternative splicing; Host cell membrane; Host cytoplasm; Host membrane;
KW Host-virus interaction; Membrane;
KW Modulation of host E3 ubiquitin ligases by virus;
KW Modulation of host ubiquitin pathway by virus; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..497
FT /note="Latent membrane protein 2"
FT /id="PRO_0000375963"
FT TOPO_DOM 1..123
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..147
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..177
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 199..211
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..241
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 242..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 263..267
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 289..296
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 297..317
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 318
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..339
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 340..354
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..375
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 376..388
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 410..422
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 444..449
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 450..470
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 471..497
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 97..101
FT /note="PPxY motif"
FT /evidence="ECO:0000250"
FT COMPBIAS 26..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 73..87
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 112
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..119
FT /note="Missing (in isoform LMP2B)"
FT /evidence="ECO:0000305"
FT /id="VSP_037376"
SQ SEQUENCE 497 AA; 52977 MW; 9AC2F07B61BE1B51 CRC64;
MGSLEMVPMG AGPPSPGGDP DGDDGGNNSQ YPSASGSSGN TPTPPNDEER ESNEEPPPPY
EDPYWGNGDR HSDYQPLGTQ DQSLYLGLQH DGNDGLPPPP YSPRDDSSQH IYEEAGRGSM
NPVCLPVIVA PYLFWLAAIA ASCFTASVST VVTATGLALS LLLLAAVASS YAAAQRKLLT
PVTVLTAVVT FFAICLTWRI EDPPFNSLLF ALLAAAGGLQ GIYVLVMLVL LILAYRRRWR
RLTVCGGIMF LACVLVLIVD AVLQLSPLLG AVTVVSMTLL LLAFVLWLSS PGGLGTLGAA
LLTLAAALAL LASLILGTLN LTTMFLLMLL WTLVVLLICS SCSSCPLSKI LLARLFLYAL
ALLLLASALI AGGSILQTNF KSLSSTEFIP NLFCMLLLIV AGILFILAIL TEWGSGNRTY
GPVFMCLGGL LTMVAGAVWL TVMTNTLLSA WILTAGFLIF LIGFALFGVI RCCRYCCYYC
LTLESEERPP TPYRNTV
