LMP2_EBVG
ID LMP2_EBVG Reviewed; 496 AA.
AC P0C729;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 1.
DT 02-JUN-2021, entry version 34.
DE RecName: Full=Latent membrane protein 2;
DE AltName: Full=Terminal protein;
GN Name=LMP2;
OS Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Lymphocryptovirus.
OX NCBI_TaxID=10376;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16306603; DOI=10.1128/jvi.79.24.15323-15330.2005;
RA Zeng M.-S., Li D.-J., Liu Q.-L., Song L.-B., Li M.-Z., Zhang R.-H.,
RA Yu X.-J., Wang H.-M., Ernberg I., Zeng Y.-X.;
RT "Genomic sequence analysis of Epstein-Barr virus strain GD1 from a
RT nasopharyngeal carcinoma patient.";
RL J. Virol. 79:15323-15330(2005).
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=P0C729-1; Sequence=Displayed;
CC Name=LMP2B; Synonyms=TP2;
CC IsoId=P0C729-2; Sequence=VSP_037377;
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}.
CC -!- CAUTION: Several frameshift have been corrected to get the correct
CC translation. {ECO:0000305}.
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DR EMBL; AY961628; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR BMRB; P0C729; -.
DR IntAct; P0C729; 2.
DR Proteomes; UP000007641; 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 Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..496
FT /note="Latent membrane protein 2"
FT /id="PRO_0000375964"
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..197
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 198..210
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..240
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 262..266
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..295
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 296..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 317
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 339..353
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..374
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 375..387
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 388..408
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 409..421
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 443..448
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 449..469
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 470..496
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_037377"
SQ SEQUENCE 496 AA; 52890 MW; 5852B6E210EC528A CRC64;
MGSLEMVPMG AGPPSPGGDP DGDDGGNNSQ YPSASGSSGN TPTPPNDEER ESNEEPPPPY
EDPYWGNGDR HSDYQPLGTQ DQSLYLGLQH DGNDGLPPPP YSPRDDSSQH IYEEAGRGSM
NPVCLPVIVA PYLFWLAAIA ASCFTASVST VVTATGLALS LLLLAAVASS YAAAQRKLLT
PVTVLTAVVF FAICLTWRIE DPPFNSLLFA LLAAAGGLQG IYVLVMLVLL ILAYRRRWRR
LTVCGGIMFL ACVLVLIVDA VLQLSPLLGA VTVVSMTLLL LAFVLWLSSP GGLGTLGAAL
LTLAAALALL ASLILGTLNL TTMFLLMLLW TLVVLLICSS CSSCPLTKIL LARLFLYALA
LLLLASALIA GGSILQTNFK SLSSTEFIPN LFCMLLLIVA GILFILAILT EWGSGNRTYG
PVFMCLGGLL TMVAGAVWLT VMTNTLLSAW ILTAGFLIFL IGFALFGVIR CCRYCCYYCL
TLESEERPPT PYRNTV
