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Reviewed, UniProtKB/Swiss-Prot P13285 (LMP2_EBVB9)

Last modified June 16, 2009. Version 59. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Latent membrane protein 2
Alternative name(s):
    Terminal protein
Gene names
Name: LMP2
OrganismEpstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4) [Complete proteome]
Taxonomic identifier10377 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeLymphocryptovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length497 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Isoform LMP2A maintains EBV latent infection of B-lymphocyte, by preventing lytic reactivation of the virus in response to surface immunoglobulin (sIg) cross-linking. Acts like a dominant negative inhibitor of the sIg-associated protein tyrosine kinases, LYN and SYK. Also blocks translocation of the B-cell antigen receptor (BCR) into lipid rafts, preventing the subsequent signaling and accelerated internalization of the BCR upon BCR cross-linking. Serves as a molecular scaffold to recruit SYK, LYN and E3 protein-ubiquitin ligases, such as ITCH and NEDD4L, leading to ubiquitination and potential degradation of both tyrosines kinases. Possesses a constitutive signaling activity in non-transformed cells, inducing bypass of normal B lymphocyte developmental checkpoints allowing immunoglobulin-negative cells to colonize peripheral lymphoid organs. Ref.5 Ref.8

Isoform LMP2B may be a negative regulator of isoform LMP2A. Ref.5 Ref.8

Subunit structure

Isoform LMP2A cytoplasmic N-terminal domain interacts with human SRC family protein tyrosine kinases SYK and LYN. Binds human ITCH, WWP2 and NEDD4L. Ref.6 Ref.9

Subcellular location

Isoform LMP2A: Host cell membrane; Multi-pass membrane protein. Note: Isoform LMP2A is localized in plasma membrane lipid rafts. Ref.10 Ref.11

Isoform LMP2B: Host endomembrane system; Multi-pass membrane protein. Host cytoplasmhost perinuclear region. Note: Isoform LMP2B localizes to perinuclear regions.

Post-translational modification

Isoform LMP2A is phosphorylated on cytoplasmic N-terminal tyrosines residues, possibly by human LYN. Ref.4

Can be ubiquitinated at by human ITCH and WWP2 on the N-terminus in a lysine-independent manner.

Miscellaneous

In healthy individuals, EBV typically establishes a persistent latent infection in which the virus can be detected in resting, nonproliferating peripheral B-lymphocytes. These latently infected cells express only 2 virally encoded genes, LMP2A and EBNA1.

Sequence similarities

Belongs to the herpesviridae LMP-2 family.

Ontologies

Keywords
   Biological processHost-virus interaction
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processinterspecies interaction between organisms

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-KW

host cell cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform LMP2A (identifier: P13285-1)

Also known as: TP1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Isoform LMP2A is localized in plasma membrane lipid rafts. Ref.10 Ref.11
Isoform LMP2B (identifier: P13285-2)

Also known as: TP2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-119: Missing.
Note: Isoform LMP2B localizes to perinuclear regions.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 497497Latent membrane protein 2
PRO_0000116280

Regions

Topological domain1 – 123123Cytoplasmic Potential
Transmembrane124 – 14421 Potential
Topological domain145 – 1473Extracellular Potential
Transmembrane148 – 16821 Potential
Topological domain169 – 1779Cytoplasmic Potential
Transmembrane178 – 19821 Potential
Topological domain199 – 21113Extracellular Potential
Transmembrane212 – 23221 Potential
Topological domain233 – 2419Cytoplasmic Potential
Transmembrane242 – 26221 Potential
Topological domain263 – 2675Extracellular Potential
Transmembrane268 – 28821 Potential
Topological domain289 – 2968Cytoplasmic Potential
Transmembrane297 – 31721 Potential
Topological domain3181Extracellular Potential
Transmembrane319 – 33921 Potential
Topological domain340 – 35415Cytoplasmic Potential
Transmembrane355 – 37521 Potential
Topological domain376 – 38813Extracellular Potential
Transmembrane389 – 40921 Potential
Topological domain410 – 42213Cytoplasmic Potential
Transmembrane423 – 44321 Potential
Topological domain444 – 4496Extracellular Potential
Transmembrane450 – 47021 Potential
Topological domain471 – 49727Cytoplasmic Potential
Motif97 – 1015PPPPY WW-binding

Amino acid modifications

Modified residue1121Phosphotyrosine; by host Potential

Natural variations

Alternative sequence1 – 119119Missing in isoform LMP2B.
VSP_016139

Experimental info

Mutagenesis741Y → F: Loss of interaction with human SYK. Ref.7
Mutagenesis851Y → F: Loss of interaction with human SYK. Ref.7
Mutagenesis1121Y → F: Complete loss of phosphorylation. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform LMP2A (TP1) [UniParc].

Last modified January 1, 1990. Version 1.
Checksum: F4DC9BB3C1FD83F1

FASTA49753,011
        10         20         30         40         50         60 
MGSLEMVPMG AGPPSPGGDP DGYDGGNNSQ YPSASGSSGN TPTPPNDEER ESNEEPPPPY 

        70         80         90        100        110        120 
EDPYWGNGDR HSDYQPLGTQ DQSLYLGLQH DGNDGLPPPP YSPRDDSSQH IYEEAGRGSM 

       130        140        150        160        170        180 
NPVCLPVIVA PYLFWLAAIA ASCFTASVST VVTATGLALS LLLLAAVASS YAAAQRKLLT 

       190        200        210        220        230        240 
PVTVLTAVVT FFAICLTWRI EDPPFNSLLF ALLAAAGGLQ GIYVLVMLVL LILAYRRRWR 

       250        260        270        280        290        300 
RLTVCGGIMF LACVLVLIVD AVLQLSPLLG AVTVVSMTLL LLAFVLWLSS PGGLGTLGAA 

       310        320        330        340        350        360 
LLTLAAALAL LASLILGTLN LTTMFLLMLL WTLVVLLICS SCSSCPLSKI LLARLFLYAL 

       370        380        390        400        410        420 
ALLLLASALI AGGSILQTNF KSLSSTEFIP NLFCMLLLIV AGILFILAIL TEWGSGNRTY 

       430        440        450        460        470        480 
GPVFMCLGGL LTMVAGAVWL TVMSNTLLSA WILTAGFLIF LIGFALFGVI RCCRYCCYYC 

       490 
LTLESEERPP TPYRNTV 

« Hide

Isoform LMP2B (TP2).

Checksum: 43526142FFAEE1DC
Show »

FASTA37840,383

References

« Hide 'large scale' references
[1]"A spliced Epstein-Barr virus gene expressed in immortalized lymphocytes is created by circularization of the linear viral genome."
Laux G., Perricaudet M., Farrell P.J.
EMBO J. 7:769-774(1988) [PubMed: 2840285] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Two related Epstein-Barr virus membrane proteins are encoded by separate genes."
Sample J., Liebowitz D., Kieff E.
J. Virol. 63:933-937(1989) [PubMed: 2536113] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LMP2A AND LMP2B).
[3]"DNA sequence and expression of the B95-8 Epstein-Barr virus genome."
Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J., Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C., Tuffnell P.S., Barrell B.G.
Nature 310:207-211(1984) [PubMed: 6087149] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM LMP2A).
[4]"An Epstein-Barr virus protein associated with cell growth transformation interacts with a tyrosine kinase."
Longnecker R., Druker B., Roberts T.M., Kieff E.
J. Virol. 65:3681-3692(1991) [PubMed: 1710288] [Abstract]
Cited for: PHOSPHORYLATION.
[5]"An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus from latency following surface immunoglobulin crosslinking."
Miller C.L., Lee J.H., Kieff E., Longnecker R.
Proc. Natl. Acad. Sci. U.S.A. 91:772-776(1994) [PubMed: 8290598] [Abstract]
Cited for: FUNCTION.
[6]"Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases."
Miller C.L., Burkhardt A.L., Lee J.H., Stealey B., Longnecker R., Bolen J.B., Kieff E.
Immunity 2:155-166(1995) [PubMed: 7895172] [Abstract]
Cited for: INTERACTION WITH HUMAN SYK AND LYN.
[7]"Tyrosine 112 of latent membrane protein 2A is essential for protein tyrosine kinase loading and regulation of Epstein-Barr virus latency."
Fruehling S., Swart R., Dolwick K.M., Kremmer E., Longnecker R.
J. Virol. 72:7796-7806(1998) [PubMed: 9733815] [Abstract]
Cited for: MUTAGENESIS OF TYR-74; TYR-85 AND TYR-112.
[8]"Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals."
Caldwell R.G., Wilson J.B., Anderson S.J., Longnecker R.
Immunity 9:405-411(1998) [PubMed: 9768760] [Abstract]
Cited for: FUNCTION.
[9]"Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3 protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases."
Winberg G., Matskova L., Chen F., Plant P., Rotin D., Gish G., Ingham R., Ernberg I., Pawson T.
Mol. Cell. Biol. 20:8526-8535(2000) [PubMed: 11046148] [Abstract]
Cited for: INTERACTION WITH HUMAN ITCH AND NEDD4L.
[10]"Epstein-Barr virus coopts lipid rafts to block the signaling and antigen transport functions of the BCR."
Dykstra M.L., Longnecker R., Pierce S.K.
Immunity 14:57-67(2001) [PubMed: 11163230] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[11]"Epstein-Barr virus latent membrane protein 2B (LMP2B) co-localizes with LMP2A in perinuclear regions in transiently transfected cells."
Lynch D.T., Zimmerman J.S., Rowe D.T.
J. Gen. Virol. 83:1025-1035(2002) [PubMed: 11961256] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[12]"Lysine-independent ubiquitination of Epstein-Barr virus LMP2A."
Ikeda M., Ikeda A., Longnecker R.
Virology 300:153-159(2002) [PubMed: 12202215] [Abstract]
Cited for: UBIQUITINATION.
[13]"Allele-dependent similarity between viral and self-peptide presentation by HLA-B27 subtypes."
Fiorillo M.T., Ruckert C., Hulsmeyer M., Sorrentino R., Saenger W., Ziegler A., Uchanska-Ziegler B.
J. Biol. Chem. 280:2962-2971(2005) [PubMed: 15537660] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 236-244.
+Additional computationally mapped references.

Cross-references

Sequence databases

M24212 mRNA. Translation: AAA45887.1.
Y00835 mRNA. Translation: CAA68762.1.
V01555 Genomic DNA. No translation available.
AJ507799 Genomic DNA. Translation: CAD53383.1. Sequence problems.
AJ507799 Genomic DNA. Translation: CAD53382.1. Sequence problems.
PIRWMBELM. A30178.

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1UXSX-ray1.55C236-244[»]
1UXWX-ray1.71C236-244[»]
2JO9NMR-B54-62[»]
3BVNX-ray2.55C/F236-244[»]
ModBaseSearch...

Family and domain databases

InterProIPR010881. Herpes_LMP2.
[Graphical view]
PfamPF07415. Herpes_LMP2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameLMP2_EBVB9
AccessionPrimary (citable) accession number: P13285
Secondary accession number(s): Q777H4, Q8AZK9
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: June 16, 2009
This is version 59 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectVirus (Virus annotation project)

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents