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P13285

- LMP2_EBVB9

UniProt

P13285 - LMP2_EBVB9

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Protein

Latent membrane protein 2

Gene

LMP2

Organism
Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.
Isoform LMP2B may be a negative regulator of isoform LMP2A.

GO - Biological processi

  1. modulation by virus of host ubiquitin-protein ligase activity Source: UniProtKB-KW
  2. viral latency Source: InterPro
Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Modulation of host E3 ubiquitin ligases by virus, Modulation of host ubiquitin pathway by virus

Names & Taxonomyi

Protein namesi
Recommended name:
Latent membrane protein 2
Alternative name(s):
Terminal protein
Gene namesi
Name:LMP2
OrganismiEpstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4)
Taxonomic identifieri10377 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeLymphocryptovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000007640: Genome

Subcellular locationi

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

GO - Cellular componenti

  1. host cell cytoplasm Source: UniProtKB-KW
  2. host cell plasma membrane Source: UniProtKB-KW
  3. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host cytoplasm, Host membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi74 – 741Y → F: Loss of interaction with human SYK. 1 Publication
Mutagenesisi85 – 851Y → F: Loss of interaction with human SYK. 1 Publication
Mutagenesisi112 – 1121Y → F: Complete loss of phosphorylation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 497497Latent membrane protein 2PRO_0000116280Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei112 – 1121Phosphotyrosine; by hostSequence Analysis

Post-translational modificationi

Isoform LMP2A is phosphorylated on cytoplasmic N-terminal tyrosines residues, possibly by human LYN.1 Publication
Can be ubiquitinated by human ITCH and WWP2 on the N-terminus in a lysine-independent manner.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Isoform LMP2A cytoplasmic N-terminal domain interacts with human SRC family protein tyrosine kinases SYK and LYN. Binds human ITCH, WWP2 and NEDD4L.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ITCHQ96J022EBI-7181113,EBI-1564678From a different organism.

Protein-protein interaction databases

IntActiP13285. 10 interactions.
MINTiMINT-6768292.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1UXSX-ray1.55C236-244[»]
1UXWX-ray1.71C236-244[»]
2JO9NMR-B54-62[»]
3BVNX-ray2.55C/F236-244[»]
3REWX-ray1.90C/F426-434[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13285.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 123123CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini145 – 1473ExtracellularSequence Analysis
Topological domaini169 – 1779CytoplasmicSequence Analysis
Topological domaini199 – 21113ExtracellularSequence AnalysisAdd
BLAST
Topological domaini233 – 2419CytoplasmicSequence Analysis
Topological domaini263 – 2675ExtracellularSequence Analysis
Topological domaini289 – 2968CytoplasmicSequence Analysis
Topological domaini318 – 3181ExtracellularSequence Analysis
Topological domaini340 – 35415CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini376 – 38813ExtracellularSequence AnalysisAdd
BLAST
Topological domaini410 – 42213CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini444 – 4496ExtracellularSequence Analysis
Topological domaini471 – 49727CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei124 – 14421HelicalSequence AnalysisAdd
BLAST
Transmembranei148 – 16821HelicalSequence AnalysisAdd
BLAST
Transmembranei178 – 19821HelicalSequence AnalysisAdd
BLAST
Transmembranei212 – 23221HelicalSequence AnalysisAdd
BLAST
Transmembranei242 – 26221HelicalSequence AnalysisAdd
BLAST
Transmembranei268 – 28821HelicalSequence AnalysisAdd
BLAST
Transmembranei297 – 31721HelicalSequence AnalysisAdd
BLAST
Transmembranei319 – 33921HelicalSequence AnalysisAdd
BLAST
Transmembranei355 – 37521HelicalSequence AnalysisAdd
BLAST
Transmembranei389 – 40921HelicalSequence AnalysisAdd
BLAST
Transmembranei423 – 44321HelicalSequence AnalysisAdd
BLAST
Transmembranei450 – 47021HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi97 – 1015PPPPY WW-binding

Sequence similaritiesi

Belongs to the herpesviridae LMP-2 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Family and domain databases

InterProiIPR010881. Herpes_LMP2.
[Graphical view]
PfamiPF07415. Herpes_LMP2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform LMP2A (identifier: P13285-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MGSLEMVPMG AGPPSPGGDP DGYDGGNNSQ YPSASGSSGN TPTPPNDEER
60 70 80 90 100
ESNEEPPPPY EDPYWGNGDR HSDYQPLGTQ DQSLYLGLQH DGNDGLPPPP
110 120 130 140 150
YSPRDDSSQH IYEEAGRGSM NPVCLPVIVA PYLFWLAAIA ASCFTASVST
160 170 180 190 200
VVTATGLALS LLLLAAVASS YAAAQRKLLT PVTVLTAVVT FFAICLTWRI
210 220 230 240 250
EDPPFNSLLF ALLAAAGGLQ GIYVLVMLVL LILAYRRRWR RLTVCGGIMF
260 270 280 290 300
LACVLVLIVD AVLQLSPLLG AVTVVSMTLL LLAFVLWLSS PGGLGTLGAA
310 320 330 340 350
LLTLAAALAL LASLILGTLN LTTMFLLMLL WTLVVLLICS SCSSCPLSKI
360 370 380 390 400
LLARLFLYAL ALLLLASALI AGGSILQTNF KSLSSTEFIP NLFCMLLLIV
410 420 430 440 450
AGILFILAIL TEWGSGNRTY GPVFMCLGGL LTMVAGAVWL TVMSNTLLSA
460 470 480 490
WILTAGFLIF LIGFALFGVI RCCRYCCYYC LTLESEERPP TPYRNTV
Length:497
Mass (Da):53,011
Last modified:January 1, 1990 - v1
Checksum:iF4DC9BB3C1FD83F1
GO
Isoform LMP2B (identifier: P13285-2) [UniParc]FASTAAdd to Basket

Also known as: TP2

The sequence of this isoform differs from the canonical sequence as follows:
     1-119: Missing.

Show »
Length:378
Mass (Da):40,383
Checksum:i43526142FFAEE1DC
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 119119Missing in isoform LMP2B. 1 PublicationVSP_016139Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
PIRiA30178. WMBELM.
RefSeqiYP_401631.1. NC_007605.1.

Genome annotation databases

GeneIDi17494212.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
PIRi A30178. WMBELM.
RefSeqi YP_401631.1. NC_007605.1.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1UXS X-ray 1.55 C 236-244 [» ]
1UXW X-ray 1.71 C 236-244 [» ]
2JO9 NMR - B 54-62 [» ]
3BVN X-ray 2.55 C/F 236-244 [» ]
3REW X-ray 1.90 C/F 426-434 [» ]
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P13285. 10 interactions.
MINTi MINT-6768292.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 17494212.

Miscellaneous databases

EvolutionaryTracei P13285.

Family and domain databases

InterProi IPR010881. Herpes_LMP2.
[Graphical view ]
Pfami PF07415. Herpes_LMP2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LMP2A AND LMP2B).
  3. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 236-244.

Entry informationi

Entry nameiLMP2_EBVB9
AccessioniPrimary (citable) accession number: P13285
Secondary accession number(s): Q777H4, Q8AZK9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: October 29, 2014
This is version 87 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3