LMP2

Epstein-Barr virus (EBV) latent membrane protein 2 (LMP2) are two viral proteins of the Epstein–Barr virus. LMP2A/LMP2B are transmembrane proteins that act to block tyrosine kinase signaling. LMP2A is a transmembrane protein that inhibits normal B-cell signal transduction by mimicking an activated B-cell receptor (BCR). The N-terminus domain of LMP2A is tyrosine phosphorylated and associates with Src family protein tyrosine kinases (PTKs) as well as spleen tyrosine kinase (Syk). PTKs and Syk are associated with BCR signal transduction.

Full Name

Latent membrane protein 2

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

Biological Process

Mdulation by virus of host protein ubiquitinationIEA:UniProtKB-KW
Modulation by virus of host ubiquitin-protein ligase activityIEA:UniProtKB-KW
Viral latencyIEA:InterPro

Cellular Location

Isoform LMP2A:
Host cell membrane
Isoform LMP2A is localized in plasma membrane lipid rafts.
Isoform LMP2B:
Host endomembrane system
Host cytoplasm, host perinuclear region
Isoform LMP2B localizes to perinuclear regions.

Topology

Cytoplasmic: 1-123
Helical: 124-144
Extracellular: 145-147
Helical: 148-168
Cytoplasmic: 169-177
Helical: 178-198
Extracellular: 199-211
Helical: 212-232
Cytoplasmic: 233-241
Helical: 242-262
Extracellular: 263-267
Helical: 268-288
Cytoplasmic: 289-296
Helical: 297-317
Extracellular: 318
Helical: 319-339
Cytoplasmic: 340-354
Helical: 355-375
Extracellular: 376-388
Helical: 389-409
Cytoplasmic: 410-422
Helical: 423-443
Extracellular: 444-449
Helical: 450-470
Cytoplasmic: 471-497

PTM

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