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.8Isoform 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.11Isoform LMP2B: Host endomembrane system; Multi-pass membrane protein. Host cytoplasm › host perinuclear region. Note: Isoform LMP2B localizes to perinuclear regions. Ref.10 Ref.11
Post-translational modification: Isoform LMP2A is phosphorylated on cytoplasmic N-terminal tyrosines residues, possibly by human LYN. Ref.4Can be ubiquitinated 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.
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