LAG3

Lymphocyte-activation protein 3 belongs to Ig superfamily and contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. The sequence data, exon/intron organization, and chromosomal localization all indicate a close relationship of LAG3 to CD4. [provided by RefSeq, Jul 2008]

lymphocyte activating 3

Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:7805750, PubMed:8647185, PubMed:20421648).
Delivers inhibitory signals upon binding to ligands, such as FGL1 (By similarity).
FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function (By similarity).
Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity).
May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1 (By similarity).
Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:7805750, PubMed:8647185, PubMed:20421648).
Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function (By similarity).
Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation (By similarity).
Binds MHC class II (MHC-II); the precise role of MHC-II-binding is however unclear (PubMed:8647185).
Secreted lymphocyte activation gene 3 protein
May function as a ligand for MHC class II (MHC-II) on antigen-presenting cells (APC), promoting APC activation/maturation and driving Th1 immune response.

Adaptive immune responseIEA:UniProtKB-KW
Cell surface receptor signaling pathwayISS:UniProtKB
Negative regulation of interleukin-2 productionIEA:Ensembl
Negative regulation of regulatory T cell differentiationISS:UniProtKB
Plasmacytoid dendritic cell activationISS:UniProtKB
Positive regulation of natural killer cell mediated cytotoxicityIEA:Ensembl
Regulation of immune responseISS:UniProtKB

Lymphocyte activation gene 3 protein:
Cell membrane
Secreted lymphocyte activation gene 3 protein:
Secreted
Produced following cleavage of the main chain.

Extracellular: 23-450
Helical: 451-471
Cytoplasmic: 472-525

Lymphocyte activation gene 3 protein
Proteolytically cleaved by ADAM10 and ADAM17 within the connecting peptide region, leading to release of Secreted lymphocyte activation gene 3 protein (sLAG-3). ADAM10 mediates constitutive cleavage, but cleavage increases following T-cell activation, whereas shedding by ADAM17 is induced by TCR signaling in a PRKCQ-dependent manner.