LAG-3

Domain

Lymphocyte activation gene 3 protein

The KIEELE motif is required for interaction with downstream signaling molecules.

Function

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.

Post-translational modifications

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.

Sequence similarities

Belongs to the LAG3 family.

Tissue specificity

Primarily expressed in activated T-cells and a subset of natural killer (NK) cells.

Cellular localization

• Lymphocyte activation gene 3 protein
• Cell membrane
• Single-pass type I membrane protein
• Secreted lymphocyte activation gene 3 protein
• Secreted
• Produced following cleavage of the main chain.

Alternative names

• Lymphocyte activation gene 3 protein
• LAG-3
• LAG3
• FDC

Database links

• entrezGene:3902
• omim:153337
• swissprot:P18627

Target type

Proteins

Primary research area

Immuno-oncology

Other research areas

• Immunology & Infectious Disease

Molecular weight

57449Da