Protein / target
Lymphocyte activation gene 3 protein
Protein at a glance
Biological role
Transmembrane signaling receptor activity
Primary system
Immune system
Strongest disease association
melanoma
Therapeutic maturity
Clinically validated target
Druggability
Antibody
Clinical development
1 approved · 5 in clinical development
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:35761082, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as MHC class II, its main ligand present at the surface of antigen-presenting cells (APCs), and FGL1, which is secreted by hepatocytes and certain types of tumor cells (PubMed:30580966, PubMed:32920841, PubMed:35761082, PubMed:39671469, PubMed:7589152, PubMed:8647185, PubMed:9159144). Ligand-binding initiates a signaling that inhibits the T-cell receptor (TCR) in the immunological synapse, preventing T-cell activation (PubMed:40101708). Mechanistically, ligand-binding promotes (1) ubiquitination of the KIEELE motif, unleashing the RRFSALE motif from the membrane and (2) leading to the formation of condensates with the TCR component CD3E, thereby disrupting the association between CD3E and LCK and preventing TCR activation (PubMed:40101708, PubMed:40592325). May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1 (By similarity). Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). 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)
Subcellular location
Domains and Gene Ontology detail (19)Hide
Domains & features
Gene Ontology
- Ccell surface
- Cexternal side of plasma membrane
- Cextracellular region
- Cplasma membrane
- Fantigen binding
- FMHC class II protein binding
- Ftransmembrane signaling receptor activity
- Padaptive immune response
- Pcell surface receptor signaling pathway
- Pnegative regulation of regulatory T cell differentiation
- Pnegative regulation of T cell activation
- Pnegative regulation of T cell mediated immune response to tumor cell
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Immune signalling
- ·Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:35761082, PubM…
- ·antigen binding
- ·adaptive immune response
- ·negative regulation of regulatory T cell differentiation
Synaptic signalling
- ·Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:35761082, PubM…
View underlying pathways (1)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Lymphocyte activation gene 3 protein inhibitor
Appears in clinical studies involving melanoma, metastatic colorectal cancer, non-small cell lung carcinoma, urinary bladder carcinoma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 675 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 6 total
melanoma · non-small cell lung carcinoma · hepatocellular carcinoma
non-small cell lung carcinoma · breast cancer · non-small cell lung carcinoma
ovarian adenocarcinoma · prostate adenocarcinoma · gastric adenocarcinoma
melanoma · colorectal cancer · bladder carcinoma in situ
melanoma · metastatic colorectal cancer · non-small cell lung carcinoma
gastroesophageal junction adenocarcinoma · gastric cancer · gastric neoplasm
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationNeoadjuvant relatlimab and nivolumab in resectable melanoma.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.