Protein / target
NKG2-A/NKG2-B type II integral membrane protein
Protein at a glance
Biological role
HLA-E specific inhibitory MHC class Ib receptor activity
Primary system
Immune system
Strongest disease association
non-small cell lung carcinoma
Therapeutic maturity
Clinical-stage target
Druggability
Antibody
Clinical development
1 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Immune inhibitory receptor involved in self-nonself discrimination. In complex with KLRD1 on cytotoxic and regulatory lymphocyte subsets, recognizes non-classical major histocompatibility (MHC) class Ib molecule HLA-E loaded with self-peptides derived from the signal sequence of classical MHC class Ia molecules. Enables cytotoxic cells to monitor the expression of MHC class I molecules in healthy cells and to tolerate self (PubMed:18083576, PubMed:37264229, PubMed:9430220, PubMed:9486650). Upon HLA-E-peptide binding, transmits intracellular signals through two immunoreceptor tyrosine-based inhibition motifs (ITIMs) by recruiting INPP5D/SHP-1 and INPPL1/SHP-2 tyrosine phosphatases to ITIMs, and ultimately opposing signals transmitted by activating receptors through dephosphorylation of proximal signaling molecules (PubMed:12165520, PubMed:9485206). Key inhibitory receptor on natural killer (NK) cells that regulates their activation and effector functions (PubMed:30860984, PubMed:9430220, PubMed:9485206, PubMed:9486650). Dominantly counteracts T cell receptor signaling on a subset of memory/effector CD8-positive T cells as part of an antigen-driven response to avoid autoimmunity (PubMed:12387742). On intraepithelial CD8-positive gamma-delta regulatory T cells triggers TGFB1 secretion, which in turn limits the cytotoxic programming of intraepithelial CD8-positive alpha-beta T cells, distinguishing harmless from pathogenic antigens (PubMed:18064301). In HLA-E-rich tumor microenvironment, acts as an immune inhibitory checkpoint and may contribute to progressive loss of effector functions of NK cells and tumor-specific T cells, a state known as cell exhaustion (PubMed:30503213, PubMed:30860984)
Subcellular location
Domains and Gene Ontology detail (19)Hide
Domains & features
Gene Ontology
- Ccell surface
- Cplasma membrane
- Creceptor complex
- Fcarbohydrate binding
- FHLA-E specific inhibitory MHC class Ib receptor activity
- Finhibitory MHC class Ib receptor activity
- FMHC class I protein complex binding
- Ftransmembrane signaling receptor activity
- Padaptive immune response
- PCD8-positive, gamma-delta intraepithelial T cell differentiation
- Pcell surface receptor signaling pathway
- Pnatural killer cell inhibitory signaling pathway
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
- ·Immune inhibitory receptor involved in self-nonself discrimination. In complex with KLRD…
- ·adaptive immune response
- ·CD8-positive, gamma-delta intraepithelial T cell differentiation
- ·negative regulation of T cell mediated cytotoxicity
Kinase signalling
- ·Immune inhibitory receptor involved in self-nonself discrimination. In complex with KLRD…
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.
NKG2-A/NKG2-B type II integral membrane protein inhibitor
Appears in clinical studies involving head and neck squamous cell carcinoma, non-small cell lung carcinoma, rheumatoid arthritis, non-small cell lung 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 478 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 · 1 total
head and neck squamous cell carcinoma · non-small cell lung carcinoma · rheumatoid arthritis
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 (12)Hide
ClinicalTrials.gov via the drug-target graph.
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.
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.