Protein / target
T-cell surface glycoprotein CD3 epsilon chain
Protein at a glance
Biological role
Signaling receptor complex adaptor activity
Primary system
Immune system
Strongest disease association
immunodeficiency 18
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
12 approved · 10 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
Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response (PubMed:15294938, PubMed:15546002, PubMed:2470098, PubMed:40592325, PubMed:8490660). When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD247/CD3Z (PubMed:2470098, PubMed:40592325). All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain (PubMed:2470098, PubMed:40592325). Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098, PubMed:40592325). CD3E ITAM phosphorylation creates docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (By similarity). In addition of this role of signal transduction in T-cell activation, CD3E plays an essential role in correct T-cell development (By similarity). Also participates in internalization and cell surface down-regulation of TCR-CD3 complexes via endocytosis sequences present in CD3E cytosolic region (PubMed:10384095, PubMed:26507128). In addition to its role as a TCR coreceptor, it serves as a receptor for ITPRIPL1 (PubMed:38614099). Ligand recognition inhibits T-cell activation by promoting interaction with NCK1, which prevents CD3E-ZAP70 interaction and blocks the ERK-NFkB signaling cascade and calcium influx (PubMed:12110186, PubMed:38614099)
Subcellular location
Domains and Gene Ontology detail (36)Hide
Domains & features
Gene Ontology
- Calpha-beta T cell receptor complex
- Ccell body
- Ccell-cell junction
- Cdendritic spine
- Cexternal side of plasma membrane
- Cimmunological synapse
- Cplasma membrane
- CT cell receptor complex
- Fidentical protein binding
- Fprotein kinase binding
- Fprotein-macromolecule adaptor activity
- FSH3 domain binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Kinase signalling
- ·Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential…
- ·protein kinase binding
- ·Phosphorylation of CD3 and TCR zeta chains
Immune signalling
- ·Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential…
- ·alpha-beta T cell receptor complex
- ·T cell receptor complex
- ·T cell receptor binding
Synaptic signalling
- ·immunological synapse
- ·Translocation of ZAP-70 to Immunological synapse
Cell adhesion
- ·cell-cell junction
- ·positive regulation of cell-cell adhesion mediated by integrin
Transcriptional regulation
- ·negative regulation of gene expression
- ·positive regulation of gene expression
G protein-coupled signalling
- ·G protein-coupled receptor signaling pathway
View underlying pathways (6)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.
T-cell surface glycoprotein CD3 epsilon chain cross-linking agent
Appears in clinical studies involving breast cancer, rectal cancer, gastric cancer
T cell surface glycoprotein CD3 cross-linking agent
Appears in clinical studies involving acute lymphoblastic leukemia, B-cell acute lymphoblastic leukemia, lymphoid leukemia, neoplasm
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.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
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 403 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 · 22 total
type 1 diabetes mellitus · type 1 diabetes mellitus · type 1 diabetes mellitus
breast cancer · rectal cancer · gastric cancer
acute lymphoblastic leukemia · B-cell acute lymphoblastic leukemia · lymphoid leukemia
type 1 diabetes mellitus · type 1 diabetes mellitus · type 1 diabetes mellitus
small cell lung carcinoma · cancer · neoplasm
acute leukemia of ambiguous lineage · acute myeloid leukemia by FAB classification · hematopoietic and lymphoid cell neoplasm
plasma cell myeloma · neoplasm · plasma cell myeloma
follicular lymphoma · B-cell non-Hodgkin lymphoma · diffuse large B-cell lymphoma
metabolic dysfunction-associated steatohepatitis · type 2 diabetes mellitus · COVID-19
melanoma
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.
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 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- New publicationCurative outcomes following blinatumomab in adults with minimal residual disease B-cell precursor acute lymphoblastic leukemia.
- New publicationThe BiTE (bispecific T-cell engager) platform: Development and future potential of a targeted immuno-oncology therapy across tumor types.
- New publicationBlinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia.
- Regulatory approval
Approval: Blincyto (EMA)
- New publicationThe HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine.
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.