Protein / target
Ephrin type-A receptor 2
Protein at a glance
Biological role
Transmembrane receptor protein tyrosine kinase activity
Primary system
Cardiovascular system
Strongest disease association
early-onset non-syndromic cataract
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
3 approved
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis
Subcellular location
Domains and Gene Ontology detail (48)Hide
Domains & features
Gene Ontology
- Ccell junction
- Ccell surface
- Cfocal adhesion
- Clamellipodium
- Clamellipodium membrane
- Cleading edge membrane
- Cplasma membrane
- Creceptor complex
- Cruffle membrane
- Ctight junction
- FATP binding
- Fcadherin binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Cell adhesion
- ·Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligand…
- ·Cell junction, focal adhesion
- ·cell junction
- ·tight junction
Kinase signalling
- ·transmembrane receptor protein tyrosine kinase activity
Immune signalling
- ·Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligand…
Metabolic enzyme activity
- ·cAMP metabolic process
View underlying pathways (12)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.
Ephrin type-A receptor 2 inhibitor
Appears in clinical studies involving colorectal cancer, metastatic colorectal cancer, colorectal neoplasm, 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 927 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 · 3 total
chronic myelogenous leukemia, BCR-ABL1 positive · acute lymphoblastic leukemia · chronic myelogenous leukemia, BCR-ABL1 positive
thyroid gland carcinoma · medullary thyroid gland carcinoma · medullary thyroid gland carcinoma
colorectal cancer · metastatic colorectal cancer · colorectal neoplasm
Tractability
Safety liabilities
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.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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 publicationEfficacy of pembrolizumab in microsatellite-stable, tumor mutational burden-high metastatic colorectal cancer: genomic signatures and clinical outcomes.
- New publicationLenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study.
- New publicationTargeted therapy for hepatocellular carcinoma.
- New publicationMolecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma.
- New publicationRandomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma.
- New publicationRegorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.
- Regulatory approval
Approval: Stivarga (EMA)
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.