Back to discover

Protein / target

Ephrin-B2

Encoded byEFNB2P52799Homo sapiensSwiss-Prot
UniProt: P52799Ensembl: ENSG00000125266HGNC: HGNC:3227NCBI Gene: 1948
Clinical-stage
Therapeutic maturity
1
Clinical candidates
Small-molecule tractable
Druggability
High-Quality Pocket
1
Research papers

Protein at a glance

Biological role

Receptor ligand

Strongest disease association

Glaucoma, Open-Angle

Via encoding gene EFNB2 · Genetic evidence · score 0.52

Therapeutic position

Clinically advancing target

Research activity

Emerging research

1 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development.

View complete UniProt function annotation

Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors 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. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons

Subcellular location

Cell membraneCell junction, adherens junction
Domains and Gene Ontology detail (31)

Domains & features

Ephrin RBD

Gene Ontology

  • Cadherens junction
  • Ccytosol
  • Cdendrite
  • Cfocal adhesion
  • Cglutamatergic synapse
  • Cnucleoplasm
  • Cplasma membrane
  • Cpostsynaptic density membrane
  • Cpresynaptic membrane
  • CSchaffer collateral - CA1 synapse
  • Fephrin receptor binding
  • Freceptor ligand activity

333 aa · 37 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationUniProt · GOSynaptic signallingGOReceptor tyrosine kinase signallingUniProtCell proliferation & survivalGOCell adhesionUniProt · GO
View supporting evidence

Cell migration

  • ·Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinas…
  • ·cell migration involved in sprouting angiogenesis
  • ·regulation of chemotaxis

Synaptic signalling

  • ·glutamatergic synapse
  • ·postsynaptic density membrane
  • ·presynaptic membrane
  • ·Schaffer collateral - CA1 synapse

Receptor tyrosine kinase signalling

  • ·Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinas…

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Cell adhesion

  • ·Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinas…
  • ·Cell junction, adherens junction
  • ·cell adhesion

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene EFNB2

Gene-level evidence surfaced through the gene EFNB2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Glaucoma, Open-Angle
0.52Moderately supported

Genetic evidence dominant · Open Targets 0.31

Glaucoma
0.52Moderately supported

Genetic evidence dominant · Open Targets 0.31

Joint Diseases
0.51Moderately supported

Genetic evidence dominant · Open Targets 0.31

Poisoning
0.51Moderately supported

Genetic evidence dominant · Open Targets 0.31

Placental abruption
0.43Limited support

Genetic evidence dominant · Open Targets 0.26

View evidence synthesis (5)
Glaucoma, Open-AngleModerately supported
0.52
agreement 0.40–0.64
Genetic100%

Open Targets aggregate 0.31 · 1 independent evidence family

GlaucomaModerately supported
0.52
agreement 0.38–0.66
Genetic98%Literature2%

Open Targets aggregate 0.31 · 2 independent evidence families

Joint DiseasesModerately supported
0.51
agreement 0.39–0.63
Genetic100%

Open Targets aggregate 0.31 · 1 independent evidence family

PoisoningModerately supported
0.51
agreement 0.39–0.63
Genetic100%

Open Targets aggregate 0.31 · 1 independent evidence family

Placental abruptionLimited support
0.43
agreement 0.31–0.55
Genetic100%

Open Targets aggregate 0.26 · 1 independent evidence family

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 per-type scores above show the calculation.

Show all associations
Glaucoma, Open-Angle0.31
Glaucoma0.31
Joint Diseases0.31
Poisoning0.31
Placental abruption0.26
Ovarian neoplasm0.23
Sleep Initiation and Maintenance Disorders0.22

Drug development

1 compounds recorded · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (1)
SEPHB4-HSAPhase 2 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (high-quality pocket) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (7)
SM · High-Quality PocketAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.16 cites

David ET · Pharmacological research · 2024

Recent

ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.

David ET · Pharmacological research · 2024

Europe PMC papers linked directly to this protein.