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Protein / target

Receptor tyrosine-protein kinase erbB-3

Encoded byERBB3P21860Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
24
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein tyrosine kinase activator

Primary biology

EGFR/ERBB growth-factor signalling

Strongest disease association

Visceral neuropathy, familial, 1, autosomal recessive

Via encoding gene ERBB3 · Genetic evidence · score 0.86

Therapeutic position

Established drug target

Small molecules and antibodies

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

Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.

View complete UniProt function annotation

Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908)

Subcellular location

Cell membraneSecreted
Domains and Gene Ontology detail (47)

Domains & features

Protein kinase

Gene Ontology

  • Capical plasma membrane
  • Cbasal plasma membrane
  • Cbasolateral plasma membrane
  • CERBB3:ERBB2 complex
  • Cextracellular space
  • Clateral plasma membrane
  • Cplasma membrane
  • Cpostsynaptic membrane
  • Creceptor complex
  • FATP binding
  • FErbB-3 class receptor binding
  • Fgrowth factor binding

1342 aa · 148 kDa · 5 isoforms

Biological roles

Reactome v97

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

Receptor tyrosine kinase signallingGO · ReactomeCell proliferation & survivalGO · ReactomeGrowth-factor signallingGOCell migrationReactomeOncogenic signallingReactomeApoptosis & cell deathGO
View supporting evidence

Receptor tyrosine kinase signalling

  • ·ERBB3:ERBB2 complex
  • ·ErbB-3 class receptor binding
  • ·cell surface receptor protein tyrosine kinase signaling pathway
  • ·ERBB2-ERBB3 signaling pathway

Cell proliferation & survival

  • ·regulation of cell population proliferation
  • ·PIP3 activates AKT signaling
  • ·PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

Growth-factor signalling

  • ·growth factor binding
  • ·epidermal growth factor receptor signaling pathway

Cell migration

  • ·ERBB2 Regulates Cell Motility

Oncogenic signalling

  • ·Constitutive Signaling by Aberrant PI3K in Cancer

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·negative regulation of neuron apoptotic process
  • ·neuron apoptotic process
View underlying pathways (15)

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

Interaction neighbourhood

STRING v12.0

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.

GRB2NRG2SHC1EGFERBB4EGFRNRG1ERBB2TGFAPIK3R1ERBB3

10 strongest partners — larger node and heavier line mean higher confidence

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.

Approved medicines with mapped indications

1 medicine · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Carcinoma, Non-Small-Cell Lung1 medicine
Pancreatic Neoplasms1 medicine

3 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

patritumab deruxtecan
Narrow target profileApprovedBinding agent

Receptor tyrosine-protein kinase erbB-3 binding agent

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

zenocutuzumab
ApprovedInhibitor

ErbB-2/ErbB-3 heterodimer inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Pancreatic Neoplasms

Acts on a complex — shared with ERBB2 · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

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 ERBB3

Gene-level evidence surfaced through the gene ERBB3that 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.

Neoplasms
0.88Well supported

Clinical evidence dominant · Open Targets 0.66

Visceral neuropathy, familial, 1, autosomal recessive
0.88Well supported

Genetic evidence dominant · Open Targets 0.73

Lethal congenital contracture syndrome 2
0.78Well supported

Genetic evidence dominant · Open Targets 0.69

Carcinoma, Non-Small-Cell Lung
0.78Well supported

Clinical evidence dominant · Open Targets 0.59

Urinary bladder carcinoma
0.71Moderately supported

Somatic mutation evidence dominant · Open Targets 0.60

View evidence synthesis (5)
NeoplasmsWell supported
0.88
agreement 0.800.97
Clinical35%Pathway23%Somatic mutation18%Genetic16%Literature9%

Open Targets aggregate 0.66 · 5 independent evidence families

Visceral neuropathy, familial, 1, autosomal recessiveWell supported
0.88
agreement 0.751.00
Genetic89%Animal model11%Genetic literaturedup

Open Targets aggregate 0.73 · 2 independent evidence families · 1 not counted as duplicate

Lethal congenital contracture syndrome 2Well supported
0.78
agreement 0.640.92
Genetic99%Literature1%Genetic literaturedup

Open Targets aggregate 0.69 · 2 independent evidence families · 1 not counted as duplicate

Carcinoma, Non-Small-Cell LungWell supported
0.78
agreement 0.660.90
Clinical59%Somatic mutation28%Literature13%

Open Targets aggregate 0.59 · 3 independent evidence families

Urinary bladder carcinomaModerately supported
0.71
agreement 0.600.82
Somatic mutation49%Pathway31%Literature11%Clinical9%

Open Targets aggregate 0.60 · 4 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Visceral neuropathy, familial, 1, autosomal recessive0.73
Lethal congenital contracture syndrome 20.69
Neoplasms0.66
Urinary Bladder Neoplasms0.60
Urinary bladder carcinoma0.60
Lethal congenital contracture syndrome type 20.60
Carcinoma, Non-Small-Cell Lung0.59
Medullary thyroid gland carcinoma0.54
Colorectal adenocarcinoma0.53

Drug development

17 compounds recorded · 3 approved · 14 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
PATRITUMAB DERUXTECANApproval
AV-203Phase 1
DULIGOTUZUMABPhase 2
VANDETANIBApproval
ZENOCUTUZUMABApproval
POZIOTINIBPhase 3
KBP5209Phase 1
SERIBANTUMABPhase 2
MM-111Phase 2
LUMRETUZUMABPhase 1 2

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesStrong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degradersEmerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (14)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

24

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (20)

WITHDRAWN · via patritumab deruxtecan · NCT05620914

ClinicalTrials.gov via the drug-target graph.

What's happening now

4

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. New publication2025-05-30
    Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial.

    Nature medicine · 2025 · 16 citations · Europe PMC · via patritumab deruxtecan

  2. New publication2025-02-01
    Efficacy of Zenocutuzumab in <i>NRG1</i> Fusion-Positive Cancer.

    The New England journal of medicine · 2025 · 78 citations · Europe PMC · via zenocutuzumab

  3. New publication2023-10-06
    Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 102 citations · Europe PMC · via patritumab deruxtecan

  4. New publication2023-09-10
    HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 188 citations · Europe PMC · via patritumab deruxtecan

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.

Related family literature

51

Papers about “ErbB Receptors” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

NSCLC: from tumorigenesis, immune checkpoint misuse to current and future targeted therapy.

Raskova Kafkova L · Frontiers in immunology · 2024

via ErbB Receptors

Amivantamab plus Lazertinib in Previously Untreated <i>EGFR</i>-Mutated Advanced NSCLC.

Cho BC · The New England journal of medicine · 2024

via ErbB Receptors

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.