Protein / target
Receptor tyrosine-protein kinase erbB-2
Protein at a glance
Biological role
Transmembrane receptor protein tyrosine kinase
Primary biology
EGFR/ERBB growth-factor signalling
Strongest disease association
Stomach Neoplasms
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
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Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization
Subcellular location
Domains and Gene Ontology detail (66)Hide
Domains & features
Gene Ontology
- Capical plasma membrane
- Cbasal plasma membrane
- Cbasolateral plasma membrane
- Ccytosol
- Cearly endosome
- Cendosome membrane
- CERBB3:ERBB2 complex
- Cmembrane
- Cmyelin sheath
- Cneuromuscular junction
- Cnucleoplasm
- Cnucleus
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Receptor tyrosine kinase signalling
- ·Protein tyrosine kinase that is part of several cell surface receptor complexes, but tha…
- ·ERBB3:ERBB2 complex
- ·ErbB-3 class receptor binding
- ·receptor tyrosine kinase binding
Cell proliferation & survival
- ·cell population proliferation
- ·PIP3 activates AKT signaling
- ·PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
Growth-factor signalling
- ·cellular response to epidermal growth factor stimulus
- ·epidermal growth factor receptor signaling pathway
Cell migration
- ·Sema4D induced cell migration and growth-cone collapse
- ·ERBB2 Regulates Cell Motility
Oncogenic signalling
- ·Constitutive Signaling by Aberrant PI3K in Cancer
Transcriptional regulation
- ·DNA-templated transcription
- ·positive regulation of transcription by RNA polymerase I
- ·TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
View underlying pathways (25)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.
Approved medicines with mapped indications
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.
Broader indication categories (1)Hide
Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.
18 medicines meet Open Targets' target-level approved-medicine definition; the 5 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
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.
Receptor protein-tyrosine kinase erbB-2 binding agent
Indicated for Breast Neoplasms, Neoplasms
Receptor protein-tyrosine kinase erbB-2 inhibitor
Indicated for Breast Neoplasms, Colorectal Neoplasms, Neoplasm Metastasis, Neoplasms
Receptor protein-tyrosine kinase erbB-2 inhibitor
Indicated for Breast Neoplasms, Neoplasms
Receptor protein-tyrosine kinase erbB-2 inhibitor
Receptor protein-tyrosine kinase erbB-2 binding agent
Receptor protein-tyrosine kinase erbB-2 cross-linking agent
View all 10 targeting drugsHide
Receptor protein-tyrosine kinase erbB-2 inhibitor
Indicated for Breast Neoplasms, Neoplasms
Receptor protein-tyrosine kinase erbB-2 inhibitor
Receptor tyrosine-protein kinase erbB-2 binding agent
ErbB-2/ErbB-3 heterodimer inhibitor
Indicated for Carcinoma, Non-Small-Cell Lung, Pancreatic Neoplasms
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
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 ERBB2
Gene-level evidence surfaced through the gene ERBB2that 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.
View evidence synthesis (5)Hide
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.
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Drug development
48 compounds recorded · 18 approved · 30 in clinical development
View all recorded compounds (10)Hide
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 — Strong
Antibodies — Strong
Protein degraders — Emerging
Other modalities — Strong
View underlying tractability evidence (15)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 6 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.
- Trial status changed
Phase I Study of the Pan-ERBB Inhibitor Neratinib Given in Combination With Everolimus, Palbociclib, or Trametinib in Advanced Cancer Subjects With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation
- Trial status changed
A Prospective, Open, Single-center Clinical Study of Disitamab Vedotin Combined With BCG Therapy in HER2-expressing High-risk Non-muscle Invasive Bladder Cancer
- Trial status changed
PIKture-01: First-in-Human Study of the PI3KαH1047R Mutant-Selective Inhibitor OKI-219 as Monotherapy in Participants With Advanced Solid Tumors and as Part of Combination Therapy in Participants With Advanced Breast Cancer
- Regulatory approval
Approval: Poherdy (EMA)
- New publicationEfficacy of Zenocutuzumab in <i>NRG1</i> Fusion-Positive Cancer.
- New publicationTucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.
- New publicationMOUNTAINEER-03 phase III study design: first-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer.
- New publicationTrastuzumab Deruxtecan with Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study.
- New publicationTrastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial.
- Regulatory approval
Approval: Tukysa (EMA)
- Regulatory approval
Approval: Enhertu (EMA)
- Regulatory approval
Approval: Nerlynx (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.
Related family literature
Papers about “ErbB Receptors” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.
via ErbB Receptors
via ErbB Receptors
via ErbB Receptors
via ErbB Receptors
via ErbB Receptors
via ErbB Receptors
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.