Protein / target
Receptor tyrosine-protein kinase erbB-2
Protein at a glance
Biological role
Transmembrane receptor protein tyrosine kinase activity
Primary system
Nervous system
Strongest disease association
gastric cancer
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
18 approved · 30 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
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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Kinase signalling
- ·Protein tyrosine kinase that is part of several cell surface receptor complexes, but tha…
- ·protein tyrosine kinase activity
- ·transmembrane receptor protein tyrosine kinase activity
- ·peptidyl-tyrosine phosphorylation
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
Synaptic signalling
- ·postsynaptic membrane
- ·presynaptic membrane
- ·neurotransmitter receptor localization to postsynaptic specialization membrane
Immune signalling
- ·Protein tyrosine kinase that is part of several cell surface receptor complexes, but tha…
Cell adhesion
- ·positive regulation of cell adhesion
Apoptosis & cell death
- ·negative regulation of apoptotic process
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.
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.
Receptor protein-tyrosine kinase erbB-2 binding agent
Appears in clinical studies involving breast cancer, HER2 positive breast carcinoma, breast neoplasm, neoplasm
Receptor protein-tyrosine kinase erbB-2 inhibitor
Appears in clinical studies involving HER2 positive breast carcinoma, metastasis, breast neoplasm, breast cancer
Receptor protein-tyrosine kinase erbB-2 inhibitor
Appears in clinical studies involving breast cancer, breast carcinoma, cancer, breast neoplasm
Receptor protein-tyrosine kinase erbB-2 inhibitor
Appears in clinical studies involving breast cancer, non-small cell lung carcinoma, lung adenocarcinoma, non-small cell lung carcinoma
Receptor protein-tyrosine kinase erbB-2 binding agent
Appears in clinical studies involving neoplasm, breast cancer, endometrial carcinoma, endometrial cancer
Receptor protein-tyrosine kinase erbB-2 cross-linking agent
Appears in clinical studies involving breast cancer, rectal cancer, gastric cancer
Receptor protein-tyrosine kinase erbB-2 inhibitor
Appears in clinical studies involving HER2 positive breast carcinoma, breast cancer, neoplasm, gastroesophageal junction adenocarcinoma
Receptor protein-tyrosine kinase erbB-2 inhibitor
Appears in clinical studies involving neoplasm, breast cancer, non-small cell lung carcinoma, glioblastoma
Receptor tyrosine-protein kinase erbB-2 binding agent
Appears in clinical studies involving breast cancer, urothelial carcinoma, gastric adenocarcinoma, gastroesophageal junction adenocarcinoma
ErbB-2/ErbB-3 heterodimer inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, pancreatic neoplasm, breast cancer, malignant pancreatic 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 1,910 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 · 48 total
breast cancer · gastric adenocarcinoma · gastric carcinoma
breast cancer · breast neoplasm · breast carcinoma
lymphoma · non-small cell lung carcinoma · breast cancer
breast cancer · breast carcinoma · cancer
prostate cancer · neoplasm
non-small cell lung carcinoma · non-small cell lung carcinoma · non-small cell lung carcinoma
biliary tract neoplasm · neoplasm · cancer
breast cancer · breast carcinoma · breast neoplasm
HER2 positive breast carcinoma · metastasis · breast 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 9 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- 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
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 publicationEffective extracellular payload release and immunomodulatory interactions govern the therapeutic effect of trastuzumab deruxtecan (T-DXd).
- 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.
- New publicationFDA approval summary: fam-trastuzumab deruxtecan-nxki for unresectable or metastatic non-small cell lung cancer with activating HER2 mutations.
- New publicationTrastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial.
- New publicationTrastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial.
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.