ERBB2

Oncogene
Receptor tyrosine-protein kinase erbB-2 UniProt accession P04626

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

Source: UniProt

Homodimer (PubMed:21454582). Heterodimer with EGFR, ERBB3 and ERBB4 (PubMed:10358079, PubMed:15093539, PubMed:16978839, PubMed:21190959). Part of a complex with EGFR and either PIK3C2A or PIK3C2B.

May interact with PIK3C2B when phosphorylated on Tyr-1196 (PubMed:10805725). Interacts with PLXNB1 (PubMed:15210733). Interacts (when phosphorylated on Tyr-1248) with MEMO1 (PubMed:15156151).

Interacts with MUC1; the interaction is enhanced by heregulin (HRG) (PubMed:12939402). Interacts (when phosphorylated on Tyr-1139) with GRB7 (via SH2 domain) (PubMed:12975581). Interacts (when phosphorylated on Tyr-1248) with ERBIN (PubMed:12444095).

Interacts with KPNB1, RANBP2, EEA1, CRM1 and CLTC (PubMed:16314522). Interacts with PTK6 (PubMed:18719096). Interacts with RPA194 and ACTB (PubMed:21555369).

Interacts with PRKCABP, SRC and MYOC (By similarity). Interacts (preferentially with the tyrosine phosphorylated form) with CPNE3; this interaction occurs at the cell membrane and is increased in a growth factor heregulin-dependent manner (PubMed:20010870). Interacts with HSP90AA1 and HSP90AB1 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (PubMed:26517842).

Interacts with SORL1; this interaction regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulates ERBB2-mediated signaling (PubMed:31138794). Interacts with SH3BGRL (PubMed:32381043). Interacts with ROR1 (PubMed:36949068)

Source: UniProt
Cell membrane — Single-pass type I membrane protein, Cell projection, ruffle membrane — Single-pass type I membrane protein Cell membrane — Single-pass type I membrane protein, Early endosome, Cytoplasm, perinuclear region, Nucleus Cytoplasm, Nucleus Cytoplasm, Nucleus
Source: UniProt

Expressed in a variety of tumor tissues including primary breast tumors and tumors from small bowel, esophagus, kidney and mouth

Source: UniProt
  • Glioma (GLM)

    Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes.

  • Ovarian cancer (OC)

    The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague.

    Consequently, most patients are diagnosed with advanced disease.

  • Lung cancer (LNCR)

    A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.

  • Gastric cancer (GASC)

    A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors.

    Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.

  • Unknown disease
  • Visceral neuropathy, familial, 2, autosomal recessive (VSCN2)

    An autosomal recessive disorder characterized by intestinal dysmotility due to aganglionosis (Hirschsprung disease), hypoganglionosis, and/or chronic intestinal pseudoobstruction. Patients also show peripheral axonal neuropathy, hypotonia, mild developmental delay, unilateral ptosis, and sensorineural hearing loss.

Source: UniProt

Click a pathway to open the interactive Reactome viewer.

Pathway list and interactive viewer: Reactome

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to ERBB2, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 3862

NCT ID Condition Brief Title Phase Status
NCT05546268 NSCLC, SCLC, High Grade Neuroendocrine Cancer, DLBCL, L-MYC and N-MYC Amplified Solid Tumors, NSCLC With High or Low L-MYC or N-MYC Expression, HR-positive, HER2-negative Breast Cancer, Prostate Cancer Study of Oral MRT-2359 in Selected Cancer Patients PHASE1, PHASE2 ACTIVE_NOT_RECRUITING
NCT05870813 Breast Cancer, HER2-negative Breast Cancer, Hormone Receptor Positive Breast Carcinoma CLEAR-B: Cancer Landscape - Early Adjuvant Retrospective Registry - Breast Cancer N/A UNKNOWN
NCT02015559 Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, Oral Complications, Progesterone Receptor-positive Breast Cancer, Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer Mucoadhesive Oral Wound Rinse in Preventing and Treating Stomatitis in Patients With ER- or PR-Positive Metastatic or Locally Recurrent Breast Cancer That Cannot be Removed by Surgery Receiving Everolimus PHASE2 COMPLETED
NCT03561740 Breast Cancer A Study of the Addition of Metronomic Capecitabine to Standard Adjuvant Therapy in High Risk HER2+ BC paTients PHASE3 RECRUITING
NCT05697146 Breast Cancer Ribociclib Real-world Treatment Patterns and Clinical Outcomes Among Women With HR+/HER2- Advanced or Metastatic Breast Cancer in France N/A ACTIVE_NOT_RECRUITING
NCT04603183 Breast Cancer Metastatic ABemaciclib, ET ± paclItaxel in aGgressive HR+/HER2- MBC trIaL PHASE2 COMPLETED
NCT04172259 Breast Cancer, Neoadjuvant Chemotherapy ACHP-THP vs EC-THP as Neoadjuvant Therapy for HER2-positive EBC PHASE2 ACTIVE_NOT_RECRUITING
NCT04597580 Breast Cancer Metastatic, Estrogen Receptor-positive Breast Cancer Personalised Disease Monitoring in Metastatic Breast Cancer N/A ACTIVE_NOT_RECRUITING
NCT06954961 Breast Cancer A Study to Evaluate D-0502 in Subjects With ER+ Her2- Locally Advanced or Metastatic Breast Cancer PHASE3 RECRUITING
NCT04513223 Gastric Cancer, Colorectal Cancer A Phase 1 Study of SHR-A1811 in Patients With Selected HER2 Expressing Tumors PHASE1 COMPLETED