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
  • Signaling by ERBB2
  • SHC1 events in ERBB2 signaling
  • PLCG1 events in ERBB2 signaling
  • PIP3 activates AKT signaling
  • GRB7 events in ERBB2 signaling
  • Downregulation of ERBB2:ERBB3 signaling
  • GRB2 events in ERBB2 signaling
  • PI3K events in ERBB2 signaling
  • Constitutive Signaling by Aberrant PI3K in Cancer
  • Sema4D induced cell migration and growth-cone collapse
  • RAF/MAP kinase cascade
  • ERBB2 Regulates Cell Motility
  • PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
  • ERBB2 Activates PTK6 Signaling
  • Downregulation of ERBB2 signaling
  • TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
  • Constitutive Signaling by Overexpressed ERBB2
  • Drug-mediated inhibition of ERBB2 signaling
  • Signaling by ERBB2 KD Mutants
  • Resistance of ERBB2 KD mutants to trastuzumab
  • Resistance of ERBB2 KD mutants to sapitinib
  • Resistance of ERBB2 KD mutants to tesevatinib
  • Resistance of ERBB2 KD mutants to neratinib
  • Resistance of ERBB2 KD mutants to osimertinib
  • Resistance of ERBB2 KD mutants to afatinib
  • Resistance of ERBB2 KD mutants to AEE788
  • Resistance of ERBB2 KD mutants to lapatinib
  • Signaling by ERBB2 ECD mutants
  • Signaling by ERBB2 TMD/JMD mutants
  • Drug resistance in ERBB2 TMD/JMD mutants
  • Developmental Lineage of Mammary Gland Myoepithelial Cells
  • Developmental Lineage of Mammary Stem Cells
Source: Reactome via UniProt

Mutations

Cancer Type Mutation Percentage
Central Nervous System Astrocytoma Grade Iv 1.04%
Lung Adenocarcinoma 2.36%
Lung Squamous Cell Carcinoma 0.95%
Oesophagus Adenocarcinoma 2.17%
Oesophagus Squamous Cell Carcinoma 0.70%
Pancreas Ductal Carcinoma 1.06%

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
NCT04158362 Cancer Metastatic Endocrine Therapy With Abemaciclib or Chemotherapy as Initial Metastatic Treatment in ER+/HER2- Breast Cancer PHASE3 ACTIVE_NOT_RECRUITING
NCT03185988 Targeted Therapy, HER2, Biliary Tract Cancer, Esophageal Squamous Cell Carcinoma, Colorectal Cancer Anti-HER2 Therapy in Patients of HER2 Positive Metastatic Carcinoma of Digestive System PHASE2 UNKNOWN
NCT07242118 Breast Cancer Female Conformal Ablative Radiotherapy in Older Women (CARMEN) With Breast Cancer Undergoing Non-Operative Management NA RECRUITING
NCT03304080 Breast Neoplasms, Breast Diseases Anastrozole, Palbociclib, Trastuzumab and Pertuzumab in HR-positive, HER2-positive Metastatic Breast PHASE1, PHASE2 ACTIVE_NOT_RECRUITING
NCT00785291 Estrogen Receptor Negative, Estrogen Receptor Positive, HER2/Neu Negative, HER2/Neu Positive, Progesterone Receptor Negative, Progesterone Receptor Positive, Recurrent Breast Carcinoma, Stage IIIC Breast Cancer AJCC v6, Stage IV Breast Cancer AJCC v6 and v7 Paclitaxel, Nab-paclitaxel, or Ixabepilone With or Without Bevacizumab in Treating Patients With Stage IIIC or Stage IV Breast Cancer PHASE3 COMPLETED
NCT05535413 Metastatic HER2 Negative Breast Carcinoma, Brain Metastases, Capecitabine, UDT1 UTD1 Combined With Capecitabine in Metastatic HER2-negative Breast Cancer Patients With Brain Metastases PHASE1, PHASE2 RECRUITING
NCT06693024 HER2-positive Breast Cancer Adjuvant Therapy With Neratinib in HER2 Positive Early Breast Cancer N/A RECRUITING
NCT07502027 Gastric Cancer (Diagnosis), Gastric Cancer (GC), Gastroesophageal Junction Adenocarcinoma A Clinical Study of Iparomlimab and Tuvonralimab Combined With SOX Following Heterogeneous Radiotherapy as First-line Treatment for Unresectable Locally Advanced or Metastatic HER2-negative Gastric or Gastroesophageal Junction Adenocarcinoma PHASE4 NOT_YET_RECRUITING
NCT05333874 Breast Cancer, Early-Onset CIPHER Study: Pilot Study to Study the Role of ctDNA in Triple Negative and HER2 Positive Early Stage EARLY_PHASE1 ACTIVE_NOT_RECRUITING
NCT06710990 Advanced Breast Cancer Investigation of Drug-drug Interaction of Ritonavir and Itraconazole on the Pharmacokinetics of SHR-A1811 in Subjects With HER2-expressing Advanced Breast Cancer PHASE1 RECRUITING