This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.
Protein class

Cancer-related genes, CD markers, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins

Predicted location

Intracellular, Membrane (different isoforms)

Single cell type specificity

Cell type enhanced (Collecting duct cells, Proximal enterocytes, Distal enterocytes)

Immune cell specificity

Immune cell enhanced (gdT-cell)

Cell line specificity

Group enriched (OE19, SK-BR-3)


Homodimer (PubMed:21454582). Heterodimer with EGFR, ERBB3 and ERBB4 (PubMed:10358079, PubMed:15093539, PubMed:21190959, PubMed:16978839). 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).

Molecular function

Activator, Kinase, Receptor, Transferase, Tyrosine-protein kinase

More Types Infomation
  • Anti-HER2-MT-vc-MMAE ADC (ADC-249CL)

    • Target: HER2
    • Linker: MT-VC
    • Drug: (S,E)-N-(4-aminophenylsulfonyl)-2,5-dimethyl-4-((S)-N,3,3-trimethyl-2-((S)-3-methyl-2-(methylamino)-3-phenylbutanamido)butanamido)hex-2-enamide
  • Anti-HER2-MT-vc-MMAE ADC (ADC-248CL)

    • Target: HER2
    • Linker: MT-VC
    • Drug: (S,E)-N-(4-aminophenylsulfonyl)-2,5-dimethyl-4-((S)-N,3,3-trimethyl-2-((S)-3-methyl-2-(methylamino)-3-phenylbutanamido)butanamido)hex-2-enamide
  • Anti-HER2-vcPAB-MMAE ADC (ADC-148CL)

    • Target: HER2
    • Linker: VC-PAB (valine-citrulline-p-aminobenzoyloxycarbonyl)
    • Drug: MMAE (Monomethyl auristatin E)

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