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Symbol ERBB3 contributors: mct/np/shn/pgu - updated : 20-06-2018
HGNC name v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)
HGNC id 3431
  • a 19 aa signal peptide (2 kda)
  • an extracellular cysteine-rich ligand binding domain (heparin-binding site)
  • a single transmembrane (1TM) protein with extensive homology to the epidermal growth factor receptor, lacking the C terminal catalytic domain (kinase domain binds ATP, but is catalytically inactive and can serve as an activator of the EGFR kinase domain)
  • a furin-like cystein rich region
  • a tyrosine kinase catalytic domain
  • specific N-glycan in domain III playing an essential role in regulating receptor dimerization and transforming activity
  • a putative NLS with three clusters of basic amino acids (RRRHIVRKRTLRR (amino acids 645-657)) in the juxtamembrane region
  • a functional nuclear localization signal sequence (
  • mono polymer homomer , heteromer , dimer
    isoforms Precursor a 1323 aa mature peptide of 146.1 kda
    interspecies ortholog to ERBB3, Pan troglodytes
    ortholog to Erbb3, Rattus norvegicus
    ortholog to Erbb3, Mus musculus
    intraspecies homolog to viral (v-erb-b) oncogene 3
    homolog to IGF1R
  • epidermal growth factor receptor (EGFR) subfamily
  • CATEGORY enzyme , protooncogene , receptor membrane tyrosine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
  • apical and lateral plasma membrane
  • basic FUNCTION
  • acting as a receptor tyrosine kinase
  • acting as a neuregulin beta 1 receptor low affinity
  • acting as an heregulin receptor
  • acting as an epidermal growth factor receptor
  • activator of the phosphatidylinositol-3-kinase/Akt pathway, regulating cell survival and vesicle trafficking, essential for the generation of precursors of Schwann cells that normally accompany peripheral axons of motor
  • neurons
  • regulating PI3K/Akt pathway, a critical survival pathway in neurons and in most cell types, through heregulin
  • contributes to tumorigenic conversion and that their expression levels may be increased by signaling initiated by TGF-alpha (
  • ERBB3 signaling may contribute to metastatic progression of melanoma
  • ERBB3 function is an important aspect of ERBB2-mediated breast cancer, prompting the need for a more thorough understanding of ERBB3 expression and dysregulation in breast cancer
  • both ERBB3 and RNF41 are dysregulated post-transcriptionally in tumors
  • functions in part, by modulating the activity of ERBB3
  • plays an essential role in ERBB2-mediated transformation, tumor progression, and drug resistance
  • regulates the balance of differentiated breast epithelial cell types by regulating their growth and survival through autocrine- and paracrine-signaling mechanisms
  • is catalytically impaired but binds ligand, and its kinase domain allosterically activates its partners
  • high levels of ERBB2, ERBB3 may not only be a target of constitutive phosphorylation and driver for enhanced cancer cell survival
  • both ERBB2 and ERBB3 are essential for normal proliferation of skin keratinocytes, but in contrast to ERBB3, ERBB2 is essential for migration of human keratinocytes
  • heart development
  • peripheral nervous system development
    signaling signal transduction
  • transmembrane receptor protein tyrosine kinase signaling pathway
  • PI3K/Akt pathway
  • a component
  • dimerizing with the ligand less receptor ERBB2
  • heterodimerizing with ERBB2 for catalytic function
  • heterodimerizing with each of the other ERBB receptors
  • heterodimers of the ligand-binding–deficient ERBB2 (HER2) receptor and the kinase impaired ERBB3 (HER3) create a potent mitogenic signal
  • chromatin (
  • RNA
    small molecule nucleotide,
  • ATP
  • protein
  • neu differentiation factor, NDF (
  • Neuregulin-2, NRG2 (
  • p23/p198 (
  • proliferation-associated 2G4, 38kDa, PA2G4 (
  • angiotensin II receptor sub-type AT2 (
  • focal adhesion kinase, FAK (
  • Sos Ras exchange protein (
  • gp130 (
  • Epidermal growth factor, EGF (
  • E3 ubiquitin-protein ligase NRDP1, NRDP1 (
  • NTAK
  • CSPG5
  • associates with RNF41 which stimulates its ubiquitination and degradation by proteasomes
  • regulator of G-protein signaling 4, RGS4 (
  • Tetraspanin CD82 (
  • v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), ERBB2 (
  • sclerostin and the C-terminal portion of the receptor tyrosine-protein kinase ERBB3
  • Neuregulin-1, NRG1 (
  • NRG1 is the ligand for ERBB3 and 4, members of the epidermal growth factor family of receptors that are involved in the genesis and progression of a number of cancers
  • interaction of CADM1 with ERBB3 inhibits the NRG1-induced ERBB3/ERBB2 signaling in epithelial cells
  • APIP plays an essential role in ERBB3 signaling as a positive regulator for tumorigenesis
  • cell & other
    activated by NRG1, NRG2
    Other regulated expression by Sox10 during development of the neural crest
    phosphorylated ERBB3 is a particularly potent signaling molecule because it activates the PI3K/AKT pathway
    regulated by N-glycosylation that controls ErbB signaling by various mechanisms
    translation of nuclear variant of ErbB3 is regulated by Neuregulin-1 (
    corresponding disease(s) LCCS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in a subset of mammary tumors
    tumoral   amplification --over  
    amplification and/or overexpression reported in numerous cancers, including prostate, bladder, and breast tumors
    tumoral     --over  
    in pilocytic astrocytoma
    tumoral     --over  
    strongly associated with tumor progression and poor prognosis of patients with gastric cancer
    Variant & Polymorphism
    Candidate gene
    Therapy target
    therapeutic inhibitors of ERBB3 should be used in combination with HER2 inhibitors and PI3K pathway inhibitors in patients with ERBB2- and PI3K-dependent cancers
    small inhibitory RNA (siRNA) showing promise as a therapeutic approach to treatment of lung adenocarcinoma
    targeting ERBB3 activation and downstream genes may provide novel therapeutic interventions for malignant melanoma
    new prognostic factor and a target of treatment in gastric cancer
    ERBB3 ablation may be therapeutically effective in tumors where ErbB3 engages PI3K/Akt signaling