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FLASH GENE
Symbol ERBB2 contributors: mct - updated : 11-06-2011
HGNC name v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)
HGNC id 3430
Location 17q12      Physical location : 37.844.392 - 37.884.914
Synonym name
  • herstatin
  • epidermal growth factor (EGF) receptor
  • c-erb B2/neu protein
  • tyrosine kinase-type cell surface receptor HER2
  • metastatic lymph node gene 19 protein
  • proto-oncogene c-ErbB-2
  • CD340 antigen
  • proto-oncogene Neu
  • Synonym symbol(s) HER2, NGL, NEU, TKR1, HER-2, c-erb B2, ERBB-2, CD340
    EC.number 2.7.10.1
    DNA
    TYPE functioning gene
    STRUCTURE 40.52 kb     30 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map see NF1 NF1
    Physical map
    FLJ43826 17q21.2 FLJ43826 protein PLXDC1 17q21.1 plexin domain containing 1 LOC390790 17 similar to Cg7197-prov protein CACNB1 17q21 calcium channel, voltage-dependent, beta 1 subunit RPL19 17q11 ribosomal protein L19 24b2/STAC2 17q21.2 24b2/STAC2 protein LOC388383 17 similar to upstream binding protein 1 MGC15482 17q21.2 F-box protein FBL2 PPARBP 17q12-q21.1 PPAR binding protein CRK7 17q21.2 CDC2-related protein kinase 7 NEUROD2 17p13.1 neurogenic differentiation 2 PPP1R1B 17q21.2 protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein, DARPP-32) STARD3 17q21.1 START domain containing 3 TCAP 17q12-q21.1 titin-cap (telethonin) PNMT 17q21.1 phenylethanolamine N-methyltransferase CAB2 17q21.2 CAB2 protein ERBB2 17q11.2-q12 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) MGC14832 GRB7 17q11.2-q12 growth factor receptor-bound protein 7 ZNFN1A3 17q11.2 zinc finger protein, subfamily 1A, 3 (Aiolos) ZPBP2 17q21.2 zona pellucida binding protein 2 GSDML 17q21.2 gasdermin-like ORMDL3 17q12 ORM1-like 3 (S. cerevisiae) LOC342669 17q21.2 similar to leucine-rich repeat domain-containing protein GSDM 17q21.2 gasdermin PSMD3 17q21.1 proteasome (prosome, macropain) 26S subunit, non-ATPase, 3 CSF3 17q11.2-q12 colony stimulating factor 3 (granulocyte) TRAP100 THRA 17q11.2 thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian) NR1D1 17q11.2 nuclear receptor subfamily 1, group D, member 1 MLN51 17q12-q21.3 nuclear receptor subfamily 1, group D, member 1 LOC339287 17q21.2 hypothetical protein LOC339287 Link-GEFII 17q21.2 Link guanine nucleotide exchange factor II WIRE 17q21.2 WIRE protein CDC6 17q21.3 CDC6 cell division cycle 6 homolog (S. cerevisiae) RARA 17q12 retinoic acid receptor, alpha GJC1 17q21.1 gap junction protein, chi 1, 31.9kDa (connexin 31.9) LOC390791 17 similar to peptidyl-Pro cis trans isomerase
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    27 - 4624 137.91 1255 - 1985 2999974
  • a 27 exons variant
  • lacking exons 1, 2, 3 and 4
  • encoding for the longest product
  • 30 splicing 4816 134.72 1225 secreted fetal liver, kidney 1999 10485918
  • a 30 exon variant
  • lacking exon 5
  • retaining intron 8 subdomain I, II
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Endocrinepancreas   highly
    Reproductivemale systemprostate  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text kidney, liver and in the developing nervous system
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an extracellular domain with four subdomains I-IV
  • a single transmembrane (TM) protein with extensive homology to the epidermal growth factor receptor
  • a cytoplasmic catalytic domain
  • a Blocking ErbB2 Degradation or BED domain, that is the factor restricting the ligand-induced degradation of ERBB2
  • 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
  • conjugated GlycoP , PhosphoP
    mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Erbb2 (88.13 pc)
    homolog to murine Erbb2 (87.73 pc)
    homolog to zebrafish erbb2 (59.08 pc)
    intraspecies homolog to avian erythroblastic leukemia viral (v-erb-b) oncogene 2
    Homologene
    FAMILY
  • epidermal growth factor (EGF) receptor family
  • class I tyrosine protein kinase family
  • erythroblastosis oncogene B (ERBB)-like oncogene family
  • CATEGORY enzyme , protooncogene , signaling , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,nucleus,nucleolus
    text
  • type I membrane protein
  • detected in the nucleus
  • basic FUNCTION
  • acting as a coreceptor for multiple stroma-derived growth factors i.e EGF-like ligands and neuregulins, and as a coreceptor for GPCR signaling in the heart
  • involved in androgen receptor transactivation of inducing prostate-specific antigen (PSA) through the MAP kinase pathway
  • playing a critical role for normal cardiac function and prevention of dilated cardiomyopathy (together with ERBB4 and neuregulin)
  • modulating epidemal growth factor signaling pathways resulting in growth arrest
  • required for the distal morphogenesis of the mammary gland
  • playing a pivotal role for integrating signaling networks involving multiple classes of extracellular signals
  • requires ITGA5 for anoikis resistance via SRC regulation of receptor activity in human mammary epithelial cells
  • ERBB2 regulation having important implications in cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor
  • controls microtubule capture by recruiting MACF1 to the plasma membrane of migrating cells
  • may be dependent on ERBB3 to drive growth and survival of breast cancer cells
  • novel function of nuclear ERBB2 in enhancing rRNA gene transcription by RNA polymerase-I (RNA Pol I)
  • nuclear ERBB2 functions as a regulator of rRNA synthesis and cellular translation, which may contribute to tumor development and progression
  • CELLULAR PROCESS cell cycle, division
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    growth factors pathway
    a component
  • heterodimerizing with other ERBBs, secreted by ligand-binding members of EGFR family
  • heterodimer with ERBB3, ERBB4
  • complexes with cofilin, ERBB2 and PLCG1
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • AP2 for regulation by oestrogen
  • WITH GRB7 (to regulating cell proliferation)
  • PRKCABP
  • PLXNB1
  • interaction with LNX1, an E3 ubiquitin ligase that can target interacting proteins for degradation through ubiquitination
  • DOCK7 functions as an intracellular substrate for ERBB2 to promote Schwann cell migration to promote Schwann cell migration
  • nuclear ERBB2 physically associates with beta-actin and RNA Pol I, coinciding with active RNA Pol I transcription sites in nucleoli
  • NRG/ERBB signaling maintains high efficacy of synaptic transmission by stabilizing the postsynaptic apparatus via phosphorylation of DTNA
  • NRG1 inhibited the GDNF-induced neuronal differentiation and GDNF negatively regulated NRG1-signaling by down-regulating the expression of its receptor, ERBB2 (PMID;
  • cell & other
    REGULATION
    activated by NRGs isoforms
    induced by PIN1 (PIN1 amplifies EGF signaling in breast cancer cells through its interaction with MAP2K1 and then enhances ERBB2 expression)
    inhibited by its alternative isoform herstatin that disrupts ERBB2 dimers
    ETV4
    Other regulated by N-glycosylation that controls ErbB signaling by various mechanisms
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in primary gastric cancer and prostate carcinoma with metastasis and poor prognosis, pancreas, colon and ovary carcinoma, cholangiocarcinoma
    tumoral       gain of function
    in primary breast and uterus endometrial cancer and in low grade osteosarcoma with increased survival
    tumoral somatic mutation      
    in dilated cardiomyopathy
    tumoral     --over  
    in neuro/glioblastoma and in non-small cell lung cancer
    tumoral   amplification    
    in many types of cancer, including breast cancer
    tumoral somatic mutation      
    in the lung squamous cell carcinoma (kinase domain mutation )
    tumoral     --over  
    in breast cancer cells with poor prognostic (with enhanced tumorigenicity, propensity to metastasize and resistance to endocrine therapy)
    tumoral   amplification    
    loss of beclin 1 and ERBB2 amplification (both on 17q21) in breast cancers
    tumoral     --over  
    patients breast cancer with higher CCNA2 and ERBB2 expressions had significantly shorter disease-free survival periods
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker overexpression in breast cancer cells are known to be poor prognostic markers and are strong predictors of benefit from treatment with ERBB2-targeting agents
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    selected RNA aptamer is a potential cancer imaging agent by targeting malignant cells of breast cancer overexpressing the ERBB2 receptor
    cancerreproductivebreast
    blockade of ERBB2:TGFB crosstalk may significantly enhance the efficiency of conventional therapies in breast cancer patients with ERBB2 overexpression
    cancerreproductivebreast
    anti-ERBB2 human compact antibody-RNase (Erb-hcAb-RNase) could be a promising candidate for the immunotherapy of ERBB2-positive tumours
    cancerreproductivebreast
    therapeutic inhibitors of ERBB3 should be used in combination with HER2 inhibitors and PI3K pathway inhibitors in patients with ERBB2- and PI3K-dependent cancers
    ANIMAL & CELL MODELS