Atlas of Genetics and Cytogenetics in Oncology and Haematology


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ERBB2 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian))

Identity

Other namesCD340
HER2
HER-2
HER-2/neu
MLN 19
NEU
NGL
TKR1
HGNC (Hugo) ERBB2
LocusID (NCBI) 2064
Location 17q12
Location_base_pair Starts at 37844337 and ends at 37884915 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Note Tyrosine-kinase receptor (RTK). The HER family of RTKs consists of four receptors: epidermal growth factor receptor (EGFR, also called HER-1 or erbB-1), HER-2 (also called erbB-2 or Neu), HER-3 and HER-4 (also called erbB-3 and erbB-4, respectively).

DNA/RNA

Description Sequence length: 40522; CDS: 3678. 30 exons, 26 coding exons; total exon length: 4816, max exon length: 969, min exon length: 48. Number of SNPs: 17.
Polymorphisms: 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 B1 (Ile-654/Ile-655); allele B2 (Ile-654/Val-655); allele B3 (Val-654/Val-655). This nucleotide polymorphism could be associated with development of gastric carcinoma and with breast cancer risk, particularly among younger women.
Transcription Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.
- mRNA transcript variant: this variant (1) represents the shorter transcript but encodes the longer isoform (a) (protein: erbB-2 isoform (a)).
- mRNA transcript variant: this variant (2) (protein: erbB-2 isoform (b)) contains additional exons at its 5' end and lacks an alternate 5' noncoding exon, compared to variant (1). These differences result in translation initiation at an in-frame, downstream AUG and an isoform (b) with a shorter N-terminus compared to isoform (a).
- mRNA transcript variant: herstatin HER2-ECD 1300 bp alternative erbB-2 transcript that retains intron 8. This alternative transcript specifies 340 residues identical to subdomains I and II from the extracellular domain of p185erbB-2 followed by a unique C-terminal sequence of 79 aa encoded by intron 8. The herstatin mRNA is expressed in normal human fetal kidney and liver, but is at reduced levels relative to p185erbB-2 mRNA in carcinoma cells that contain an amplified erbB-2 gene.
- mRNA transcript variant: an alternative transcript form of the human homologous gene erbB-2, containing an in-frame deletion encompassing exon 19, has been detected in human breast carcinomas.
- mRNA transcript variant: an alternative transcript form of the human homologous gene erbB-2, called HER2Δ16, has been detected in human breast carcinomas. This splicing variant, contains an in-frame deletion and encodes a receptor lacking exon 16, which immediately precedes the transmembrane domain containing two cysteines. The loss of these cysteine residues might induce a change in the conformation of HER2 receptor extracellular domain that promotes intermolecular disulfide bonding and, in turn, homodimers capable of transforming cells. Ectopic expression of HER2Δ16 promotes receptor dimerization, cell invasion, and trastuzumab resistant tumor cell lines. The potential metastatic and oncogenic properties of HER2Δ16 were mediated through direct coupling of HER2Δ16 to Src kinase.

Protein

 
  HER2 protein: schematic representation. Receptor tyrosin-kinases (RTKs) are cell surface allosteric enzymes consisting of: an extracellular ligand-binding domain (blue); a single transmembrane (TM) domain has an extensive homology to the epidermal grow factor receptor (brown); a cytoplasmic domain with catalityc activity (green).
Description erbB2 encodes a 185-kDa, 1255 amino acids, orphan receptor tyrosine kinase, and displays potent oncogenic activity when overexpressed. The proto-oncogene consists of three domains: a single transmembrane domain that separates an intracellular kinase domain from an extracellular ligand-binding domain. An aberrant form of HER2, missing the extracellular domain, so-called HER2p95, has been found in some breast cancers. HER2p95 is constitutively active because the external domain of these receptors acts as an inhibitor until they are bound by ligand. This isoform can cause resistance to trastuzumab, an antibody that works by binding to a domain in the external domain of HER2. HER2p95 fragments arise through at least 2 different mechanisms: proteolytic shedding of the extracellular domain of the full-length receptor and translation of the mRNA encoding HER2 from internal initiation codons. Shedding of the ectodomain of HER2 generates a 95- to 100-kDa HER2 p95 membrane-anchored fragment. Translation of the mRNA encoding HER2 can be initiated from the AUG codon that gives rise to the full-length protein of 1255 amino acids or, alternatively, from 2 internal initiation codons at positions 611 and 678, located upstream and downstream of the transmembrane domain, respectively.
Expression HER2 protein is expressed in several human organs and tissues: normal epithelium, endometrium and ovarian epithelium and at neuromuscular level; prostate, pancreas, lung, kidney, liver, heart, hematopoietic cells. HER2 expression is low in mononuclear cells from bone marrow, peripheral blood (PB) and mobilized PB. The higher expression has been found in cord blood-derived cells. Quiescent CD34+ progenitor cells from all blood sources and resting lymphocytes are HER2 negative, but the expression of this receptor is up-regulated during cell-cycle recruitment of progenitor cells. Similarly, it increases in mature, hematopoietic proliferating cells, underlying the correlation between HER2 and the proliferating status of hematopoietic cells.
Localisation Plasma membrane.
Function Activation and interactions
For the other member of the HER family, ligand binding induces receptor homo- or heterodimerization, which is essential for TKs activation and subsequent recruitment of target proteins, in turn initiating a complex signaling cascade that leads into distinct transcriptional programs. There are several HER-specific ligands. HER2, which apparently has no direct or specific ligand, plays a major coordinating role in the HER network because of its ability to enhance and stabilize the dimerization: each receptor with a specific ligand appears in fact to prefer HER-2 as its heterodimeric partner. HER-2-containing heterodimers are characterized by extremely high signaling potency because HER-2 dramatically reduces the rate of ligand dissociation, allowing strong and prolonged activation of downstream signaling pathways.

Signaling and cellular
The most important intracellular pathways activated by HER2 are those involving mitogen activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K). HER2 expression in cancer, besides its role in proliferation, enhances and prolongs survivals signals, associating up-regulation of this receptor to the malignant phenotype. At the same time, and depending on cellular status, the role of this receptor in controlling cell fate can also lead to differentiation and apoptosis.

Physiological
Role in development and differentiation:
- HER2 has several non-oncogenic roles in regulating growth, differentiation, apoptosis and/or remodeling in normal mammary glands. Dominant-negative forms of HER2 have significant defects in mammary development and lactation.
- HER2 has an important role in development and function of heart. Cre-Lox technology to mutate erbB-2 specifically in ventricular cardiomyocytes leads to a severe cardiomyopathy. This is inferred also by the adverse cardiac side effects observed in breast cancer patients treated with the monoclonal anti-HER2 Ab Trastuzumab.
- HER2 has a role in control of Schwann cell myelination and it has been demonstrated that HER2 signaling is also critical for oligodendrocyte differentiation in vivo.
- HER2 has a dual role in both muscle spindle maintenance and survival of myoblasts. Muscle-specific HER2 KO results in fact in viable mice with a progressive defect in proprioception due to loss of muscles spindles.

Homology Homolog to avian erythroblastic leukemia viral (v-erb-b) oncogen 2.

Mutations

Somatic The Cancer Genome Project and Collaborative Group sequenced the erbB-2 gene from 120 primary lung tumors and identified 4% that had mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations.
In non small cell lung cancer (adenocarcinoma) the following erbB-2 mutations were found: insertion/duplication of GCATACGTGATG at nucleotide 2322 of the erbB-2 gene, resulting in a 4-amino acid insertion (AYVM) at codon 774. Insertion of CTGTGGGCT at nucleotide 2335 of the erbB-2 gene, resulting in a 3-amino acid insertion (VGS) starting at codon 779; a 2-bp substitution in the erbB-2 gene, TT-CC at nucleotides 2263 and 2264, resulting in a leu755-to-pro (L755P) substitution.
In lung cancer a C44645G transition in the erbB-2 gene that caused a pro1170-to-ala substitution (P1170A).
In a glioblastoma a 2740G-A transition in the erbB-2 gene that caused a glu914-to-lys substitution (E914K).
In a gastric tumor a 2326G-A transition in the erbB-2 gene that caused a gly776-to-ser (G776S) substitution.
In an ovarian tumor, a 2570A-G transition in the erbB-2 gene that caused an asn857-to-ser (N857S) substitution.

Implicated in

Entity Hematological malignancies
Disease HER2 expression can be detected in blast cells from patients with hematological malignancies including acute lymphoblastic leukemia (ALL). It could be used as a potential target for the application of HER2-directed treatment strategies in ALL including vaccination approaches.
  
Entity Bladder cancer
Prognosis HER2 is overexpressed in 25% to 40% of several human tumors and associated with the malignancy of the disease, high mitotic index and a shorter survival time for the patient. Overexpression of ErbB-2 is also associated with transitional cell carcinoma of the bladder. HER2 overexpression occurs in muscle-invasive urothelial carcinomas of the bladder and is associated with worse survival; amplifications of erbB-2 gene are also frequently linked to alterations of the TOP2A gene in bladder cancer. Furthermore, HER2 overexpression and amplification in urothelial carcinoma of the bladder is found associated with MYC co-amplification.
  
Entity Breast carcinoma
Prognosis Normal tissues have a low content of HER2 membrane protein. Overexpression of HER2 is seen in 20% of breast and it confers worse biological behavior and clinical aggressiveness in breast cancer. Breast cancers can have up to 25 to 50 copies of the HER2 gene and up to a 40- to 100-fold increase in HER2 protein resulting in 2 million receptors expressed at the tumor cell surface. The differential HER2 expression between normal tissues and tumors helps to define HER2 as an ideal treatment target. Trastuzumab, the first treatment targeting HER2, is well tolerated in patients and has little toxicity because its effects are relatively specific for cancer cells overexpressing HER2. HER2 amplification is a relatively early event in human breast tumorigenesis, occurring in almost 50% of in situ carcinomas. HER2 status is maintained during progression to invasive disease and to nodal and distant metastasis. The fact that only 20% of invasive breast cancers are HER2 amplified suggests that many HER2-amplified in situ cancers never progress to the invasive stage. HER2 amplification defines a subtype of breast cancer with a unique signature of genes and this is maintained during progression. Some tumors lose HER2 expression following treatment with trastuzumab, presumably by selection of a HER2-negative clone not killed by treatment. Conversely, HER2 may become positive in some initially negative tumors over time, especially after endocrine therapy targeting ER. Indeed, estrogen receptor has been shown to downregulate HER2 and, conversely, HER2 is able to downregulate ER expression. Therefore, it is not surprising that blocking ER might upregulate HER2 and that blocking HER2 might upregulate ER. HER2-amplified breast cancers have unique biological and clinical characteristics. They have increased sensitivity to certain cytotoxic agents such as doxorubicin, relative resistance to hormonal agents, and propensity to metastasize to the brain and viscera. HER2-amplified tumors have an increased sensitivity to doxorubicin possibly due to coamplification of the topoisomerase-2 gene, which is near the HER2 locus on chromosome 17 and is the target of the drug. Half of HER2-positive breast cancers are ER positive but they generally have lower ER levels, and many have p53 alterations. These tumors have higher proliferation rates and more aneuploidy and are associated with poorer patient prognosis. The poor outcome is dramatically improved with appropriate chemotherapy combined with the HER2-targeting drug trastuzumab. Overexpression of the erbB-2 gene is associated with tumor aggressiveness, and with patient responsiveness to doxorubicin, cyclophosphamide, methotrexate, fluorouracil (CMF), and to paclitaxel, whereas tamoxifen was found to be ineffective and even detrimental in patients with HER2-positive tumors. In Paget's disease of breast, HER2 protein overexpression is caused by amplification of the erbB-2 gene. HER2 has a role in this disease of the breast, where the epidermis of the nipple is infiltrated by large neoplastic cells of glandular origin. It seems that binding of heregulin-alpha to the receptor complex on Paget cells results in chemotaxis of these breast cancer cells. The isoforms HER2p95 and HER2Δ16 are found in some breast cancers and the expression of these hyperactive forms of HER2 may contribute to the malignant progression.
  
Entity Cervical cancer
Prognosis HER2 may be activated in the early stage of pathogenesis of cervical carcinoma in geriatric patients and is frequently amplified in squamous cell carcinoma of the uterine cervix.
  
Entity Childhood medulloblastoma
Prognosis Overexpression of HER2 in medulloblastoma is associated with poor prognosis and metastasis and HER2-HER4 receptor heterodimerization is of particular biological significance in this disease.
  
Entity Colorectal cancer
Prognosis Overexpression of HER2 occurs in a significant number of colorectal cancers. It was significantly associated with poor survival and related to tumor progression in colorectal cancer.
  
Entity Oral squamous cell carcinoma
Prognosis E6/E7 proteins of HPV type 16 and HER2 cooperate to induce neoplastic transformation of primary normal oral epithelial cells. Overexpression of HER2 receptor is a frequent event in oral squamous cell carcinoma and is correlated with poor survival.
  
Entity Gastric cancer
Prognosis HER2 amplification/overexpression does not seem to play a role in the molecular pathogenesis of most gastrinomas. However, mild gene amplification occurs in a subset of them, and overexpression of this receptor is associated with aggressiveness of the disease. HER2 overexpression in patients with gastric cancer, and it has been solidly correlated to poor outcomes and a more aggressive disease. The overall HER2 positive rate is about 22%. HER2 overexpression rate in gastric cancer varies according to the site of the tumor. A higher overexpression rate (36%) was shown in gastroesophageal junction (GEJ) tumors in comparison to 21% in gastric tumors.
  
Entity Germ-cell testicular tumor
Prognosis A significant correlation was observed between HER2 overexpression and clinical outcome in germ-cell testicular tumors.
  
Entity Cholangiocarcinoma
Prognosis Data are still controversial about HER2 role in this carcinoma. Increased HER2 expression contributes to the development of cholangiocarcinogenesis into an advanced stage associated with tumor metastasis. In addition, overexpression of HER2 and COX-2 correlated directly with tumor differentiation. However, other studies report that HER2 expression is associated with more favorable clinical features, such as a polypoid macroscopic type and absence of other organ involvement, and has been reported that the proportion of HER2-positive cases in papillary adenocarcinoma is higher than in other histological types and is associated with an early disease stage. HER2 is preferentially expressed in well differentiated component, and it is also expressed in dedifferentiated components in progressive cases.
  
Entity Lung cancer
Prognosis HER2 is overexpressed in less than 20% of patients with non-small cell lung cancer (NSCLC) and studies have shown that overexpression of this receptor is correlated with a poor prognosis in both resected and advanced NSCLC. HER2 overexpression has an important function in the biology of NSCLC and may have a prognostic value for patients with metastatic NSCLC.
  
Entity Osteosarcoma
Prognosis Higher frequency of HER2 expression has been observed in samples from patients with metastatic disease at presentation and at the time of relapse, and it correlates with worse histologic response and decreased event-free survival. HER2 could be an effective target for the immunotherapy of osteosarcoma, especially the type with high metastatic potential.
  
Entity Ovarian cancer
Prognosis HER2 overexpression varies from 9% to 32% of all cases of ovarian cancer and its overexpression is more frequent in advanced stage of ovarian cancer. Overexpression of HER2 in ovarian cancer cells leads to faster cell growth, higher abilities in DNA repair and colony formation. A cross-talk between HER2 and estrogen receptor (ER) was identified in ovarian cancer cells. Estrogen has been proven to induce the phosphorylation of HER2, and initiate the HER2's signaling pathway.
  
Entity Pancreatic adenocarcinoma
Prognosis Overexpression of HER-2 in pancreatic adenocarcinoma seems to be a result of increased transcription rather than gene amplification. The coexpression of HER2 oncogene protein, epidermal growth factor receptor, and TGF-beta1 in pancreatic ductal adenocarcinoma is related to the histopathological grades and clinical stages of tumors. The blockade of HER2 inhibits the growth of pancreatic cancer cells in vitro. HER2 overexpression was reported to accumulate in well differentiated pancreas adenocarcinomas whereas it is only infrequently found in poorly differentiated or undifferentiated tumors, in vivo and in vitro analyses have suggested that targeting HER2 might increase treatment effects of conventional chemotherapies of pancreas adenocarcinoma. However, unlike in breast cancer, the application of antibodies directed against HER2 has not yet become an established therapy for pancreas adenocarcinoma.
  
Entity Prostate cancer
Prognosis HER2 plays pivotal roles in prostate cancer. Studies have shown that 25% of untreated primary tumors, 59% of localized tumors after neoadjuvant hormone therapy, and 78% of metastatic tumors overexpressed HER2. Several lines of evidence have implicated HER2 as a key mediator in the recurrence of prostate cancer to a hormone-refractory, androgen-independent tumor, which is the hallmark of prostate cancer progress. The driving force for prostate cancer recurrence is the reactivation of androgen receptor (AR), which is a type of nuclear receptors, activated by steroid hormone but ablated in hormonal therapy. Phosphorylation and reactivation of AR stimulate cancer cell growth and trigger tumor progression. It has been observed that overexpression of HER2 kinase enhanced AR function and hormone-independent growth in prostate tumor cells. HER2 activated AR through the MAPK pathway. Additionally, the HER2/HER3 dimmer increases AR protein stability and promotes the binding of AR to the promoter region of its target genes, resulting in AR activation in an androgen-depleted environment.
  
Entity Salivary gland tumor
Prognosis Several results demonstrated significant positive staining of HER2 in the salivary tumorigenic tissue but not in the surrounding non-tumorigenic tissue, pointing to a biological role in the tumorigenic process. HER2 amplification is present predominantly in tumors with high HER2 expression and seems to be the dominant mechanism for HER2 overexpression in this tumor type.
  

To be noted

Possible therapeutic strategies: 1) growth inhibitory antibodies (like Trastuzumab), used alone or in combination with standard chemotherapeutics; 2) tyrosin kinase inhibitors (TKI); 3) active immunotherapy, because HER2 oncoprotein is immunogenic in some breast carcinoma patients; 4) dimerization inhibitor antibodies, like Pertuzumab: its binding to HER2 inhibits the dimerization of HER2 with other HER receptors.

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004 rhabID5004

External links

Nomenclature
HGNC (Hugo)ERBB2   3430
Cards
AtlasERBB2ID162ch17q11
Entrez_Gene (NCBI)ERBB2  2064  v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2
GeneCards (Weizmann)ERBB2
Ensembl (Hinxton)ENSG00000141736 [Gene_View]  chr17:37844337-37884915 [Contig_View]  ERBB2 [Vega]
ICGC DataPortalENSG00000141736
cBioPortalERBB2
AceView (NCBI)ERBB2
Genatlas (Paris)ERBB2
WikiGenes2064
SOURCE (Princeton)NM_001005862 NM_001289936 NM_001289937 NM_001289938 NM_004448
Genomic and cartography
GoldenPath (UCSC)ERBB2  -  17q12   chr17:37844337-37884915 +  17q11.2-q12   [Description]    (hg19-Feb_2009)
EnsemblERBB2 - 17q11.2-q12 [CytoView]
Mapping of homologs : NCBIERBB2 [Mapview]
OMIM137800   164870   211980   613659   
Gene and transcription
Genbank (Entrez)AB025286 AF177761 AK131568 AK295195 AK296908
RefSeq transcript (Entrez)NM_001005862 NM_001289936 NM_001289937 NM_001289938 NM_004448
RefSeq genomic (Entrez)AC_000149 NC_000017 NC_018928 NG_007503 NT_010783 NW_001838435 NW_004929407
Consensus coding sequences : CCDS (NCBI)ERBB2
Cluster EST : UnigeneHs.446352 [ NCBI ]
CGAP (NCI)Hs.446352
Alternative Splicing : Fast-db (Paris)GSHG0012462
Alternative Splicing GalleryENSG00000141736
Gene ExpressionERBB2 [ NCBI-GEO ]     ERBB2 [ SEEK ]   ERBB2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP04626 (Uniprot)
NextProtP04626  [Medical]
With graphics : InterProP04626
Splice isoforms : SwissVarP04626 (Swissvar)
Catalytic activity : Enzyme2.7.10.1 [ Enzyme-Expasy ]   2.7.10.12.7.10.1 [ IntEnz-EBI ]   2.7.10.1 [ BRENDA ]   2.7.10.1 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)   
Domains : Interpro (EBI)EGF_rcpt_L [organisation]   Furin-like_Cys-rich_dom [organisation]   Furin_repeat [organisation]   Growth_fac_rcpt_N_dom [organisation]   Kinase-like_dom [organisation]   Prot_kinase_dom [organisation]   Protein_kinase_ATP_BS [organisation]   Ser-Thr/Tyr_kinase_cat_dom [organisation]   Tyr_kinase_AS [organisation]   Tyr_kinase_cat_dom [organisation]   Tyr_kinase_EGF/ERB/XmrK_rcpt [organisation]  
Related proteins : CluSTrP04626
Domain families : Pfam (Sanger)Furin-like (PF00757)    Pkinase_Tyr (PF07714)    Recep_L_domain (PF01030)   
Domain families : Pfam (NCBI)pfam00757    pfam07714    pfam01030   
Domain families : Smart (EMBL)FU (SM00261)  TyrKc (SM00219)  
DMDM Disease mutations2064
Blocks (Seattle)P04626
PDB (SRS)1MFG    1MFL    1MW4    1N8Z    1OVC    1QR1    1S78    2A91    2JWA    2KS1    2L4K    3BE1    3H3B    3MZW    3N85    3PP0    3RCD    4GFU    4HRL    4HRM    4HRN   
PDB (PDBSum)1MFG    1MFL    1MW4    1N8Z    1OVC    1QR1    1S78    2A91    2JWA    2KS1    2L4K    3BE1    3H3B    3MZW    3N85    3PP0    3RCD    4GFU    4HRL    4HRM    4HRN   
PDB (IMB)1MFG    1MFL    1MW4    1N8Z    1OVC    1QR1    1S78    2A91    2JWA    2KS1    2L4K    3BE1    3H3B    3MZW    3N85    3PP0    3RCD    4GFU    4HRL    4HRM    4HRN   
PDB (RSDB)1MFG    1MFL    1MW4    1N8Z    1OVC    1QR1    1S78    2A91    2JWA    2KS1    2L4K    3BE1    3H3B    3MZW    3N85    3PP0    3RCD    4GFU    4HRL    4HRM    4HRN   
Human Protein AtlasENSG00000141736 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP04626
HPRD01281
IPIIPI00300384   IPI00845478   IPI00941360   IPI01009701   IPI00384288   IPI00964086   
Protein Interaction databases
DIP (DOE-UCLA)P04626
IntAct (EBI)P04626
FunCoupENSG00000141736
BioGRIDERBB2
InParanoidP04626
Interologous Interaction database P04626
IntegromeDBERBB2
STRING (EMBL)ERBB2
Ontologies - Pathways
Ontology : AmiGORNA polymerase I core binding  positive regulation of protein phosphorylation  protein tyrosine kinase activity  protein tyrosine kinase activity  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  receptor signaling protein tyrosine kinase activity  transmembrane signaling receptor activity  epidermal growth factor-activated receptor activity  protein binding  ATP binding  nucleus  cytoplasm  plasma membrane  plasma membrane  plasma membrane  transcription, DNA-templated  protein phosphorylation  signal transduction  cell surface receptor signaling pathway  enzyme linked receptor protein signaling pathway  transmembrane receptor protein tyrosine kinase signaling pathway  transmembrane receptor protein tyrosine kinase signaling pathway  epidermal growth factor receptor signaling pathway  nervous system development  axon guidance  peripheral nervous system development  heart development  neuromuscular junction development  protein C-terminus binding  motor neuron axon guidance  cell proliferation  fibroblast growth factor receptor signaling pathway  endosome membrane  phosphatidylinositol 3-kinase signaling  integral component of membrane  basolateral plasma membrane  apical plasma membrane  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  growth factor binding  protein phosphatase binding  signal transduction by phosphorylation  signal transduction by phosphorylation  positive regulation of cell growth  mammary gland development  cytoplasmic vesicle  positive regulation of Rho GTPase activity  regulation of microtubule-based process  negative regulation of immature T cell proliferation in thymus  Fc-epsilon receptor signaling pathway  wound healing  myelination  identical protein binding  ErbB-3 class receptor binding  receptor complex  receptor complex  positive regulation of MAP kinase activity  innate immune response  positive regulation of translation  regulation of angiogenesis  positive regulation of cell adhesion  positive regulation of transcription from RNA polymerase I promoter  positive regulation of transcription from RNA polymerase III promoter  protein autophosphorylation  protein heterodimerization activity  protein heterodimerization activity  protein heterodimerization activity  protein dimerization activity  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  phosphatidylinositol-mediated signaling  perinuclear region of cytoplasm  positive regulation of epithelial cell proliferation  regulation of ERK1 and ERK2 cascade  
Ontology : EGO-EBIRNA polymerase I core binding  positive regulation of protein phosphorylation  protein tyrosine kinase activity  protein tyrosine kinase activity  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  receptor signaling protein tyrosine kinase activity  transmembrane signaling receptor activity  epidermal growth factor-activated receptor activity  protein binding  ATP binding  nucleus  cytoplasm  plasma membrane  plasma membrane  plasma membrane  transcription, DNA-templated  protein phosphorylation  signal transduction  cell surface receptor signaling pathway  enzyme linked receptor protein signaling pathway  transmembrane receptor protein tyrosine kinase signaling pathway  transmembrane receptor protein tyrosine kinase signaling pathway  epidermal growth factor receptor signaling pathway  nervous system development  axon guidance  peripheral nervous system development  heart development  neuromuscular junction development  protein C-terminus binding  motor neuron axon guidance  cell proliferation  fibroblast growth factor receptor signaling pathway  endosome membrane  phosphatidylinositol 3-kinase signaling  integral component of membrane  basolateral plasma membrane  apical plasma membrane  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  growth factor binding  protein phosphatase binding  signal transduction by phosphorylation  signal transduction by phosphorylation  positive regulation of cell growth  mammary gland development  cytoplasmic vesicle  positive regulation of Rho GTPase activity  regulation of microtubule-based process  negative regulation of immature T cell proliferation in thymus  Fc-epsilon receptor signaling pathway  wound healing  myelination  identical protein binding  ErbB-3 class receptor binding  receptor complex  receptor complex  positive regulation of MAP kinase activity  innate immune response  positive regulation of translation  regulation of angiogenesis  positive regulation of cell adhesion  positive regulation of transcription from RNA polymerase I promoter  positive regulation of transcription from RNA polymerase III promoter  protein autophosphorylation  protein heterodimerization activity  protein heterodimerization activity  protein heterodimerization activity  protein dimerization activity  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  phosphatidylinositol-mediated signaling  perinuclear region of cytoplasm  positive regulation of epithelial cell proliferation  regulation of ERK1 and ERK2 cascade  
Pathways : BIOCARTARole of ERBB2 in Signal Transduction and Oncology [Genes]    Trefoil Factors Initiate Mucosal Healing [Genes]   
Pathways : KEGGErbB signaling pathway    Calcium signaling pathway    HIF-1 signaling pathway    Focal adhesion    Adherens junction    Pathways in cancer    Proteoglycans in cancer    MicroRNAs in cancer    Pancreatic cancer    Endometrial cancer    Prostate cancer    Bladder cancer    Non-small cell lung cancer   
Protein Interaction DatabaseERBB2
Wikipedia pathwaysERBB2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ERBB2
snp3D : Map Gene to Disease2064
SNP (GeneSNP Utah)ERBB2
SNP : HGBaseERBB2
Genetic variants : HAPMAPERBB2
Exome VariantERBB2
1000_GenomesERBB2 
ICGC programENSG00000141736 
Cancer Gene: CensusERBB2 
Somatic Mutations in Cancer : COSMICERBB2 
CONAN: Copy Number AnalysisERBB2 
Mutations and Diseases : HGMDERBB2
Mutations and Diseases : intOGenERBB2
Genomic VariantsERBB2  ERBB2 [DGVbeta]
dbVarERBB2
ClinVarERBB2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM137800    164870    211980    613659   
MedgenERBB2
GENETestsERBB2
Disease Genetic AssociationERBB2
Huge Navigator ERBB2 [HugePedia]  ERBB2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneERBB2
Homology/Alignments : Family Browser (UCSC)ERBB2
Phylogenetic Trees/Animal Genes : TreeFamERBB2
Chemical/Protein Interactions : CTD2064
Chemical/Pharm GKB GenePA27844
Drug Sensitivity ERBB2
Clinical trialERBB2
Cancer Resource (Charite)ENSG00000141736
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=ERBB2
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineERBB2
iHOPERBB2
OncoSearchERBB2

Bibliography

Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL.
Science. 1987 Jan 9;235(4785):177-82.
PMID 3798106
 
EGF receptor and erbB-2 tyrosine kinase domains confer cell specificity for mitogenic signaling.
Di Fiore PP, Segatto O, Taylor WG, Aaronson SA, Pierce JH.
Science. 1990 Apr 6;248(4951):79-83.
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Written12-2004Patrizia Casalini, Marilena V Iorio
Molecular Targeting Unit, Experimental Oncology Dept., Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milano, Italy
Updated05-2011Luca Braccioli, Marilena V Iorio, Patrizia Casalini
Molecular Targeting Unit, Experimenatal Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo, 42, 20133 Milano, Italy

Citation

This paper should be referenced as such :
Braccioli, L ; Iorio, MV ; Casalini, P
ERBB2 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian))
Atlas Genet Cytogenet Oncol Haematol. 2011;15(11):956-964.
Free online version   Free pdf version   [Bibliographic record ]
History of this paper:
Braccioli, L ; Iorio, MV ; Casalini, P. ERBB2 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)). Atlas Genet Cytogenet Oncol Haematol. 2011;15(11):956-964.
http://documents.irevues.inist.fr/bitstream/handle/2042/46053/05-2011-ERBB2ID162ch17q11.pdf
URL : http://AtlasGeneticsOncology.org/Genes/ERBB2ID162ch17q11.html

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