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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. [provided by RefSeq, Jul 2008]
ERBB2, commonly referred to as HER2, is amplified and/or overexpressed in 20-30% of invasive breast carcinomas. HER2-positive breast cancer is treated in a separate manner from other subtypes of breast cancer and commonly presents as more aggressive disease. Metastatic HER2-positive breast cancer is now commonly treated with HER2-targeted therapy. Apart from being amplified/overexpressed, ERBB2 activating mutations have been shown to have clinical importance in HER2-negative breast cancer. These mutations have shown sensitivity to the tyrosine kinase inhibitor neratinib, and highlight the importance of clinical sequencing efforts in treating breast cancer.
ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2) is a Protein Coding gene. Diseases associated with ERBB2 include Glioma Susceptibility 1 and Gastric Cancer. Among its related pathways are Association Between Physico-Chemical Features and Toxicity Associated Pathways and RET signaling. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is EGFR.
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB family. Four members of the ErbB family have been identified; EGFR (ErbB1, HER1), ErbB2 (HER2), ErbB3 (HER3) and ErbB4 (HER4). EGFR signaling drives many cellular responses.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0001042 | RNA polymerase I core binding | IDA | 21555369 |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IGI,TAS | -- |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IDA | 7514177 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IEA,IDA | 16314522 |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005768 | endosome | IEA | -- |
GO:0005769 | early endosome | IEA | -- |
GO:0005829 | cytosol | IDA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Signaling by ERBB2 | ||
3 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
4 | GAB1 signalosome |
.89
|
|
5 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0001934 | positive regulation of protein phosphorylation | ISS | -- |
GO:0006357 | regulation of transcription by RNA polymerase II | TAS | -- |
GO:0006468 | protein phosphorylation | TAS | 10851066 |
GO:0007165 | signal transduction | IDA | 10572067 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Lapatinib | Approved, Investigational | Pharma | Target, antagonist, Inhibition, inhibitor, Biomarker | EGFR/HER2 inhibitor,potent,selective and reversible, HER2 and EGFR kinase inhibitor, HER2 Inhibitors, Kinase Inhibitors, Epidermal growth factor receptor (EGFR) inhibitors | 314 | |
Trastuzumab | Approved, Investigational | Pharma | Target, antibody, antagonist, Biomarker, inhibitor | HER2 antagonist, HER2 Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors | 1006 | |
Pertuzumab | Approved | Pharma | Target, antibody, Biomarker, inhibitor | HER2 Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors, HER2 Dimerization Inhibitor | 194 | |
trastuzumab emtansine | Approved, Investigational | Pharma | Target, antibody | 0 | ||
afatinib | Approved | Pharma | Target, inhibitor | Kinase Inhibitors, Epidermal growth factor receptor (EGFR) inhibitors | 187 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
CP 724714 |
|
383432-38-0 |
|
|
Compound | Action | Cas Number |
---|---|---|
AG 490 | EGFR-kinase inhibitor. Also JAK2, JAK3 inhibitor | 133550-30-8 |
CGP 52411 | EGFR inhibitor. Also inhibits Abeta42 fibril formation | 145915-58-8 |
CP 724714 | Potent and selective ErbB2 inhibitor | 383432-38-0 |
Genistein | EGFR kinase inhibitor. Also estrogen and PPARgamma ligand | 446-72-0 |
Compound | Action | Cas Number |
---|---|---|
AC480 (BMS-599626) | HER1/2 inhibitor,selective and efficacious | 714971-09-2 |
AEE788 (NVP-AEE788) | EGFR/HER-2/VEGFR inhibitor | 497839-62-0 |
Afatinib (BIBW2992) | Irreversible EGFR/HER2 inhibitor | 439081-18-2 |
Afatinib dimaleate | 850140-73-7 | |
AG-1478 | EGFR inhibitor,potent and selective | 153436-53-4 |
ARRY-380 | Tyrosine kinase HER2 and p95-HER2 inhibitor | 937265-83-3 |