Covered on Genetics Home Reference: neuroblastomalung cancerFrom NCBI Gene: Lung cancerNeoplasm of stomachGlioma susceptibility 1From UniProt: Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2. Ovarian cancer (OC): The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. [MIM:167000] Hereditary diffuse gastric cancer (HDGC): A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. [MIM:137215] Gastric cancer (GASC): A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. [MIM:613659] Glioma (GLM): Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. [MIM:137800] Lung cancer (LNCR): A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. [MIM:211980]

     From NCBI Gene: 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] From UniProt: Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.

The following transcription factors affect gene expression:

• PPAR-gamma1
• p53
• c-Myc
• p300

Tissue specificity:

Expressed in a variety of tumor tissues including primary breast tumors and tumors from small bowel, esophagus, kidney and mouth.

Enzyme Regulation:

Activated by dimerization. Not activated by EGF, TGF-alpha and amphiregulin. Interaction with PTK6 increases its intrinsic kinase activity.

Molecular Function:

• Rna Polymerase I Core Binding
• Protein Tyrosine Kinase Activity
• Transmembrane Receptor Protein Tyrosine Kinase Activity
• Signal Transducer, Downstream Of Receptor, With Protein Tyrosine Kinase Activity
• Transmembrane Signaling Receptor Activity
• Ras Guanyl-Nucleotide Exchange Factor Activity
• Atp Binding
• Protein C-Terminus Binding
• Protein Phosphatase Binding
• Identical Protein Binding
• Erbb-3 Class Receptor Binding
• Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Activity
• Protein Heterodimerization Activity
• Protein Dimerization Activity

Biological Processes:

• Mapk Cascade
• Positive Regulation Of Protein Phosphorylation
• 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
• Peripheral Nervous System Development
• Heart Development
• Neuromuscular Junction Development
• Motor Neuron Axon Guidance
• Cell Proliferation
• Phosphatidylinositol 3-Kinase Signaling
• Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Positive Regulation Of Cell Growth
• Regulation Of Microtubule-Based Process
• Negative Regulation Of Immature T Cell Proliferation In Thymus
• Erbb2 Signaling Pathway
• Wound Healing
• Myelination
• Positive Regulation Of Map Kinase Activity
• Positive Regulation Of Gtpase Activity
• 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
• Phosphatidylinositol-Mediated Signaling
• Oligodendrocyte Differentiation
• Positive Regulation Of Epithelial Cell Proliferation
• Regulation Of Erk1 And Erk2 Cascade
• Cellular Response To Growth Factor Stimulus
• Cellular Response To Epidermal Growth Factor Stimulus
• Positive Regulation Of Protein Targeting To Membrane
• Regulation Of Cell Motility

Drug Bank:

• Afatinib
• Pertuzumab
• Trastuzumab
• Lapatinib
• Ado-Trastuzumab Emtansine