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ERBB2

GeneName

ERBB2

Summary

ERBB2, also known as HER2 or neu, is a 138kDa transmembrane receptor that is primarily expressed in epithelial tissues, including breast, gastric, and ovarian tissues. It is a member of the ErbB family of receptor tyrosine kinases and is localised to various membrane compartments, including the apical and basal plasma membranes. ERBB2 plays a crucial role in cell signalling pathways, particularly those activated by growth factors such as epidermal growth factor (EGF). It functions as a coreceptor, often forming heterodimers with other ErbB receptors, such as ERBB3 and EGFR, to mediate downstream signalling that promotes cell proliferation, differentiation, and survival. The receptor is involved in several biological processes, including heart development, myelination, and neuron differentiation, and is also implicated in the regulation of angiogenesis and wound healing.

Importance

ERBB2 is relevant to: - Breast cancer research due to its overexpression in a significant subset of breast tumours, making it a target for therapies such as trastuzumab. - Understanding mechanisms of resistance to targeted therapies in cancer treatment, as alterations in ERBB2 signalling can affect treatment outcomes. - Investigating its role in other cancers, including gastric and ovarian cancers, where it may also contribute to tumour progression. - Exploring its functions in normal physiological processes, such as heart development and neuronal function, which can provide insights into developmental biology and regenerative medicine.

Top Products

For researchers investigating ERBB2, we highly recommend the top-selling recombinant antibody, Anti-ErbB2 / HER2 antibody [EP1045Y] (ab134182). This antibody has been validated in knockout models, ensuring its reliability for your experiments. It is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and immunoprecipitation (IP), making it a versatile choice for your research needs. With 85 citations, this antibody is well-regarded in the scientific community, reflecting its effectiveness and trustworthiness in ERBB2 studies. The Anti-ErbB2 / HER2 antibody ELISA Kit (ab134182), supported by 85 citations, is an excellent option for researchers looking to accurately measure ERBB2 levels in their samples.

Abcam Product Citation Summary

The data indicates that ERBB2 is being studied in various human cancer contexts, particularly in gastric cancer and breast cancer (MDA-MB-231 cells). The use of different applications such as Western blotting and immunohistochemistry with fluorescence suggests a focus on both protein expression and epitope mapping of anti-HER2 antibodies.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab134182
Human
WB
Gastric cancer cells
28292264
ab8054
Human
IHC-IF
Huh7 cells
23033967
ab8054
Human
WB
MDA-MB-231 cells
33540545

Function

The protein expressed by the ERBB2 gene is a protein tyrosine kinase involved in several cell surface receptor complexes, requiring a coreceptor for ligand binding. It is an essential component of a neuregulin-receptor complex, although neuregulins do not bind to it directly. GP30 is a potential ligand for this receptor. ERBB2 regulates the outgrowth and stabilization of peripheral microtubules (MTs) via the MEMO1-RHOA-DIAPH1 signaling pathway, which, upon activation, phosphorylates and inhibits GSK3B at the cell membrane. This prevents APC and CLASP2 phosphorylation, allowing their association with the cell membrane, facilitating MACF1 localization necessary for microtubule capture and stabilization. In the nucleus, ERBB2 is involved in transcriptional regulation, associating with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter to activate transcription. It is implicated in the transcriptional activation of CDKN1A, involving STAT3 and SRC, and participates in the transcription of rRNA genes by RNA Pol I, thereby enhancing protein synthesis and cell growth. This supplementary information is collated from multiple sources and compiled automatically.

Involvement in disease

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.

None

The gene represented in this entry is involved in disease pathogenesis.

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.

None

The gene represented in this entry is involved in disease pathogenesis.

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.

None

The gene represented in this entry is involved in disease pathogenesis.

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.

None

The protein represented in this entry is involved in disease pathogenesis.

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.

Visceral neuropathy, familial, 2, autosomal recessive

VSCN2

An autosomal recessive disorder characterized by intestinal dysmotility due to aganglionosis (Hirschsprung disease), hypoganglionosis, and/or chronic intestinal pseudoobstruction. Patients also show peripheral axonal neuropathy, hypotonia, mild developmental delay, unilateral ptosis, and sensorineural hearing loss.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Autophosphorylated. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (Probable). Ligand-binding increases phosphorylation on tyrosine residues (PubMed:27134172, PubMed:33497358). Signaling via SEMA4C promotes phosphorylation at Tyr-1248 (PubMed:17554007). Dephosphorylated by PTPN12 (PubMed:27134172).

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.

Tissue Specificity

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

Cellular localization

Alternative names

CD340, HER2, MLN19, NEU, NGL, ERBB2, Receptor tyrosine-protein kinase erbB-2, Metastatic lymph node gene 19 protein, Proto-oncogene Neu, Proto-oncogene c-ErbB-2, Tyrosine kinase-type cell surface receptor HER2, p185erbB2, MLN 19

swissprot:P04626 entrezGene:2064 omim:164870

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