ERBB3 (Erb-B2 Receptor Tyrosine Kinase 3): Gene, Function, and Clinical Significance
A comprehensive overview of ERBB3, a key member of the EGFR family, its role in development, cancer, and therapeutic targeting.
Gene Information Card
| Symbol | ERBB3 |
|---|---|
| Full Name | Erb-B2 Receptor Tyrosine Kinase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.2 |
| NCBI Gene ID | 2065 ncbi.nlm.nih.gov/gene/2065 |
| Ensembl ID | ENSG00000065361 |
| UniProt ID | P21860 |
| OMIM ID | 190151 |
| HGNC ID | 3431 |
| Aliases | HER3, LCCS2, MDA-BF1, c-erbB3, ErbB3, erbB3-S, p180-ErbB3, p45-sErbB3, p85-sErbB3 |
Description
ERBB3 (Erb-B2 Receptor Tyrosine Kinase 3), also known as HER3, is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. Unlike other family members, ERBB3 has impaired kinase activity and relies on heterodimerization with other ErbB receptors, particularly ERBB2 (HER2), to transduce signals. ERBB3 is involved in cell proliferation, differentiation, and survival, and is frequently overexpressed or mutated in various cancers, making it a significant therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (breast, lung, ovarian, gastric, colorectal) | Overexpression or mutation leads to enhanced PI3K/AKT signaling via heterodimerization with ERBB2, promoting tumor growth and resistance to therapy. | COSMIC, ClinVar, multiple studies |
| Lethal congenital contracture syndrome 2 (LCCS2) | Homozygous mutations in ERBB3 cause severe developmental defects, including joint contractures and skeletal abnormalities. | OMIM, PubMed |
| Non-small cell lung cancer (NSCLC) | ERBB3 mutations (e.g., V855A) can activate signaling pathways, contributing to oncogenesis. | COSMIC, ClinVar |
| Colorectal cancer | ERBB3 mutations (e.g., G284R, D297Y) are found in a subset of tumors, potentially driving tumorigenesis. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.3 | Medium |
| Esophagus | 10.8 | Medium |
| Gastrointestinal tract | 8.5 | Low |
| Breast | 7.2 | Low |
| Lung | 6.1 | Low |
| Brain | 4.5 | Low |
| Liver | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression; ERBB2/ERBB3 signaling active |
| A549 (lung cancer) | 8.7 | Moderate expression; associated with proliferation |
| HCT116 (colorectal cancer) | 6.4 | Low expression; mutations may drive signaling |
| HEK293 (embryonic kidney) | 3.1 | Low endogenous expression; used for transfection studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| V855A | Missense | ~1% in NSCLC | Kinase domain mutation; may increase signaling activity |
| G284R | Missense | ~2% in colorectal cancer | Extracellular domain mutation; affects ligand binding |
| D297Y | Missense | ~1% in colorectal cancer | Extracellular domain mutation; alters receptor conformation |
| E1261K | Missense | Rare | Kinase domain mutation; potential gain-of-function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ERBB3 are rare but can impair signaling, leading to developmental defects (e.g., LCCS2).
Gain of Function (GOF)
Gain-of-function mutations, such as V855A, enhance kinase-independent signaling via heterodimerization, promoting oncogenesis.
Dominant Negative (DN)
Dominant-negative mutations may interfere with heterodimerization, reducing downstream signaling, but are not well-documented.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • Protein tyrosine kinase activity |
| • Receptor signaling protein tyrosine kinase activity | • Transmembrane receptor protein tyrosine kinase signaling pathway |
| • Cell surface receptor signaling pathway | • Positive regulation of cell proliferation |
| • Positive regulation of cell migration | • Positive regulation of phosphatidylinositol 3-kinase activity |
Pathways
• ErbB signaling pathway
• PI3K-Akt signaling pathway
• MAPK signaling pathway
• EGFR tyrosine kinase inhibitor resistance
• Signaling by Receptor Tyrosine Kinases
Protein Summary
ERBB3 is a 180 kDa transmembrane glycoprotein with an extracellular ligand-binding domain and an intracellular tyrosine kinase domain that is catalytically impaired. It binds neuregulins (NRG1, NRG2) but cannot homodimerize; instead, it forms heterodimers with ERBB2, leading to potent activation of the PI3K/AKT and MAPK pathways. ERBB3 is crucial for normal development of the nervous system, heart, and other tissues, and its dysregulation is implicated in multiple cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ERBB3 Knockout HEK293 Cell Line | EDJ-KQ654 | Human | 2065 | Details Get a Quote |
| ERBB3 Knockout A-549 Cell Line | EDJ-KQ19159 | Human | 2065 | Details Get a Quote |
| ERBB3 Knockout HCT 116 Cell Line | EDJ-KQ19160 | Human | 2065 | Details Get a Quote |
| ERBB3 Knockout HeLa Cell Line | EDJ-KQ53171 | Human | 2065 | Details Get a Quote |
| ERBB3 (p.S1119C) Point Mutation in HAP1 Cell Line | EDC03463 | Human | 2065 | Details Get a Quote |
| ERBB3 (c.3503-7C>T )Point Mutation in HAP1 Cell Line | EDC03464 | Human | 2065 | Details Get a Quote |
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