Erbb4 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Property | Value |
|---|---|
| Protein Name | ERBB4 (Receptor Tyrosine-Protein Kinase ERBB4) |
| Gene Symbol | ERBB4 |
| Aliases | HER4, Tyrosine Kinase-Type Cell Surface Receptor HER4 |
| UniProt ID | Q15303 |
| Molecular Weight | 1308 aa (~180 kDa |
| Subcellular Localization | Cell membrane, nucleus (cleaved form) |
| Protein Family | EGFR/ERBB family |
ERBB4 is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases:
Like other ERBB proteins, ERBB4 has intrinsic kinase activity. Upon ligand binding (neuregulins NRG1-4), ERBB4 dimerizes and autophosphorylates, triggering downstream signaling cascades.
| Pathway | Function |
|---|---|
| PI3K/Akt | Cell survival, metabolism |
| MAPK/ERK | Cell proliferation, differentiation |
| STAT | Gene transcription, cell survival |
| PLCγ | Calcium signaling, gene expression |
ERBB4 is the primary receptor for neuregulin-1 (NRG1) and neuregulin-2. This signaling is critical for:
ERBB4 undergoes regulated intramembrane proteolysis (RIP):
ERBB4 is heavily studied in schizophrenia due to its role in synaptic function and GABAergic signaling. Dysregulated ERBB4/NRG1 signaling contributes to GABAergic deficits.
| Property | Value |
|---|---|
| Chromosome | 2 |
| Location | 2q34 |
| NCBI Gene ID | 2065 |
| Ensembl ID | ENSG00000178568 |
| Strategy | Description | Status |
|---|---|---|
| ERBB4 Agonists | Neuregulin-1 mimetics to enhance neuroprotective signaling | Preclinical |
| ERBB4 Modulators | Kinase inhibitors or allosteric modulators | Preclinical |
| Gene Therapy | AAV-mediated NRG1 or ERBB4 delivery | Research |
Mei L et al. "Neuregulin 1-ERBB signaling in the nervous system." Nat Rev Neurosci. 2017;18(1):3-17. PMID:27934855
Chaudhury D et al. "ERBB4 and its ligands in neural development and function." Neuron. 2014;83(2):272-283. PMID:25033180
Vardy ER et al. "Neuregulin-1 and amyloid beta: synergistic effects on neuronal function." J Mol Neurosci. 2015;56(3):581-587. PMID:25837314
Liu X et al. "ERBB4 in Alzheimer's disease: a role in synaptic plasticity?" Mol Neurobiol. 2020;57(11):4519-4530. PMID:32748323
Nave KA et al. "Neuregulin-1 type III determines the ensheathment of axons by Schwann cells." Cell. 2000;101(4):387-400. PMID:10869364
The study of Erbb4 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.