Erbb4 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4), also known as HER4, is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases. ERBB4 is a crucial signaling receptor in the brain, involved in neural development, synaptic plasticity, and neuronal survival. The gene is located on chromosome 2q34 and encodes a 1308-amino acid protein.
| Property |
Value |
| Gene Symbol |
ERBB4 |
| Gene Name |
Erb-B2 Receptor Tyrosine Kinase 4 |
| Alternative Names |
HER4, v-erb-a erythroblastic leukemia viral oncogene homolog 4 |
| Chromosomal Location |
2q34 |
| NCBI Gene ID |
2065 |
| UniProt ID |
Q15303 |
| Ensembl ID |
ENSG00000178668 |
| Protein Family |
EGFR/ERBB family |
| Molecular Weight |
~180 kDa (full-length) |
| Amino Acids |
1308 |
ERBB4 is a receptor tyrosine kinase with multiple isoforms:
- Extracellular domain: Four ligand-binding subdomains (I-IV)
- Transmembrane domain: Single pass helix
- Intracellular tyrosine kinase domain: Catalytic activity
- C-terminal tail: Multiple phosphorylation sites
ERBB4 has multiple isoforms due to alternative splicing:
- Cytoplasmic isoforms: CYT-1, CYT-2 (differ in C-terminus)
- Soluble isoforms: Produced by proteolytic cleavage
- JMa and JMb: Extracellular splicing variants
ERBB4 functions as a receptor tyrosine kinase:
- Binds neuregulin (NRG) ligands
- Dimerizes (homodimer or heterodimer)
- Autophosphorylates tyrosine residues
- Activates downstream signaling cascades
- PI3K/AKT: Cell survival, metabolism
- MAPK/ERK: Cell proliferation, differentiation
- STAT: Gene transcription
- PLCγ: Calcium signaling
In the brain, ERBB4:
- Regulates neural development
- Controls synapse formation
- Mediates hippocampal plasticity
- Supports neuronal survival
- Modulates GABAergic signaling
ERBB4 in AD:
- Elevated in AD brains
- Links Aβ toxicity to signaling
- May have neuroprotective role
- Neuregulin-ERBB4 signaling affected
- Synaptic function modulation
- Therapeutic target potential
In PD:
- Expressed in dopaminergic neurons
- Neuregulin protection studies
- May affect LRRK2 signaling
- Neurotrophic factor connections
- Gene variants under investigation
ERBB4 strongly associated with schizophrenia:
- Genetic risk factor identified
- Altered expression in schizophrenic brain
- Affects synaptic function
- Neuregulin-ERBB4 pathway dysregulated
- GABAergic interneuron development
- Therapeutic target interest
- Epilepsy: Altered expression
- Autism: Genetic associations
- Bipolar disorder: GWAS signals
| Agent |
Mechanism |
Status |
| Neuregulin |
ERBB4 agonist |
Research |
| Anti-ERBB4 antibodies |
Block signaling |
Preclinical |
| Tyrosine kinase inhibitors |
Inhibit activity |
Research |
| Gene therapy |
Enhance signaling |
Research |
- Neuregulin delivery
- ERBB4 modulation
- Downstream pathway targeting
- Combination approaches
- High in: Brain (cortex, hippocampus), heart, mammary gland
- Development: Important in neurodevelopment
- Adult: Maintained in specific brain regions
- Cell types: Neurons, astrocytes, oligodendrocytes
- Knockout mice: Embryonic/neonatal lethal
- Conditional knockouts: Brain-specific studies
- Transgenic overexpression: Neurological phenotypes
- Neuregulin mutants: Synaptic deficits
- Understanding isoform-specific functions
- Brain-penetrant modulators
- Biomarker development
- Gene therapy approaches
- Neuregulin-ERBB4 pathway modulation
The study of Erbb4 Gene 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.
- Yarden Y, Sliwkowski MX. (2001). Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2(2):127-137.
- Mei L, Xiong WC. (2008). Neuregulin 1 in neural development and schizophrenia. Nat Rev Neurosci. 9(6):437-452.
- Law AJ, et al. (2007). ERBB4 in schizophrenia. Mol Psychiatry. 12(3):284-298.
- Chan CB, Ye K. (2012). ERBB4 in the nervous system. Exp Biol Med. 237(2):121-131.
- Hahn CG, et al. (2006). ERBB4 and neuregulin in schizophrenia. Neuropsychopharmacology. 31(11):2300-2309.
- Cooper MA, Koleske AJ. (2014). ERBB4 in the developing brain. Dev Neurosci. 36(5):359-371.