DAB1 encodes Disabled-1, an essential adaptor protein in the Reelin signaling pathway that controls neuronal migration and brain development. This page provides information about its structure, function, and role in neurological disorders.
DAB1 (Disabled-1) is a key intracellular adaptor protein in the Reelin signaling pathway. The Reelin-DAB1 pathway is crucial for proper brain development, cortical layer formation, and synaptic plasticity. DAB1 mediates the effects of Reelin on neuronal positioning, dendrite maturation, and long-term potentiation.
| Property |
Value |
| Gene Symbol |
DAB1 |
| Full Name |
Disabled-1 |
| Chromosomal Location |
1p32-p31 |
| NCBI Gene ID |
1600 |
| Ensembl ID |
ENSG00000170522 |
| UniProt ID |
D3DX7A |
| OMIM |
603448 |
| Property |
Value |
| Protein Name |
Disabled-1 (DAB1) |
| Molecular Weight |
~80 kDa (625 amino acids) |
| Subcellular Localization |
Cytoplasm, postsynaptic densities |
| Protein Family |
Disabled family |
¶ Domain Structure
- N-terminal domain: Protein interactions
- Proline-rich region: SH3 domain binding
- Phosphotyrosine-binding (PTB) domain: Reelin receptor binding
- Multiple tyrosine phosphorylation sites: Signaling regulation
- Binds to Reelin receptors (ApoER2, VLDLR)
- Mediates Reelin-induced neuronal positioning
- Controls cortical layer formation
- Regulates dendrite maturation
- Essential for brain lamination
- Controls neuronal migration
- Regulates spine development
- Supports synaptic formation
- Modulates NMDA receptor function
- Regulates AMPA receptor trafficking
- Supports LTP and learning
- Memory consolidation role
- DAB1 expression altered in AD brain
- Reelin-DAB1 pathway impaired
- May affect amyloid processing
- Possible therapeutic target
- Genetic association with schizophrenia
- Altered DAB1 expression
- Neurodevelopmental implications
- Synaptic dysfunction link
- DAB1 dysregulation in epilepsy
- Possible seizure mechanisms
- Developmental origins
- Autism: Possible neurodevelopmental role
- Intellectual disability: Developmental pathways
- Brain regions: High expression in cortex, hippocampus, cerebellum
- Cellular expression: Neurons, especially pyramidal cells
- Subcellular: Cytoplasm, dendritic compartments, postsynaptic densities
- Expression pattern: High during development, maintained in adult
| Approach |
Status |
Description |
| Small molecule modulators |
Research |
Enhance Reelin-DAB1 signaling |
| Gene therapy |
Preclinical |
Restore DAB1 function |
| Peptide agonists |
Research |
Activate pathway |
- Knockout mice: Severe brain lamination defects
- Reeler mice: Natural DAB1 pathway mutation
- Transgenic models: Conditional knockouts
- RELN: Reelin - extracellular ligand
- VLDLR: Very low-density lipoprotein receptor
- ApoER2: Apolipoprotein E receptor 2
- FYN: Src family kinase
- NMDA receptors: Synaptic signaling
- PI3K: Downstream signaling
- Reelin binds to ApoER2/VLDLR
- DAB1 recruited to receptors
- DAB1 phosphorylation by Src family kinases
- Activation of PI3K/Akt pathway
- Regulation of microtubule dynamics
- Control of neuronal positioning
- Understanding pathway dysregulation in disease
- Therapeutic modulation approaches
- Biomarker development
- Clinical translation
The study of Dab1 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.
- Honda et al., DAB1 in brain development (2020)
- Frotscher et al., Reelin and DAB1 in synaptic plasticity (2019)
- Fatemi et al., DAB1 in neuropsychiatric disorders (2021)
- Hack et al., DAB1 phosphorylation and signaling (2018)