Shank3 Sh3 And Multiple Ankyrin Repeat Domains 3 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
SHANK3 (SH3 and Multiple Ankyrin Repeat Domains 3) is a critical synaptic scaffolding protein essential for synapse formation, function, and plasticity. It is encoded by the SHANK3 gene located on chromosome 22q13.33. Also known as PROSAP2, SHANK3 is one of the most enriched proteins in the postsynaptic density (PSD) and plays a central role in organizing the synaptic machinery.
| SHANK3 | |
|---|---|
| Gene Symbol | SHANK3 |
| Full Name | SH3 and Multiple Ankyrin Repeat Domains 3 |
| Chromosome | 22q13.33 |
| NCBI Gene ID | 85358 |
| Ensembl ID | ENSG00000132924 |
| UniProt ID | Q9BYB0 |
| Protein Length | 1,620 amino acids |
| Molecular Weight | ~180 kDa |
SHANK3 contains multiple protein-protein interaction domains:
| Domain | Position | Function |
|---|---|---|
| ANK repeats | N-terminal (6 repeats) | Bind to actin cytoskeleton |
| SH3 domain | Central | Proline-rich motif binding |
| PDZ domain | Central | S/T-X-V/L motif binding |
| Proline-rich region | C-terminal | Various protein interactions |
| SAM domain | C-terminal | Multimerization |
SHANK3 is a master organizer of the postsynaptic density:
SHANK3 exhibits brain-region specific expression:
| Brain Region | Expression Level |
|---|---|
| Cerebral cortex | High |
| Hippocampus | High (CA1-CA3, DG) |
| Striatum | High |
| Cerebellum | Moderate |
| Thalamus | Moderate |
| Spinal cord | Lower |
SHANK3 alterations in AD:
SHANK3 is one of the most important ASD risk genes:
| Model | Key Findings | Reference |
|---|---|---|
| SHANK3 knockout mice | Reduced synaptic proteins, social deficits | PMID:21885688 |
| SHANK3 knockdown | Impaired LTP, behavior abnormalities | PMID:22932670 |
| SHANK3 transgenic | Rescue of synaptic defects | PMID:24662623 |
| Strategy | Approach | Status |
|---|---|---|
| Gene therapy | Viral SHANK3 delivery | Preclinical |
| Small molecules | Upregulate endogenous SHANK3 | Research |
| ASO therapy | Splice-modulating approaches | Research |
| Cell therapy | Stem cell-derived neurons | Future |
The study of Shank3 Sh3 And Multiple Ankyrin Repeat Domains 3 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.