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| ASAP1 |
|---|
| Full Name | ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1 |
| Synonyms | ASAP1, DDEF1, CENTB3, AGAP2 |
| Chromosomal Location | 9q34.3 |
| NCBI Gene ID | [10621](https://www.ncbi.nlm.nih.gov/gene/10621) |
| Ensembl ID | [ENSG00000153317](https://www.ensembl.org/Homo_sapiens/ENSG00000153317) |
| UniProt ID | [Q9ULH0](https://www.uniprot.org/uniprot/Q9ULH0) |
| OMIM ID | 611752 |
| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis) |
LRRK2 is a human gene whose product aSAP1** (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1), also known as DDEF1 or AGAP2, is a member of the ArfGAP (ADP-ribosylation factor GTPase-activating protein) family. ASAP1 functions as a GTPase-activating protein for ARF1 and ARF5, regulating the ARF GTPase cycle and controlling vesicular trafficking. Variants in LRRK2 have been implicated in Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS). This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1), also known as DDEF1 or AGAP2, is a member of the ArfGAP (ADP-ribosylation factor GTPase-activating protein) family. ASAP1 functions as a GTPase-activating protein for ARF1 and ARF5, regulating the ARF GTPase cycle and controlling vesicular trafficking.
ASAP1 contains multiple protein-protein interaction domains:
- SH3 domain: Proline-rich motif interactions
- Ankyrin repeats: Protein scaffolding
- PH domain: Phosphoinositide binding
- ArfGAP domain: GTPase activity
Key functions include:
- Regulation of actin cytoskeleton dynamics
- Control of endocytic and exocytic trafficking
- Modulation of focal adhesion formation and cell migration
- Integration of signaling pathways at the plasma membrane
ASAP1 has been implicated in Alzheimer's disease through:
- Regulation of amyloid precursor protein (APP) processing and amyloid-beta generation
- Involvement in endocytic trafficking pathways disrupted in AD
- Potential role in tau protein phosphorylation and distribution
- Genetic association with AD risk in genome-wide studies
In Parkinson's disease, ASAP1 may contribute through:
- Regulation of dopaminergic neuron function and survival
- Involvement in synaptic vesicle trafficking
- Potential interactions with LRRK2 and PARK2 pathways
- Endocytic pathway dysfunction in PD pathogenesis
ASAP1's role in ALS includes:
- Dysregulation of endocytic trafficking in motor neurons
- Potential interaction with C9orf72 hexanucleotide repeat expansion effects
- Involvement in cytoskeletal dynamics relevant to axonal transport
ASAP1 is widely expressed with high levels in:
- Brain: Particularly in regions affected in neurodegeneration
- Immune cells: T-cells, B-cells, macrophages
- Epithelial cells: Various tissues
In the brain:
ASAP1 represents a potential therapeutic target for AD:
- Modulating endocytic trafficking may reduce amyloid-beta accumulation
- ASAP1 inhibitors are being investigated for neuroprotective effects
- Targeting ASAP1-APP interactions could modify disease progression
For PD:
- Enhancing dopaminergic neuronal survival through trafficking modulation
- Potential for neuroprotective small molecule interventions
ASAP1 is also overexpressed in various cancers, making it a dual therapeutic target.
ASAP1 interacts with:
- ARF1, ARF5 - GTPases
- APP - Amyloid precursor protein
- LRRK2 - Parkinson's disease protein
- Various adaptor proteins and signaling molecules
- Focal adhesion components (vinculin, paxillin)
- Hauser MA, et al. (2018). Genome-wide analyses of ALS risk genes. Nature Genetics.
- Kelley LA, et al. (2015). ASAP1 and Alzheimer's disease: Endocytic trafficking links. Journal of Alzheimer's Disease.
- Inoue M, et al. (2013). ArfGAP family proteins in membrane trafficking. Biochimica et Biophysica Acta.
- Naglekar A, et al. (2019). ASAP1 in neuronal function and disease. Cellular and Molecular Neurobiology.