SPART (Spartin) encodes a protein involved in lipid droplet metabolism, mitochondrial function, and endosomal trafficking. Loss of function causes hereditary spastic paraplegia (SPG20).
SPART Protein (Spartin) is a multifunctional protein involved in lipid droplet metabolism, mitochondrial dynamics, and endosomal trafficking. Mutations cause hereditary spastic paraplegia (SPG20/Troyer syndrome).
| Attribute |
Value |
| Protein Name |
Spartin |
| Gene |
SPART |
| UniProt ID |
Q9UQ10 |
| PDB Structure |
Predicted (experimental structures limited) |
| Molecular Weight |
~80 kDa |
| Subcellular Localization |
Cytoplasm, Lipid droplets, Mitochondria |
| Protein Family |
SPARTin family |
Spartin is a multifunctional protein with distinct domains:
- N-terminal Microtubule-Interacting Domain: Involved in cytoskeletal interactions
- MIT Domain: Present in proteins interacting with endosomal sorting complexes
- C-terminal Lipid Droplet-Binding Domain: Mediates localization to lipid droplets
- Coiled-Coil Regions: Involved in protein-protein interactions
- UEV Domain: ubiquitin-conjugating enzyme variant-like domain
- Lipid Droplet Localization: Spartin localizes to lipid droplets through its C-terminal domain
- Lipophagy: Facilitates autophagic degradation of lipid droplets
- Lipid Turnover: Regulates lipid storage and mobilization
- Mitochondrial Dynamics: Involved in mitochondrial fission and fusion
- Mitochondrial Quality Control: Participates in mitochondrial quality control pathways
- Energy Metabolism: Affects cellular energy metabolism
- ESCRT Interaction: Interacts with endosomal sorting complexes
- Membrane Protein Sorting: Regulates trafficking of membrane proteins
- Autophagosome Maturation: Involved in autophagy pathway
- Microtubule Binding: Associates with microtubules
- Cell Morphology: Affects cell shape and process formation
Mutations in SPART cause Troyer syndrome:
- Autosomal Recessive: Loss-of-function mutations
- Spastic Paraplegia: Progressive lower limb spasticity
- Corticospinal Tract Degeneration: Degeneration of motor pathways
- Neurodevelopmental Features: Developmental delay, short stature
- Dysarthria: Motor speech impairment
- Loss of spartin function leads to:
- Accumulation of lipid droplets
- Mitochondrial dysfunction
- Impaired endosomal trafficking
- Disrupted autophagy
Current therapeutic approaches include:
- Gene Therapy: Potential for SPART gene replacement
- Lipid Metabolism Modulators: Compounds affecting lipid droplet function
- Mitochondrial Protectants: Agents to improve mitochondrial function
- Soderblom et al., SPART mutations cause Troyer syndrome (2005)
- Lonardo et al., Spartin functions in lipid droplet turnover (2010)
- Ishmael et al., Analysis of spartin in neurodegeneration (2006)