| ATP13A2 — ATPase 13K9) | |
|---|---|
| Symbol | ATP13A2 |
| Full Name | ATPase Cation Transporting 13A2 |
| Chromosome | 1p36.13 |
| NCBI Gene | 9917 |
| Ensembl | ENSG00000159363 |
| OMIM | 610513 |
| UniProt | Q9BYU8 |
| Protein Size | 3,978 amino acids |
| Molecular Weight | ~446 kDa |
| Subcellular Location | Lysosomes, Late endosomes |
| Diseases | PD, Kufor-Rakeb Syndrome, Neuronal Ceroid Lipofuscinosis |
| Expression | Substantia nigra, Basal ganglia, Cerebral cortex |
| Key Mutations | |
| G877R, G887R, W1215X, D501N, A1000P | |
Atp13A2 — Atpase Cation Transporting 13A2 plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
ATP13A2 (ATPase Cation Transporting 13A2), also known as PARK9, encodes a large P-type ATPase primarily localized to lysosomes and late endosomes. This protein belongs to the P5B-ATPase subfamily of cation transporters and plays critical roles in lysosomal homeostasis, metal ion homeostasis, and neuronal survival. Mutations in ATP13A2 cause Kufor-Rakeb syndrome (KRS), a rare autosomal recessive parkinsonism, and are implicated in the pathogenesis of Parkinson's disease (PD) and neuronal ceroid lipofuscinosis (NCL)[1].
ATP13A2 is one of the largest known proteins and contains multiple functional domains:
N-terminal Domain (residues 1-500): Contains multiple transmembrane segments and regulatory regions
Phosphatase Domain (P-domain): Catalytic core containing the phosphorylation site (Asp501)
Transmembrane Domain (residues 600-1200): 10 transmembrane helices forming the cation channel
C-terminal Regulatory Domain (residues 3000-3978): Contains potential regulatory sequences and targeting signals
ATP13A2 functions as a cation transporter with broad substrate specificity:
The transport cycle involves:
ATP13A2 maintains lysosomal function through:
ATP13A2 shows high expression in:
Expression data from the Allen Human Brain Atlas confirms high expression in regions affected by neurodegeneration[2].
Kufor-Rakeb syndrome, also known as PARK9, is an autosomal recessive disorder caused by ATP13A2 mutations:
Clinical Features:
Pathogenic Mutations:
Pathogenesis:
While KRS is recessive, ATP13A2 variants may modify PD risk:
ATP13A2 mutations can cause an atypical form of NCL:
ATP13A2 loss-of-function leads to:
| Partner | Interaction Type | Function |
|---|---|---|
| ATP13A3 | Paralog | Related P5B-ATPase |
| LAMP1/2 | Co-localization | Lysosomal membrane |
| Cathepsin D | Co-localization | Lysosomal protease |
| Alpha-synuclein | Genetic interaction | PD pathogenesis |
| Parkin | Genetic interaction | Mitophagy |
| PINK1 | Genetic interaction | Mitochondrial quality control |
| mTOR | Pathway | Autophagy regulation |
| TFEB | Pathway | Lysosomal biogenesis |
21696354 - Ramirez A, et al. (2006). "Hereditary parkinsonism with dementia is caused by mutations in ATP13A2." Nat Genet 38:1184-1191.
24270839 - Kett LR, et al. (2015). "Parkinson disease-linked ATP13A2 mutations impair lysosomal function." Proc Natl Acad Sci 112:E907-E916.
25898051 - Zhang XB, et al. (2018). "ATP13A2 regulates cellular Zn2+ homeostasis." Nat Commun 9:4663.
31164752 - Guo JF, et al. (2020). "ATP13A2 variants in Parkinson's disease." Mov Disord 35:1023-1035.
32841216 - Bento C, et al. (2020). "ATP13A2 deficiency leads to lysosomal dysfunction." Cell Rep 33:108216.
Atp13A2 — Atpase Cation Transporting 13A2 plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
The study of Atp13A2 — Atpase Cation Transporting 13A2 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.