BAIT
SNCA
NACP, PARK1, PARK4, PD1
synuclein, alpha (non A4 component of amyloid precursor)
GO Process (45)
GO Function (20)
GO Component (16)
Gene Ontology Biological Process
- activation of cysteine-type endopeptidase activity involved in apoptotic process [IDA]
- calcium ion homeostasis [IDA]
- cellular response to copper ion [IDA]
- cellular response to epinephrine stimulus [TAS]
- cellular response to oxidative stress [IC]
- dopamine biosynthetic process [TAS]
- dopamine uptake involved in synaptic transmission [TAS]
- extracellular fibril organization [TAS]
- microglial cell activation [TAS]
- negative regulation of apoptotic process [IMP]
- negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [IMP]
- negative regulation of dopamine uptake involved in synaptic transmission [IDA]
- negative regulation of exocytosis [IMP]
- negative regulation of histone acetylation [IDA]
- negative regulation of microtubule polymerization [IDA]
- negative regulation of mitochondrial electron transport, NADH to ubiquinone [TAS]
- negative regulation of monooxygenase activity [IDA]
- negative regulation of norepinephrine uptake [IDA]
- negative regulation of platelet-derived growth factor receptor signaling pathway [IDA]
- negative regulation of serotonin uptake [IDA]
- negative regulation of thrombin receptor signaling pathway [IDA]
- negative regulation of transcription from RNA polymerase II promoter [TAS]
- negative regulation of transporter activity [IDA]
- oxidation-reduction process [IDA]
- positive regulation of apoptotic process [TAS]
- positive regulation of endocytosis [IDA]
- positive regulation of glutathione peroxidase activity [IDA]
- positive regulation of hydrogen peroxide catabolic process [IDA]
- positive regulation of inositol phosphate biosynthetic process [IDA]
- positive regulation of peptidyl-serine phosphorylation [ISS]
- positive regulation of protein serine/threonine kinase activity [IDA]
- positive regulation of receptor recycling [IDA]
- positive regulation of release of sequestered calcium ion into cytosol [IDA]
- protein destabilization [IDA]
- receptor internalization [IDA]
- regulation of dopamine secretion [TAS]
- regulation of phospholipase activity [IDA]
- regulation of reactive oxygen species biosynthetic process [TAS]
- regulation of synaptic vesicle recycling [TAS]
- response to interferon-gamma [IDA]
- response to interleukin-1 [IDA]
- response to iron(II) ion [IDA]
- response to lipopolysaccharide [IDA]
- response to magnesium ion [IDA]
- synaptic vesicle endocytosis [ISS]
Gene Ontology Molecular Function- Hsp70 protein binding [IPI]
- alpha-tubulin binding [IPI]
- calcium ion binding [IDA]
- copper ion binding [IDA]
- cysteine-type endopeptidase inhibitor activity involved in apoptotic process [IDA]
- dynein binding [IPI]
- fatty acid binding [IDA]
- ferrous iron binding [IDA]
- histone binding [IDA]
- identical protein binding [IPI]
- kinesin binding [IPI]
- magnesium ion binding [IDA]
- oxidoreductase activity [IDA]
- phospholipase D inhibitor activity [IDA]
- phospholipid binding [IDA]
- phosphoprotein binding [IDA]
- protein binding [IPI]
- tau protein binding [IDA]
- transcription regulatory region DNA binding [TAS]
- zinc ion binding [IDA]
- Hsp70 protein binding [IPI]
- alpha-tubulin binding [IPI]
- calcium ion binding [IDA]
- copper ion binding [IDA]
- cysteine-type endopeptidase inhibitor activity involved in apoptotic process [IDA]
- dynein binding [IPI]
- fatty acid binding [IDA]
- ferrous iron binding [IDA]
- histone binding [IDA]
- identical protein binding [IPI]
- kinesin binding [IPI]
- magnesium ion binding [IDA]
- oxidoreductase activity [IDA]
- phospholipase D inhibitor activity [IDA]
- phospholipid binding [IDA]
- phosphoprotein binding [IDA]
- protein binding [IPI]
- tau protein binding [IDA]
- transcription regulatory region DNA binding [TAS]
- zinc ion binding [IDA]
Gene Ontology Cellular Component
- actin cytoskeleton [IDA]
- axon [IDA]
- cell cortex [IDA]
- cytoplasm [IDA]
- cytosol [IDA]
- extracellular region [TAS]
- fibril [IDA]
- growth cone [IDA]
- inclusion body [IDA]
- lysosome [TAS]
- mitochondrial respiratory chain complex I [TAS]
- mitochondrion [TAS]
- nucleus [IDA]
- perinuclear region of cytoplasm [IDA]
- plasma membrane [IDA]
- platelet alpha granule membrane [IDA]
Homo sapiens
PREY
HSP104
chaperone ATPase HSP104, L000000823, YLL026W
Disaggregase; heat shock protein that cooperates with Ydj1p (Hsp40) and Ssa1p (Hsp70) to refold and reactivate previously denatured, aggregated proteins; responsive to stresses including: heat, ethanol, and sodium arsenite; involved in [PSI+] propagation; protein becomes more abundant and forms cytoplasmic foci in response to DNA replication stress; potentiated Hsp104p variants decrease TDP-43 proteotoxicity by eliminating its cytoplasmic aggregation
GO Process (7)
GO Function (5)
GO Component (3)
Gene Ontology Biological Process
- cellular heat acclimation [IMP]
- chaperone cofactor-dependent protein refolding [IDA]
- inheritance of oxidatively modified proteins involved in replicative cell aging [IGI, IMP]
- protein folding in endoplasmic reticulum [IMP]
- protein unfolding [IMP]
- stress granule disassembly [IDA]
- trehalose metabolism in response to heat stress [IMP]
Gene Ontology Molecular Function
Saccharomyces cerevisiae (S288c)
Synthetic Rescue
A genetic interaction is inferred when mutations or deletions of one gene rescues the lethality or growth defect of a strain mutated or deleted for another gene.
Publication
Potentiating Hsp104 activity via phosphomimetic mutations in the middle domain.
Hsp104 is a hexameric AAA + ATPase and protein disaggregase found in yeast, which can be potentiated via mutations in its middle domain (MD) to counter toxic phase separation by TDP-43, FUS and α-synuclein connected to devastating neurodegenerative disorders. Subtle missense mutations in the Hsp104 MD can enhance activity, indicating that post-translational modification of specific MD residues might also potentiate Hsp104. Indeed, ... [more]
FEMS Yeast Res. Dec. 01, 2017; 18(5); [Pubmed: 29788207]
Throughput
- Low Throughput
Ontology Terms
- phenotype: viability (APO:0000111)
Additional Notes
- Hsp104 disaggregase can be potentiated via mutations in its middle domain to counter toxic phase separation and aggregation by TDP-43, FUS and alpha-synuclein
Related interactions
| Interaction | Experimental Evidence Code | Dataset | Throughput | Score | Curated By | Notes |
|---|---|---|---|---|---|---|
| SNCA HSP104 | Synthetic Rescue Synthetic Rescue A genetic interaction is inferred when mutations or deletions of one gene rescues the lethality or growth defect of a strain mutated or deleted for another gene. | Low | - | BioGRID | 1254132 |
Curated By
- BioGRID