SNCA

Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. Alternatively spliced transcripts encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2016]

Synuclein Alpha

Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:28288128, PubMed:30404828, PubMed:20798282, PubMed:26442590).
Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores (PubMed:28288128, PubMed:30404828).
Mechanistically, acts by increasing local Ca2+ release from microdomains which is essential for the enhancement of ATP-induced exocytosis (PubMed:30404828).
Acts also as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5 (PubMed:20798282).
This chaperone activity is important to sustain normal SNARE-complex assembly during aging (PubMed:20798282).
Plays also a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity (PubMed:26442590).

Activation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIDA:BHF-UCL
Adult locomotory behaviorIEA:Ensembl
Cellular response to copper ionManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to epinephrine stimulusManual Assertion Based On ExperimentTAS:UniProtKB
Cellular response to oxidative stress1 PublicationIC:ParkinsonsUK-UCL
Chemical synaptic transmissionManual Assertion Based On ExperimentIBA:GO_Central
Dopamine biosynthetic processManual Assertion Based On ExperimentTAS:UniProtKB
Dopamine uptake involved in synaptic transmissionManual Assertion Based On ExperimentTAS:UniProtKB
Excitatory postsynaptic potentialIEA:Ensembl
Fatty acid metabolic processIEA:Ensembl
Long-term synaptic potentiationIEA:Ensembl
Microglial cell activationManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Mitochondrial ATP synthesis coupled electron transportIEA:Ensembl
Mitochondrial membrane organizationIEA:Ensembl
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of chaperone-mediated autophagyManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of dopamine uptake involved in synaptic transmissionManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of exocytosisManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of histone acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of microtubule polymerizationManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of mitochondrial electron transport, NADH to ubiquinoneManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Negative regulation of monooxygenase activityManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of neuron apoptotic processIEA:Ensembl
Negative regulation of neuron deathManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of norepinephrine uptakeManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of platelet-derived growth factor receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of protein kinase activityManual Assertion Based On ExperimentTAS:ARUK-UCL
Negative regulation of serotonin uptakeManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of thrombin-activated receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Negative regulation of transporter activityManual Assertion Based On ExperimentIDA:UniProtKB
Neutral lipid metabolic processIEA:Ensembl
Phospholipid metabolic processIEA:Ensembl
Positive regulation of apoptotic processManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Positive regulation of endocytosisManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of exocytosisManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of glutathione peroxidase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of hydrogen peroxide catabolic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of inflammatory responseManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of inositol phosphate biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of neuron deathManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of neurotransmitter secretionIEA:Ensembl
Positive regulation of peptidyl-serine phosphorylationISS:BHF-UCL
Positive regulation of protein serine/threonine kinase activityManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of receptor recyclingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of release of sequestered calcium ion into cytosolManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of SNARE complex assemblyManual Assertion Based On ExperimentIDA:CACAO
Protein destabilizationManual Assertion Based On ExperimentIDA:UniProtKB
Protein tetramerizationManual Assertion Based On ExperimentIDA:UniProtKB
Receptor internalizationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of acyl-CoA biosynthetic processIEA:Ensembl
Regulation of dopamine secretionManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of glutamate secretionIEA:Ensembl
Regulation of locomotionIEA:Ensembl
Regulation of long-term neuronal synaptic plasticityIEA:Ensembl
Regulation of macrophage activationIEA:Ensembl
Regulation of neuron deathManual Assertion Based On ExperimentIBA:GO_Central
Regulation of norepinephrine uptakeManual Assertion Based On ExperimentIGI:ARUK-UCL
Regulation of phospholipase activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of presynapse assemblyManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Regulation of reactive oxygen species biosynthetic processManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of synaptic vesicle recyclingManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of transmembrane transporter activityManual Assertion Based On ExperimentIGI:ARUK-UCL
Response to interferon-gammaManual Assertion Based On ExperimentIDA:UniProtKB
Response to interleukin-1Manual Assertion Based On ExperimentIDA:UniProtKB
Response to iron(II) ionManual Assertion Based On ExperimentIDA:UniProtKB
Response to lipopolysaccharideManual Assertion Based On ExperimentIDA:UniProtKB
Response to magnesium ionManual Assertion Based On ExperimentIDA:UniProtKB
Response to xenobiotic stimulusIEA:Ensembl
SNARE complex assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Supramolecular fiber organizationManual Assertion Based On ExperimentTAS:UniProtKB
Synapse organizationManual Assertion Based On ExperimentIBA:GO_Central
Synaptic vesicle endocytosisISS:UniProtKB
Synaptic vesicle exocytosisManual Assertion Based On ExperimentIDA:UniProtKB
Synaptic vesicle primingManual Assertion Based On ExperimentIMP:UniProtKB
Synaptic vesicle transportIEA:Ensembl

Cytoplasm
Membrane
Nucleus
Cell junction, synapse
Secreted
Cell projection, axon
Membrane-bound in dopaminergic neurons (PubMed:15282274).
Expressed and colocalized with SEPTIN4 in dopaminergic axon terminals, especially at the varicosities (By similarity).

Parkinson disease 1, autosomal dominant (PARK1):
A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.
Parkinson disease 4, autosomal dominant (PARK4):
A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.
Dementia, Lewy body (DLB):
A neurodegenerative disorder characterized by mental impairment leading to dementia, parkinsonism, fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.

Phosphorylated, predominantly on serine residues. Phosphorylation by CK1 appears to occur on residues distinct from the residue phosphorylated by other kinases. Phosphorylation of Ser-129 is selective and extensive in synucleinopathy lesions. In vitro, phosphorylation at Ser-129 promoted insoluble fibril formation. Phosphorylated on Tyr-125 by a PTK2B-dependent pathway upon osmotic stress.
Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers.
Ubiquitinated. The predominant conjugate is the diubiquitinated form.
Acetylation at Met-1 seems to be important for proper folding and native oligomeric structure.