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.
Function
Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores. Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis. Also acts 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. This chaperone activity is important to sustain normal SNARE-complex assembly during aging. Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity.
Protein Name
Alpha-SynucleinNon-A Beta Component Of Ad AmyloidNon-A4 Component Of Amyloid PrecursorNacp
CytoplasmMembraneNucleusSynapseSecretedCell ProjectionAxonMembrane-Bound In Dopaminergic NeuronsExpressed And Colocalized With Septin4 In Dopaminergic Axon TerminalsEspecially At The Varicosities
Alternative Protein Names
Alpha-Synuclein proteinNon-A Beta Component Of Ad Amyloid proteinNon-A4 Component Of Amyloid Precursor proteinNacp proteinSNCA proteinNACP proteinPARK1 protein
