Tissue Specificity | Highly expressed in presynaptic terminals in the central nervous system. Expressed principally in brain. |
Post Translational Modifications | 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. 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. 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. |
Peptide Name | Alpha-SynucleinNon-A Beta Component Of Ad AmyloidNon-A4 Component Of Amyloid PrecursorNacp |
Database Links | Reactome: R-HSA-977225Reactome: R-HSA-9833482 |
Cellular Localisation | CytoplasmMembraneNucleusSynapseSecretedCell ProjectionAxonMembrane-Bound In Dopaminergic NeuronsExpressed And Colocalized With Septin4 In Dopaminergic Axon TerminalsEspecially At The Varicosities |
Alternative Peptide Names | Alpha-Synuclein proteinNon-A Beta Component Of Ad Amyloid proteinNon-A4 Component Of Amyloid Precursor proteinNacp proteinSNCA proteinNACP proteinPARK1 protein |
Information sourced from Uniprot.org