Alpha-synuclein protein properties

Alpha-synuclein

Function

Alpha-synculein is a protein encoded by the SNCA gene. It has been found to play a role in autosomal dominant Parkinson Disease. It is believed to be involved in regulating dopamine release and transport, and in lessening the responsiveness of apoptotic stimuli. The SMART tool on the EMBL site provided a lot of interesting methods of exploring the protein, including a protein interaction network. Alpha-synuclein interacts with many proteins, most notably, with UBE2L6, SNCAIP, and PARK2, all three of which in turn interact with one another. Each of these proteins has been found to play a role in PD.

Family, Domains, and Motifs

Alpha-synuclein is a member of the synuclein family. Members of the family are characterized by a

“Highly conserved alpha-helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins” (EMBL-EBI).

Both the ProfileScan Server and the PROSCAN revealed 3 motifs in the synuclein family:

1. Casein kinase II phosphorylation site

2. Tyrosine kinase phosphorylation site

3. N-myristoylation site

UniProt identified the NAC domain, which is involved in fibril formation. It also suggests that the C-terminus could be involved in the regulation of the aggregation and size determination of filaments.

Physical Properties

The 3-D structure from the Protein Data Bank:















Length: 140AA
Molecular Weight: 14460 Da

Coiled-coil predictions
COILS predicted no coiled-coils

Phosphorylation predictions
NetPhos 2.0 Prediction Server predicted 1 serine, 3 threonine, and 3 tyrosine phosphorylation sites.

Sulfation predictions
The Sulfinator predicted 3 sulfated tyrosines.

Transmembrane prediction: conflicting results?
The DAS site predicts where transmembrane regions are within the protein. The alpha-synuclein prediction looks like this:

It predicts three possible transmembrane segments. One from aa67-77, one from 69-75, and one from 87-91.
However...the TMpred server graphs a similar output, but does not find any significant transmembrane regions:

Localization

Alpha-synuclein is generally found in the presynaptic terminals of brain tissue.
From PSORT II:

52.2 %: cytoplasmic
30.4 %: nuclear
8.7 %: mitochondrial
4.3 %: vacuolar
4.3 %: vesicles of secretory system

From WoLF PSORT:
cyto: 13 (40.6%), mito: 9 (28.1%), extr: 6 (18.8%), nucl: 4 (12.5%)

From literature:
Primarily cytoplasmic. Also found in the nucleus.