Halia 2014 #2073 truncation table tail, Splice variation (4 αSyn transcripts SNCA-140/-126/-112/-98), Beyer 2008 Neurogenetics alignment, TAK-341 epitope on exon 5, Pathological Conversion + Pathological Aggregation cycle figure, Structure of aSyn opener, Brain Res 2012 1432:90 α-synuclein domain figure, 4q21.3-q22 chromosome diagram
(Halia, 2014 #2073) — truncation isoform table tail
α-synuclein domain map labels: N-terminal | Amphipathic region | NAC domain | Acidic C-terminal
Mutation labels: A30P, A53T, E46K, H50Q, aggregation, Tyr/125
Splice isoform map: SNCA-140 (full-length); SNCA-126 (lacks exon 3); SNCA-112 (lacks exon 5); SNCA-98 (lacks exons 3 and 5)
Splice variation
Four major aSYN transcripts:
- SNCA-140 (full length)
- SNCA-126 (lacks exon 3)
- SNCA-112 (lacks exon 5)
- SNCA-98 (lacks exons 3 and 5)
(Cosk et al., 2018 Neurogenetics)
aa sequence schematic showing alphabetical alignment.
Underlined: Coded by exon 3
Red: TAK-341 epitope (102-130)
(Beyer et al. 2008 Neurogenetics) Fig. Sequence alignment of alpha-synuclein 140 and alpha-synuclein 98. (1) Protein-membrane interacting domain (four alpha-helices); (2) NAC; and (4) unrecognized C-terminal. Alpha-synuclein 98 is characterized by in-frame deletions of exon 3 (interruption of the proteins-membrane interacting domain) and exon 5 (C-terminal shortening).
The TAK-341 epitope is coded by exon 5 which is absent in the SNCA-112 and SNCA-98 isoforms, which constitute a sizeable fraction of total αSyn
Pathological Conversion → Pathological Aggregation cycle
Series labels: Monomeric α-synuclein → Aggregated α-synuclein → Pathologic fibrils → Lewy bodies
Right side cycle: Pathological Conversion → Oligomers → Protofibrils → Fibrils
Structure of aSyn
5 exons with total transcript length of 3041 bps, maps on 4q21.3-q22
Sequence alignment figure for α-syn140 / α-syn112 / α-syn126 / α-syn98
α-SYNUCLEIN — Brain Res 2012, 1432: 90
Figure 1 Schematic representation of the full length 140 amino acid α-synuclein transcript. Pathogenic mutations, phosphorylation, and nitration sites are indicated.
Domain regions:
- Region 1 (aa 1-60)
- Region 2 (aa 61-95)
- Region 3 (aa 96-140)
Pathogenic mutations: A30P, E46K, H50Q, A53T
Phosphorylation sites: Tyr 125, Tyr 133, Tyr 136, Ser 12, Ser 87, Tyr 39 (etc.)
Nitration sites: TBP (NITRATION SITE)
Note: 11 aa imperfect repeats with KTKEGV-like highly conserved KTKEGV motif
4q21.3-q22 chromosome / 14.5 kDa, 140 a.a. protein
- Chromosome 4 / SNCA
- 111.06 kb α-synuclein mRNA
Domain layout:
- Amphipathic region | NAC domain | Acidic tail
- Exons: Exon 1 / Exon 2 / Exon 3 / Exon 4 / Exon 5