SIAH1:UBE2L6:Ubiquitin ubiquitinates SNCA

Stable Identifier
Reaction [transition]
Homo sapiens
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SIAH1 transfers ubiquitin from UBE2L6 to SNCA, generating monoubiquitinated SNCA (Ub-SNCA) (Liani et al 2004, Rott et al. 2008, Lee et al. 2008). Monoubiquitination of SNCA promotes its aggregation in vitro and in vivo, which is toxic to cells. Lewy Bodies, a characteristic of Parkinson's Disease, contain monoubiquitinted SNCA deposits (Hasegawa et al. 2002). Mass spectrometry analysis demonstrates that SIAH monoubiquitinates alpha-synuclein at lysines 12, 21, and 23 (Rott et al. 2008).

Monoubiquitination is generally thought to lead to degradation via the lysosomal pathway (d'Azzo et al. 2005) but monoubiquitinated SNCA appears to be preferentially targeted for degradation by the proteasome (Rott et al. 2011).

Literature References
PubMed ID Title Journal Year
18070888 Monoubiquitylation of alpha-synuclein by seven in absentia homolog (SIAH) promotes its aggregation in dopaminergic cells

Liani, E, Avraham, E, Rott, R, Engelender, S, Shainskaya, A, Haskin, J, Szargel, R, Manov, I, Shani, V

J. Biol. Chem. 2008
Catalyst Activity

ubiquitin-protein transferase activity of SIAH1,SIAH2:UBE2L6:Ubiquitin:SNCA [cytosol]

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