Reactome | SIAH1:UBE2L6:Ubiquitin ubiquitinates SNCA

SIAH1:UBE2L6:Ubiquitin ubiquitinates SNCA

Stable Identifier

R-HSA-5660753

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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SIAH1:UBE2L6:Ubiquitin ubiquitinates SNCA

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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