SIAH1, SIAH2 ubiquitinate SNCAIP

Stable Identifier
R-HSA-5667107
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
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Seven in absentia homolog (SIAH1) and 2 (SIAH2) are E3 ubiquitin-protein ligases that mediate ubiquitination of a number of target proteins including Synphilin-1 (SNCAIP) (Nagano et al. 2003, Liani et al. 2004). When ubiquitinated by SIAH1, SNCAIP is targetted for proteasomal degradation (Nagano et al. 2003). SIAH1 and SIAH2 are inhibited by the 1A isoform of SNCAIP (Szargel et al. 2009). SIAH1 can bind the brain-enriched E2 ubiquitin-conjugating enzyme UBE2L6 (Lee et al. 2008) but the E2 involved in SNCAIP ubiquitination has not been established.

Synphilin-1 (SNCAIP) is a presynaptic protein that associates with synaptic vesicles (Ribeiro et al. 2002). It is present in many types of cytoplasmic inclusions, where it colocalizes with alpha-synuclein. It is associated with Parkinson's Disease (PD) because it is an intrinsic component of Lewy bodies (Wakabayashi et al. 2000) and a mutation of the SNCAIP gene has been identified in some PD patients (Marx et al. 2003), suggesting that accumulation of synphilin-1 and its interaction with alpha-synuclein may be relevant for Lewy body formation in PD.

Synphilin-1 (SNCAIP) is ubiquitinated by several other E3 ubiquitin-ligases, including Parkin (Chung et al. 2001) and Dorfin (Ito et al. 2003).

Literature References
PubMed ID Title Journal Year
15064394 Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease

Liani, E, Eyal, A, Avraham, E, Shemer, R, Szargel, R, Berg, D, Bornemann, A, Riess, O, Ross, CA, Rott, R, Engelender, S

Proc. Natl. Acad. Sci. U.S.A. 2004
14506261 Siah-1 facilitates ubiquitination and degradation of synphilin-1

Nagano, Y, Yamashita, H, Takahashi, T, Kishida, S, Nakamura, T, Iseki, E, Hattori, N, Mizuno, Y, Kikuchi, A, Matsumoto, M

J. Biol. Chem. 2003
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ubiquitin-protein transferase activity of SIAH1, SIAH2:SNCAIP [cytosol]
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Activity
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