SIAH1, SIAH2 bind SNCAIP

Stable Identifier
R-HSA-5658092
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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SIAH1, SIAH2 bind SNCAIP
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Seven in absentia homolog 1 (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) and alpha-synuclein (Liani et al. 2004). They are inhibited by the 1A isoform of SNCAIP (Szargel et al. 2009). When ubiquitinated by SIAH1, SNCAIP is targetted for proteasomal degradation (Nagano et al. 2003).

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
14506261 Siah-1 facilitates ubiquitination and degradation of synphilin-1

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

J. Biol. Chem. 2003
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

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

Proc. Natl. Acad. Sci. U.S.A. 2004
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Output
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Authored
Jupe, S  (2014-12-17)
Reviewed
Perry, G  (2015-11-09)
Created
Jupe, S  (2014-12-17)
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