Search results for PARK2

Showing 14 results out of 15

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Protein (2 results from a total of 2)

Identifier: R-HSA-201579
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PRKN: O60260
Identifier: R-HSA-5689094
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PRKN: O60260

Reaction (6 results from a total of 7)

Identifier: R-HSA-5689111
Species: Homo sapiens
Compartment: cytosol
Ubiquitin conjugates linked via lysine-48 (K48) target substrates to the proteasome, whereas those linked via any of the six other ubiquitin lysines can alter the function of the modified protein without leading to degradation. Parkin (PARK2) was found to autoubiquitinate itself predominantly via K6, K27, K29 and K63-linked ubiquitination, rather than via K48 (Durcan et al. 2011).
Identifier: R-HSA-5667111
Species: Homo sapiens
Compartment: cytosol
SNCAIP is ubiquitinated by several different E3 ubiquitin-ligases, including Parkin (PARK2). PARK2 overexpression with SNCAIP in cell culture leads to the formation of protein aggregates (Chung et al. 2001). PARK2 preferentially mediates the addition of lysine-63 (K63)-linked polyubiquitination of SNCAIP (Lim et al. 2005). This leads to SNCAIP degradation only at an unusually high PARK2 to SNCAIP ratio (Lim et al. 2005). K63-linked ubiquitination may be a signal that leads to the degradation of inclusions by autophagy when the ubiquitin-proteasome system is dysfunctional (Lim et al. 2005, Tan et al. 2008).
Identifier: R-HSA-5658574
Species: Homo sapiens
Compartment: cytosol
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 (SNCA). 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 SNCAIP and its interaction with SNCA may be relevant for Lewy body formation in PD.

SNCAIP is ubiquitinated by several different E3 ubiquitin-ligases, including Parkin (PARK2). PARK2 overexpression with SNCAIP in cell culture leads to the formation of protein aggregates (Chung et al. 2001). PARK2 preferentially mediates the addition of lysine-63 (K63)-linked polyubiquitination of SNCAIP (Lim et al. 2005). This leads to SNCAIP degradation only at an unusually high PARK2 to SNCAIP ratio (Lim et al. 2005). K63-linked ubiquitination may be a signal that leads to the degradation of inclusions by autophagy when the ubiquitin-proteasome system is dysfunctional (Lin et al. 2005, Tan et al. 2008).
Identifier: R-HSA-5689085
Species: Homo sapiens
Compartment: cytosol
Ataxin-3 (ATXN3) binds to poly-ubiquitinated Parkin (PARK2) but not unubiquitinated or mono-ubiquitinated PARK2 (Durcan et al. 2011).
Identifier: R-HSA-5688837
Species: Homo sapiens
Compartment: cytosol
Ataxin-3 (ATXN3) deubiquitinates the C-terminus of PARK2 (Parkin) (Winborn et al. 2008, Durcan et al. 2011). This promotes the degradation of PARK2.

An unstable CAG trinucleotide repeat expansion in the ATXN3 gene leads to elongation of the polyglutamine (polyQ) tract within the ATXN3 protein, and is believed to be the cause of Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3), the most common dominantly inherited form of ataxia (Martins et al. 2007). Both wild-type and polyQ-expanded ATXN3 can deubiquitinate PARK2, regardless of the lysine residue used to assemble poly-Ub chains. The polyQ-expanded ATXN3 deubiquitinates PARK2 more efficiently than wild-type ATXN3, but the mutant rather than the wild-type ATXN3 promoted the clearance of PARK2 via the autophagy pathway. This apparent contradiction may be due to increased removal of K27- and K29-linked Ub conjugates on PARK2 by the polyQ-expanded ATXN3; Ub conjugates linked in this manner to PARK2 may protect it from autophagic degradation (Durcan et al. 2011).
Identifier: R-HSA-5696872
Species: Homo sapiens
Compartment: mitochondrial outer membrane, cytosol
USP30 is a deubiquitinating enzyme that associates with the mitochondrial outer membrane. RNAi depletion of USP30 induces elongated, interconnected mitochondria, suggesting that USP30 contributes to mitochondrial morphology (Nakamura & Hirose 2008). Overexpression of USP30 removes ubiquitin attached to damaged mitochondria by PARK2 (Parkin), preventing PARK2-induced mitophagy, whereas reducing USP30 enhances mitochondrial degradation in neurons. Multiple mitochondrial substrates were found to be oppositely regulated by PARK2 and USP30. Knockdown of USP30 rescues defective mitophagy caused by pathogenic mutations in parkin and improves mitochondrial integrity in parkin- or Pink1-deficient flies. Knockdown of Usp30 in dopaminergic neurons protects flies against paraquat toxicity in vivo, ameliorating defects in dopamine levels, motor function, and organismal survival (Bingol et al. 2014).

Complex (4 results from a total of 4)

Identifier: R-HSA-5205683
Species: Homo sapiens
Compartment: mitochondrial outer membrane
Identifier: R-HSA-5689586
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-5658565
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-5689561
Species: Homo sapiens
Compartment: cytosol

Interactor (1 results from a total of 1)

Identifier: O60260-5
Species: Homo sapiens
Primary external reference: UniProt: O60260-5

Icon (1 results from a total of 1)

Species: Homo sapiens
E3 ubiquitin-protein ligase parkin
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