GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:10888878

From GONUTS
Jump to: navigation, search
Citation

Shimura, H, Hattori, N, Kubo, S, Mizuno, Y, Asakawa, S, Minoshima, S, Shimizu, N, Iwai, K, Chiba, T, Tanaka, K and Suzuki, T (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat. Genet. 25:302-5

Abstract

Autosomal recessive juvenile parkinsonism (AR-JP), one of the most common familial forms of Parkinson disease, is characterized by selective dopaminergic neural cell death and the absence of the Lewy body, a cytoplasmic inclusion body consisting of aggregates of abnormally accumulated proteins. We previously cloned PARK2, mutations of which cause AR-JP (ref. 2), but the function of the gene product, parkin, remains unknown. We report here that parkin is involved in protein degradation as a ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7, and that mutant parkins from AR-JP patients show loss of the ubiquitin-protein ligase activity. Our findings indicate that accumulation of proteins that have yet to be identified causes a selective neural cell death without formation of Lewy bodies. Our findings should enhance the exploration of the molecular mechanisms of neurodegeneration in Parkinson disease as well as in other neurodegenerative diseases that are characterized by involvement of abnormal protein ubiquitination, including Alzheimer disease, other tauopathies, CAG triplet repeat disorders and amyotrophic lateral sclerosis.

Links

PubMed Online version:10.1038/77060

Keywords

Humans; Ligases/genetics; Ligases/metabolism; Parkinson Disease/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Tumor Cells, Cultured; Ubiquitin-Conjugating Enzymes; Ubiquitin-Protein Ligases; Ubiquitins/genetics; Ubiquitins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PRKN

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P68036

F

Seeded From UniProt

complete

HUMAN:UB2L3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60260

F

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UB2L3

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UB2L3

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.