Gene Set: BIOCARTA_PARKIN_PATHWAY

Standard name BIOCARTA_PARKIN_PATHWAY
Systematic name M13917
Brief description Role of Parkin in the Ubiquitin-Proteasomal Pathway
Full description or abstract The motor defects of Parkinson's disease are related to the loss of dopaminergic neurons in specific brain regions. Examination of these neurons in diseased tissue has revealed the presence of Lewy bodies, dense aggregates that include the protein alpha-synuclein. A genetic basis for most cases of Parkinson's disease has not yet been identified, but mutations in alpha-synuclein have been associated with at least one rare form of the disease, and mutations in another protein, the parkin gene, are associated with another inherited form of Parkinson's disease. Parkin is found in Lewy bodies along with alpha-synuclein and the parkin protein is an E3 ubiquitin ligase. Parkin appears to work in conjuction with ubiquitin activating (Uba)1, an E1 protein and the ubiquitin-conjugating (Ubc) enzymes UbcH7 and 8. The E1 delivers ubiquitin to the E2 in a cycle that creates an increasing chain of ubiquitin. The Parkin E3 ligates this onto substrates and so tags these proteins in normal cells, targeting them for destruction in the proteosome. One of the proteins that parkin normally targets for destruction is a specific O-glycosylated form of alpha-synuclein. Failure of parkin-mediated degradation of alpha-synuclein may be a key factor leading to the death of dopaminergic neurons. Another substrate of parkin is a GPCR-like protein called Pael-R that accumulates in the ER of affected cells and may cause neuronal cell death. The involvement of Parkin and alpha-synuclein mutations in genetic forms of Parkinson's suggest that failure of ubiquitination and protein degradation may be causative in other forms of Parkinson's. Questions remaining include the cause of the lack of effective ubiquitination in individuals lacking obvious genetic defects in this pathway and how to use this knowledge of ubiquitination and protein degradation in Parkinson's disease to identify therapeutic strategies.
Collection C2: curated gene sets
      CP: canonical pathways
            CP:BIOCARTA: BioCarta gene sets
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External links http://www.biocarta.com/pathfiles/h_parkinPathway.asp
http://www.biocarta.com/pathfiles/PathwayProteinList.asp?showPFID=217
Organism Homo sapiens
Contributed by BioCarta
Source platform EntrezGeneIds
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Compute overlaps C1: positional gene sets
C2: curated gene sets
      CGP: chemical and genetic perturbations
      CP: canonical pathways
            CP:BIOCARTA: BioCarta gene sets
            CP:KEGG: KEGG gene sets
            CP:REACTOME: Reactome gene sets
C3: motif gene sets
      MIR: microRNA targets
      TFT: transcription factor targets
C4: computational gene sets
      CGN: cancer gene neighborhoods
      CM: cancer modules
C5: GO gene sets
      BP: GO biological process
      CC: GO cellular component
      MF: GO molecular function
Compendia expression profiles Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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