STANDARD_NAME	BIOCARTA_PARKIN_PATHWAY
SYSTEMATIC_NAME	M13917
COLLECTION	C2:CP:BIOCARTA
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BIOCARTA_PARKIN_PATHWAY
NAMESPACE	HUMAN_SEQ_ACCESSION
DESCRIPTION_BRIEF	Role of Parkin in the Ubiquitin-Proteasomal Pathway
DESCRIPTION_FULL	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.
PMID	
GEOID	
AUTHORS	
CONTRIBUTOR	BioCarta
CONTRIBUTOR_ORG	BioCarta
EXACT_SOURCE	
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	https://data.broadinstitute.org/gsea-msigdb/msigdb/biocarta/human/h_parkinPathway.gif
SOURCE_MEMBERS	BC017241,BF966147,NM_000345,NM_001005781,NM_001005782,NM_001009939,NM_001146054,NM_001146055,NM_001202489,NM_001242935,NM_002688,NM_003342,NM_003343,NM_003352,NM_005302,NM_005460,NM_007308,NM_080678,NM_182688
GENE_SYMBOLS	UBE2G2,,SNCA,SUMO1,SUMO1,SEPTIN5,SNCA,SNCA,UBE2G2,SNCAIP,SEPTIN5,UBE2G1,UBE2G2,SUMO1,GPR37,SNCAIP,SNCA,UBE2F,UBE2G2
FOUNDER_NAMES