Parkin (ligase)

Parkin (ligase)

Identifiers Symbols PARK2; AR-JP; LPRS2; PDJ; PRKN External IDs OMIM: 602544 MGI: 1355296 HomoloGene: 3355 GeneCards: PARK2 Gene EC number 6.3.2.19

Gene Ontology
Molecular function	• ubiquitin-protein ligase activity • protein binding • zinc ion binding • kinase binding • protein kinase binding • PDZ domain binding • ubiquitin protein ligase binding • chaperone binding
Cellular component	• nucleus • cytoplasm • mitochondrion • endoplasmic reticulum • Golgi apparatus • cytosol • aggresome • perinuclear region of cytoplasm
Biological process	• protein polyubiquitination • mitochondrion degradation • negative regulation of protein phosphorylation • ubiquitin-dependent protein catabolic process • protein monoubiquitination • central nervous system development • cell death • regulation of autophagy • negative regulation of actin filament bundle assembly • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • positive regulation of I-kappaB kinase/NF-kappaB cascade • negative regulation of neuron apoptotic process • protein autoubiquitination • negative regulation of cell death • protein K63-linked ubiquitination • aggresome assembly • protein K48-linked ubiquitination • neuron death • negative regulation of release of cytochrome c from mitochondria • regulation of reactive oxygen species metabolic process
Sources: Amigo / QuickGO

RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez 5071 50873 Ensembl ENSG00000185345 ENSMUSG00000023826 UniProt O60260 Q9WVS6 RefSeq (mRNA) NM_004562.2 NM_016694.3 RefSeq (protein) NP_004553.2 NP_057903.1 Location (UCSC) Chr 6:
161.77 – 163.15 Mb Chr 17:
11.07 – 11.64 Mb PubMed search

Parkin is a protein which in humans is encoded by the PARK2 gene. The precise function of this protein is unknown; however, the protein is a component of a multiprotein E3 ubiquitin ligase complex which in turn is part of the ubiquitin-proteasome system that mediates the targeting of proteins for degradation. Mutations in this gene are known to cause a familial form of Parkinson's disease known as autosomal recessive juvenile Parkinson disease.

How loss of function of the parkin protein leads to dopaminergic cell death in this disease is unclear. The prevailing hypothesis is that parkin helps degrade one or more proteins toxic to dopaminergic neurons. Putative substrates of parkin include synphilin-1, CDC-rel1, cyclin E, p38 tRNA synthase, Pael-R, synaptotagmin XI, sp22 and parkin itself (see also ubiquitin ligase). Additionally, Parkin contains a C-terminal motif that binds PDZ domains. Parkin has been shown to associate in a PDZ dependent manner with the PDZ domain containing proteins CASK and PICK1.