Description
Product Characteristics: Function: Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. These substrates include SYT11, CCNE1, GPR37, STUB1, a 22 kDa O-linked glycosylated isoform of SNCAIP and SEPT5. May play a more general role in the ubiquitin proteasomal pathway by participating in the removal and/or detoxification of abnormally folded or damaged protein. Loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of PARK2. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. Regulates cyclin E during neuronal apoptosis. May represent a tumor suppressor gene.
Subcellular location: Cytoplasm. Nucleus. Note: Co-localizes with SYT11 in neutrites. Co-localizes with SNCAIP in brainstem Lewy bodies.
Tissue specificity: Highly expressed in the brain including the substantia nigra. Expressed in heart, testis and skeletal muscle. Expression is down-regulated or absent in tumor biopsies, and absent in the brain of PARK2 patients. Overexpression protects dopamine neurons from kainate-mediated apoptosis. Also known as: AR JP, E3 ubiquitin protein ligase parkin, FRA6E, LPRS 2, LPRS2, PARK 2, PARK2, Parkinson disease (autosomal recessive juvenile) 2, Parkinson disease protein 2, Parkinson juvenile disease protein 2, PDJ, PRKN 2, PRKN, PRKN2, Ubiquitin E3 ligase PRKN.
Target Information: The precise function of this gene is unknown\, however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]