PARK2

From Ganfyd

Jump to: navigation, search

The PARK2 gene at 6q26 codes for the 441 amino acid E3 ubiquitin-protein ligase parkin. This is a component of the multiprotein E3 ubiquitin ligase complex, and catalyzes the covalent attachment of ubiquitin onto substrate proteins, a process important in autophagy. It participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of these misfolded proteins. Phosphorylation at Ser-65 by mitochondrial serine/threonine-protein kinase PINK1 and binding to phosphorylated ubiquitin, leads to unlocking of repression of the catalytic Cys-431 by the RING-0 region via an allosteric mechanism and converting it to its fully-active form.

PARK2 (OMIM:600116) is also used as the term for a recessive form of juvenile familial Parkinson's disease caused by homozygous or compound heterozygous mutations in PARK2. Those affected have more prominant disorders of retropulsion, dystonia of the feet, and hyperreflexia than is usual in later onset Parkinson's disease. There is response to levodopa.

Personal tools