Parkin (ligase)

Parkin is a is_associated_with::protein which in humans is encoded by the PARK2 is_associated_with::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 is_associated_with::ubiquitin-proteasome system that mediates the targeting of proteins for degradation. Mutations in this gene are known to cause a familial form of is_associated_with::Parkinson's disease known as autosomal recessive juvenile Parkinson's disease (AR-JP).

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

Parkinson's disease
PARK2 (is_associated_with::OMIM *602544) is the parkin gene that may cause a form of autosomal recessive juvenile Parkinson disease (is_associated_with::OMIM 600116) due to a mutation in the parkin protein. This form of genetic mutation may be one of the most common known genetic causes of early-onset is_associated_with::Parkinson disease. In one study of patients with onset of Parkinson disease prior to age 40 (10% of all PD patients), 18% had parkin mutations, with 5% is_associated_with::homozygous mutations. Patients with an autosomal recessive family history of parkinsonism are much more likely to carry parkin mutations if age at onset is less than 20 (80% vs. 28% with onset over age 40).

Patients with parkin mutations (PARK2) do not have Lewy bodies. Such patients develop a syndrome that closely resembles the sporadic form of PD; however, they tend to develop symptoms at a much younger age.

Interactions
Parkin (ligase) has been shown to interact with:


 * is_associated_with::Alpha-synuclein,
 * is_associated_with::CASK,
 * is_associated_with::CUL1,
 * is_associated_with::FBXW7 and
 * is_associated_with::GPR37,
 * is_associated_with::HSPA1A,
 * is_associated_with::HSPA8,
 * is_associated_with::Multisynthetase complex auxiliary component p38,
 * is_associated_with::PDCD2,
 * is_associated_with::SEPT5,
 * is_associated_with::SNCAIP,
 * is_associated_with::STUB1,
 * is_associated_with::SYT11, and
 * is_associated_with::Ubiquitin C.