• Activity

  Reaction conditions will need to be optimized for each specific application.  As supplied, Parkin C431S has no E3 ligase activity as determined by the lack of autoubiquitination in an      in vitro assay.

• Source

  Spodoptera frugiperda,     Sf 21 (baculovirus)-derived Contains a substitution at Cys431Ser

• Accession #

• Predicted Molecular Mass

  52 kDa

Background: Parkin

The E3 Ubiquitin ligase Parkin (encoded by the PARK2 gene) is an essential part of the cellular machinery that participates in the removal of damaged mitochondria. Mutations in PARK2 are known to cause a form of Parkinson's disease known as autosomal recessive juvenile Parkinson's disease (AR-JP), and the mechanisms by which defective Parkin ligase contributes to the dopaminergic cell death in this disease is an area of intense investigation.

Reported substrates for Parkin include BCL2, GPR37, MIRO1, MFN1, MFN2, TOMM20, USP30, and many others. Parkin (an RBR-class Ubiquitin ligase) structures have recently been reported by multiple groups, and reveal that the ligase is folded upon itself to produce an auto-inhibited state. The auto-inhibition is relieved by interactions with PINK1 kinase (which can phosphorylate both Parkin and Ubiquitin at serine residue number 65) and pS65 phospho-Ubiquitin by mechanisms that are under investigation.

In vitro, wild-type Parkin may be activated by treatment with recombinant PINK1, or addition of low concentrations of pS65-phosphoubiquitin.  Parkin has been reported to generate poly-Ubiquitin chains in K6, K11, K48, and K63 linkages both in vitro and in vivo.  This recombinant protein is untagged, and is not active as determined by an autoubiquitination assay--it is intended as a negative control.

• References:

1. Bingol, B.         et al. (2014)         Nature         510: 370

2. Ordureau, A.         et al. (2014)         Mol. Cell         56: 360

3. Riley, B.E.         et al. (2013)         Nat. Comm.         4: doi:10.1038/ncomms2982

4. Saraff, S.A.         et al. (2013)         Nature         496: 372

5. Spratt, D.E.         et al. (2013)         Nat. Comm.         4: doi:10.1038/ncomms2983

6. Trempe, J.F.         et al. (2013)         Science         340: 1451

7. Wauer T.         etal. (2015)         Nature         524: 370

8. Wauer T. & Komander, D. (2013) EMBO J         32: 2099

• Long Name:

  Parkinson Disease [autosomal recessive, juvenile] 2, Parkin [PARK2], transcript variant 1

• Entrez Gene IDs:

  5071 (Human); 50873 (Mouse); 56816 (Rat)

• Alternate Names:

  AR-JP; E3 ubiquitin ligase; E3 ubiquitin-protein ligase parkin; EC 6.3.2.-; LPRS2; PARK2; parkin 2; Parkin; Parkinson disease protein 2; Parkinson juvenile disease protein 2; parkinson protein 2, E3 ubiquitin protein ligase (parkin); PDJ; PDJjuvenile) 2, parkin; PRKN