in part podocyte hypertrophy. Protein structure Human UCH-L1 and the closely related protein UCHL3 have one of the most complicated knot structure yet discovered for a protein, with five knot crossings. It is speculated that a knot structure may increase a protein's resistance to degradation in the proteasome. The conformation of the UCH-L1 protein may also be an important indication of neuroprotection or pathology. For example, the UCH-L1 dimer has been shown to exhibit the potentially pathogenic ligase activity and may lead to the aforementioned increase in aggregation of α-synuclein. The S18Y polymorphism of UCH-L1 has been shown to be less-prone to dimerization. Interactions Ubiquitin carboxy-terminal hydrolase L1 has been shown to interact with COP9 constitutive photomorphogenic homolog subunit 5. UCH-L1 has also been shown to interact with α-synuclein, another protein implicated in the pathology of Parkinson disease. This activity is reported to be the result of its ubiquityl ligase activity which may be associated with the I93M pathogenic mutation in the gene. Most recently, UCH-L1 has been demonstrated to interact with the E3 ligase, parkin. Parkin has been demonstrated to bind and ubiquitinylate UCH-L1 to promote lysosomal degradation of UCH-L1. See also Ubiquitin carboxyl-terminal esterase L3—the gene UCHL3 Alpha synuclein Parkinson disease Proteasome References Further reading External links EC 3.1.2 Molecular neuroscience