UBQLN2

Ubiquilin-2 is a is_associated_with::protein that in humans is encoded by the UBQLN2 is_associated_with::gene.

Function
This gene encodes a is_associated_with::ubiquitin-like protein (is_associated_with::ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both is_associated_with::proteasomes and is_associated_with::ubiquitin ligases, and are thus thought to functionally link the ubiquitination machinery to the proteasome to effect in vivo protein degradation. This ubiquilin has also been shown to bind the is_associated_with::ATPase domain of the is_associated_with::Hsp70-like Stch protein.

Similarity to Other Proteins
Human UBQLN2 shares a high degree of similarity with related ubiquilins including is_associated_with::UBQLN1 and is_associated_with::UBQLN4.

Clinical significance
In a small proportion of familial is_associated_with::amyotrophic lateral sclerosis (fALS), the UBQLN2 gene is mutated, causing formation of a non-functional Ubiquilin 2 enzyme. This non-functioning enzyme leads to the accumulation of ubiquinated proteins in the lower motor neurons and upper corticospinal motor neurons, due to the fact that ubiquilin 2 normally degrades these ubiquinated proteins, but cannot if the ALS mutation is present. The same accumulations occur in patients without UBQLN2 mutations, but with mutations in other genes, including TDP-43 and C9ORF72.

Interactions
UBQLN2 has been shown to interact with is_associated_with::HERPUD1 and is_associated_with::UBE3A.