This report describes neurodegenerative disease modeled by the Drosophila ubiquilin gene Ubqn. There are five ubiquilin genes in human, at least one of which (UBQLN2) is implicated in neurodegenerative disease. Ubiquilins are a family of ubiquitin-like proteins that play a role in the regulation of different protein degradation pathways and are thought to functionally link the ubiquitination machinery to the proteasome. In Drosophila, Ubqn is the highest-scoring ortholog of all five human genes; a less similar ubiquilin gene, CG31528, is also present in D. melanogaster. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\Ubqn.
Multiple UAS constructs of the human Hsap\UBQLN2 gene have been introduced into flies, including wild-type and variants associated with ALS15; see the human disease model report 'amyotrophic lateral sclerosis 15' (FBhh0000823).
Ubiquitous reduction in Dmel\Ubqn expression effected by RNAi results in lethality. Neuronal reduction effected by RNAi results in locomotor and neuranatomy defects; accumulation of polyubiquitinated proteins is observed. Physical and genetic interactions of Dmel\Ubqn have been described; see below and in the Ubqn gene report.
[updated Jun. 2018 by FlyBase; FBrf0222196]
Ubiquilins encode ubiquitin-like proteins that plays a role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and the endoplasmic reticulum-associated protein degradation (ERAD) pathway. They physically associate with both proteasomes and ubiquitin ligases, thus, are thought to functionally link the ubiquitination machinery to the proteasome. [Gene Cards, UBQLN1, UBQLN2; 2018.06.29]
High-scoring ortholog of human UBQLN1, UBQLN2, UBQLN4; moderate-scoring ortholog of UBQLNL and UBQLN3 (2 Drosophila to 5 human). Dmel\Ubqn shares 46-50% identity and 63-67% similarity with UBQLN1, UBQLN2, UBQLN4; it shares 26-32% identity and 44-46% similarity with UBQLNL and UBQLN3.