USP46 belongs to the peptidase C19 family, USP12/USP46 subfamily. Deubiquitinating enzymes (DUBs) are a large group of proteases which are also commonly referred to as deubiquitinating peptidases, deubiquitinating isopeptidases, deubiquitinases, ubiquitin proteases, ubiquitin hydrolyases, ubiquitin isopeptidases, or Dubs. They regulate ubiquitin-dependent metabolic pathways by cleaving ubiquitin-protein bonds. They also may act as negative and positive regulators of the ubiquitin system. Besides ubiquitin recycling, they are also involved in processing of ubiquitin precursors, in proofreading of protein ubiquitination and in disassembly of inhibitory ubiquitin chains. USP46 is a deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. It may act by mediating the deubiquitination of GAD1/GAD67. USP46 has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have high activity and it is not involved in deubiquitination of monoubiquitinated FANCD2.
ubiquitin specific peptidase 46
- Joo HY, et al. (2011) Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46. J Biol Chem. 286(9):7190-201.
- Kushima I, et al. (2010) Association study of ubiquitin-specific peptidase 46 (USP46) with bipolar disorder and schizophrenia in a Japanese population. J Hum Genet. 55(3):133-6.
- Cohn MA, et al. (2009) UAF1 is a subunit of multiple deubiquitinating enzyme complexes. J Biol Chem. 284(8):5343-51.