InterPro domain: IPR033841

Ubiquitin carboxyl-terminal hydrolases (UCH) ( 3.1.2.12 ) [ 1 ] are thiol proteases that recognise and hydrolyse the peptide bond at the C-terminal glycine of ubiquitin. These enzymes are involved in the processing of poly-ubiquitin precursors as well as that of ubiquinated proteins. The deubiquitinsing proteases can be split into 2 size ranges, 20-30kDa( IPR001578 ) and 100-200kDa [ 2 ]: the second class consist of large proteins (800 to 2000 residues) that belong to the peptidase family C19, and this group is currently represented by yeast UBP1 [ 3 ].

This entry contains the peptidase domain for ubiquitin-specific peptidase 48 (USP48; MEROPS identifier C19.068). In animals, USP48 is found in the nucleus where it trims long Lys48-linked free and substrate-anchored ubiquitin-chains, rather than completely disassembling them; a catalytic property only shared with ataxin-3 and otubain-1. USP48 ubiquitin-chain-trimming activity is regulated by casein-kinase-2-mediated phosphorylation in response to cytokine-stimulation. USP48 controls the turnover of activated NF-kB/RelA in the nucleus together with the CSN and contributes to a timely control of immune responses [ 4 ].

In plants, the gene name is USP26, which should not be confused with USP26 from mammals. USP26 deubiquitinates histone H2B and is required for heterochromatin silencing [ 5 ].

1. Genetic analysis of the ubiquitin system. Biochim. Biophys. Acta 1089, 127-39
2. Families of cysteine peptidases. Meth. Enzymol. 244, 461-86
3. Cloning and functional analysis of the ubiquitin-specific protease gene UBP1 of Saccharomyces cerevisiae. J. Biol. Chem. 266, 12021-8
4. CSN-associated USP48 confers stability to nuclear NF-κB/RelA by trimming K48-linked Ub-chains. Biochim. Biophys. Acta 1853, 453-69
5. UBIQUITIN-SPECIFIC PROTEASE 26 is required for seed development and the repression of PHERES1 in Arabidopsis. Genetics 180, 229-36