InterPro domain: IPR036959

This group of cysteine peptidases belong to the MEROPS peptidase family C12 (ubiquitin C-terminal hydrolase family, clan CA). Families within the CA clan are loosely termed papain-like as protein fold of the peptidase unit resembles that of papain, the type example for clan CA. The type example is the human ubiquitin C-terminal hydrolase UCH-L1.

Ubiquitin is highly conserved, commonly found conjugated to proteins in eukaryotic cells, where it may act as a marker for rapid degradation, or it may have a chaperone function in protein assembly [ 1 ]. The ubiquitin is released by cleavage from the bound protein by a protease [ 2 ]. A number of deubiquitinising proteases are known: all are activated by thiol compounds [ 2 , 2 ], and inhibited by thiol-blocking agents and ubiquitin aldehyde [ 3 , 3 ], and as such have the properties of cysteine proteases [ 4 ].

The deubiquitinsing proteases can be split into 2 size ranges: 20-30kDa (this entry) and 100-200kDa ( IPR001394 ) [ 4 ]. The 20-30kDa group includes the yeast yuh1, which is known to be active only against small ubiquitin conjugates, being inactive against conjugated beta-galactosidase [ 4 ]. A mammalian homologue, UCH (ubiquitin conjugate hydrolase), is one of the most abundant proteins in the brain [ 4 ]. Only one conserved cysteine can be identified, along with two conserved histidines. The spacing between the cysteine and the second histidine is thought to be more representative ofthe cysteine/histidine spacing of a cysteine protease catalytic dyad [ 4 ].

1. Families of cysteine peptidases. Meth. Enzymol. 244, 461-86
2. Mechanism of ubiquitin carboxyl-terminal hydrolase. Borohydride and hydroxylamine inactivate in the presence of ubiquitin. J. Biol. Chem. 261, 10210-7
3. Ubiquitin-aldehyde: a general inhibitor of ubiquitin-recycling processes. Proc. Natl. Acad. Sci. U.S.A. 84, 1829-33