InterPro

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 [PMID: 7845226]. The ubiquitin is released by cleavage from the bound protein by a protease [PMID: 7845226]. A number of deubiquitinising proteases are known: all are activated by thiol compounds [PMID: 7845226, PMID: 3015923], and inhibited by thiol-blocking agents and ubiquitin aldehyde [PMID: 7845226, PMID: 3031653], and as such have the properties of cysteine proteases [PMID: 7845226].

The deubiquitinsing proteases can be split into 2 size ranges: 20-30 kDa (this entry) and 100-200 kDa (IPR001394) [PMID: 7845226]. The 20-30 kDa group includes the yeast yuh1, which is known to be active only against small ubiquitin conjugates, being inactive against conjugated beta-galactosidase [PMID: 7845226]. A mammalian homologue, UCH (ubiquitin conjugate hydrolase), is one of the most abundant proteins in the brain [PMID: 7845226]. 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 of the cysteine/histidine spacing of a cysteine protease catalytic dyad [PMID: 7845226].