PROSITE documentation PDOC50600

Ubiquitin-like protease family profile

Deubiquitinating enzymes (DUB) form a large family of cysteine protease that can deconjugate ubiquitin or ubiquitin-like proteins from ubiquitin-conjugated proteins. They can be classified in 3 families according to sequence homology [1,2]: ubiquitin carboxyl-terminal hydrolases (UCH) (see <PDOC00127>), ubiquitin-specific processing proteases (UBP) (see <PDOC00750>), and ubiquitin-like proteases (ULP) (EC 3.4.22.68) specific for deconjugating ubiquitin-like proteins. In contrast to the UBP pathway, which is very redundant (16 UBP enzymes in yeast), there is few ubiquitin-like protease (only one in yeast, ULP1).

ULP1 catalyses two critical functions in the SUMO/Smt3 pathway via its cysteine protease activity. ULP1 processes the Smt3 C-terminal sequence (-GGATY) to its mature form (-GG), and it deconjugates Smt3 from the lysine epsilon-amino group of the target protein [3].

Crystal structure of yeast ULP1 bound to Smt3 [4] revealed that the catalytic and interaction interface is situated in a shallow and narrow cleft where conserved residues recognize the Gly-Gly motif at the C-terminal extremity of Smt3 protein. Ulp1 adopts a novel architecture despite some structural similarity with other cysteine protease. The secondary structure is composed of seven α helices and seven β strands. The catalytic domain includes the central α helix, β-strands 4 to 6, and the catalytic triad (Cys-His-Asp) (see <PDB:1EUV>).

We developed a profile directed against the C-terminal part of ULP proteins that displays full proteolytic activity [4].