Deubiquitinating enzymes (DUB) form a large family of cysteine protease that can deconjugate ubiquitin or ubiquitin-like proteins from ubiquitin-conjugated proteins. All DUBs contain a catalytic domain surrounded by one or more subdomains, some of which contribute to target recognition. The ~120-residue DUSP (domain present in ubiquitin-specific proteases) domain is one of these specific subdomains. Single or tandem DUSP domains are located both N- and C-terminal to the ubiquitin carboxyl-terminal hydrolase catalytic core domain [(PUBMED:16298993)].

The DUSP domain displays a tripod-like AB3 fold with a three-helix bundle and a three-stranded anti-parallel beta-sheet resembling the legs and seat of the tripod. Conserved residues are predominantly involved in hydrophobic packing interactions within the three alpha-helices. The most conserved DUSP residues, forming the PGPI motif, are flanked by two long loops that vary both in length and sequence. The PGPI motif packs against the three-helix bundle and is highly ordered [(PUBMED:16298993)].

The function of the DUSP domain is unknown but it may play a role in protein/protein interaction or substrate recognition. This domain is associated with ubiquitin carboxyl-terminal hydrolase family 2 (IPR001394, MEROPS peptidase family C19). They are a family 100 to 200 kDa peptides which includes the Ubp1 ubiquitin peptidase from yeast; others include:

• Mammalian ubiquitin carboxyl-terminal hydrolase 4 (USP4),
• Mammalian ubiquitin carboxyl-terminal hydrolase 11 (USP11),
• Mammalian ubiquitin carboxyl-terminal hydrolase 15 (USP15),
• Mammalian ubiquitin carboxyl-terminal hydrolase 20 (USP20),
• Mammalian ubiquitin carboxyl-terminal hydrolase 32 (USP32),
• Vertebrate ubiquitin carboxyl-terminal hydrolase 33 (USP33),
• Vertebrate ubiquitin carboxyl-terminal hydrolase 48 (USP48).