Protein ubiquitination is a fundamental mechanism that affects nearly all aspects of cellular life. Deubiquitinating enzymes (DUBs) play important roles in ubiquitin (Ub) signaling by Ub cleavage from adducts. The Ub C-terminal hydrolase (UCH) family of deubiquitinases (DUBs) contains four members including UCH37 (also called ubiquitin carboxy-terminal hydrolase isozyme L5, UCHL-5) and BAP1 which share high similarity in the catalytic domain (UCH) and the C-terminal region, termed the UCH37-like domain (ULD), responsible for binding interaction partners. The ULD is important for regulation of the DUB activity of BAP1 and UCH-L5 by binding proteins with a DEUBiquitinase ADaptor (DEUBAD) domain, ASXL1 for BAP1, and RPN13 (ADRM1) and INO80G (NFRKB) for UCH-L5 [1,2,3,4,5].

The DEUBAD domain is made of eight α helices that form a helical bundle surrounding a compact hydrophobic core (see <PDB:2KR0>) [6]. It has a modular architecture with the core (α1-α4), primarily responsible for binding to ULD, and accessory elements that lead to full activation, or inhibition, of the UCH activity [7,8].

The profile we developed covers the entire DEUBAD domain.