This entry represents the DEUBiquitinase ADaptor (DEUBAD) domain from Asx and homologues, which contain a characteristic LXXLL motif [, ], detected in diverse transcription factors, coactivators and co-repressors and is implicated in mediating interactions between them []. This domain interacts with the UCH37-like domain (ULD) from Calypso and BAP1 deubiquitinases (DUBs), an interaction that is required for DUB activity activation [, , , ].
Additional sex combs-like protein 1 (ASXL1) is the vertebrate homologue of Drosophila additional sex combs []. ASXL1 is a polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. ASX is a non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, consisting at least of BAP1 and ASX. The PR-DUB complex specifically mediates the removal of monoubiquitin from H2A [].
Additional sex combs (ASX) is an atypical polycomb group protein, which may be involved in both polycomb group (PcG) and trithorax group (trxG) complexes. PcG and trxG proteins act by forming multiprotein complexes, which are respectively required to maintain the transcriptionally repressive and transcriptionally active state of homeotic genes throughout development. ASX is required for maintenance of stable repression of homeotic genes during Drosophila development []. ASX is a non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, consisting at least of BAP1 and ASX. The PR-DUB complex specifically mediates the removal of monoubiquitin from H2A [].
Protein ubiquitination is a fundamental mechanism that affects nearly all aspects of cellular life. Deubiquitinating enzymes (DUBs) play important roles in ubiquitin (Ub) signalling 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) which is responsible for binding interaction partners and is also involved in the regulation of DUB activity. ULD from BAP1 and UCH-L5 binds the DEUBiquitinase ADaptor (DEUBAD) domain present in their interacting partners, e.g., ASXL1 for BAP1, and RPN13 (ADRM1) and INO80G (NFRKB) for UCH-L5 [, , , , ].This entry represents the DEUBAD domain which consists of eight α-helices that form a helical bundle surrounding a compact hydrophobic core []. It has a modular architecture with the core formed by helices 1-4, primarily responsible for binding to ULD, and accessory elements that lead to full activation, or inhibition, of the UCH activity [, ].
