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>) . 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.
Daou S. Barbour H. Ahmed O. Masclef L. Baril C. Sen Nkwe N. Tchelougou D. Uriarte M. Bonneil E. Ceccarelli D. Mashtalir N. Tanji M. Masson J.Y. Thibault P. Sicheri F. Yang H. Carbone M. Therrien M. Affar E.B.
Monoubiquitination of ASXLs controls the deubiquitinase activity of the tumor suppressor BAP1.
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