{PDOC51916}
{PS51916; DEUBAD}
{BEGIN}
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* DEUBAD (DEUBiquitinase ADaptor) domain profile *
**************************************************

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 alpha helices that form a helical bundle
surrounding a  compact hydrophobic core (see <PDB:2KR0>) [6]. It has a modular
architecture with  the core (alpha1-alpha4), 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: March 2020 / First entry.

[ 1] Sanchez-Pulido L., Kong L., Ponting C.P.
     "A common ancestry for BAP1 and Uch37 regulators."
     Bioinformatics 28:1953-1956(2012).
     PubMed=22645167; DOI=10.1093/bioinformatics/bts319
[ 2] Jiao L., Ouyang S., Shaw N., Song G., Feng Y., Niu F., Qiu W., Zhu H.,
     Hung L.W., Zuo X., Eleonora Shtykova V., Zhu P., Dong Y.-H., Xu R.,
     Liu Z.-J.
     "Mechanism of the Rpn13-induced activation of Uch37."
     Protein. Cell. 5:616-630(2014).
     PubMed=24752541; DOI=10.1007/s13238-014-0046-z
[ 3] Sahtoe D.D., van Dijk W.J., Ekkebus R., Ovaa H., Sixma T.K.
     "BAP1/ASXL1 recruitment and activation for H2A deubiquitination."
     Nat. Commun. 7:10292-10292(2016).
     PubMed=26739236; DOI=10.1038/ncomms10292
[ 4] 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."
     Nat. Commun. 9:4385-4385(2018).
     PubMed=30349006; DOI=10.1038/s41467-018-06854-2
[ 5] Foglizzo M., Middleton A.J., Burgess A.E., Crowther J.M.,
     Dobson R.C.J., Murphy J.M., Day C.L., Mace P.D.
     "A bidentate Polycomb Repressive-Deubiquitinase complex is required
     for efficient  activity on nucleosomes."
     Nat. Commun. 9:3932-3932(2018).
     PubMed=30258054; DOI=10.1038/s41467-018-06186-1
[ 6] Chen X., Lee B.-H., Finley D., Walters K.J.
     "Structure of proteasome ubiquitin receptor hRpn13 and its activation
     by the scaffolding protein hRpn2."
     Mol. Cell. 38:404-415(2010).
     PubMed=20471946; DOI=10.1016/j.molcel.2010.04.019
[ 7] Sahtoe D.D., van Dijk W.J., El Oualid F., Ekkebus R., Ovaa H.,
     Sixma T.K.
     "Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in
     RPN13 and INO80G."
     Mol. Cell. 57:887-900(2015).
     PubMed=25702870; DOI=10.1016/j.molcel.2014.12.039
[ 8] De I., Chittock E.C., Groetsch H., Miller T.C.R., McCarthy A.A.,
     Mueller C.W.
     "Structural Basis for the Activation of the Deubiquitinase Calypso by
     the Polycomb Protein ASX."
     Structure 27:528-536.e4(2019).
     PubMed=30639226; DOI=10.1016/j.str.2018.11.013

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