PROSITE documentation PDOC52049UCH37-like (ULD) domain profile
Ubiquitin (see <PDOC00271>) is a small (8.6 kDa) highly conserved protein that is best known for its role in targeting proteins for degradation by the 26S proteasome. Ubiquitin has been implicated in numerous cellular processes, including cell cycle control, oncoprotein degradation, receptor function, apoptosis, regulation of transcription, stress responses, maintenance of chromatin structure, DNA repair, signaling pathways, antigen presentation and the degradation of abnormal proteins. Ubiquitination works as a reversible post-translational modification, like phosphorylation. Deubiquitinating enzymes, or DUBs, can hydrolytically remove ubiquitin from protein adducts, thereby opposing the action of ubiquitin conjugating machinery. The DUBs family consists of five distinct subfamilies. Four sub-families are papain-like cysteine proteases: the ubiquitin C-terminal hydrolases (UCHs), the ubiquitin-specific proteases (USPs/UBPs) (see <PDOC00750>), the ovarian tumor (OTU) domain (see <PDOC50802>), and the Josephin domain (MJD) (see <PDOC50957>) DUBs. The fifth family is a collection of zinc-dependent metalloproteases, for example the JAB1.MPN/Mov34 metalloenzyme (JAMM) domain protease (see <PDOC50249>) [1,2,3,4].
The UCH DUB subfamily includes UCH-L1, UCH-L3, UCHL5 (UCH37), and BRCA1-associated protein-1 (BAP1). UCHs are cysteine proteases that share a canonical catalytic domain (see <PDOC52048>), the minimal module for Ub binding and hydrolysis. BAP1 and UCH-L5 also have C-terminal domains, including a 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 (see <PDOC51916>). The ULDs adopt a wide range of positions relative to the UCH. Activator and inhibitor may lock this domain in particular conformations. As a consequence of the ULD's proximity to the ubiquitin docking site, some of these conformations are sterically incompatible with ubiquitin binding while others allow efficient ubiquitin binding [5,6,7].
The ULD has two α helices and provides the main binding platform for the DEUBAD (see <PDB:6HGC>) [6].
Some proteins known to contain an ULD are listed below:
- Mamalian UCH-L5/UCH37.
- Mamalian BRCA1 (breast cancer early-onset 1)-associated protein 1 (BAP1), a deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1.
- Insect Calypso, the homologue of BAP1, binds to the polycomb repressor DUB complex. It can remove monoUb (mono-ubiquitin) from histone H2A.
- Yeast YUH1.
The profile we developed covers the entire ULD.
Last update:September 2024 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Johnston S.C. Larsen C.N. Cook W.J. Wilkinson K.D. Hill C.P. |
| Title | Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution. | |
| Source | EMBO. J. 16:3787-3796(1997). | |
| PubMed ID | 9233788 | |
| DOI | 10.1093/emboj/16.13.3787 |
| 2 | Authors | Johnston S.C. Riddle S.M. Cohen R.E. Hill C.P. |
| Title | Structural basis for the specificity of ubiquitin C-terminal hydrolases. | |
| Source | EMBO. J. 18:3877-3887(1999). | |
| PubMed ID | 10406793 | |
| DOI | 10.1093/emboj/18.14.3877 |
| 3 | Authors | Nishio K. Kim S.-W. Kawai K. Mizushima T. Yamane T. Hamazaki J. Murata S. Tanaka K. Morimoto Y. |
| Title | Crystal structure of the de-ubiquitinating enzyme UCH37 (human UCH-L5) catalytic domain. | |
| Source | Biochem. Biophys. Res. Commun. 390:855-860(2009). | |
| PubMed ID | 19836345 | |
| DOI | 10.1016/j.bbrc.2009.10.062 |
| 4 | Authors | Morrow M.E. Kim M.-I. Ronau J.A. Sheedlo M.J. White R.R. Chaney J. Paul L.N. Lill M.A. Artavanis-Tsakonas K. Das C. |
| Title | Stabilization of an unusual salt bridge in ubiquitin by the extra C-terminal domain of the proteasome-associated deubiquitinase UCH37 as a mechanism of its exo specificity. | |
| Source | Biochemistry 52:3564-3578(2013). | |
| PubMed ID | 23617878 | |
| DOI | 10.1021/bi4003106 |
| 5 | Authors | Sanchez-Pulido L. Kong L. Ponting C.P. |
| Title | A common ancestry for BAP1 and Uch37 regulators. | |
| Source | Bioinformatics 28:1953-1956(2012). | |
| PubMed ID | 22645167 | |
| DOI | 10.1093/bioinformatics/bts319 |
| 6 | Authors | De I. Chittock E.C. Groetsch H. Miller T.C.R. McCarthy A.A. Mueller C.W. |
| Title | Structural Basis for the Activation of the Deubiquitinase Calypso by the Polycomb Protein ASX. | |
| Source | Structure 27:528-536.e4(2019). | |
| PubMed ID | 30639226 | |
| DOI | 10.1016/j.str.2018.11.013 |
| 7 | Authors | Sahtoe D.D. van Dijk W.J. El Oualid F. Ekkebus R. Ovaa H. Sixma T.K. |
| Title | Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in RPN13 and INO80G. | |
| Source | Mol. Cell. 57:887-900(2015). | |
| PubMed ID | 25702870 | |
| DOI | 10.1016/j.molcel.2014.12.039 |
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