PROSITE documentation PDOC52048Ubiquitin carboxyl-terminal hydrolase (UCH) catalytic 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].
UCHs are deubiquitinating enzymes which hydrolyze C-terminal esters and amides of ubiquitin. They have a catalytic core domain consisting of about 230 amino acids [3,5].
The UCH catalytic domain is organized around a six-stranded antiparallel β-sheet sandwiched by α-helices on either side to form an α-β-α fold (see <PDB:3RII>). The overall arrangement of secondary structural elements gives an appearance of a bilobal architecture with the active site, harboring a nucleophile Cys, a general base His and an Asp, located in a cleft between the two lobes. A Gln acts as an oxyanion-intermediate stabilizing residue [1,2,3,4,6].
The UCH catalytic domain constitutes the peptidase family C12 [E1].
Some proteins known to contain an UCH catalytic domain are listed below:
- Mamalian UCH-L1/PGP9.5 (protein gene product 9.5), a deubiquitinase that plays a role in the regulation of several processes such as maintenance of synaptic function, cardiac function, inflammatory response or osteoclastogenesis.
- Mamalian UCH-L3.
- 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.
- Drosophila 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 UCH catalytic domain.
Last update:August 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 | Larsen C.N. Krantz B.A. Wilkinson K.D. |
| Title | Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. | |
| Source | Biochemistry 37:3358-3368(1998). | |
| PubMed ID | 9521656 | |
| DOI | 10.1021/bi972274d |
| 6 | Authors | Maiti T.K. Permaul M. Boudreaux D.A. Mahanic C. Mauney S. Das C. |
| Title | Crystal structure of the catalytic domain of UCHL5, a proteasome-associated human deubiquitinating enzyme, reveals an unproductive form of the enzyme. | |
| Source | FEBS. J. 278:4917-4926(2011). | |
| PubMed ID | 21995438 | |
| DOI | 10.1111/j.1742-4658.2011.08393.x |
| E1 | Title | https://www.ebi.ac.uk/merops/cgi-bin/famsum?family=C12 |
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