NCBI CDD Logo
?
cl08306: Peptidase_C12 Superfamily 
Click on image for an interactive view with Cn3D
Cysteine peptidase C12 contains ubiquitin carboxyl-terminal hydrolase (UCH) families L1, L3, L5 and BAP1
The ubiquitin C-terminal hydrolase (UCH; ubiquitinyl hydrolase; ubiquitin thiolesterase) family of deubiquitinating enzymes (DUBs) consists of four members to date: UCH-L1, UCH-L3, UCH-L5 (UCH37) and BRCA1-associated protein-1 (BAP1), all containing a conserved catalytic domain with cysteine peptidase activity. UCH-L1 hydrolyzes carboxyl terminal esters and amides of ubiquitin (Ub). Dysfunction of this hydrolase activity can lead to an accumulation of alpha-synuclein, which is linked to Parkinson's disease (PD) and neurofibrillary tangles, linked to Alzheimer's disease (AD). UCH-L1, in its dimeric form, has additional enzymatic activity as a ubiquitin ligase. UCH-L3 hydrolyzes isopeptide bonds at the C-terminal glycine of either Ub or Nedd8, a ubiquitin-like protein. UCH-L3 can also interact with Lys48-linked Ub dimers to protect it from degradation while inhibiting its hydrolase activity at the same time. UCH-L1 and UCH-L3 are the most closely related of the UCH members. UCH-L5 (UCH37) is involved in the deubiquitinating activity in the 19S proteasome regulatory complex. It is also associated with the human Ino80 chromatin-remodeling complex (hINO80) in the nucleus. BAP1 binds to the wild-type BRCA1 RING finger domain, localized in the nucleus. It consists of the N-terminal UCH domain and two predicted nuclear localization signals (NLSs), only one of which is functional. The full-length human BRCA1 is a ubiquitin ligase. However, BAP1 does not appear to function in the deubiquitination of autoubiquitinated BRCA1. There is growing evidence that UCH enzymes and human malignancies are closely correlated. Studies show that UCH enzymes play a crucial role in some signaling pathways and in cell-cycle regulation.
Links
?
Taxonomy: Eukaryota
PubMed: 36 links
Book:
Protein: Related Protein
Related Structure
Statistics
?
Accession: cl08306
PSSM Id: 263579
Name: Peptidase_C12
Created: 8-Feb-2008
Updated: 16-Jan-2014
Superfamily
Click to see Superfamily Help
Curated CD Hierarchy
Click to see Curated CD Hierarchy Help
cd02255:Peptidase_C12cd09616:Peptidase_C12_UCH_L1_L3cd09617:Peptidase_C12_UCH37_BAP1
CD Hierarchy
Imported CD
Click to see Imported CD Help
     
Citing CDD
Marchler-Bauer A et al. (2013), "CDD: conserved domains and protein three-dimensional structure.", Nucleic Acids Res. 41(D1):D384-52.
| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
Click on image for an interactive view with Cn3D