Protein Variants | Comment | Organism |
---|---|---|
additional information | in UCH-L3 knockout mice, the levels of both Nedd8 and the apoptotic protein p53 and Bax are elevated upon cryptorchid injury, the accumulation of Nedd8-conjugated proteins in UCH-L3 knockout mice contributed to profound germ cell loss via apoptosis | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | UCH-L1 can hydrolyze isopeptide bonds between the C-terminal glycine of Ub and the alpha- or gamma-amino group of lysine on the target proteins. UCH-L3 recognizes and hydrolyzes isopeptide bonds at the C-terminal glycine of either ubiquitin or Nedd8, a ubiquitin-like protein. It shows no ligase activity. UCH-L3 can interact with Lys48-linked ubiquitin dimers to protect it from degradation and meanwhile to inhibit its hydrolase activity, D33 and C95 are essential for the interaction with di-ubiquitin. Neither UCH37 alone nor the UCH37-Adrm1 or UCH37-Adrm1-hRpn2 complexes can hydrolyse Lys48-linked di-ubiquitin efficiently, rather, their incorporation into the 19S complex is required to enable UCH37 to process large ubiquitin protein conjugates such as di-ubiquitin | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
ubiquitination | monoubiquitination is a posttranslational modification of UCH-L1 that controls the function of UCH-L1. It may occur reversibly to a lysine residue near the active site, probably K157, of UCH-L1. This modification restricts enzyme activity by preventing binding to the ubiquitinated targets, and permanent mono-ubiquitination, as mimicked by a ubiquitin-UCH-L1 fusion, inhibits UCH-L1 in its capacity to increase free ubiquitin levels. However, the lifetime of this modification on UCH-L1 is regulated by auto-deubiquitination | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
additional information | UCH-L1 levels are high in various types of malignancies: acute lymphoblastic leukemia, non-small cell lung cancer, neuroblastoma, pancreatic, prostate, medullary thyroid, esophageal, colorectal and renal carcinomas | Homo sapiens | - |
uterine cervix | UCH37 activity is up-regulated in cervical carcinoma biopsies as well as cell lines, while UCH-L1 activity is lower in cervical carcinomas | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | UCH-L1 can hydrolyze isopeptide bonds between the C-terminal glycine of Ub and the alpha- or gamma-amino group of lysine on the target proteins. UCH-L3 recognizes and hydrolyzes isopeptide bonds at the C-terminal glycine of either ubiquitin or Nedd8, a ubiquitin-like protein. It shows no ligase activity. UCH-L3 can interact with Lys48-linked ubiquitin dimers to protect it from degradation and meanwhile to inhibit its hydrolase activity, D33 and C95 are essential for the interaction with di-ubiquitin. Neither UCH37 alone nor the UCH37-Adrm1 or UCH37-Adrm1-hRpn2 complexes can hydrolyse Lys48-linked di-ubiquitin efficiently, rather, their incorporation into the 19S complex is required to enable UCH37 to process large ubiquitin protein conjugates such as di-ubiquitin | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | UCH-L1 can form dimers, whose form seems to act as another enzymatic activity in UCH-L1, ubiquitin ligase activity | Mus musculus |
dimer | UCH-L1 can form dimers, whose form seems to act as another enzymatic activity in UCH-L1, ubiquitin ligase activity | Homo sapiens |
monomer | no dimerization of UCH-L3 | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
More | the enzymes belong to the deubiquitinating enzymes of the protease superfamily, and are cysteine peptidases of subfamily ubiquitin C-terminal hydrolases, UCHs, overview | Mus musculus |
More | the enzymes belong to the deubiquitinating enzymes of the protease superfamily, and are cysteine peptidases of subfamily ubiquitin C-terminal hydrolases, UCHs, overview | Homo sapiens |
Ub isopeptidase | - |
Homo sapiens |
ubiquitin C-terminal hydrolase | - |
Mus musculus |
ubiquitin C-terminal hydrolase | - |
Homo sapiens |
UCH | - |
Mus musculus |
UCH | - |
Homo sapiens |
UCH-L1 | - |
Mus musculus |
UCH-L1 | - |
Homo sapiens |
UCH-L3 | - |
Mus musculus |
UCH-L3 | - |
Homo sapiens |
UCH37 | - |
Mus musculus |
UCH37 | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | UCH enzymes and human malignancies are closely correlated with roles of UCH enzymes in oncogenesis, UCH-L1 enhances tumor cell invasion and migration capability via the Akt-mediated pathway, overview. Dysfunction of UCH-L1 hydrolase activity can lead to an accumulation of alpha-synuclein and neurofibrillary tangles, which links to Parkinson's disease and Alzheimer's disease, respectively. Increased levels of both UCH-L1 and UCH-L3 mRNA are associated with early tumor recurrence of invasive breast cancer and poor prognosis. UCH37 activity is up-regulated in cervical carcinoma biopsies as well as cell lines. UCH-L1 levels are high in various types of malignancies: acute lymphoblastic leukemia, non-small cell lung cancer, neuroblastoma, pancreatic, prostate, medullary thyroid, esophageal, colorectal and renal carcinomas, although lowered in cervical carcinomas | Homo sapiens |
metabolism | UCH-L1 in cell signaling, detailed overview | Mus musculus |
metabolism | UCH-L1 in cell signaling, detailed overview | Homo sapiens |
physiological function | UCH-L1 is responsible for hydrolyzing carboxyl terminal esters and amides of ubiquitin. Additionally, it possesses ubiquitin ligase activity and functions as a mono-ubiquitin stabilizer, which is independent of enzymatic activity, and is also involved in the co-translational processing of pro-ubiquitin and ribosomal proteins translated as ubiquitin fusions. UCH-L3 is a kind of ubiquitin-protein hydrolase involved in the processing of both ubiquitin precursors and ubiquitinated substrates, generating free monomeric ubiquitin. UCH37, different from other UCH members, is responsible for the Ub isopeptidase activity in the 19S proteasome regulatory complex, overview. UCH-L3 shows deneddylating activity, the only target proteins for neddylation are cullins, which are involved in cell-cycle control, therefore UCH-L3 might function as a cell-cycle regulator | Mus musculus |
physiological function | UCH-L1 plays a crucial role in regulating certain signalings. UCH-L1 forms endogenous complexes with beta-catenin, stabilizes it and up-regulates beta-catenin/TCF/Lef-dependent transcription. Reciprocally, as indicated, beta-catenin/TCF/Lef signaling up-regulates the expression of endogenous UCH-L1 mRNA and protein. UCH-L1 is responsible for hydrolyzing carboxyl terminal esters and amides of Ub. Additionally, it possesses ubiquitin ligase activity and functions as a mono-ubiquitin stabilizer, which is independent of enzymatic activity, and is also involved in the co-translational processing of pro-ubiquitin and ribosomal proteins translated as ubiquitin fusions. UCH-L3 is a kind of ubiquitin-protein hydrolase involved in the processing of both ubiquitin precursors and ubiquitinated substrates, generating free monomeric ubiquitin. UCH37, different from other UCH members, is responsible for the Ub isopeptidase activity in the 19S proteasome regulatory complex, overview. Upregulation of TGF-beta signaling by UCH37 | Homo sapiens |