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Literature summary for 3.4.19.12 extracted from

  • Fang, Y.; Fu, D.; Shen, X.Z.
    The potential role of ubiquitin C-terminal hydrolases in oncogenesis (2010), Biochim. Biophys. Acta, 1806, 1-6.
    View publication on PubMed

Protein Variants

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/ Products (Substrates)

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 ?
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?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
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Mus musculus
-
-
-

Posttranslational Modification

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

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
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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
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Substrates and Products (Substrate)

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

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

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
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Homo sapiens
ubiquitin C-terminal hydrolase
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Mus musculus
ubiquitin C-terminal hydrolase
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Homo sapiens
UCH
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Mus musculus
UCH
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Homo sapiens
UCH-L1
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Mus musculus
UCH-L1
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Homo sapiens
UCH-L3
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Mus musculus
UCH-L3
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Homo sapiens
UCH37
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Mus musculus
UCH37
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Homo sapiens

General Information

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