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Literature summary for 3.4.22.B70 extracted from
- Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with essential, non-catalytic functions (2012), EMBO Rep., 13, 930-938.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of wild-type Flag-tagged C13orf22l and C13orf22lcat mutant comprising amino acid residues 312-649 in HeLa cells | Danio rerio |
| recombinant expression of YFP-tagged enzyme USPL1 in HeLa cell nucleoplasm, and of HA-tagged enzyme in Cajal bodies, co-expression with suicide inhibitor Strep-TEV-HA-SUMO-vinylmethylester, recombinant expression of truncated enzyme variant USPL1cat as His-GST-TEV-USPL1cat | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| C236S | site-directed mutagenesis, the mutant is not inhibited by suicide inhibitor Strep-TEV-HA-SUMO-vinylmethylester in contrast to the wild-type enzyme | Homo sapiens |
| additional information | wild-type and inactive USPL1 variants rescue proliferation and coilin localization. Construction of His-GST-TEV-USPL1cat variants and analysis of their SUMO-AMC hydrolysis and SUMO binding. Four mutants show severe and two mutants moderate loss of activity, accompanied by severe or moderate reduction in binding | Homo sapiens |
| W229L | site-directed mutagenesis, mutation to the residue found in USP2 and other ubiquitin-specific USPs dramatically impairs SUMO binding and cleavage | Homo sapiens |
| W237F | site-directed mutagenesis, mutation to the residue found in USP2 and other ubiquitin-specific USPs dramatically impairs SUMO binding and cleavage | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 2-(4-chlorophenyl)-2-oxoethyl 4-(benzoylamino)benzoate | - |
Homo sapiens |  |
| 2-(4-chlorophenyl)-2-oxoethyl 4-[(3,4-diethoxybenzoyl)amino]benzoate | - |
Homo sapiens | |
| 2-(4-chlorophenyl)-2-oxoethyl 4-[(3,4-dimethoxybenzoyl)amino]benzoate | - |
Homo sapiens | |
| 2-(4-chlorophenyl)-2-oxoethyl 4-[(3-aminobenzoyl)amino]benzoate | - |
Homo sapiens | |
| 2-(4-chlorophenyl)-2-oxoethyl 4-[(3-fluorobenzoyl)amino]benzoate | - |
Homo sapiens | |
| 2-(4-chlorophenyl)-2-oxoethyl 4-[(3-hydroxybenzoyl)amino]benzoate | - |
Homo sapiens | |
| 2-(4-chlorophenyl)-2-oxoethyl 4-[(3-methoxybenzoyl)amino]benzoate | - |
Homo sapiens | |
| 2-(4-chlorophenyl)-2-oxoethyl 4-[[3-(benzyloxy)benzoyl]amino]benzoate | - |
Homo sapiens | |
| haemagglutinin-SUMO-vinylmethylester | a suicide inhibitor, Strep-TEV-HA-SUMO-vinylmethylester | Danio rerio | |
| haemagglutinin-SUMO-vinylmethylester | a suicide inhibitor, Strep-TEV-HA-SUMO-vinylmethylester. Enzyme USPL1 requires its catalytic cysteine to react with the inhibitor | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| Cajal body | - |
Danio rerio | 15030 | - |
| Cajal body | enzyme USPL1 is a low-abundance protein that colocalizes with coilin in cajal bodies. USPL1 is an essential Cajal body component | Homo sapiens | 15030 | - |
| nucleoplasm | - |
Homo sapiens | 5654 | - |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 120000 | - |
- |
Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Danio rerio | enzyme USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells | ? | - |
? | |
| additional information | Homo sapiens | enzyme USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Danio rerio | - |
- |
- |
| Homo sapiens | Q5W0Q7 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| embryo | - |
Danio rerio | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | enzyme USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells | Danio rerio | ? | - |
? | |
| additional information | enzyme USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells | Homo sapiens | ? | - |
? | |
| additional information | enzyme USPL1 binds SUMO but not ubiquitin, no activity with ubiquitin-7-amido-4-methylcoumarin | Danio rerio | ? | - |
? | |
| additional information | enzyme USPL1 binds SUMO but not ubiquitin, no activity with ubiquitin-7-amido-4-methylcoumarin | Homo sapiens | ? | - |
? | |
| SUMO-7-amido-4-methylcoumarin + H2O | - |
Danio rerio | SuMo + 7-amino-4-methylcoumarin | - |
? | |
| SUMO-7-amido-4-methylcoumarin + H2O | - |
Homo sapiens | SuMo + 7-amino-4-methylcoumarin | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| C13orf22l | - |
Danio rerio |
| SUMO isopeptidase | - |
Danio rerio |
| SUMO isopeptidase | - |
Homo sapiens |
| SUMO protease | - |
Danio rerio |
| SUMO protease | - |
Homo sapiens |
| SUMO-specific protease | - |
Danio rerio |
| SUMO-specific protease | - |
Homo sapiens |
| ubiquitin-specific protease-like 1 | - |
Homo sapiens |
| USPL1 | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Danio rerio |
| 30 | - |
assay at | Homo sapiens |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.00108 | - |
pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-[[3-(benzyloxy)benzoyl]amino]benzoate | |
| 0.00118 | - |
pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-(benzoylamino)benzoate | |
| 0.00174 | - |
pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-[(3-fluorobenzoyl)amino]benzoate | |
| 0.00186 | - |
pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-[(3-methoxybenzoyl)amino]benzoate | |
| 0.00239 | - |
pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-[(3-methoxybenzoyl)amino]benzoate | |
| 0.00354 | - |
pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-(benzoylamino)benzoate | |
| 0.05 | - |
above, pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-[(3,4-dimethoxybenzoyl)amino]benzoate | |
| 0.05 | - |
above, pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-[(3,4-diethoxybenzoyl)amino]benzoate | |
| 0.05 | - |
above, pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-[(3-aminobenzoyl)amino]benzoate | |
| 0.05 | - |
above, pH and temperature not specified in the publication | Homo sapiens | 2-(4-chlorophenyl)-2-oxoethyl 4-[(3-hydroxybenzoyl)amino]benzoate | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | C13orf22l is a member of the C19 cysteine protease USP family, two families of SUMO isopeptidases are known, and C13orf22l represents a third type of SUMO protease. Zebrafish C13orf22l is a functional homologue of human USPL1 | Danio rerio |
| evolution | USPL1 is a member of the C19 cysteine protease USP family, two families of SUMO isopeptidases are known, and USPL1 represents a third type of SUMO protease. W229, W237, Q405 and H421 are strictly conserved in USPL1 proteins, but different from residues in all other USPs | Homo sapiens |
| malfunction | enzyme USPL1 depletion does not affect global sumoylation, but causes striking coilin mislocalization and impairs cell proliferation, functions that are not dependent on USPL1 catalytic activity | Homo sapiens |
| malfunction | many cells of enzyme heterozygous mutants c13orf22lhi3662Tg/hi3662Tg reveal a striking accumulation of coilin in nucleoli. Enzyme disruption is lethal to the embryo in zebrafish with strong necrotic phenotype in the central nervous system and eye at 2 days post fertilization and death at 4-5 days post fertilization | Danio rerio |
| additional information | enzyme USPL1 has a catalytic domain with a C236-H456-D472 triad. Two tryptophanes close to the catalytic cysteine are needed to stably position the C-terminal diglycine motif of SUMO in the substrate tunnel | Homo sapiens |
| physiological function | C13orf22l is required for integrity of Cajal bodies in zebrafish embryos | Danio rerio |
| physiological function | USPL1 is an essential Cajal body protein required for coilin localization and cell proliferation. USPL1 represents a third type of SUMO protease, with essential functions in Cajal body biology. The conserved areas in USPL1 might be involved in SUMO recognition | Homo sapiens |
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