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Information on EC 3.4.22.68 - Ulp1 peptidase
for references in articles please use BRENDA:EC3.4.22.68
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EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.22 Cysteine endopeptidases
3.4.22.68 Ulp1 peptidase
IUBMB Comments
The enzyme from Saccharomyces cerevisiae can also recognize small ubiquitin-like modifier 1 (SUMO-1) from human as a substrate in both SUMO-processing (α-linked peptide bonds) and SUMO-deconjugation (ε-linked peptide bonds) reactions [1,2,3]. Ulp1 has several functions, including an essential role in chromosomal segregation and progression of the cell cycle through the G2/M phase of the cell cycle. Belongs in peptidase family C48.
The enzyme appears in viruses and cellular organisms
- 3.4.22.68
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desumoylation
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ubiquitin-related
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senps
-
deconjugation
- sumo1
- isopeptidase
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sentrin-specific
- hypoxia
-
ni-nta
-
sumo-conjugating
-
sumo2/3
- piasy
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sumo-dependent
- nemo
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sumo-modified
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sumoylation-deficient
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sumo-targeted
- synthesis
- medicine
- biotechnology
- molecular biology
Reaction Schemes
showHydrolysis of the alpha-linked peptide bond in the sequence Gly-Gly-/-Ala-Thr-Tyr at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptide, Smt3, leading to the mature form of the protein. A second reaction involves the cleavage of an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein
Synonyms
senp1, senp2, sumo protease, senp6, sumo-specific protease, senp7, smt3ip1, ulp1 protease, sumo protease 1, sumo-specific protease 2, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C48.001
-
-
-
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Small ubiquitin-related modifier protein 1 conjugate proteinase
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-
-
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Smt3-protein conjugate proteinase
-
-
-
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SUMO protease
SUMO-specific protease
Ubl-specific protease 1
Ulp1
Ulp1 endopeptidase
Ulp1 protease
Ulp1
-
-
-
-
Ulp1 endopeptidase
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Hydrolysis of the alpha-linked peptide bond in the sequence Gly-Gly-/-Ala-Thr-Tyr at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptide, Smt3, leading to the mature form of the protein. A second reaction involves the cleavage of an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
252852-50-9
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
His6-Smt3-hemagglutinin fusion protein + H2O
?
Substrates: -
Products: -
Products: -
?
His6-Smt3-Leu-beta-galactosidase + H2O
?
Substrates: -
Products: -
Products: -
?
His6-Smt3-Met-beta-galactosidase + H2O
?
Substrates: -
Products: -
Products: -
?
small ubiquitin-related modifier-CENP-I + H2O
small ubiquitin-related modifier-protein + CENP-I
-
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
small ubiquitin-related modifier-Mdm2 + H2O
small ubiquitin-related modifier-protein + Mdm2
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
SUMO-GFP fusion substrate + H2O
SUMO + GFP
Substrates: pH 8.0, 25°C, in the presence of 5 mM 2-mercaptoethanol
Products: -
Products: -
?
SUMO-MMP13 + H2O
?
Substrates: cleavage occurs only to 60%
Products: -
Products: -
?
small ubiquitin-like modifier protein + H2O
?
Substrates: -
Products: Ulp1 catalyzes the proteolytic processing of SUMO to its mature form
Products: Ulp1 catalyzes the proteolytic processing of SUMO to its mature form
?
small ubiquitin-like modifier protein + H2O
?
Substrates: -
Products: Ulp1 catalyzes the proteolytic processing of SUMO to its mature form
Products: Ulp1 catalyzes the proteolytic processing of SUMO to its mature form
?
small ubiquitin-related modifier-Mdm2 + H2O
small ubiquitin-related modifier-protein + Mdm2
-
Substrates: co-localization of SENP2 with SUMO conjugated Mdm2. SUMO conjugation of Mdm2 induces its co-localization and association with SENP2 at the PML bodies
Products: -
Products: -
r
small ubiquitin-related modifier-Mdm2 + H2O
small ubiquitin-related modifier-protein + Mdm2
-
Substrates: SENP2 catalyzes the desumoylation process of Mdm2
Products: -
Products: -
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
-
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
-
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
-
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
Smt3 + H2O
?
Substrates: a Yeast ER sequestration screening-based protease-substrate specificity characterization (YESS-PSSC) system is applied to systematically profile the substrate specificity of the Ulp1 at the P2-P1-/-P1' (GG-/-A) position of the SUMO protein (Smt3). The special tapered active pocket of Ulp1 confers the selectivity of small residues at the P1-P2 position of Smt3, such as Gly, Ala, Ser and Cys, and only which can smoothly deliver the-scissile bond into the active site for cleavage. The P1' position Ala of Smt3 plays a vital role in maintaining Ulp1's precise cleavage after the Gly-Gly motif and replacing Ala with Gly in this position could expand Ulp1 inclusivity against the P1 and P2 position
Products: -
Products: -
?
Smt3 + H2O
?
Substrates: a Yeast ER sequestration screening-based protease-substrate specificity characterization (YESS-PSSC) system is applied to systematically profile the substrate specificity of the Ulp1 at the P2-P1-/-P1' (GG-/-A) position of the SUMO protein (Smt3). The special tapered active pocket of Ulp1 confers the selectivity of small residues at the P1-P2 position of Smt3, such as Gly, Ala, Ser and Cys, and only which can smoothly deliver the-scissile bond into the active site for cleavage. The P1' position Ala of Smt3 plays a vital role in maintaining Ulp1's precise cleavage after the Gly-Gly motif and replacing Ala with Gly in this position could expand Ulp1 inclusivity against the P1 and P2 position
Products: -
Products: -
?
SUMO-1 protein + H2O
?
Substrates: Ulp1 catalyzes two essential functions in the SUMO pathway: 1. the processing of full-length SUMO to its mature form and 2. deconjugation of SUMO from target proteins. Ulp1 can proteolyze large folded SUMO-conjugated proteins without altering their structure
Products: -
Products: -
?
SUMO-1 protein + H2O
?
Substrates: the enzyme plays an essential role in the G2/M phase of the cell cycle
Products: -
Products: -
?
additional information
?
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Substrates: ELS1, but not ELS1C461S, is capable of cleaving the extension oV the carboxyl terminus of SUMO1
Products: -
Products: -
?
additional information
?
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Substrates: ELS1, but not ELS1C461S, is capable of cleaving the extension oV the carboxyl terminus of SUMO1
Products: -
Products: -
?
additional information
?
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Substrates: ELS1, but not ELS1C461S, is capable of cleaving the extension oV the carboxyl terminus of SUMO1
Products: -
Products: -
?
additional information
?
-
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Substrates: substrate specificities of different SENPS with different SUMOs, wild-types and mutants, very detailed overview. the SENP6 and SENP7 subclass displays a clear proteolytic cleavage preference for SUMO2/3 isoformsm structural determinants, overview. Identification of a unique sequence insertion in the SENP6 and SENP7 subclass that is essential for their proteolytic activity and that forms a more extensive interface with SUMO during the proteolytic reaction. Structure-based comparisons combined with biochemical and mutagenesis analysis reveal Loop 1 insertion in SENP6 and SENP7 as a platform to discriminate between SUMO1 and SUMO2/3 isoforms in this subclass of the SUMO protease family. Loop 1 SENP7 interacts with SUMO2. Deconjugation of diSUMO2(D71K) with SENP7 loop 1 mutant constructs, although proteolytic cleavage of diSUMO2(D71K) substrate shows a decrease in the proteolytic activity for all SENP7 constructs tested, including the wild type form. Mutation D71K, on the surface of SUMO2 distant from the cleavage site, can produce marked defects in the proteolytic activity of SENP7, with an approximately loss of 20fold with respect to the diSUMO2 wild type reaction
Products: -
Products: -
?
additional information
?
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Substrates: PfSENP1 has unique substrate sequence specificity, comparison to human SENPs, mutational analysis, overview
Products: -
Products: -
?
additional information
?
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Substrates: the NH2-terminal regulatory domain of Ulp1 restricts Ulp1 activity towards certain sumoylated proteins while enabling the cleavage of others, the COOH-terminal catalytic domain of Ulp1 is both necessary and sufficient for the essential function of the protein in cell cycle progression and for Smt3 precursor cleavage
Products: -
Products: -
?
additional information
?
-
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Substrates: the enzyme is specifically required for cell cycle progression
Products: -
Products: -
?
additional information
?
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Substrates: Ulp1 is responsible for both removing SUMO/Smt3 from specific target proteins and for processing precursor SUMO into its conjugation-competent form. Multiple features in the catalytic domain of Ulp1 affect SUMO interactions, analysis of features of Ulp1 required for substrate targeting, structure-function analysis, overview. D451 is required for targeting of sumoylated proteins and the C580S mutation is required for retention of Ulp1 at the septin ring. Kap121-independent SUMO-targeting information resides in the catalytic domain of Ulp1. The Ulp1 Kap121-interacting domain (region 1), the Ulp1 Kap60/Kap95-interacting domain (region 2) and the catalytic domain (region 3) fail to interact with the Smt3-binding domain
Products: -
Products: -
?
additional information
?
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Substrates: Ulp1 liberates poly-Smt3 from a substrate chain. In vitro, Ulp1 is highly active even in very low concentrations. Substrate specificity analysis of immobilized recombinant enzyme, overview
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
small ubiquitin-related modifier-CENP-I + H2O
small ubiquitin-related modifier-protein + CENP-I
-
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
small ubiquitin-related modifier-Mdm2 + H2O
small ubiquitin-related modifier-protein + Mdm2
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Substrates: co-localization of SENP2 with SUMO conjugated Mdm2. SUMO conjugation of Mdm2 induces its co-localization and association with SENP2 at the PML bodies
Products: -
Products: -
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
additional information
?
-
-
Substrates: the enzyme is specifically required for cell cycle progression
Products: -
Products: -
?
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
-
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
-
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
-
Substrates: SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
Products: -
Products: -
r
SUMO-1 protein + H2O
?
Substrates: Ulp1 catalyzes two essential functions in the SUMO pathway: 1. the processing of full-length SUMO to its mature form and 2. deconjugation of SUMO from target proteins. Ulp1 can proteolyze large folded SUMO-conjugated proteins without altering their structure
Products: -
Products: -
?
SUMO-1 protein + H2O
?
Substrates: the enzyme plays an essential role in the G2/M phase of the cell cycle
Products: -
Products: -
?
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-[(4-[[2-([(2R,3R)-3-[benzyl(cyclohexa-1,3-dien-1-ylmethyl)carbamoyl]-3-chlorooxiran-2-yl]carbonyl)-2-(carboxymethyl)hydrazinyl]carbonyl]benzyl)carbamoyl]benzoic acid
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partial inhibition of the enzyme
3-[(4-[[2-[(2E)-4-[bis(naphthalen-1-ylmethyl)amino]-4-oxobut-2-enoyl]-2-(carboxymethyl)hydrazinyl]carbonyl]benzyl)carbamoyl]benzoic acid
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3-[(4-[[2-[4-[bis(naphthalen-1-ylmethyl)amino]-2,3-dichloro-4-oxobutanoyl]-2-(carboxymethyl)hydrazinyl]carbonyl]benzyl)carbamoyl]benzoic acid
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the chlorohydrin form of JCP-666 may inhibit the target SENP by SN2-like displacement of the chloride by the active site cysteine
3-[(4-[[2-[4-[bis(naphthalen-1-ylmethyl)amino]-3-chloro-2-hydroxy-4-oxobutanoyl]-2-(carboxymethyl)hydrazinyl]carbonyl]benzyl)carbamoyl]benzoic acid
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i.e. JCP-666
Gu-HCl
500 mM reduces cleavage to 60%, 1 M reduces cleavage to 0%
hSUMO-VS
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human SUMO protein modified with a vinyl sulfone reactive group after the C-terminal di-glycine, contains the full length SUMO protein fused to a reactive vinyl sulfone group, an irreversible inhibitor of SENP proteases
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N-ethylmaleimide
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NEM, blocks SENP activity by acting as a general alkylating agent that modifies the active site cysteine in parasite lysates
NaCl
500 mM reduces cleavage to 60%, 1 M reduces cleavage to 30%
additional information
-
inhibitor screening, overview. No inhibition by 3-[(4-[[2-[[(2R,3R)-3-(benzylcarbamoyl)-3-chlorooxiran-2-yl]carbonyl]-2-(carboxymethyl)hydrazinyl]carbonyl]benzyl)carbamoyl]benzoic acid, i.e. JCP-667
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additional information
there may be a connection between a defect in SUMO-1 conjugation to the PML protein and acute promyelocytic leukemia (ALP). Specific Ulp inhibitors can therefore have therapeutic value for ALP
-
additional information
no inhibitory effects are observed with Triton X100 (1 M), imidazole (300 mM), reduced glutathione (20 mM), maltose (20 mM), glycerol (20% v/v), ethylene glycol (20% v/v), sucrose (20% w/v), ethanol (10% v/v)
-
additional information
-
no inhibitory effects are observed with Triton X100 (1 M), imidazole (300 mM), reduced glutathione (20 mM), maltose (20 mM), glycerol (20% v/v), ethylene glycol (20% v/v), sucrose (20% w/v), ethanol (10% v/v)
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
Michaelis-Menten steady-state kinetics are performed for SENP6 by introduction of S9C and C52A point mutants into SUMO1 and SUMO1 mutant A68N/H71D to allow for fluorophore addition
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
constructed strain contains a single ulp1-I615N mutation
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the NH2-terminal domain of the enzyme, residues between position 144 and 346, includes sequences necessary and sufficient to concentrate Ulp1 at nuclear envelope
brenda
additional information
-
Ulp1 localizes predominantly to nuclear pore complexes but also deconjugates sumoylated septins at the bud-neck of dividing cells. A 218-amino acid, substrate-trapping mutant of the catalytic domain of Ulp1, Ulp1(3) C580S is necessary and sufficient for septin localization
brenda
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Ulp1 localizes predominantly to nuclear pore complexes but also deconjugates sumoylated septins at the bud-neck of dividing cells
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brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
additional information
evolution
-
Plasmodium falciparum has only two predicted SENP proteases whereas human hosts have six SENPs
evolution
-
in humans, the SENP/ULP protease family is comprised of seven members, six are SUMO-specific proteases, SENP1, SENP2, SENP3, SENP5, SENP6, and SENP7, whereas one is specific for another ubiquitin-like protein, Nedd8, or SENP8, also named DEN1 or NEDP1. SENP6 and SENP7 are the most divergent members in their conserved catalytic domain
malfunction
growth defects caused by loss of ESD4 function are not due to increased synthesis of the stress signal salicylic acid, enzyme depletion causes delay in flowering
malfunction
growth defects caused by loss of ESD4 function are not due to increased synthesis of the stress signal salicylic acid. ELS1 depletion causes no measurable alterations in flowering and leaf development
malfunction
-
slencing of SENP1 inhibits growth and colony formation of DLD-1 cells, results in G1-phase arrest, and upregulates the expression of some CDK inhibitors, overview
malfunction
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targeted disruption of SENP2 impairs the G-S transition required for mitotic and endoreupliation cell cycles during expansion of trophoblast stem cells and their differentiation into polyploidy cells, respectively. The disruption disturbs the subcellular distribution and SUMO modification of Mdm2, leading to interference with p53 degradation. SUMO conjugated Mdm2 is elevated in the SENP2-null cells
malfunction
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cells lacking SENP6 show defects in spindle assembly and metaphase chromosome congression. A subset of proteins become undetectable on inner kinetochores after SENP6 depletion, particularly the CENP-H/I/K complex, whereas other changes in kinetochore composition mimick defects previously reported to result from CENP-H/I/K depletion, SENP6 depletion results in loss of the CENP-H/I/K complex from kinetochores, detailed overview
malfunction
-
an ulp1 temperature-sensitive strain ulp1-333SGG with inactivated enzyme Ulp1 at restrictive temperature accumulates unprocessed SUMO protein
malfunction
-
an ulp1 temperature-sensitive strain ulp1-333SGG with inactivated enzyme Ulp1 at restrictive temperature accumulates unprocessed SUMO protein
-
physiological function
SUMO protease ESD4 and ESD4-like SUMO protease 1, i.e. ELS1 or AtULP1a, show close sequence similarity, but different properties and are functionally distinct, overview
physiological function
-
Ulp1 facilitates sumoylation by processing precursor SUMO into its conjugation competent form. Conversely, Ulp1 also facilitates desumoylation by removing SUMO from nuclear and cytosolic proteins after conjugation. The essential small ubiquitin-like modifier, SUMO, protease Ulp1 is responsible for both removing SUMO/Smt3 from specific target proteins and for processing precursor SUMO into its conjugation-competent form
physiological function
-
SENP1 is essential for cell growth in the colon cancer cell line. SENP1 might play a role in cell cycle regulation of colon cancer cells
physiological function
-
nucleolar SUMO-specific protease, SMT3IP1/SENP3, controls the p53Mdm2 pathway. SMT3IP1 interacts with p53 and Mdm2, and desumoylates both proteins. SMT3IP1 bound to the acidic domain of Mdm2, which also mediates the p53 interaction, and competes with p53 for binding. Increasing expression of SMT3IP1 suppresses Mdm2-mediated p53 ubiquitination and subsequent proteasomal degradation. Desumoylation activity of SMT3IP1 is not necessary for p53 stabilization
physiological function
-
the key genetic pathway SENP2-Mdm2-p53 is essential for trophoblast development, mechanism underlying the isoform-specific SENP2 mediated regulation of Mdm2 critical for genome integrity in p53-induced cellular stress, overview. SENP2 catalyzes the desumoylation process of Mdm2. Dynamic SUMO modification is involved in a variety of cellular processes, including protein trafficking, transcriptional regulation, cell survival and death, and protein stability. High levels of SENP2, but not the other two forms, SENP2-M and SENP2-S, drastically diminished the cellular levels of p53. SENP2-mediated downregulation of p53 and p21, but not SENP2-mediated desumoylation of Mdm2, is sensitive to the Nutlin-3 treatment
physiological function
-
SUMO proteases can regulate the amounts of SUMO-conjugated proteins in the cell by cleaving off the isopeptidic bond between SUMO and the target protein
physiological function
-
the SUMO protease SENP6 is essential for inner kinetochore assembly. SENP6 stabilizes CENP-I by antagonizing RNF4, RNF4, a ubiquitin ligase which targets polysumoylated proteins for proteasomal degradation. CENP-I is degraded through the action of RNF4
physiological function
-
the enzyme Ulp1 does not appear to play a major role in the inactivation of the SUMO stress response consisting of consist of a simple SUMO conjugation-deconjugation cycle, overview. Isozyme Ulp1 is required for activation of the SUMO pro-protein, but SUMO stress response does not require proteasome-mediated degradation or Ulp1 activity
physiological function
in fission yeast lacking nucleoporin Nup132, Ulp1 is delocalized and can no longer antagonize sumoylation of the PIAS family SUMO E3 ligase, Pli1. Pli1 is targeted for proteasomal degradation by the concerted action of a SUMO-targeted ubiquitin ligase (STUbL) and Cdc48-Ufd1-Npl4
physiological function
-
the catalytic UD domains of both Saccharomyces cerevisiae ScUlp1 and Kluyveromyces marxianus KmUlp1 show a high degree of sequence conservation, complement a Ulp1 deletion mutant in vivo, and process a SUMO precursor in vitro. Catalytically inactive recombinant fragments of the UD domains are able to efficiently bind a variety of purified SUMO isoforms and bind immobilized SUMO1 with nanomolar affinity
physiological function
-
the catalytic UD domains of both Saccharomyces cerevisiae ScUlp1 and Kluyveromyces marxianus KmUlp1 show a high degree of sequence conservation, complement a Ulp1 deletion mutant in vivo, and process a SUMO precursor in vitro. Catalytically inactive recombinant fragments of the UD domains are able to efficiently bind a variety of purified SUMO isoforms and bind immobilized SUMO1 with nanomolar affinity
physiological function
in fission yeast lacking nucleoporin Nup132 (Sc/HuNUP133), Ulp1 is delocalized and can no longer antagonize sumoylation of the PIAS family SUMO E3 ligase, Pli1. Consequently, SUMO chain-modified Pli1 is targeted for proteasomal degradation by the concerted action of a SUMO-targeted ubiquitin ligase (STUbL) and Cdc48-Ufd1-Npl4
physiological function
-
the enzyme Ulp1 does not appear to play a major role in the inactivation of the SUMO stress response consisting of consist of a simple SUMO conjugation-deconjugation cycle, overview. Isozyme Ulp1 is required for activation of the SUMO pro-protein, but SUMO stress response does not require proteasome-mediated degradation or Ulp1 activity
-
physiological function
Kluyveromyces marxianus BY28356
-
the catalytic UD domains of both Saccharomyces cerevisiae ScUlp1 and Kluyveromyces marxianus KmUlp1 show a high degree of sequence conservation, complement a Ulp1 deletion mutant in vivo, and process a SUMO precursor in vitro. Catalytically inactive recombinant fragments of the UD domains are able to efficiently bind a variety of purified SUMO isoforms and bind immobilized SUMO1 with nanomolar affinity
-
additional information
-
SUMO conjugation of Mdm2 induces its co-localization and association with SENP2 at the PML bodies
additional information
-
a simple, cost effective procedure for the large scale production of active Ulp1 is developed that can be used for industrial scale requirements
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ULP1_YEAST
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
621
0
72378
Swiss-Prot
-
ULP1_SCHPO
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
568
0
64941
Swiss-Prot
other Location (Reliability: 1)
G0RZV7_CHATD
Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)
1186
0
134509
TrEMBL
-
ULP2_YEAST
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
1034
0
116883
Swiss-Prot
Mitochondrion (Reliability: 5)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C461S
site-directed mutagenesis, ELS1C461S is not capable of cleaving the extension oV the carboxyl terminus of SUMO1
C517S
C580S
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site-directed mutagenesis, generation of a catalytically inactive mutant of Ulp1, the mutant is greatly enriched at the septin ring of dividing yeast cells. The 218-amino acid, substrate-trapping mutant of the catalytic domain of Ulp1 is necessary and sufficient for septin localization
D451N
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the mutation destroys an essential salt bridge formed between Smt3 and Ulp1
D451N/C580S
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site-directed mutagenesis, abolished accumulation of the full-length Ulp1 double-mutant at the septin ring
I435V/N450S/I504T/C580S
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site-directed mutagenesis, the mutant shows a reduced ability to enrich at the septin ring
additional information
additional information
plant enzymes ELS1 and ESD4 differ in their ability to complement yeast Ulp1 mutants, mutant phenotypes, overview
additional information
plant enzymes ELS1 and ESD4 differ in their ability to complement yeast Ulp1 mutants, mutant phenotypes, overview
additional information
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plant enzymes ELS1 and ESD4 differ in their ability to complement yeast Ulp1 mutants, mutant phenotypes, overview
additional information
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modification of recombinant proteins by SUMOylation often dramatically increases solubility and stability during expression of the fusion proteins in bacteria relative to unfused proteins. After expressing a protein as a fusion to SUMO, it is often desirable to cleave the SUMO off of the fusion protein using a SUMO-specific protease such as Ulp1. To facilitate such processing, a dual expression vector is constructed encoding two fusion proteins: one consisting of SUMO fused to Ulp1 and a second consisting of SUMO fused to a His-tagged protein of interest. The SUMOUlp1 cleaves both itself and the other SUMO fusion protein in the bacterial cells prior to lysis, and the proteins retain solubility after cleavage, method evaluation, overview
additional information
-
a genetic mutation inactivating all three gene products of SENP2 is generated by alternative splicing
additional information
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generation of a collection of GFP-tagged Ulp1 truncations and domains that were expressed under control of the Ulp1 promoter. truncations and domains of Ulp1, that retain substrate targeting information, also localize to the septin ring in G2/M-arrested cells. Usage of the targeting and SUMO-binding properties of Ulp1(3)(C580S) to purify Smt3-modified proteins from cell extracts. Deletion of the entire SBS domain on the localization of Ulp1(3)(C580S). The Ulp1(3)(C580S)SBSDELTA construct does not localize to the septin ring in the majority of cells
additional information
immobilization of isozyme Ulp1 via its C-terminal FLAG tag
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
GST-tagged small fragment of ubiquitin-like specific protease 1 immobilized on superparamagnetic iron oxide silica-GSH nanoparticles (covalent binding of glutathione on magnetic nanoparticles) retains 87% enzyme activity of free protease before immobilization
immobilization of SpUlp1 catalytic domain on chitosan-coated iron nanoparticles is demonstrated with operational stability and reusability up to 100 cycles
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, 50% glycerol, 75 mM Tris-HCl pH 8.0, 0.5 mM DTT, 1 mM EDTA, 6 months, no detectable decay of activity
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
high yield purification of Ulp1 is required during the isolation and purification of SUMO-tagged recombinant proteins. When expressed as a soluble protein, Ulp1 is toxic to Escherichia coli host cells and most of the protein forms inclusion bodies. The extraction of insoluble Ulp1 followed by its purification and refolding into its active form is a lengthy and costly procedure. A simple, cost effective procedure for the large scale production of active Ulp1 is developed that can be used for industrial scale requirements
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recombinant catalytic domains of human SENP2-(364-589), SENP6-(637-1112), and SENP7-(662-984) and of mutant SENP-7s from Escherichia coli by metal affinity chromatography and gel filtration
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recombinant FLAG-tagged and maltose-binding protein-fused isozyme Ulp1, containing a TEV protease recognition site, from Escherichia coli strain BL21 by affinity chromatography
recombinant His-tagged SUMO-S-GroQ by nickel affinity chromatography to over 95% purity, SUMO is clevaed off by co-expressed SUMO-fused SUMO-specific protease Ulp1
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression of catalytic domains of human SENP2-(364-589), SENP6-(637-1112), and SENP7-(662-984) and of mutant SENP-7s in Escherichia coli
-
expression of FLAG-SMT3IP1 in COS-7 cells, coexpression with His6-ubiquitin. Overexpression of SMT3IP1 in cells results in the accumulation of Mdm2 in the nucleolus and increased stability of the p53 protein
-
expression of SUMO-S-GroQ fusion protein, i.e. SUMO fused to the Q domain of Drosophila melanogaster Groucho, containing sequences encoding the mature form of SUMO followed by a 6-His tag and a multiple cloning site harbouring the fused protein S-GroQ, co-expression of SUMO-fused SUMO-specific protease Ulp1
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expression of the wild-type full-length PfSENP1 and the catalytic domain of PfSENP1
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expression of wild-type and mutant enzymes, expression of the SBS domain as a SBS-GFP fusion protein
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gene ESD4, DNA and amino acid sequence determination, genotyping
gene ULP1A, DNA and amino acid sequence determination, genotyping, recombinant expression in Arabidopsis thaliana plants and in leaves of Nicotioana bentamiana using transfection via Agrobacterium tumefaciens. An expressed GFP-ELS1 construct has a generally non-nuclear localization, being detectable at membranes and in the cytoplasm
isozyme Ulp1, expression of recombinant FLAG-tagged and maltosse-binding protein-fused isozyme Ulp1, containing a TEV protease recognition site, in Escherichia coli strain BL21, recombinant expression of GST-tagged isozyme Ulp1
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
medicine
there may be a connection between a defect in SUMO-1 conjugation to the PML protein and acute promyelocytic leukemia (ALP). Specific Ulp inhibitors can therefore have therapeutic value for ALP
molecular biology
synthesis
biotechnology
-
substrate-trapping Ulp1(3)(C580S) interacts robustly with human SUMO1, SUMO2 and SUMO2 chains, making it a potentially useful tool for the analysis and purification of SUMO-modified proteins
biotechnology
a simple and rapid protein purification method based on cell-surface display of SUMO-fused recombinant protein and Ulp1 protease is described
biotechnology
-
a simple and rapid protein purification method based on cell-surface display of SUMO-fused recombinant protein and Ulp1 protease is described
-
molecular biology
-
usage of the targeting and small ubiquitin-like modifier, SUMO, binding properties of Ulp1(3)(C580S) to purify Smt3-modified proteins from cell extracts
molecular biology
-
modification of recombinant proteins by SUMOylation often dramatically increases solubility and stability during expression of the fusion proteins in bacteria relative to unfused proteins. After expressing a protein as a fusion to SUMO, it is often desirable to cleave the SUMO off of the fusion protein using a SUMO-specific protease such as Ulp1. To facilitate such processing, a dual expression vector is constructed encoding two fusion proteins: one consisting of SUMO fused to Ulp1 and a second consisting of SUMO fused to a His-tagged protein of interest. The SUMO-Ulp1 cleaves both itself and the other SUMO fusion protein in the bacterial cells prior to lysis, and the proteins retain solubility after cleavage, method evaluation, overview
synthesis
-
immobilization of Ulp1 as a tool for cleavage of the SUMO tag of recombinant proteins. Ulp1 immobilized on N-hydroxysuccinimide-activated Sepharose maintains 95% substrate-cleavage ability and significantly enhanced pH and thermal stability. The immobilized Ulp1 can tolerate 15% (v/v) DMSO and 20% (v/v) ethanol. It can be reused for more than 15 batch reactions with 90% activity retention
synthesis
-
comparison of Ulp1 protease in active upon expression as inclusion bodies and soluble protein. Fusion of the N-terminal selfassembling peptide GFIL8 to Ulp1 increases production of active inclusion bodies in Escherichia coli. Attachment of the N-terminal cellulose-binding module facilitates the immobilization on regenerated amorphous cellulose with a binding capacity up to about 235 mg protein per gram of cellulose. The immobilized soluble Ulp1 maintains about 42% initial cleavage activity with repetitive use, whereas the aggregated Ulp1 loses its cleavage capacity after cleaving the protein substrate once. Crosslinking of inclusion bodies using glutaraldehyde inactivates Ulp1
synthesis
-
optimization of expression of the catalytic domain. Optimization of cultivation conditions at shake flask results in Ulp1 expression of 195 mg/l in TB medium. Ni-NTA affinity purification of Ulp1 using 0.1% Triton X-100, 0.01mM DTT, 0.02mM EDTA and 1% glycerol leads to a purity of about 95% with a recovery yield of 80% and specific activity of 398600 U/mg. The protease cleaves the SUMO tag even at 1:10,000 enzyme to substrate ratio The in vivo cleavage of SUMO tag via coexpression strategy also results in more than 80% cleavage of SUMO fusion protein
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Li, S.J.; Hochstrasser, M.
A new protease required for cell-cycle progression in yeast
Nature
398
246-251
1999
Saccharomyces cerevisiae (Q02724)
brenda
Mossessova, E.; Lima, C.D.
Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast
Mol. Cell
5
865-876
2000
Saccharomyces cerevisiae (Q02724), Saccharomyces cerevisiae
brenda
Li, S.J.; Hochstrasser, M.
The Ulp1 SUMO isopeptidase: distinct domains required for viability, nuclear envelope localization, and substrate specificity
J. Cell. Biol.
160
1069-1081
2003
Saccharomyces cerevisiae
brenda
Lima, C.D.
Ulp1 endopeptidase
Handbook of Proteolytic Enzymes (Barrett, A. J. ; Rawlings, N. D. ; Woessner, eds. )
2
1340-1344
2004
Saccharomyces cerevisiae (Q02724), Schizosaccharomyces pombe (O42957)
-
brenda
Malakhov, M.P.; Mattern, M.R.; Malakhova, O.A.; Drinker, M.; Weeks, S.D.; Butt, T.R.
SUMO fusions and SUMO-specific protease for efficient expression and purification of proteins
J. Struct. Funct. Genomics
5
75-86
2004
Saccharomyces cerevisiae (Q02724), Saccharomyces cerevisiae
brenda
Soustelle, C.; Vernis, L.; Freon, K.; Reynaud-Angelin, A.; Chanet, R.; Fabre, F.; Heude, M.
A new Saccharomyces cerevisiae strain with a mutant Smt3-deconjugating Ulp1 protein is affected in DNA replication and requires Srs2 and homologous recombination for its viability
Mol. Cell. Biol.
24
5130-5143
2004
Saccharomyces cerevisiae (Q02724)
brenda
Dobson, M.J.; Pickett, A.J.; Velmurugan, S.; Pinder, J.B.; Barrett, L.A.; Jayaram, M.; Chew, J.S.
The 2 microm plasmid causes cell death in Saccharomyces cerevisiae with a mutation in Ulp1 protease
Mol. Cell. Biol.
25
4299-4310
2005
Saccharomyces cerevisiae (Q02724), Saccharomyces cerevisiae
brenda
Jiang, M.; Chiu, S.Y.; Hsu, W.
SUMO-specific protease 2 in Mdm2-mediated regulation of p53
Cell Death Differ.
18
1005-1015
2011
Mus musculus
brenda
Mukhopadhyay, D.; Arnaoutov, A.; Dasso, M.
The SUMO protease SENP6 is essential for inner kinetochore assembly
J. Cell Biol.
188
681-692
2010
Homo sapiens
brenda
Nishida, T.; Yamada, Y.
The nucleolar SUMO-specific protease SMT3IP1/SENP3 attenuates Mdm2-mediated p53 ubiquitination and degradation
Biochem. Biophys. Res. Commun.
406
285-291
2011
Mus musculus
brenda
Elmore, Z.C.; Donaher, M.; Matson, B.C.; Murphy, H.; Westerbeck, J.W.; Kerscher, O.
Sumo-dependent substrate targeting of the SUMO protease Ulp1
BMC Biol.
9
74
2011
Saccharomyces cerevisiae
brenda
Ponder, E.; Albrow, V.; Leader, B.; Bekes, M.; Mikolajczyk, J.; Fonovic, U.; Shen, A.; Drag, M.; Xiao, J.; Deu, E.; Campbell, A.; Powers, J.; Salvesen, G.; Bogyo, M.
Functional characterization of a SUMO deconjugating protease of Plasmodium falciparum using newly identified small molecule inhibitors
Chem. Biol.
18
711-721
2011
Plasmodium falciparum
brenda
Alegre, K.; Reverter, D.
Swapping small ubiquitin-like modifier (SUMO) isoform specificity of SUMO proteases SENP6 and SENP7
J. Biol. Chem.
286
36142-36151
2011
Homo sapiens
brenda
Hermkes, R.; Fu, Y.-F.; Nuerrenberg, K.; Budhiraja, R.; Schmelzer, E.; Elrouby, N.; Dohmen, R.J.; Bachmair, A.; Coupland, G.
Distinct roles for Arabidopsis SUMO protease ESD4 and its closest homolog ELS1
Planta
233
63-73
2011
Arabidopsis thaliana (Q94F30), Arabidopsis thaliana (Q8GYL3), Arabidopsis thaliana
brenda
Kuo, D.; Nie, M.; De Hoff, P.; Chambers, M.; Phillips, M.; Hirsch, A.M.; Courey, A.J.
A SUMO-Groucho Q domain fusion protein: characterization and in vivo Ulp1-mediated cleavage
Protein Expr. Purif.
76
65-71
2011
Drosophila melanogaster
brenda
Eckhoff, J.; Dohmen, R.J.
In vitro studies reveal a sequential mode of chain processing by the yeast SUMO-specific protease Ulp2
J. Biol. Chem.
19
12268-12281
2015
Saccharomyces cerevisiae (Q02724)
brenda
Lewicki, M.C.; Srikumar, T.; Johnson, E.; Raught, B.
The S. cerevisiae SUMO stress response is a conjugation-deconjugation cycle that targets the transcription machinery
J. Proteomics
118
39-48
2015
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4741/2
brenda
Liang, Q.; Huang, Z.; Zhang, Y.; Li, H.
Immobilization of Ulp1 protease on NHS-activated Sepharose a useful tool for cleavage of the SUMO tag of recombinant proteins
Biotechnol. Lett.
39
1025-1031
2017
Saccharomyces cerevisiae
brenda
Babbal, B.; Adivitiya, B.; Mohanty, S.; Khasa, Y.P.
Bioprocess optimization for the overproduction of catalytic domain of ubiquitin-like protease 1 (Ulp1) from S. cerevisiae in E. coli fed-batch culture
Enzyme Microb. Technol.
120
98-109
2019
Saccharomyces cerevisiae
brenda
Nie, M.; Boddy, M.N.
Pli1(PIAS1) SUMO ligase protected by the nuclear pore-associated SUMO protease Ulp1SENP1/2
J. Biol. Chem.
290
22678-22685
2015
Schizosaccharomyces pombe (O42957), Schizosaccharomyces pombe
brenda
Jiang, L.; Xiao, W.; Zhou, X.; Wang, W.; Fan, J.
Comparative study of the insoluble and soluble Ulp1 protease constructs as carrier free and dependent protein immobilizates
J. Biosci. Bioeng.
127
23-29
2019
Saccharomyces cerevisiae
brenda
Peek, J.; Harvey, C.; Gray, D.; Rosenberg, D.; Kolla, L.; Levy-Myers, R.; Yin, R.; McMurry, J.; Kerscher, O.
SUMO targeting of a stress-tolerant Ulp1 SUMO protease
PLoS ONE
13
e0191391
2018
Saccharomyces cerevisiae, Kluyveromyces marxianus, Kluyveromyces marxianus BY28356
brenda
Zhou, X.F.; Zhang, C.L.; Gao, X.P.; Wang, W.L.; He, Z.F.; Jiang, F.Y.; Pang, Y.L.; Li, J.H.; Ren, X.J.; Zhou, H.B.; Tan, G.Q.; Lyu, J.X.; Wang, W.
A simple and rapid protein purification method based on cell-surface display of SUMO-fused recombinant protein and Ulp1 protease
AMB Express
10
65
2020
Saccharomyces cerevisiae (Q02724), Saccharomyces cerevisiae ATCC 204508 (Q02724)
brenda
Kuan, W.; Lai, J.; Lee, W.
Covalent binding of glutathione on magnetic nanoparticles Application for immobilizing small fragment ubiquitin-like-specific protease 1
Enzyme Microb. Technol.
143
109697
2021
Saccharomyces cerevisiae (Q02724)
brenda
Babbal, M.; Mohanty, S.; Khasa, Y.P.
Designing Ubiquitin-like protease 1 (Ulp1) based nano biocatalysts A promising technology for SUMO fusion proteins
Int. J. Biol. Macromol.
255
128258
2024
Schizosaccharomyces pombe
brenda
Zhang, F.; Zheng, H.; Xian, Y.; Song, H.; Wang, S.; Yun, Y.; Yi, L.; Zhang, G.
Profiling substrate specificity of the SUMO protease Ulp1 by the YESS-PSSC system to advance the conserved mechanism for substrate cleavage
Int. J. Mol. Sci.
23
188
2022
Saccharomyces cerevisiae (Q02724), Saccharomyces cerevisiae ATCC 204508 (Q02724)
brenda
Reddy Patakottu, B.K.; Vedire, V.R.; Reddy, C.R.
Robust production of active Ulp1 (SUMO protease) from inclusion bodies
Protein Expr. Purif.
211
106328
2023
Saccharomyces cerevisiae
brenda
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