Information on EC 3.4.22.68 - Ulp1 peptidase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
3.4.22.68
-
RECOMMENDED NAME
GeneOntology No.
Ulp1 peptidase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C48.001
-
-
-
-
ELS1
Q8GYL3, Q94F30
an ESD4 homologue
SENP2
-
-
SENP7
-
-
small ubiquitin-like modifier protease
-
-
Small ubiquitin-related modifier protein 1 conjugate proteinase
-
-
-
-
Smt3-protein conjugate proteinase
-
-
-
-
SMT3IP1
-
-
SMT3IP1/SENP3
-
-
SUMO deconjugating protease
-
-
SUMO protease
Q8GYL3, Q94F30
-
SUMO protease
-
-
SUMO protease
-
-
SUMO protease 1
Q02724
-
SUMO-specific protease
-
-
SUMO-specific protease
-
-
SUMO-specific protease
-
-
SUMO-specific protease
-
-
SUMO-specific protease 1
-
-
SUMO-specific protease 2
-
-
Ubl-specific protease 1
Q02724
-
Ubl-specific protease 1
O42957
-
Ulp1
-
-
-
-
Ulp1 endopeptidase
-
-
-
-
Ulp1 endopeptidase
Q02724
-
Ulp1 endopeptidase
O42957
-
Ulp1 protease
-
-
Ulp1 protease
Q02724
-
CAS REGISTRY NUMBER
COMMENTARY
252852-50-9
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
isozymes SENP2, SENP2-M, and SENP2-S
-
-
Manually annotated by BRENDA team
constructed strain contains a single ulp1-I615N mutation
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
-
SENP1 is a member of SENP family
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
-
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
-
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
-
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
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
-
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
-
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
-
nucleolar SUMO-specific protease, SMT3IP1/SENP3, controls the p53–Mdm2 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
-
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
-
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
Q8GYL3, Q94F30
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; 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
malfunction
Q8GYL3, Q94F30
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; 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
additional information
-
SUMO conjugation of Mdm2 induces its co-localization and association with SENP2 at the PML bodies
additional information
Q8GYL3, Q94F30
active site residue is Cys461; active site residue is Cys461
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
His6-Smt3-hemagglutinin fusion protein + H2O
?
show the reaction diagram
Q02724
-
-
-
?
His6-Smt3-Leu-beta-galactosidase + H2O
?
show the reaction diagram
Q02724
-
-
-
?
pro-small ubiquitin-related modifier + H2O
small ubiquitin-related modifier + ?
show the reaction diagram
-
SENP1 processes the precursor SUMO to its mature form by catalyzing the cleavage of a scissile peptide bond
-
-
?
small ubiquitin-like modifier protein + H2O
?
show the reaction diagram
-
-
Ulp1 catalyzes the proteolytic processing of SUMO to its mature form
-
?
small ubiquitin-like modifier protein + H2O
?
show the reaction diagram
O42957
-
Ulp1 catalyzes the proteolytic processing of SUMO to its mature form
-
?
small ubiquitin-related modifier-CENP-I + H2O
small ubiquitin-related modifier-protein + CENP-I
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-Mdm2 + H2O
small ubiquitin-related modifier-protein + Mdm2
show the reaction diagram
-
co-localization of SENP2 with SUMO conjugated Mdm2. SUMO conjugation of Mdm2 induces its co-localization and association with SENP2 at the PML bodies, SENP2 catalyzes the desumoylation process of Mdm2
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
Q8GYL3, Q94F30
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins. SUMOylation is a dynamic process
-
-
r
SMT3precursor + H2O
?
show the reaction diagram
-
-
-
-
?
SUMO-1 protein + H2O
?
show the reaction diagram
-
-
-
-
?
SUMO-1 protein + H2O
?
show the reaction diagram
Q02724
-
-
-
?
SUMO-1 protein + H2O
?
show the reaction diagram
-
-, 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
-
-
?
SUMO-1 protein + H2O
?
show the reaction diagram
Q02724
the enzyme plays an essential role in the G2/M phase of the cell cycle
-
-
?
SUMO-GFP fusion substrate + H2O
SUMO + GFP
show the reaction diagram
-
pH 8.0, 25°C, in the presence of 5 mM 2-mercaptoethanol
-
-
?
SUMO-MMP13 + H2O
?
show the reaction diagram
-
cleavage occurs only to 60%
-
-
?
His6-Smt3-Met-beta-galactosidase + H2O
?
show the reaction diagram
Q02724
-
-
-
?
additional information
?
-
-
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, the enzyme is specifically required for cell cycle progression
-
-
-
additional information
?
-
Q8GYL3, Q94F30
ELS1, but not ELS1C461S, is capable of cleaving the extension oV the carboxyl terminus of SUMO1
-
-
-
additional information
?
-
-
PfSENP1 has unique substrate sequence specificity, comparison to human SENPs, mutational analysis, overview
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
pro-small ubiquitin-related modifier + H2O
small ubiquitin-related modifier + ?
show the reaction diagram
-
SENP1 processes the precursor SUMO to its mature form by catalyzing the cleavage of a scissile peptide bond
-
-
?
small ubiquitin-related modifier-CENP-I + H2O
small ubiquitin-related modifier-protein + CENP-I
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-Mdm2 + H2O
small ubiquitin-related modifier-protein + Mdm2
show the reaction diagram
-
co-localization of SENP2 with SUMO conjugated Mdm2. SUMO conjugation of Mdm2 induces its co-localization and association with SENP2 at the PML bodies
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
Q8GYL3, Q94F30
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
show the reaction diagram
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins. SUMOylation is a dynamic process
-
-
r
SMT3precursor + H2O
?
show the reaction diagram
-
-
-
-
?
SUMO-1 protein + H2O
?
show the reaction diagram
-
-
-
-
?
SUMO-1 protein + H2O
?
show the reaction diagram
-
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
-
-
?
SUMO-1 protein + H2O
?
show the reaction diagram
Q02724
the enzyme plays an essential role in the G2/M phase of the cell cycle
-
-
?
additional information
?
-
-
the enzyme is specifically required for cell cycle progression
-
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2Z)-3-(naphthalen-2-yl)-N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]prop-2-enamide
-
-
1-(1H-indol-3-ylmethyl)-3-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea
-
3% inhibition at 0.02 mM
1-(3-hydroxy-4-methylphenyl)-3-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea
-
5% inhibition at 0.02 mM
1-(5-aminopentyl)-3-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea
-
43% inhibition at 0.02 mM
1-(cyclohexylmethyl)-3-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea
-
5% inhibition at 0.02 mM
1-(naphthalen-2-ylmethyl)-3-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea
-
26% inhibition at 0.02 mM
1-naphthalen-1-yl-3-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea
-
7% inhibition at 0.02 mM
1-naphthalen-2-yl-3-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea
-
30% inhibition at 0.02 mM
1-[2-(1H-indol-3-yl)ethyl]-3-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea
-
24% inhibition at 0.02 mM
1-[2-(naphthalen-2-yl)ethyl]-3-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea
-
45% inhibition at 0.02 mM
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
-
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
-
-
3-[(4-[[2-[4-[bis(naphthalen-1-ylmethyl)amino]-2,3-dichloro-4-oxobutanoyl]-2-(carboxymethyl)hydrazinyl]carbonyl]benzyl)carbamoyl]benzoic acid
-
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
-
i.e. JCP-666
3-[(acetyloxy)amino]-N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]benzamide
-
-
3-[(benzyloxy)amino]-N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]benzamide
-
-
4-methyl-N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]benzenesulfonamide
-
17% inhibition at 0.02 mM
4-[(benzyloxy)amino]-N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]benzamide
-
-
benzyl (3-[[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]phenyl)carbamate
-
-
benzyl (4-[[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]phenyl)carbamate
-
-
benzyl [4-(2-oxo-2-[[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]amino]ethoxy)phenyl]carbamate
-
23% inhibition at 0.02 mM
Gu-HCl
-
500 mM reduces cleavage to 60%, 1 M reduces cleavage to 0%
N-ethylmaleimide
-
NEM, blocks SENP activity by acting as a general alkylating agent that modifies the active site cysteine in parasite lysates
N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]pyridine-2-carboxamide
-
7% inhibition at 0.02 mM
NaCl
-
500 mM reduces cleavage to 60%, 1 M reduces cleavage to 30%
naphthalen-2-yl [2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]sulfamate
-
-
phenyl [2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamate
-
-
phenyl [[1-(2-hydroxyethyl)-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]carbamate
-
-
phenyl [[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]carbamate
-
-
phenyl [[2-oxo-1-(4-oxobutyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]carbamate
-
-
tert-butyl [3-([[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]amino)propyl]carbamate
-
4% inhibition at 0.02 mM
Ubiquitin aldehyde
-
-
-
Urea
-
2 M reduces cleavage to 95%, 3 M reduces cleavage to 5%
hSUMO-VS
-
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
-
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
-
design, synthesis, and biological evaluation of benzodiazepine-based SUMO-specific protease 1 inhibitors, structure–activity relationship, overview
-
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
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
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
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0218
-
(2Z)-3-(naphthalen-2-yl)-N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]prop-2-enamide
-
pH and temperature not specified in the publication
0.1
-
3-[(acetyloxy)amino]-N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]benzamide
-
pH and temperature not specified in the publication
0.1
-
3-[(benzyloxy)amino]-N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]benzamide
-
pH and temperature not specified in the publication
0.1
-
4-[(benzyloxy)amino]-N-[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]benzamide
-
pH and temperature not specified in the publication
0.0092
-
benzyl (3-[[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]phenyl)carbamate
-
pH and temperature not specified in the publication
0.0155
-
benzyl (4-[[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]phenyl)carbamate
-
pH and temperature not specified in the publication
0.0212
-
naphthalen-2-yl [2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]sulfamate
-
pH and temperature not specified in the publication
0.1
-
phenyl [2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamate
-
pH and temperature not specified in the publication
0.1
-
phenyl [[1-(2-hydroxyethyl)-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]carbamate
-
pH and temperature not specified in the publication
0.0272
-
phenyl [[2-oxo-1-(2-oxoethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]carbamate
-
pH and temperature not specified in the publication
0.1
-
phenyl [[2-oxo-1-(4-oxobutyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamoyl]carbamate
-
pH and temperature not specified in the publication
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
high expression level
Manually annotated by BRENDA team
Q8GYL3, Q94F30
-
Manually annotated by BRENDA team
additional information
-
quantitative real-time quantitative expression PCR analysis
Manually annotated by BRENDA team
additional information
-
parasites in human red blood cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
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
Manually annotated by BRENDA team
-
the NH2-terminal domain of the enzyme, residues between position 144 and 346, includes sequences necessary and sufficient to concentrate Ulp1 at nuclear envelope
Manually annotated by BRENDA team
-
Ulp1 localizes predominantly to nuclear pore complexes but also deconjugates sumoylated septins at the bud-neck of dividing cells
-
Manually annotated by BRENDA team
-
SENP6 and SENP7
Manually annotated by BRENDA team
additional information
Q8GYL3, Q94F30
not in the nucleus
-
Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 31000, SDS-PAGE
additional information
-
in the crystal structure of human SENP1 complexed with unprocessed SUMO1, PDB: 2IY1, the catalytic Cys603 is located in a cleft which, upon substrate binding, closes to form a channel-like structure
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Ulp1-Smt3 crystal structure, hanging drop vapor diffusion
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
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
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
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
-
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
-
recombinant His-tagged catalytic domain SENP1c, aa419-aa643 from Escherichia coli strain BL21 by nickel affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
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
Q8GYL3, Q94F30
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
-
cloning of the His-tagged catalytic domain of SENP1, SENP1c, aa419-aa643, from PC-3 cell cDNA library, cloned into pET28a(+) vector, and expressed in Escherichia coli strain BL21
-
expression of catalytic domains of human SENP2-(364-589), SENP6-(637-1112), and SENP7-(662-984) and of mutant SENP-7s in Escherichia coli
-
quantitative real-time quantitative expression PCR analysis
-
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 SENP1 and SENP2 isozymes in HCT-116 cells
-
expression of the wild-type full-length PfSENP1 and the catalytic domain of PfSENP1
-
expression in Escherichia coli
-
expression of wild-type and mutant enzymes, expression of the SBS domain as a SBS-GFP fusion protein
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
K691A
-
site-directed mutagenesis of SENP7
K691E
-
site-directed mutagenesis of SENP7
C580S
-
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
-
the mutation destroys an essential salt bridge formed between Smt3 and Ulp1
D451N/C580S
-
site-directed mutagenesis, abolished accumulation of the full-length Ulp1 double-mutant at the septin ring
C461S
Q8GYL3, Q94F30
site-directed mutagenesis, ELS1C461S is not capable of cleaving the extension oV the carboxyl terminus of SUMO1
additional information
Q8GYL3, Q94F30
plant enzymes ELS1 and ESD4 differ in their ability to complement yeast Ulp1 mutants, mutant phenotypes, overview; plant enzymes ELS1 and ESD4 differ in their ability to complement yeast Ulp1 mutants, mutant phenotypes, overview
additional information
-
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
P686G/P687G/P688G/P689G
-
site-directed mutagenesis of SENP7
additional information
-
a genetic mutation inactivating all three gene products of SENP2 is generated by alternative splicing
I435V/N450S/I504T/C580S
-
site-directed mutagenesis, the mutant shows a reduced ability to enrich at the septin ring
additional information
-
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
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
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
drug development
-
SENP1 is a potential therapeutic target for the treatment of prostate cancers
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
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
-
usage of the targeting and small ubiquitin-like modifier, SUMO, binding properties of Ulp1(3)(C580S) to purify Smt3-modified proteins from cell extracts