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Information on EC 3.4.22.B70 - SENP1 peptidase and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC3.4.22.B70preliminary BRENDA-supplied EC number
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3.4.22.B70 SENP1 peptidaseSpecify your search results
Word Map
- 3.4.22.B70
-
desumoylation
-
deconjugating
-
senp-1
- medicine
-
sumo-modified
-
senp1-mediated
- drug development
- ranbp2
- sumo-2
- diagnostics
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
The enzyme catalyzes two essential functions in the SUMO pathway: processing of full-length SUMO-1, SUMO-2 and SUMO-3 to their mature forms and deconjugation of SUMO-1, SUMO-2 and SUMO-3 from targeted proteins. Deconjugates SUMO-1 from homeodomain-interacting protein kinase 2. Deconjugates SUMO-1 from histone deacetylase 1, which decreases its transcriptional repression activity. Cleavage of Gly97-/-His98 bond in the SUMO-1 precursor with release of the propeptide His-Ser-Thr-Val. Cleavage of Gly93-/-Val94 bond in the SUMO-2 precursor with release of the propeptide Val94-Thyr. Cleavage of the Gly92-/-Val93 in the SUMO-3 precursor with release of the propeptide Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe.
Synonyms
sumo isopeptidase, sumo-specific protease 1, uspl1, sentrin/sumo-specific protease 1, sumo-specific isopeptidase, sentrin-specific protease 1, ubiquitin-specific protease-like 1, small ubiquitin-like modifier protein-specific protease 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
SENP1
sentrin-specific protease 1
SUMO isopeptidase
SUMO protease
SUMO-specific protease
SENP1
-
-
SENP1
-
SYSTEMATIC NAME
IUBMB Comments
Q9P0U3 {SwissProt}
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(SUMO-1)-homeodomain-interacting protein kinase 2 conjugate + H2O
SUMO-1 + homeodomain-interacting protein kinase 2 conjugate
(SUMO-1)-K2P1 potassium channel + H2O
SUMO-1 + K2P1 potassium channel
silent K2P1 channels in excised plasma membrane patches are activated by SENP1
-
-
?
(SUMO-1)-K2P1 subunit of potassium channel + H2O
SUMO-1 + K2P1 subunit of potassium channel
SUMO1 is conjugated to the epsilon-amino group of Lys274 of the K2P1 potassium channel. When mutated to Gln, Arg, Glu, Asp, Cys, or Ala, the channels are constitutively active and insensitive to SUMO1 and SENP1. Wild-type channels in plasma membrane have two K2P1 subunits and assemble with two SUMO1 monomers. Although channels engineered with one Lys274 site carry just one SUMO1 they are activated and silenced by SENP1 and SUMO1 like wild-type channels
-
-
?
(SUMO-1)-Ran GTPase-activating protein 1 conjugate + H2O
SUMO-1 + Ran GTPase-activating protein 1
rates at which SUMO-1, SUMO-2 and SUMO-3 are deconjugated from RanGAP1 are indistinguishable
-
-
?
(SUMO-1)-RanGAP1 conjugate + H2O
SUMO-1 + RanGAP1
SENP1 binding is accompanied by a conformational change in the substrate
-
-
?
(SUMO-2)-Ran GTPase-activating protein 1 conjugate + H2O
SUMO-2 + Ran GTPase-activating protein 1
rates at which SUMO-1, SUMO-2 and SUMO-3 are deconjugated from RanGAP1 are indistinguishable
-
-
?
(SUMO-2)-RanGAP1 conjugate + H2O
SUMO-2 + RanGAP1
SENP1 binding is accompanied by a conformational change in the substrate
-
-
?
(SUMO-2)n-glutathione S-transferase-promyelocytic leukemia protein conjugate + H2O
?
glutathione S-transferase-promyelocytic leukemia protein bearing a polymeric chain of SUMO-2
-
-
?
(SUMO-3)-Ran GTPase-activating protein 1 conjugate + H2O
SUMO-3 + Ran GTPase-activating protein 1
rates at which SUMO-1, SUMO-2 and SUMO-3 are deconjugated from RanGAP1 are indistinguishable
-
-
?
CrSUMO148 precursor + H2O
CrSUMO148 + peptide
-
CrSUMO148 is a SUMO homolog from Chlamydomonas reinhardtii with 148 amino acids. SENP1 solely cleaves CrSUMO148 at the peptide bond after the first diglycine motif, although there are four putative cleavage sites in the primary amino acid sequence
-
-
?
CrSUMO148-conjugated protein + H2O
CrSUMO148 + protein
-
CrSUMO96 is a SUMO homolog from Chlamydomonas reinhardtii with 148 amino acids
-
-
?
CrSUMO96 precursor + H2O
CrSUMO96 + peptide
-
CrSUMO96 is a SUMO homolog from Chlamydomonas reinhardtii with 96 amino acids. SENP1 shows more processing activity for CrSUMO97 than for CrSUMO96
-
-
?
CrSUMO96-conjugated protein + H2O
CrSUMO96 + protein
-
CrSUMO96 is a SUMO homolog from Chlamydomonas reinhardtii with 96 amino acids
-
-
?
CrSUMO97 precursor + H2O
CrSUMO97 + peptide
-
CrSUMO97 is a SUMO homolog from Chlamydomonas reinhardtii with 97 amino acids. SENP1 shows more processing activity for CrSUMO97 than for CrSUMO96
-
-
?
CrSUMO97-conjugated protein + H2O
CrSUMO97 + protein
-
CrSUMO96 is a SUMO homolog from Chlamydomonas reinhardtii with 97 amino acids
-
-
?
polyCrSUMO148 + H2O
?
-
CrSUMO148 is a SUMO homolog from Chlamydomonas reinhardtii with 148 amino acids. polyCrSUMO148 chains aree completely deconjugated by SENP1
-
-
?
polyCrSUMO96 + H2O
?
-
CrSUMO96 is a SUMO homolog from Chlamydomonas reinhardtii with 96 amino acids. polyCrSUMO96 chains aree completely deconjugated by SENP1. SENP1 displays a similar efficiency to deconjugate either polymeric CrSUMO96 or CrSUMO97 chains
-
-
?
polyCrSUMO97 + H2O
?
-
CrSUMO97 is a SUMO homolog from Chlamydomonas reinhardtii with 97 amino acids. polyCrSUMO97 chains aree completely deconjugated by SENP1. SENP1 displays a similar efficiency to deconjugate either polymeric CrSUMO96 or CrSUMO97 chains
-
-
?
pro-small ubiquitin-related modifier + H2O
small ubiquitin-related modifier + ?
-
SENP1 processes the precursor SUMO to its mature form by catalyzing the cleavage of a scissile peptide bond
-
-
?
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
SUMO-7-amido-4-methylcoumarin + H2O
SuMo + 7-amino-4-methylcoumarin
-
-
-
?
SUMO-homeodomain-interacting protein kinase 1 conjugate + H2O
SUMO + homeodomain-interacting protein kinase 1 conjugate
-
-
-
?
SUMO-hypoxia-inducible factor 1 conjugate + H2O
SUMO + hypoxia-inducible factor 1
-
-
-
?
SUMOylated androgen receptor + H2O
androgen receptor + SUMO1
-
deconjugation
-
-
?
SUMOylated peroxisome proliferator-activated receptor coactivator 1alpha + H2O
deSUMOylated peroxisome proliferator-activated receptor coactivator 1alpha + SUMO1
-
deSUMOylation
-
-
?
(SUMO-1)-androgen receptor conjugate + H2O
SUMO-1 + androgen receptor conjugate
-
-
-
?
(SUMO-1)-androgen receptor conjugate + H2O
SUMO-1 + androgen receptor conjugate
SENP1 markedly contributes to the androgen-stimulated proliferation of prostate cancer cells
-
-
?
(SUMO-1)-histone deacetylase 1 conjugate + H2O
SUMO-1 + histone deacetylase 1
-
-
-
?
(SUMO-1)-histone deacetylase 1 conjugate + H2O
SUMO-1 + histone deacetylase 1
SENP1 regulates that androgen receptor-dependent transcription through desumoylation of histone deacetylase 1 (HDAC1)
-
-
?
(SUMO-1)-homeodomain-interacting protein kinase 2 conjugate + H2O
SUMO-1 + homeodomain-interacting protein kinase 2 conjugate
-
-
-
?
(SUMO-1)-homeodomain-interacting protein kinase 2 conjugate + H2O
SUMO-1 + homeodomain-interacting protein kinase 2 conjugate
desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) may be regulated by the cytoplasmic-nuclear shuttling of SENP1. Desumoylation induces dissociation of homeodomain-interacting protein kinase 2 conjugate from nuclear bodies
-
-
?
Pin1 + H2O
?
-
Pin1 is SUMOylated on Lys6 in the WW domain and on Lys63 in the PPIase domain, deSUMOlation by SENP1
-
-
?
Pin1 + H2O
?
-
Pin1 is SUMOylated on Lys6 in the WW domain and on Lys63 in the PPIase domain, deSUMOlation by SENP1. SENP1 is more efficient in deSUMOylating Pin1 than SENP2, whereas SENP3 is barely active
-
-
?
SUMO-1 precursor + H2O
SUMO-1 + His-Ser-Thr-Val
cleavage of the -Gly-Gly-/-His-Ser-Thr-Val bond. The maturation reaction is the first committed step for subsequent sumoylation
-
-
?
SUMO-1 precursor + H2O
SUMO-1 + His-Ser-Thr-Val
pre-SUMO-1 is processed rapidly
-
-
?
SUMO-1 precursor + H2O
SUMO-1 + His-Ser-Thr-Val
SENP1 is capable of processing all SUMO-1, -2 and -3 in vitro but with different efficiencies. Cleavage of the -Gly-Gly-/-His-Ser-Thr-Val bond. Over 90% of SUMO-1 is hydrolysed
-
-
?
SUMO-1 precursor + H2O
SUMO-1 + His-Ser-Thr-Val
SENP1 preferentially processes SUMO-1 over SUMO-2. Discrimination between unprocessed SUMO-1 and SUMO-2 by SENP1 is based on a catalytic step rather than substrate binding. SENP1 binding is accompanied by a conformational change in the substrate
-
-
?
SUMO-2 precursor + H2O
SUMO-2 + Val-Tyr
cleavage of the -Gly-Gly-/-Val-Tyr. The maturation reaction is the first committed step for subsequent sumoylation
-
-
?
SUMO-2 precursor + H2O
SUMO-2 + Val-Tyr
pre-SUMO-2 is processed slowly
-
-
?
SUMO-2 precursor + H2O
SUMO-2 + Val-Tyr
SENP1 is capable of processing all SUMO-1, -2 and -3 in vitro but with different efficiencies. Over 90% of SUMO-2 is hydrolysed. Cleavage of the -Gly-Gly-/-Val-Tyr
-
-
?
SUMO-2 precursor + H2O
SUMO-2 + Val-Tyr
SENP1 preferentially processes SUMO-1 over SUMO-2. Discrimination between unprocessed SUMO-1 and SUMO-2 by SENP1 is based on a catalytic step rather than substrate binding. SENP1 binding is accompanied by a conformational change in the substrate
-
-
?
SUMO-3 precursor + H2O
SUMO-3 + Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe
cleavage of the -Gly-Gly-/-Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe bond. The maturation reaction is the first committed step for subsequent sumoylation
-
-
?
SUMO-3 precursor + H2O
SUMO-3 + Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe
pre-SUMO-3 is processed at an intermediate rate
-
-
?
SUMO-3 precursor + H2O
SUMO-3 + Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe
SENP1 is capable of processing all SUMO-1, -2 and -3 in vitro but with different efficiencies. 50% of SUMO-3 is hydrolysed. Cleavage of the -Gly-Gly-/-Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe bond
-
-
?
SUMO-Elk-1 conjugate + H2O
SUMO + Elk-1
SENP1 participates in the dynamic regulation of Elk-1 SUMOylation
-
-
?
additional information
?
-
SENP1 appears catalytically competent in their apo forms. Upon SUMO interaction, local conformational rearrangement of Trp465, His529 and Trp534 occurs, while Cys603 separates from the catalytic triad to attack the carbonyl-C of Gly97 of SUMO. After the cleavage event, SUMO is released from the complex and converted into its apo form ready for the next reaction cycle
-
-
?
additional information
?
-
SENP1 is potent in removing both SUMO-1 and SUMO-2 from cellular proteins. SENP1 does not seem to differentiate between SUMO-1 and SUMO-2
-
-
?
additional information
?
-
enzyme USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells
-
-
?
additional information
?
-
-
nucleoporin Nup153 binds to SENP1 by interacting with the unique N-terminal domain of Nup153 as well as a specific region within the C-terminal FG-rich region. Nup153 is a substrate for SUMOylation, with this modification kept in check by the SUMO protease
-
-
?
additional information
?
-
-
the enzyme SUMO protease removes SUMO conjugate from proteins
-
-
?
additional information
?
-
enzyme USPL1 binds SUMO but not ubiquitin, no activity with ubiquitin-7-amido-4-methylcoumarin
-
-
?
additional information
?
-
-
the enzyme SENP1 interacts with SUMO1-FL, SUMO1-GG, SUMO11-92 (containing residues 1-92, with C-terminus truncated) or peptides corresponding to the C-terminus of SUMO1. The exchange rates between free SENP1 and SENP1 in complex with SUMO1-FL or SUMO1-GG are mostly slow to intermediate, relative to the NMR chemical shift timescale, and both SUMO-GG and SUMO-FL produce similar chemical shift perturbation. The beta-grasp domain of SUMO1 interacts with enzyme SENP1 in a manner similar to that in the context of SUMO1-FL, effects of beta-grasp domain on the enzyme, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(SUMO-1)-androgen receptor conjugate + H2O
SUMO-1 + androgen receptor conjugate
SENP1 markedly contributes to the androgen-stimulated proliferation of prostate cancer cells
-
-
?
(SUMO-1)-histone deacetylase 1 conjugate + H2O
SUMO-1 + histone deacetylase 1
SENP1 regulates that androgen receptor-dependent transcription through desumoylation of histone deacetylase 1 (HDAC1)
-
-
?
(SUMO-1)-homeodomain-interacting protein kinase 2 conjugate + H2O
SUMO-1 + homeodomain-interacting protein kinase 2 conjugate
desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) may be regulated by the cytoplasmic-nuclear shuttling of SENP1. Desumoylation induces dissociation of homeodomain-interacting protein kinase 2 conjugate from nuclear bodies
-
-
?
(SUMO-1)-K2P1 potassium channel + H2O
SUMO-1 + K2P1 potassium channel
silent K2P1 channels in excised plasma membrane patches are activated by SENP1
-
-
?
Pin1 + H2O
?
-
Pin1 is SUMOylated on Lys6 in the WW domain and on Lys63 in the PPIase domain, deSUMOlation by SENP1
-
-
?
pro-small ubiquitin-related modifier + H2O
small ubiquitin-related modifier + ?
-
SENP1 processes the precursor SUMO to its mature form by catalyzing the cleavage of a scissile peptide bond
-
-
?
small ubiquitin-related modifier-protein + H2O
small ubiquitin-related modifier-protein + protein
-
SUMO-specific proteases, SENPs, reversibly remove small ubiquitin-related modifier-protein, SUMO, from the SUMOylated proteins
-
-
r
SUMO-1 precursor + H2O
SUMO-1 + His-Ser-Thr-Val
cleavage of the -Gly-Gly-/-His-Ser-Thr-Val bond. The maturation reaction is the first committed step for subsequent sumoylation
-
-
?
SUMO-2 precursor + H2O
SUMO-2 + Val-Tyr
cleavage of the -Gly-Gly-/-Val-Tyr. The maturation reaction is the first committed step for subsequent sumoylation
-
-
?
SUMO-3 precursor + H2O
SUMO-3 + Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe
cleavage of the -Gly-Gly-/-Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe bond. The maturation reaction is the first committed step for subsequent sumoylation
-
-
?
SUMO-Elk-1 conjugate + H2O
SUMO + Elk-1
SENP1 participates in the dynamic regulation of Elk-1 SUMOylation
-
-
?
SUMO-hypoxia-inducible factor 1 conjugate + H2O
SUMO + hypoxia-inducible factor 1
-
-
-
?
additional information
?
-
enzyme USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells
-
-
?
additional information
?
-
-
nucleoporin Nup153 binds to SENP1 by interacting with the unique N-terminal domain of Nup153 as well as a specific region within the C-terminal FG-rich region. Nup153 is a substrate for SUMOylation, with this modification kept in check by the SUMO protease
-
-
?
additional information
?
-
-
the enzyme SUMO protease removes SUMO conjugate from proteins
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
the enzyme effectively removes SUMO-1 moiety, in the presence of Ca2+ rather than Mn2+, from the sumoylated homeodomain-interacting protein kinase 2 conjugate
Mn2+
the enzyme effectively removes SUMO-1 moiety, in the presence of Ca2+ rather than Mn2+, from the sumoylated homeodomain-interacting protein kinase 2 conjugate
INHIBITOR
ORGANISM
UNIPROT
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-[(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
haemagglutinin-SUMO-vinylmethylester
a suicide inhibitor, Strep-TEV-HA-SUMO-vinylmethylester. Enzyme USPL1 requires its catalytic cysteine to react with the inhibitor
-
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
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
-
-
SUMO-1-GG
product inhibition, competitive, inhibits cleavage of the SUMO-1 precursor, SUMO-2 precursor, (SUMO-1)-RanGAP1 conjugate and (SUMO-2)-RanGAP1 conjugate
-
SUMO-2-GG
product inhibition, competitive, inhibits cleavage of the SUMO-1 precursor, SUMO-2 precursor, (SUMO-1)-RanGAP1 conjugate and (SUMO-2)-RanGAP1 conjugate
-
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
additional information
-
design, synthesis, and biological evaluation of benzodiazepine-based SUMO-specific protease 1 inhibitors, structureactivity relationship, overview
-
additional information
-
2-(4-chlorophenyl)-2-oxoethyl 4-benzamidobenzoate derivatives, evaluation of a class of SENP1 inhibitors by virtual screening, synthesis and biological evaluation, structure-activity relationship, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
desumoylation is enhanced either by the forced translocation of SENP1 into the nucleus or by the SENP1 NES (nuclear export sequence) mutant
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
enzyme-substrate complex formation kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
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
Homo sapiens
-
pH and temperature not specified in the publication
0.05
2-(4-chlorophenyl)-2-oxoethyl 4-[(3,4-diethoxybenzoyl)amino]benzoate
Homo sapiens
above, pH and temperature not specified in the publication
0.05
2-(4-chlorophenyl)-2-oxoethyl 4-[(3,4-dimethoxybenzoyl)amino]benzoate
Homo sapiens
above, pH and temperature not specified in the publication
0.05
2-(4-chlorophenyl)-2-oxoethyl 4-[(3-aminobenzoyl)amino]benzoate
Homo sapiens
above, pH and temperature not specified in the publication
0.00174
2-(4-chlorophenyl)-2-oxoethyl 4-[(3-fluorobenzoyl)amino]benzoate
Homo sapiens
pH and temperature not specified in the publication
0.05
2-(4-chlorophenyl)-2-oxoethyl 4-[(3-hydroxybenzoyl)amino]benzoate
Homo sapiens
above, pH and temperature not specified in the publication
0.00108
2-(4-chlorophenyl)-2-oxoethyl 4-[[3-(benzyloxy)benzoyl]amino]benzoate
Homo sapiens
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
pH and temperature not specified in the publication
0.00118
2-(4-chlorophenyl)-2-oxoethyl 4-(benzoylamino)benzoate
Homo sapiens
pH and temperature not specified in the publication
0.00354
2-(4-chlorophenyl)-2-oxoethyl 4-(benzoylamino)benzoate
Homo sapiens
pH and temperature not specified in the publication
0.00186
2-(4-chlorophenyl)-2-oxoethyl 4-[(3-methoxybenzoyl)amino]benzoate
Homo sapiens
pH and temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
enzyme SENP1 levels are positively correlated with substrate Pin1 levels in human breast cancer specimens
-
enzyme SENP1 is upregulated in pancreatic ductal adenocarcinoma tissues compared with adjacent normal tissues
-
elevation of SENP1 mRNA in prostate cancer cells as compared with normal prostate epithelial cells
-
elevation of SENP1 mRNA in prostate cancer cells as compared with normal prostate epithelial cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
enzyme USPL1 is a low-abundance protein that colocalizes with coilin in cajal bodies. USPL1 is an essential Cajal body component
-
C603S is exclusively nuclear in comparison with the wild-type SENP1, which is consistently present in the cytoplasm, albeit at low steady state levels
SENP1 is localized in the cytoplasm where it is complexed with an antioxidant protein thioredoxin. Tumor necrosis factor (TNF) induces the release of SENP1 from thioredoxin as well as nuclear translocation of SENP1
SENP1 shuttles between the cytoplasm and the nucleus. SENP1 contains the nuclear export sequence (NES) within the extreme carboxyl-terminal region, and SENP1 is exported to the cytoplasm in a NES-dependent manner
-
SENP1 expresses nuclear export sequences that allow these 2 SENPs to shuttle in and out of the nucleus
-
C603S is exclusively nuclear in comparison with the wild-type SENP1, which is consistently present in the cytoplasm, albeit at low steady state levels. Presence of a single nonconsensus nuclear localization signal within the N-terminus of the protein. Residues within the predicted NLS1 region around positions 170-180 are critical for the nuclear localization of SENP1. SENP1 localization may be influenced by the expression of proteins that are targets of SUMO-1 modification, such as HDAC4 and PML, which affects the relative levels and localization of SUMO-1 conjugates within the cell
SENP1 is localized in the cytoplasm where it is complexed with an antioxidant protein thioredoxin. Tumor necrosis factor (TNF) induces the release of SENP1 from thioredoxin as well as nuclear translocation of SENP1
SENP1 shuttles between the cytoplasm and the nucleus. SENP1 contains the nuclear export sequence (NES) within the extreme carboxyl-terminal region, and SENP1 is exported to the cytoplasm in a NES-dependent manner. As sumoylations are nuclear events and most SUMO-conjugates are located within the nucleus, it appears that SENP1 might find its cellular targets subsequent to its nuclear relocalization
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
additional information
evolution
-
the enzyme belongs to the superfamily of Ubl-specific proteases being Cys proteases. In all SENPs, an aromatic side chain, such as that of Trp or Phe, forms the channel lid. The catalytic Cys residues are located within the closed catalytic channels for binding the C-termini of ubiquitin-likes, and the catalytic residues undergo conformational changes when these proteases form complexes with their substrates. SENP1 is a model system for the Ubl-specific proteases in the Cys protease superfamily because it shares the same biochemical mechanism and its catalytic Cys is similarly buried as those of other Ubl-specific proteases. The mode of substrate recognition and binding of SENP1 may be shared by other de-Ubl enzymes
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
malfunction
defects in adipocyte differentiation as well as PPARgamma expression in Senp1-/- mouse embryonic fibroblast cells induced by adipogenic stimuli. Deficiency in SUMOylation reduces Sharp-1 suppression of adipogenesis
malfunction
-
differential localization of nucleoporins upon codepletion of SENP1 and SENP2 in HeLa cells, immunohistochemic analysis, overview
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
malfunction
-
inhibition of endogenous enzyme SENP1 via the SENP1 dominant-negative mutant or shRNA-induced Pin1 SUMOylation in vivo. Knockdown of endogenous enzyme SENP1 expression also reduces Pin1-mediated cyclin D1 activation and again the enhanced ability of Pin1K6/63R to activate the cyclin D1 promoter is not reduced by enzyme SENP1
malfunction
-
knockdown of SENP1 by SENP1-siRNA inhibits pancreatic cancer cell proliferation, migration, and invasion. Silencing of SENP1 results in downregulation of MMP-9, which is pivotal for PDAC cell growth and migration
malfunction
RNA interference-mediated knockdown of SENP1 delays sister chromatid separation at metaphase
malfunction
-
specifically, either RNAi depletion of SENP1/SENP2 or expression of dominantly interfering mutants of these proteins results in increased sumoylation of endogenous Nup153. Catalytically inactive SENP1 maintains specific attributes, although it has enhanced interaction with sumoylated Nup153, overview. Truncated SENP1CD is modified by both SUMO1 and SUMO2
malfunction
-
the enzyme SENP1 inhibition by siRNA significantly suppresses neuroblastoma cell migration and invasion, overexpression of SENP1 promotes neuroblastoma cells migration and invasion
physiological function
-
abrogation of elevated SENP1 mRNA in prostate cancer cells significantly decreases androgen-mediated cell growth. Increased SENP1 expression directly modulates androgen receptor-dependent cell proliferation and transcription, SENP1 could play an important role in prostate carcinogenesis
physiological function
may be required for proliferation of normal human cells
physiological function
mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance apoptosis signal-regulating kinase-1-dependent apoptosis
physiological function
-
modification of proteins by small ubiquitin-like modifier (SUMO) plays an important role in the function, compartmentalization, and stability of target proteins, contributing to the regulation of diverse processes. SUMO-1 modification can be regulated not only at the level of conjugation, it may also be reversed by a class of proteases known as the SUMO-specific proteases
physiological function
SENP1 can regulate that androgen receptor-dependent transcription through desumoylation of histone deacetylase
physiological function
SENP1 reverses the ligand-induced SUMOylation of androgen receptor and helps fine tune the cellular responses to androgens in a target promoter-selective manner. SENP1 stimulates the activity of holo-androgen receptor on compound androgen response element-containing promoters. The effects of SENP1 on androgen receptor dependent transcription are dependent on catalytic activity and require intact SUMO acceptor sites in androgen receptor, indicating that their coactivating effects are mainly due to their direct isopeptidase activity on holo-androgen receptor
physiological function
-
SENP1, can transform normal prostate epithelia to a dysplasic state and directly modulate several oncogenic pathways in prostate cells, including AR, c-Jun, and Cyclin D1
physiological function
enzyme SENP1 is an important mediator of precise spatial and temporal control of sumoylation in mitosis required for chromosome segregation
physiological function
-
enzyme SENP1 plays a key role in tumor angiogenesis, because it regulates the stability of hypoxia-inducible factor 1alpha, which is a key player in the formation of new blood vessels to support tumor growth. It is highly expressed in human prostate cancer specimens and regulates androgen receptor activities The enzyme is responsible for processing small ubiquitin-like modifier, SUMO
physiological function
-
Pin1 is SUMOylated on Lys6 in the WW domain and on Lys63 in the PPIase domain. Pin1 SUMOylation inhibits its protein activity and oncogenic function, the enzyme removes the SUMO conjugates and activates Pin1 promoting the ability of Pin1 to induce centrosome amplification and cell transformation, overview. Enzyme SENP1 also increases Pin1 protein stability in cell cultures, and Pin1 levels are positively correlated with SENP1 levels in human breast cancer specimens. Pin1 SUMOylation on Lys6/63 as a distinct mechanism to inhibit its activity and function but also identify a critical role for SENP1-mediated deSUMOylation in promoting Pin1 function during tumorigenesis
physiological function
-
SENP1 is a specific protease to regulate the SUMOylation status of peroxisome proliferator-activated receptor coactivator 1alpha, i.e. PGC-1alpha. The enzyme SENP1 also promotes PGC-1alpha transcription activity, which is essential for the expression of mitochondrial genes and subsequently mitochondrial biogenesis. SENP1 is essential for expression of nuclear mitochondrial genes
physiological function
-
SENP1, as well as SENP2, regulates the proper localization of nucleoporins, overview. The enzyme interacts with the nucleoporin Nup153 via a dual interface that includes a bridging interaction with the soluble transport receptor importin beta and a SUMO-mediated mechanism. SENP1 and SENP2 are not required for localization of the transmembrane proteins nucleoporin POM121 and inner nuclear envelope protein Sun1 or expansion of the interphase nuclear envelope
physiological function
-
SUMO-specific protease 1 regulates pancreatic cancer cell proliferation and invasion by targeting MMP-9. Enzyme SENP1 is positively associated with lymph node metastasis and TNM stage
physiological function
the enzyme controls adipocyte differentiation. Adipocyte differentiation is regulated by a transcriptional cascade that mainly includes CCAAT/enhancer-binding protein family members and the nuclear receptor peroxisome proliferator-activated receptor gamma, PPARgamma. SENP1 is a specific de-SUMOylation protease for Sharp-1, a repressor for PPARgamma transcription and adipogenesis. SENP1 enhances adipogenesis through de-SUMOylation of Sharp-1, which then releases Sharp-1 repression of PPARgamma expression and adipocyte differentiation
physiological function
-
the enzyme plays an important role in the occurrence and development of prostate cancer
physiological function
-
the enzyme SENP1 is involved in deconjugation of proteins, such as the androgen receptor, from small ubiquitin modifier, SUMO, proteins, a dynammic and reversible posttranslational modification. The enzyme is essential to cadmium-induced enhancement of androgen receptor activity
physiological function
-
the SUMO protease SENP1 regulates cell migration and invasion in neuroblastoma and can regulate the expression of CDH1, MMP9 and MMP2, overview. SUMO proteases remove SUMO, i.e. small ubiquitin-like modifier, conjugate from proteins, and their expression is deregulated in diverse cancers. SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities
physiological function
-
the SUMO proteases play roles both in processing SUMO during the biogenesis of this peptide moiety and also in reversing SUMO modification on specific targets to control the activities conferred by this posttranslational modification. Specificity of the role for SENP1 and SENP2 in maintaining desumoylation of Nup153
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
physiological function
an enrichment of inflammation signatures is observed in HUVECs with SENP1 3'-untranslated region (3'UTR) overexpression which is positively correlated with TGFBR2 signaling pathway. TGFBR2 is competing endogenous RNA target of SENP1 and the downstream effectors Smad2/3 are also overexpressed in HUVECs with SENP1 3'UTR overexpression. Injection of SENP1 siRNA following LPS treatment attenuates lipopolysaccharide-induced sepsis. TGFBR2 overexpression partially abrogates SENP1 siRNA-mediated inhibition on lipopolysaccharide-induced sepsis
physiological function
SENP1 physically interacts with the chromatin remodeler chromodomain helicase DNA-binding protein CHD3. CHD3-and SENP1-KO cells reveal a large degree of overlap in differential chromatin openness between these two mutant cell lines. CHD3 and SENP1 may associate with CCCTC-binding factor (CTCF) and SUMOylated chromatin-associated factors. SENP1 and CHD3 proteins co-regulate the expression of several genes
physiological function
-
silencing of SENP1 promotes cellular apoptosis, and inhibits proliferation and migration of PC-3M cells. SENP1 silencing increases the SMAD4 expression at protein level, upregulates E-cadherin and downregulates vimentin expression. SMAD4 interference abolishes SENP1-mediated upregulation of E-cadherin. SENP1 overexpression in LNCaP cells reduces SMAD4 protein, and promotes epithelial mesenchymal transition via decreasing E-cadherin and increasing vimentin
additional information
-
enzyme SENP1 silencing has no influence on androgen receptor expression
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
additional information
-
NMR enzyme-substrate complex analysis, the distally bound beta-grasp domain of SUMO1 induces realignment of the catalytic residues that enhance the enzyme activity, mode of substrate recognition and binding, molecular dynamics, overview
additional information
-
SENP1 is a target of SUMO modification and has targeting preference for SUMO paralogues and substrates
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). SENP1_HUMAN
644
0
73481
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
sumoylation
-
SENP1 is itself a target for SUMO-1 modification but that this modification is normally rapidly reversed by an autocatalytic activity removing the SUMO-1, with little of the modified form accumulating. In the mutant SENP1 (C603S), the absence of proteolytic activity resulted in the detection of the conjugated form
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals of the human SENP1 catalytic domain are obtained at room temperature by hanging-drop vapour diffusion. When interpreting a medium-resolution electron-density map of the catalytic domain of human sentrin-specific protease 1 (SENP1), a strong feature indicative of an ordered divalent cation is noted. This is assigned as Co2+, an essential component of the crystallization mixture. The ion displays tetrahedral coordination by Glu430 and His640 from one molecule and the corresponding residues from a symmetry-related molecule. Analysis of the data derived from a previous structure of SENP1 suggest that Co2+ has been overlooked and rerefinement support this conclusion. Highthroughput automated re-refinement protocols also failed to mark the Co2+ position
SENP1 crystallization is performed at 20°C using a sitting drop vapour-diffusion method. Single diamond-shaped crystals are grown after 2 days from equal volumes of protein solution (20 mg/ml in 20 mM Tris/HCl, pH 8.0, and 50 mM NaCl) and reservoir solution containing 100 mM CoCl2, 0.1 M Mes, pH 6.5, and 1.8 M (NH4)2SO4. The structure of SENP1 is determined to 2.45 A. NaBH4 is used to trap a stable thiohemiacetal transition-state analogue between Cys602 of SENP1 and Gly92 of SUMO-2, determination of the structure of this complex to 3.2 A. Crystallization and structure determination of the SENP1-SUMO-2 complex
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C236S
site-directed mutagenesis, the mutant is not inhibited by suicide inhibitor Strep-TEV-HA-SUMO-vinylmethylester in contrast to the wild-type enzyme
C602A
completely inactive in processing of SUMO-2 and in deconjugating SUMO-2
C603A
the mutant is unable to desumoylate the (SUMO-1)-homeodomain-interacting protein kinase 2 conjugate
C603S
D441A
mutant protein is indistinguishable from that of the wild-type protein in both processing and deconjugation
D468A
mutated protein is only slightly impaired in processing and not at all in deconjugation
D550A
completely inactive in processing of SUMO-2 and in deconjugating SUMO-2
F496A
altered protein retains significant levels of deconjugation activity
H529A
altered protein retains significant levels of deconjugation activity
H533A
completely inactive in processing of SUMO-2 and in deconjugating SUMO-2
Q596A
mutant of SENP1 is severely impaired in both deconjugation and processing
W229L
site-directed mutagenesis, mutation to the residue found in USP2 and other ubiquitin-specific USPs dramatically impairs SUMO binding and cleavage
W237F
site-directed mutagenesis, mutation to the residue found in USP2 and other ubiquitin-specific USPs dramatically impairs SUMO binding and cleavage
W512A
mutant has a reduced deconjugation activity in vitro, its deconjugation activity in vivo is only impaired to a small extent
additional information
C603S
-
inactive mutant enzyme. C603S is exclusively nuclear in comparison with the wild-type SENP1, which is consistently present in the cytoplasm, albeit t low steady state levels. SENP1 is itself a target for SUMO-1 modification but that this modification is normally rapidly reversed by an autocatalytic activity removing the SUMO-1, with little of the modified form accumulating. In the mutant SENP1 (C603S), the absence of proteolytic activity resul in the detection of the conjugated form
additional information
residues 415643 of SENP1 are expressed and purified from Escherichia coli and are shown to be catalytically active in SUMO processing and deconjugation
additional information
the deletion of the C-terminal portion to aa 634 induces the nuclear localization of SENP1. Further deletion to aa 574 results in the diffused localization of SENP1 both to the nucleus and the cytoplasm. This result suggests that there might be a motif for the nuclear localization of SENP1 in the region from aa 574 to 633
additional information
-
very few cells express the exogenous SENP1 436-644 core domain construct, and in any positive cells expression is at extremely low levels. The SENP1 436-644 C603S construct, however, is readily detected, often with very high levels of expression
additional information
-
construction of a SENP1 catalytically inactive/dominant negative Cys-to-Ser SENP1 mutant or a SENP1 shRNA construct, enzyme SENP1 silencing by expression of siRNA
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged catalytic domain SENP1c, aa419-aa643 from Escherichia coli strain BL21 by nickel affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
crystallization of a complex of SENP1 C603A bound to full-length SUMO-1 and determination of the structure by X-ray crystallography. Two structures of SENP1 C603A in complex with the SUMO-1 precursor and RanGAP1-SUMO-1
expression of wild-type and mutant enzymes in MEF, 293T, and 3T3-L1 cells, real-time quantitative PCR expression analysis
gene SP1, recombinant expression of GFP-tagged or untagged SENP1 and the catalytically dead enzyme mutant transiently in HeLa cells
-
overexpression of a catalytically inactive/dominant negative Cys-to-Ser SENP1 mutant
-
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
the catalytic core domain of SENP1 (amino acids 415-643) and mutants are cloned into the vector pEHISTEV and expressed as a N-terminally His-tagged protein. The recombinant proteins are expressed in Escherichia coli Bl21(DE3) cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
SENP1 expression can be induced by hypoxia. Induction of SENP1 expression is mediated by hypoxia-inducible factor HIF-1alpha
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
drug development
medicine
diagnostics
-
enzyme SENP1 is an important cancer metastasis-related molecule and may be a prognostic marker and a therapeutic target for metastasis in prostate cancer patients
diagnostics
-
SENP1 may serve as a potential diagnostic and therapeutic target of pancreatic ductal adenocarcinoma
drug development
-
SENP1 is a potential therapeutic target for the treatment of prostate cancers
drug development
-
SENP1 is an essential gene and is a potential target for developing therapeutic agents for cancer
drug development
-
the enzyme is a drug target for development of small molecule drugs against prostate cancer
medicine
-
diagnostic value of measuring the urinary content of SENP1 mRNAs for detection of tumor recurrence
medicine
-
SENP1 is overexpressed in most of colon cancer tissues. SENP1 regulates the in vitro and in vivo growth of colon cancer cells with the upregulated expression of CDK inhibitors
medicine
-
SENP1, can transform normal prostate epithelia to a dysplasic state and directly modulate several oncogenic pathways in prostate cells, including AR, c-Jun, and Cyclin D1
medicine
SENP1 expression has strong prognostic impact in a molecularly defined subset of cancers. In the subgroup of ERG positive, PTEN undeleted cancers, the prognostic role of SENP1 expression is independent of the preoperative PSA level, tumor stage, Gleason grade, and the status of the resection
medicine
the expression of SENP1 is positively correlated with the malignant grades of astrocytoma. The NF-kappaB and Akt signaling pathways in glioblastoma multiforme tissues are activated. Knock-down of endogenous SENP1 promotes cell apoptosis. Downregulation of SENP1 expression can inhibit the phosphorylation of IkappaBalpha and Akt, and also the expression of its downstream regulation factors Bcl-xL and cyclinD1
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Xu, Z.; Chau, S.F.; Lam, K.H.; Chan, H.Y.; Ng, T.B.; Au, S.W.
Crystal structure of the SENP1 mutant C603S-SUMO complex reveals the hydrolytic mechanism of SUMO-specific protease
Biochem. J.
398
345-352
2006
Homo sapiens (Q9P0U3)
Bawa-Khalfe, T.; Cheng, J.; Wang, Z.; Yeh, E.T.
Induction of the SUMO-specific protease 1 transcription by the androgen receptor in prostate cancer cells
J. Biol. Chem.
282
37341-37349
2007
Homo sapiens
Shen, L.; Tatham, M.H.; Dong, C.; Zagorska, A.; Naismith, J.H.; Hay, R.T.
SUMO protease SENP1 induces isomerization of the scissile peptide bond
Nat. Struct. Mol. Biol.
13
1069-1077
2006
Homo sapiens (Q9P0U3)
Rimsa, V.; Eadsforth, T.; Hunter, W.N.
The role of Co2+ in the crystallization of human SENP1 and comments on the limitations of automated refinement protocols
Acta Crystallogr. Sect. F
67
442-445
2011
Homo sapiens (Q9P0U3), Homo sapiens
Yates, K.E.; Korbel, G.A.; Shtutman, M.; Roninson, I.B.; DiMaio, D.
Repression of the SUMO-specific protease Senp1 induces p53-dependent premature senescence in normal human fibroblasts
Aging Cell
7
609-621
2008
Homo sapiens (Q9P0U3)
Ohbayashi, N.; Kawakami, S.; Muromoto, R.; Togi, S.; Ikeda, O.; Kamitani, S.; Sekine, Y.; Honjoh, T.; Matsuda, T.
The IL-6 family of cytokines modulates STAT3 activation by desumoylation of PML through SENP1 induction
Biochem. Biophys. Res. Commun.
371
823-828
2008
Homo sapiens (Q9P0U3)
Xu, Z.; Au, S.W.
Mapping residues of SUMO precursors essential in differential maturation by SUMO-specific protease, SENP1
Biochem. J.
386
325-330
2005
Homo sapiens (Q9P0U3)
Shen, L.N.; Dong, C.; Liu, H.; Naismith, J.H.; Hay, R.T.
The structure of SENP1-SUMO-2 complex suggests a structural basis for discrimination between SUMO paralogues during processing
Biochem. J.
397
279-288
2006
Homo sapiens (Q9P0U3)
Witty, J.; Aguilar-Martinez, E.; Sharrocks, A.D.
SENP1 participates in the dynamic regulation of Elk-1 SUMOylation
Biochem. J.
428
247-254
2010
Homo sapiens (Q9P0U3)
Brems-Eskildsen, A.S.; Zieger, K.; Toldbod, H.; Holcomb, C.; Higuchi, R.; Mansilla, F.; Munksgaard, P.P.; Borre, M.; Orntoft, T.F.; Dyrskjot, L.
Prediction and diagnosis of bladder cancer recurrence based on urinary content of hTERT, SENP1, PPP1CA, and MCM5 transcripts
BMC Cancer
10
646
2010
Homo sapiens
Xu, Y.; Li, J.; Zuo, Y.; Deng, J.
Wang, L.S.; Chen, G.Q.: SUMO-specific protease 1 regulates the in vitro and in vivo growth of colon cancer cells with the upregulated expression of CDK inhibitors
Cancer Lett.
309
78-84
2011
Homo sapiens
Li, X.; Luo, Y.; Yu, L.; Lin, Y.; Luo, D.; Zhang, H.; He, Y.; Kim, Y.O.; Kim, Y.; Tang, S.; Min, W.
SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis
Cell Death Differ.
15
739-750
2008
Homo sapiens (Q9P0U3)
Kim, Y.H.; Sung, K.S.; Lee, S.J.; Kim, Y.O.; Choi, C.Y.; Kim, Y.
Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1
FEBS Lett.
579
6272-6278
2005
Homo sapiens (Q9P0U3)
Bawa-Khalfe, T.; Yeh, E.T.
SUMO losing balance: SUMO proteases disrupt SUMO homeostasis to facilitate cancer development and progression
Genes Cancer
1
748-752
2010
Homo sapiens
Bailey, D.; O'Hare, P.
Characterization of the localization and proteolytic activity of the SUMO-specific protease, SENP1
J. Biol. Chem.
279
692-703
2004
Homo sapiens
Xu, Y.; Zuo, Y.; Zhang, H.; Kang, X.; Yue, F.; Yi, Z.; Liu, M.; Yeh, E.T.; Chen, G.; Cheng, J.
Induction of SENP1 in endothelial cells contributes to hypoxia-driven VEGF expression and angiogenesis
J. Biol. Chem.
285
36682-36688
2010
Homo sapiens (Q9P0U3)
Cheng, J.; Wang, D.; Wang, Z.; Yeh, E.T.
SENP1 enhances androgen receptor-dependent transcription through desumoylation of histone deacetylase 1
Mol. Cell. Biol.
24
6021-6028
2004
Homo sapiens (Q9P0U3)
Kaikkonen, S.; Jskelinen, T.; Karvonen, U.; Rytinki, M.M.; Makkonen, H.; Gioeli, D.; Paschal, B.M.; Palvimo, J.J.
SUMO-specific protease 1 (SENP1) reverses the hormone-augmented SUMOylation of androgen receptor and modulates gene responses in prostate cancer cells
Mol. Endocrinol.
23
292-307
2009
Homo sapiens (Q9P0U3)
Shin, Y.C.; Liu, B.Y.; Tsai, J.Y.; Wu, J.T.; Chang, L.K.; Chang, S.C.
Biochemical characterization of the small ubiquitin-like modifiers of Chlamydomonas reinhardtii
Planta
232
649-662
2010
Homo sapiens
Plant, L.D.; Dementieva, I.S.; Kollewe, A.; Olikara, S.; Marks, J.D.; Goldstein, S.A.
One SUMO is sufficient to silence the dimeric potassium channel K2P1
Proc. Natl. Acad. Sci. USA
107
10743-10748
2010
Homo sapiens (Q9P0U3), Homo sapiens
Qiao, Z.; Wang, W.; Wang, L.; Wen, D.; Zhao, Y.; Wang, Q.; Meng, Q.; Chen, G.; Wu, Y.; Zhou, H.
Design, synthesis, and biological evaluation of benzodiazepine-based SUMO-specific protease 1 inhibitors
Bioorg. Med. Chem. Lett.
21
6389-6392
2011
Homo sapiens
Chen, Y.; Wen, D.; Huang, Z.; Huang, M.; Luo, Y.; Liu, B.; Lu, H.; Wu, Y.; Peng, Y.; Zhang, J.
2-(4-Chlorophenyl)-2-oxoethyl 4-benzamidobenzoate derivatives, a novel class of SENP1 inhibitors: Virtual screening, synthesis and biological evaluation
Bioorg. Med. Chem. Lett.
22
6867-6870
2012
Homo sapiens
Yan, X.M.; Xu, Z.Q.; Zhou, Y.; Wang, J.; Pan, J.; Yuan, L.Q.; Fu, M.C.; Xia, H.L.; Cao, X.; Zhang, T.
SENP1 regulates cell migration and invasion in neuroblastoma
Biotechnol. Appl. Biochem.
63
435-440
2016
Homo sapiens
Chen, C.H.; Chang, C.C.; Lee, T.H.; Luo, M.; Huang, P.; Liao, P.H.; Wei, S.; Li, F.A.; Chen, R.H.; Zhou, X.Z.; Shih, H.M.; Lu, K.P.
SENP1 deSUMOylates and regulates Pin1 protein activity and cellular function
Cancer Res.
73
3951-3962
2013
Homo sapiens
Schulz, S.; Chachami, G.; Kozaczkiewicz, L.; Winter, U.; Stankovic-Valentin, N.; Haas, P.; Hofmann, K.; Urlaub, H.; Ovaa, H.; Wittbrodt, J.; Meulmeester, E.; Melchior, F.
Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with essential, non-catalytic functions
EMBO Rep.
13
930-938
2012
Danio rerio, Homo sapiens (Q5W0Q7)
Cai, R.; Yu, T.; Huang, C.; Xia, X.; Liu, X.; Gu, J.; Xue, S.; Yeh, E.T.; Cheng, J.
SUMO-specific protease 1 regulates mitochondrial biogenesis through PGC-1alpha
J. Biol. Chem.
287
44464-44470
2012
Homo sapiens
Liu, B.; Wang, T.; Mei, W.; Li, D.; Cai, R.; Zuo, Y.; Cheng, J.
Small ubiquitin-like modifier (SUMO) protein-specific protease 1 de-SUMOylates Sharp-1 protein and controls adipocyte differentiation
J. Biol. Chem.
289
22358-22364
2014
Homo sapiens (Q9P0U3)
Cubenas-Potts, C.; Goeres, J.D.; Matunis, M.J.
SENP1 and SENP2 affect spatial and temporal control of sumoylation in mitosis
Mol. Biol. Cell
24
3483-3495
2013
Homo sapiens (Q9P0U3)
Chow, K.H.; Elgort, S.; Dasso, M.; Powers, M.A.; Ullman, K.S.
The SUMO proteases SENP1 and SENP2 play a critical role in nucleoporin homeostasis and nuclear pore complex function
Mol. Biol. Cell
25
160-168
2014
Homo sapiens
Chen, C.H.; Namanja, A.T.; Chen, Y.
Conformational flexibility and changes underlying activation of the SUMO-specific protease SENP1 by remote substrate binding
Nat. Commun.
5
4968
2014
Homo sapiens
Chow, K.H.; Elgort, S.; Dasso, M.; Ullman, K.S.
Two distinct sites in Nup153 mediate interaction with the SUMO proteases SENP1 and SENP2
Nucleus
3
349-358
2012
Homo sapiens
Wu, R.; Cui, Y.; Yuan, X.; Yuan, H.; Wang, Y.; He, J.; Zhao, J.; Peng, S.
SUMO-specific protease 1 modulates cadmium-augmented transcriptional activity of androgen receptor (AR) by reversing AR SUMOylation
Toxicol. Lett.
229
405-413
2014
Homo sapiens
Ma, C.; Wu, B.; Huang, X.; Yuan, Z.; Nong, K.; Dong, B.; Bai, Y.; Zhu, H.; Wang, W.; Ai, K.
SUMO-specific protease 1 regulates pancreatic cancer cell proliferation and invasion by targeting MMP-9
Tumour Biol.
35
12729-12735
2014
Homo sapiens
Zhang, C.; Li, J.; Qiu, X.; Chen, Y.; Zhang, X.
SUMO protease SENP1 acts as a ceRNA for TGFBR2 and thus activates TGFBR2/Smad signaling responsible for LPS-induced sepsis
Biomed. Pharmacother.
112
108620
2019
Homo sapiens (Q9P0U3)
Burdelski, C.; Menan, D.; Tsourlakis, M.C.; Kluth, M.; Hube-Magg, C.; Melling, N.; Minner, S.; Koop, C.; Graefen, M.; Heinzer, H.; Wittmer, C.; Sauter, G.; Simon, R.; Schlomm, T.; Steurer, S.; Krech, T.
The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion
BMC Cancer
15
538
2015
Homo sapiens (Q9P0U3)
Xia, W.; Tian, H.; Cai, X.; Kong, H.; Fu, W.; Xing, W.; Wang, Y.; Zou, M.; Hu, Y.; Xu, D.
Inhibition of SUMO-specific protease 1 induces apoptosis of astroglioma cells by regulating NF-kappaB/Akt pathways
Gene
595
175-179
2016
Homo sapiens (Q9P0U3), Homo sapiens
Zhang, X.; Wang, H.; Wang, H.; Xiao, F.; Seth, P.; Xu, W.; Jia, Q.; Wu, C.; Yang, Y.; Wang, L.
SUMO-specific cysteine protease 1 promotes epithelial mesenchymal transition of prostate cancer cells via regulating SMAD4 deSUMOylation
Int. J. Mol. Sci.
18
808
2017
Homo sapiens
Rodriguez-Castaneda, F.; Lemma, R.B.; Cuervo, I.; Bengtsen, M.; Moen, L.M.; Ledsaak, M.; Eskeland, R.; Gabrielsen, O.S.
The SUMO protease SENP1 and the chromatin remodeler CHD3 interact and jointly affect chromatin accessibility and gene expression
J. Biol. Chem.
293
15439-15454
2018
Homo sapiens (Q9P0U3)
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