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Information on EC 3.4.22.B72 - SENP3 peptidase and Organism(s) Homo sapiens and UniProt Accession Q9H4L4
for references in articles please use BRENDA:EC3.4.22.B72preliminary BRENDA-supplied EC number
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3.4.22.B72 SENP3 peptidaseSpecify your search results
Word Map
- 3.4.22.B72
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sumoylation
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senps
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deconjugation
- isopeptidase
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de-sumoylation
- ranbp2
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de-conjugating
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 the desumoylation of SUMO2 or SUMO3-modified target proteins, but has only weak activity against SUMO1 conjugates. SENP2 catalyzes deconjugation of SUMO2 from nucleophosmin 1.
Synonyms
senp3, sumo-specific protease 3, sumo2/3-specific protease, sumo-specific proteases 3, sentrin-specific protease 3, sumo-2/3-specific protease, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
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-3)-hypoxia-inducible factor-1alpha protein + H2O
SUMO-3 + hypoxia-inducible factor-1alpha protein
SENP3 can remove SUMO3, but not SUMO1 from hypoxia-inducible factor-1alpha protein
-
-
?
(SUMO-2)-p300 protein + H2O
(SUMO-2) + p300 protein
removing SUMO2/3 from p300 enhances its binding to HIF-1alpha. SENP3 is a redox sensor that regulates hypoxia-inducible factor-1alpha transcriptional activity under oxidative stress through the de-SUMOylation of p300
-
-
?
(SUMO-2/3)-promyelocytic leukemia protein + H2O
SUMO-2/3 + promyelocytic leukemia protein
-
-
-
?
(SUMO-2/3)-promyelocytic leukemia protein + H2O
SUMO-2/3 + promyelocytic leukemia protein
SENP3 appears to be a key mediator in mild oxidative stress-induced cell proliferation via regulation of the SUMOylation status of promyelocytic leukemia protein. SENP3-mediated de-conjugation of SUMO2/3 from PML is responsible for accelerated cell proliferation and decreased promyelocytic leukemia bodies under mild oxidative stress
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-
?
(SUMO2)-Borealin protein + H2O
SUMO2 + Borealin protein
Borealin is dynamically modified by SUMO2/3 during mitosis
-
-
?
(SUMO-2)-nucleophosmin 1 conjugate + H2O
SUMO-2 + nucleophosmin 1
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SENP3 as an essential factor for ribosome biogenesis. It is suggested that deconjugation of SUMO2 from nucleophosmin 1 (NPM1) by SENP3 is critically involved in 28S rRNA maturation
-
-
?
SUMOylated FOXC2 + H2O
FOXC2 + SUMO
-
deSUMOylation by enzyme SENP3, deconjugation of SUMO2/3
-
-
?
SUMOylated GTPase Drp1 + H2O
GTPase Drp1 + SUMO
-
the substrate is a key target for SENP3-mediated deSUMOylation
-
-
?
SUMOylated GTPase Drp1 + H2O
GTPase Drp1 + SUMO
-
Drp1 is both SUMO-1 and SUMO-2/3 conjugated, SUMO-2/3-specific deSUMOylating by enzyme SENP3
-
-
?
SUMOylated RbBP5 + H2O
RbBP5 + SUMO
-
deSUMOylation by enzyme SENP3, the protein is part of SET1/MLL complexes
-
-
?
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-2)-p300 protein + H2O
(SUMO-2) + p300 protein
removing SUMO2/3 from p300 enhances its binding to HIF-1alpha. SENP3 is a redox sensor that regulates hypoxia-inducible factor-1alpha transcriptional activity under oxidative stress through the de-SUMOylation of p300
-
-
?
(SUMO-2/3)-promyelocytic leukemia protein + H2O
SUMO-2/3 + promyelocytic leukemia protein
SENP3 appears to be a key mediator in mild oxidative stress-induced cell proliferation via regulation of the SUMOylation status of promyelocytic leukemia protein. SENP3-mediated de-conjugation of SUMO2/3 from PML is responsible for accelerated cell proliferation and decreased promyelocytic leukemia bodies under mild oxidative stress
-
-
?
(SUMO2)-Borealin protein + H2O
SUMO2 + Borealin protein
Borealin is dynamically modified by SUMO2/3 during mitosis
-
-
?
(SUMO-2)-nucleophosmin 1 conjugate + H2O
SUMO-2 + nucleophosmin 1
-
SENP3 as an essential factor for ribosome biogenesis. It is suggested that deconjugation of SUMO2 from nucleophosmin 1 (NPM1) by SENP3 is critically involved in 28S rRNA maturation
-
-
?
SUMOylated GTPase Drp1 + H2O
GTPase Drp1 + SUMO
-
the substrate is a key target for SENP3-mediated deSUMOylation
-
-
?
SUMOylated RbBP5 + H2O
RbBP5 + SUMO
-
deSUMOylation by enzyme SENP3, the protein is part of SET1/MLL complexes
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
PERK activation is required for decreased SENP3 activity, overexpression of HA-tagged PERK causes loss of Flag-tagged SENP3 activity in HEK293 cells via a mechanism dependent on PERK kinase activity, which is blocked by overexpression of the PERK inhibitor p58IPK
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
B23/nucleophosmin
-
B23/nucleophosmin physically interacts with SENP3 and SENP5 and regulates their abundance. It thus plays a critical role in controlling the profile of SUMO conjugates within nucleoli through SENP3 and SENP5
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
SENP3 is over-accumulated in a variety of primary human cancers including colon adenocarcinoma. SENP3-mediated de-SUMO2/3 of promyelocytic leukemia might contribute to the development or progression of human cancers
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correlation between SENP3 expression and gastric cancer metastasis
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immunohistochemical evaluation of SENP3 in patients and oral epithelial tissue adjacent to tumor, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
reactive oxygen species cause SENP3 to redistribute from the nucleoli to the nucleoplasm, allowing it to regulate nuclear events
reactive oxygen species cause SENP3 to redistribute from the nucleoli to the nucleoplasm, allowing it to regulate nuclear events
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SENP3 localizes within the granular component of the nucleolus, a subnucleolar compartment that contains B23/nucleophosmin
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the nucleolar SUMO-specific protease SENP3 is associated with nucleophosmin, a crucial factor in ribosome biogenesis
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reactive oxygen species regulate enzyme SENP3 stability and localization. Reactive oxygen species induce SENP3 redistribution from the nucleoli to the nucleoplasm
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
upon depletion of SENP3 the amount of Borealin-SUMO2/3 conjugates is significantly increased
physiological function
malfunction
metabolism
physiological function
additional information
physiological function
SENP3 appears to be a key mediator in mild oxidative stress-induced cell proliferation via regulation of the SUMOylation status of promyelocytic leukemia protein
physiological function
SENP3 is a redox sensor that regulates hypoxia-inducible factor-1alpha transcriptional activity under oxidative stress through the de-SUMOylation of p300
physiological function
hepatic SENP3 is upregulated in nonalcoholic fatty liver disease patients and after loading hepatocytes with free fatty acids in vitro. SENP3 gene silencing is associated in vitro with amelioration of lipid accumulation and overexpression with enhancement of lipid accumulation. Among SENP3 related genes in nonalcoholic fatty liver disease, apoe, a2m and tnfrsf11b are regulated by SENP3 with free fatty acid stimulation
malfunction
-
depletion of SENP3 by short interfering RNA interferes with nucleolar ribosomal RNA processing and inhibits the conversion of the 32S rRNA species to the 28S form, thus phenocopying the processing defect observed on depletion of nucleophosmin 1 (NPM1)
malfunction
-
downregulation of SENP3 increases Drp1 SUMO-2/3ylation and decreases its mitochondrial association, which reduces Drp1-dependent cytochrome c release via reduced mitochondrial fission and fragmentation. Depletion of enzyme SENP3 prolongs GTPase Drp1 SUMOylation, which suppresses Drp1-mediated cytochrome c release and caspase-mediated cell death. SENP3 levels recover following reoxygenation after oxygen/glucose deprivation allowing deSUMOylation of Drp1, which facilitates Drp1 localization at mitochondria and promotes fragmentation and cytochrome c release. RNAi knockdown of SENP3 protects cells from reoxygenation-induced cell death via a mechanism that requires Drp1 SUMOylation
malfunction
-
expression of mesenchymal marker genes and cell migration ability are enhanced in SENP3-overexpressing gastric cancer cells and attenuated in SENP3-knockdown cells
malfunction
-
in the absence of SENP3, the association of menin and Ash2L with the DLX3 geneis impaired, leading to decreased H3K4 methylation and reduced recruitment of active RNA polymerase II
metabolism
-
molecular mechanisms of SUMOylation in the cellular response to oxygen/glucose deprivation, overview
physiological function
-
SENP3 as an essential factor for ribosome biogenesis. It is suggested that deconjugation of SUMO2 from nucleophosmin 1 (NPM1) by SENP3 is critically involved in 28S rRNA maturation
physiological function
-
enzyme SENP3 may play an important role in the development of oral squamous cell carcinoma under oxidative stress
physiological function
-
enzyme SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia
physiological function
-
SUMO-specific isopeptidase SENP3 regulates MLL1/MLL2 methyltransferase complexes and controls osteogenic differentiation of and DLX3 and RUNX2 expression in human dental follicle stem cells. SUMO-specific isopeptidase SENP3 controls H3K4 methylation by regulating histone-modifying SET1/MLL complexes. SET1/MLL complexes are composed of a histone methyltransferase and the regulatory components WDR5, RbBP5, Ash2L, and DPY-30. MLL1/MLL2 complexes contain menin as additional component and are particularly important for the activationof HOX genes
physiological function
-
the enzyme potentiates the transcriptional activity of FOXC2 through deSUMOylation, in favor of the induction of specific mesenchymal gene expression in gastric cancer metastasis. And the enzyme upregulates the transcription of N-cadherin through deSUMOlyation of FOXC2
additional information
-
the SUMO-2/3-specific protease SENP3 is degraded during oxygen/glucose deprivation, proteolysis of SENP3 requires PERK kinase activity, in vitro modeling of ischaemia, via a pathway involving the unfolded protein response kinase PERK and the lysosomal enzyme cathepsin B, overview. SENP3 degradation does not involve ubiquitination
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). POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
polyubiquitination
SUMO2/3 protease SENP3 is regulated by Hsc70-interacting protein (CHIP) and heat shock protein 90 (Hsp90)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
SENP3 is continuously degraded through the ubiquitin proteasome pathway under basal condition. Reactive oxygen species inhibit this degradation
SENP3 is maintained at a low basal level under non-stress condition due to heat shock protein 90 (Hsp90)-independent Hsc70-interacting protein (CHIP)-mediated ubiquitination. Upon mild oxidative stress, SENP3 undergoes thiol modification, which recruits Hsp90. Hsp90/SENP3 association protects SENP3 from CHIP-mediated ubiquitination and subsequent degradation. This effect of Hsp90 requires the presence of CHIP
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-expression of Flag-tagged SENP3 with HA-tagged endoplasmic reticulum kinase PERK in HEK293 cells. Overexpression of HA-PERK causes loss of Flag-SENP3 in HEK293 cells, which is blocked by overexpression of the PERK inhibitor p58IPK
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of SUMO2/3-specific protease, SENP3 increases after treatment with 50 mM H2O2, and this increase occurs in a dose-dependent manner
SENP3 is over-accumulated in a variety of primary human cancers including colon adenocarcinoma
correlation between the clinicopathological features and SENP3 expression, overview
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Haindl, M.; Harasim, T.; Eick, D.; Muller, S.
The nucleolar SUMO-specific protease SENP3 reverses SUMO modification of nucleophosmin and is required for rRNA processing
EMBO Rep.
9
273-279
2008
Homo sapiens
Huang, C.; Han, Y.; Wang, Y.; Sun, X.; Yan, S.; Yeh, E.T.; Chen, Y.; Cang, H.; Li, H.; Shi, G.; Cheng, J.; Tang, X.; Yi, J.
SENP3 is responsible for HIF-1 transactivation under mild oxidative stress via p300 de-SUMOylation
EMBO J.
28
2748-2762
2009
Homo sapiens (Q9H4L4)
Yan, S.; Sun, X.; Xiang, B.; Cang, H.; Kang, X.; Chen, Y.; Li, H.; Shi, G.; Yeh, E.T.; Wang, B.; Wang, X.; Yi, J.
Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90
EMBO J.
29
3773-3786
2010
Homo sapiens (Q9H4L4)
Han, Y.; Huang, C.; Sun, X.; Xiang, B.; Wang, M.; Yeh, E.T.; Chen, Y.; Li, H.; Shi, G.; Cang, H.; Sun, Y.; Wang, J.; Wang, W.; Gao, F.; Yi, J.
SENP3-mediated de-conjugation of SUMO2/3 from promyelocytic leukemia is correlated with accelerated cell proliferation under mild oxidative stress
J. Biol. Chem.
285
12906-12915
2010
Homo sapiens (Q9H4L4), Homo sapiens
Yun, C.; Wang, Y.; Mukhopadhyay, D.; Backlund, P.; Kolli, N.; Yergey, A.; Wilkinson, K.D.; Dasso, M.
Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases
J. Cell Biol.
183
589-595
2008
Homo sapiens
Klein, U.R.; Haindl, M.; Nigg, E.A.; Muller, S.
RanBP2 and SENP3 function in a mitotic SUMO2/3 conjugation-deconjugation cycle on Borealin
Mol. Biol. Cell
20
410-418
2009
Homo sapiens (Q9H4L4)
Guo, C.; Hildick, K.L.; Luo, J.; Dearden, L.; Wilkinson, K.A.; Henley, J.M.
SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia
EMBO J.
32
1514-1528
2013
Homo sapiens
Nayak, A.; Viale-Bouroncle, S.; Morsczeck, C.; Muller, S.
The SUMO-specific isopeptidase SENP3 regulates MLL1/MLL2 methyltransferase complexes and controls osteogenic differentiation
Mol. Cell
55
47-58
2014
Homo sapiens
Sun, Z.; Hu, S.; Luo, Q.; Ye, D.; Hu, D.; Chen, F.
Overexpression of SENP3 in oral squamous cell carcinoma and its association with differentiation
Oncol. Rep.
29
1701-1706
2013
Homo sapiens
Ren, Y.H.; Liu, K.J.; Wang, M.; Yu, Y.N.; Yang, K.; Chen, Q.; Yu, B.; Wang, W.; Li, Q.W.; Wang, J.; Hou, Z.Y.; Fang, J.Y.; Yeh, E.T.; Yang, J.; Yi, J.
De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells
Oncotarget
5
7093-7104
2014
Homo sapiens
Liu, Y.; Yu, F.; Han, Y.; Li, Q.; Cao, Z.; Xiang, X.; Jiang, S.; Wang, X.; Lu, J.; Lai, R.; Wang, H.; Cai, W.; Bao, S.; Xie, Q.
SUMO-specific protease 3 is a key regulator for hepatic lipid metabolism in non-alcoholic fatty liver disease
Sci. Rep.
6
37351
2016
Homo sapiens (Q9H4L4), Homo sapiens, Rattus norvegicus (G3V7S5)
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