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Information on EC 3.4.22.B72 - SENP3 peptidase
for references in articles please use BRENDA:EC3.4.22.B72
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preliminary BRENDA-supplied EC number
EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.22 Cysteine endopeptidases
3.4.22.B72 SENP3 peptidase
The enzyme appears in viruses and cellular organisms
- 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
Reaction Schemes
showThe 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, sumo-2/3-specific protease, sentrin-specific protease 3, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
SENP3
small ubiquitin-like modifier-specific protease 3
SUMO-specific protease 3
SUMO-specific proteases 3
SENP3
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(SUMO-2/3)-IQGAP2 + H2O
SUMO-2/3 + IQGAP2
Substrates: -
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(SUMO-3)-hypoxia-inducible factor-1alpha protein + H2O
SUMO-3 + hypoxia-inducible factor-1alpha protein
Substrates: SENP3 can remove SUMO3, but not SUMO1 from hypoxia-inducible factor-1alpha protein
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SUMOylated transcription factor BACH2 + H2O
?
Substrates: -
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(SUMO-2)-AurA + H2O
SUMO-2 + AurA
Substrates: AurA is SUMOylated at K258
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(SUMO-2)-nucleophosmin 1 conjugate + H2O
SUMO-2 + nucleophosmin 1
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Substrates: 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
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(SUMO-2)-nucleophosmin 1 conjugate + H2O
SUMO-2 + nucleophosmin 1
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Substrates: -
Products: -
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(SUMO-2)-p300 protein + H2O
(SUMO-2) + p300 protein
Substrates: 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
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(SUMO-2)-p300 protein + H2O
(SUMO-2) + p300 protein
Substrates: -
Products: -
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(SUMO-2/3)-promyelocytic leukemia protein + H2O
SUMO-2/3 + promyelocytic leukemia protein
Substrates: 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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(SUMO-2/3)-promyelocytic leukemia protein + H2O
SUMO-2/3 + promyelocytic leukemia protein
Substrates: -
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(SUMO2)-Borealin protein + H2O
SUMO2 + Borealin protein
Substrates: Borealin is dynamically modified by SUMO2/3 during mitosis
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(SUMO2)-Borealin protein + H2O
SUMO2 + Borealin protein
Substrates: -
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SUMO3-beta-catenin + H2O
SUMO3 + beta-catenin
Substrates: -
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SUMO3-beta-catenin + H2O
SUMO3 + beta-catenin
Substrates: SENP3 interacted with beta-catenin and inhibits its proteasome-dependent degradation via de-SUMOylation of beta-catenin
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?
SUMO3-beta-catenin + H2O
SUMO3 + beta-catenin
Substrates: -
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?
SUMOylated FOXC2 + H2O
FOXC2 + SUMO
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Substrates: deSUMOylation by enzyme SENP3
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SUMOylated FOXC2 + H2O
FOXC2 + SUMO
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Substrates: deSUMOylation by enzyme SENP3, deconjugation of SUMO2/3
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SUMOylated GTPase Drp1 + H2O
GTPase Drp1 + SUMO
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Substrates: the substrate is a key target for SENP3-mediated deSUMOylation
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SUMOylated GTPase Drp1 + H2O
GTPase Drp1 + SUMO
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Substrates: Drp1 is both SUMO-1 and SUMO-2/3 conjugated, SUMO-2/3-specific deSUMOylating by enzyme SENP3
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SUMOylated RbBP5 + H2O
RbBP5 + SUMO
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Substrates: deSUMOylation by enzyme SENP3, the protein is part of SET1/MLL complexes
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SUMOylated RbBP5 + H2O
RbBP5 + SUMO
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Substrates: deSUMOylation by enzyme SENP3
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additional information
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Substrates: SUMO-2/3-conjugated targets are more successfully deconjugated by SENP3 than SUMO-1-containing species
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additional information
?
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Substrates: enzyme SENP3 deconjugates SUMO2/3 from protein substrates
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additional information
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Substrates: SUMO-2/3-conjugated targets are more successfully deconjugated by SENP3 than SUMO-1-containing species
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additional information
?
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Substrates: enzyme SENP3 deconjugates SUMO2/3 from protein substrates
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(SUMO-2)-nucleophosmin 1 conjugate + H2O
SUMO-2 + nucleophosmin 1
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Substrates: 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
Products: -
Products: -
?
(SUMO-2)-p300 protein + H2O
(SUMO-2) + p300 protein
Substrates: 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
Products: -
Products: -
?
(SUMO-2/3)-promyelocytic leukemia protein + H2O
SUMO-2/3 + promyelocytic leukemia protein
Substrates: 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
Products: -
Products: -
?
(SUMO2)-Borealin protein + H2O
SUMO2 + Borealin protein
Substrates: Borealin is dynamically modified by SUMO2/3 during mitosis
Products: -
Products: -
?
SUMO3-beta-catenin + H2O
SUMO3 + beta-catenin
Substrates: SENP3 interacted with beta-catenin and inhibits its proteasome-dependent degradation via de-SUMOylation of beta-catenin
Products: -
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SUMOylated FOXC2 + H2O
FOXC2 + SUMO
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Substrates: deSUMOylation by enzyme SENP3
Products: -
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SUMOylated GTPase Drp1 + H2O
GTPase Drp1 + SUMO
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Substrates: the substrate is a key target for SENP3-mediated deSUMOylation
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SUMOylated RbBP5 + H2O
RbBP5 + SUMO
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Substrates: deSUMOylation by enzyme SENP3, the protein is part of SET1/MLL complexes
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?
additional information
?
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Substrates: SUMO-2/3-conjugated targets are more successfully deconjugated by SENP3 than SUMO-1-containing species
Products: -
Products: -
?
additional information
?
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Substrates: SUMO-2/3-conjugated targets are more successfully deconjugated by SENP3 than SUMO-1-containing species
Products: -
Products: -
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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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
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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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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Acute Lung Injury
SENP3 in monocytes/macrophages up-regulates tissue factor and mediates lipopolysaccharide-induced acute lung injury by enhancing JNK phosphorylation.
Brain Injuries
Expression and Cell Distribution of SENP3 in the Cerebral Cortex After Experimental Subarachnoid Hemorrhage in Rats: A Pilot Study.
Brain Injuries, Traumatic
Expression and Cell Distribution of SENP3 in Brain Tissue After Traumatic Brain Injury in Mice: A Pilot Study.
Breast Neoplasms
E2F1 sumoylation as a protective cellular mechanism in oxidative stress response.
Breast Neoplasms
SENP3 loss promotes M2 macrophage polarization and breast cancer progression.
Carcinogenesis
High SENP3 Expression Promotes Cell Migration, Invasion, and Proliferation by Modulating DNA Methylation of E-Cadherin in Osteosarcoma.
Carcinogenesis
Mitotic Phosphorylation of SENP3 Regulates De-SUMOylation of Chromosome-Associated Proteins and Chromosome Stability.
Carcinogenesis
Upregulation of SENP3/SMT3IP1 promotes epithelial ovarian cancer progression and forecasts poor prognosis.
Carcinoma
Nuclear Nrf2 Activity in Laryngeal Carcinoma is Regulated by SENP3 After Cisplatin-Induced Reactive Oxygen Species Stress.
Carcinoma
Overexpression of SENP3 in oral squamous cell carcinoma and its association with differentiation.
Carcinoma, Hepatocellular
Combined identification of ARID1A, CSMD1, and SENP3 as effective prognostic biomarkers for hepatocellular carcinoma.
Carcinoma, Ovarian Epithelial
Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC).
Carcinoma, Ovarian Epithelial
Upregulation of SENP3/SMT3IP1 promotes epithelial ovarian cancer progression and forecasts poor prognosis.
Cardiovascular Diseases
The Critical Roles of the SUMO-Specific Protease SENP3 in Human Diseases and Clinical Implications.
Colonic Neoplasms
SENP3-mediated de-conjugation of SUMO2/3 from promyelocytic leukemia is correlated with accelerated cell proliferation under mild oxidative stress.
Colorectal Neoplasms
SENP3 senses oxidative stress to facilitate STING-dependent dendritic cell antitumor function.
Epilepsy
SUMO proteases SENP3 and SENP5 spatiotemporally regulate the kinase activity of Aurora A.
Fatty Liver
SUMO-specific protease 3 is a key regulator for hepatic lipid metabolism in non-alcoholic fatty liver disease.
Head and Neck Neoplasms
SUMOylation and SENP3 regulate STAT3 activation in head and neck cancer.
Leukemia
SENP3-mediated de-conjugation of SUMO2/3 from promyelocytic leukemia is correlated with accelerated cell proliferation under mild oxidative stress.
Liver Diseases
SUMO-specific protease 3 is a key regulator for hepatic lipid metabolism in non-alcoholic fatty liver disease.
Lymphatic Metastasis
Upregulation of SENP3/SMT3IP1 promotes epithelial ovarian cancer progression and forecasts poor prognosis.
Myocardial Ischemia
The desumoylating enzyme sentrin-specific protease 3 contributes to myocardial ischemia reperfusion injury.
Neoplasm Metastasis
De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells.
Neoplasm Metastasis
Upregulation of SENP3/SMT3IP1 promotes epithelial ovarian cancer progression and forecasts poor prognosis.
Neoplasms
An upregulation of SENP3 after spinal cord injury: implications for neuronal apoptosis.
Neoplasms
Arf-induced turnover of the nucleolar nucleophosmin-associated SUMO-2/3 protease Senp3.
Neoplasms
Assessment of SENP3-interacting proteins in hepatocytes treated with diethylnitrosamine by BioID assay.
Neoplasms
De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells.
Neoplasms
E2F1 sumoylation as a protective cellular mechanism in oxidative stress response.
Neoplasms
High SENP3 Expression Promotes Cell Migration, Invasion, and Proliferation by Modulating DNA Methylation of E-Cadherin in Osteosarcoma.
Neoplasms
Nuclear Nrf2 Activity in Laryngeal Carcinoma is Regulated by SENP3 After Cisplatin-Induced Reactive Oxygen Species Stress.
Neoplasms
Overexpression of SENP3 in oral squamous cell carcinoma and its association with differentiation.
Neoplasms
Redox-sensitive enzyme SENP3 mediates vascular remodeling via de-SUMOylation of ?-catenin and regulation of its stability.
Neoplasms
SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation.
Neoplasms
SENP3 regulates the global protein turnover and the Sp1 level via antagonizing SUMO2/3-targeted ubiquitination and degradation.
Neoplasms
SENP3 senses oxidative stress to facilitate STING-dependent dendritic cell antitumor function.
Neoplasms
SENP3-mediated de-conjugation of SUMO2/3 from promyelocytic leukemia is correlated with accelerated cell proliferation under mild oxidative stress.
Neoplasms
SUMO Losing Balance: SUMO Proteases Disrupt SUMO Homeostasis to Facilitate Cancer Development and Progression.
Neoplasms
The Critical Roles of the SUMO-Specific Protease SENP3 in Human Diseases and Clinical Implications.
Neoplasms
Upregulation of SENP3/SMT3IP1 promotes epithelial ovarian cancer progression and forecasts poor prognosis.
Non-alcoholic Fatty Liver Disease
SUMO-specific protease 3 is a key regulator for hepatic lipid metabolism in non-alcoholic fatty liver disease.
Osteosarcoma
High SENP3 Expression Promotes Cell Migration, Invasion, and Proliferation by Modulating DNA Methylation of E-Cadherin in Osteosarcoma.
Ovarian Neoplasms
Upregulation of SENP3/SMT3IP1 promotes epithelial ovarian cancer progression and forecasts poor prognosis.
Prostatic Neoplasms
SUMO Losing Balance: SUMO Proteases Disrupt SUMO Homeostasis to Facilitate Cancer Development and Progression.
Reperfusion Injury
Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury.
Reperfusion Injury
The desumoylating enzyme sentrin-specific protease 3 contributes to myocardial ischemia reperfusion injury.
Sarcoma
High SENP3 Expression Promotes Cell Migration, Invasion, and Proliferation by Modulating DNA Methylation of E-Cadherin in Osteosarcoma.
senp3 peptidase deficiency
DeSUMOylation of MKK7 kinase by the SUMO2/3 protease SENP3 potentiates lipopolysaccharide-induced inflammatory signaling in macrophages.
senp3 peptidase deficiency
SENP3 loss promotes M2 macrophage polarization and breast cancer progression.
senp3 peptidase deficiency
SENP3 Suppresses Osteoclastogenesis by De-conjugating SUMO2/3 from IRF8 in Bone Marrow-Derived Monocytes.
Sepsis
SENP3 in monocytes/macrophages up-regulates tissue factor and mediates lipopolysaccharide-induced acute lung injury by enhancing JNK phosphorylation.
Shock, Septic
DeSUMOylation of MKK7 kinase by the SUMO2/3 protease SENP3 potentiates lipopolysaccharide-induced inflammatory signaling in macrophages.
Spinal Cord Injuries
An upregulation of SENP3 after spinal cord injury: implications for neuronal apoptosis.
Squamous Cell Carcinoma of Head and Neck
Overexpression of SENP3 in oral squamous cell carcinoma and its association with differentiation.
Starvation
A fine-tuning mechanism underlying self-control for autophagy: deSUMOylation of BECN1 by SENP3.
Stomach Neoplasms
De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells.
Stomach Neoplasms
SENP3 regulates the global protein turnover and the Sp1 level via antagonizing SUMO2/3-targeted ubiquitination and degradation.
Subarachnoid Hemorrhage
Expression and Cell Distribution of SENP3 in the Cerebral Cortex After Experimental Subarachnoid Hemorrhage in Rats: A Pilot Study.
Subarachnoid Hemorrhage
Inhibition of SENP3 by lentivirus induces suppression of apoptosis in experimental subarachnoid hemorrhage in rats.
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SwissProt
brenda
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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
brenda
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correlation between SENP3 expression and gastric cancer metastasis
brenda
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immunohistochemical evaluation of SENP3 in patients and oral epithelial tissue adjacent to tumor, overview
brenda
SENP3 is highly expressed in vascular smooth muscle cells of remodeled arteries. In cultured vascular smooth muscle cells, SENP3 protein levels are enhanced by oxidized low-density lipoprotein and angiotensin II in a ROS-dependent manner
brenda
additional information
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dynamic changes in SENP3 expression in the cerebral cortex and in its cellular localization in traumatic brain injury compared to normal, overview
brenda
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dynamic changes in SENP3 expression in the cerebral cortex and in its cellular localization in traumatic brain injury compared to normal, overview
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brenda
additional information
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immunohistochemical and expression anaysis of the enzyme in brain tissues, overview
brenda
additional information
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immunohistochemical and expression anaysis of the enzyme in brain tissues, overview
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brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
in addition to its widespread cytoplasmic distribution, SENP3 is concentrated around the mitotic chromosomes and partially colocalized in the spindle areas. During anaphase, SENP3 quickly relocates back to the chromosomes while the nuclear envelope reassembles
brenda
SENP3 is concentrated around the mitotic chromosomes and partially colocalized in the spindle areas
brenda
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SENP3 localizes within the granular component of the nucleolus, a subnucleolar compartment that contains B23/nucleophosmin
brenda
reactive oxygen species cause SENP3 to redistribute from the nucleoli to the nucleoplasm, allowing it to regulate nuclear events
brenda
the mTOR kinase phosphorylates the N-terminal region of SENP3, leading to the translocation of SENP3 to the nucleolus and regulating the nucleolar targeting of SENP3
brenda
reactive oxygen species cause SENP3 to redistribute from the nucleoli to the nucleoplasm, allowing it to regulate nuclear events
brenda
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the nucleolar SUMO-specific protease SENP3 is associated with nucleophosmin, a crucial factor in ribosome biogenesis
brenda
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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
brenda
SENP3 is predominantly expressed in the nucleus of Sertoli and spermatocyte cells in adult mouse testis
brenda
within individual cells, Senp3 is confined to the nucleus
brenda
Highest Expressing Human Cell Lines
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
evolution
malfunction
metabolism
physiological function
additional information
drug target
may provide a potentially innovative approach to treatment of atherosclerosis
drug target
SENP3 plays an important role in the pathological process of vascular remodeling. Therefore, SENP3 might represent a novel therapeutic target for vascular remodeling-related cardiovascular diseases
drug target
SENP3 may provide a promising therapeutic target for ovarian cancer. Targeting SENP3 alone or in combination with current therapies might provide powerful targeted therapeutic strategies for the treatment of cardiovascular diseases, neurological diseases, and various cancers
drug target
blocking the expression of SENP3 or its interaction with c-Jun would be a new and promising therapeutic approach for ischemic stroke and probably other neuroinflammatory disorders
drug target
SENP3 plays an important role in the pathological process of vascular remodeling. Therefore, SENP3 might represent a novel therapeutic target for vascular remodeling-related cardiovascular diseases
evolution
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the enzyme is a member of the small ubiquitin-like modifier-specific protease family
evolution
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the enzyme is a member of the small ubiquitin-like modifier-specific protease family
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evolution
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the enzyme is a member of the SUMO-specific protease family
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malfunction
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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
upon depletion of SENP3 the amount of Borealin-SUMO2/3 conjugates is significantly increased
malfunction
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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
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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
malfunction
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expression of mesenchymal marker genes and cell migration ability are enhanced in SENP3-overexpressing gastric cancer cells and attenuated in SENP3-knockdown cells
malfunction
under pathological conditions, if the SUMOylation process of proteins is affected by variations in SENP3 levels, it will cause a cellular reaction and ultimately lead to abnormal cellular activities and the occurrence and development of human diseases, including cardiovascular diseases, neurological diseases, and various cancers
malfunction
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in H9C2 cells SENP3 knockdown reduces survival following ischemia-reperfusion
malfunction
microglia-specific SENP3 knockdown ameliorates ischemic brain injury in mice
malfunction
knockdown of the SUMO proteases SENP3 and SENP5 disrupts the deSUMOylation of AurA, leading to increased kinase activity and abnormalities in spindle assembly and chromosome segregation
metabolism
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molecular mechanisms of SUMOylation in the cellular response to oxygen/glucose deprivation, overview
metabolism
deferiprone treatment leads to the stabilization of the SUMO protease SENP3, which is mediated by downregulation of the E3 ubiquitin ligase CHIP
metabolism
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cytosolic levels of SENP3 were dramatically reduced by ischemia and ischemia-reperfusion
physiological function
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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
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
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the enzyme SENP3 is critical for maintaining the level of SUMOylated and un-SUMOylated substrates required for normal physiology because of its isopeptidase activity, whereby it cleaves the isopeptide bond between SUMO and substrate proteins, as a result, SENP3 may weaken the neuroprotective effect of SUMO-2/3
physiological function
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enzyme SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia
physiological function
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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
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enzyme SENP3 may play an important role in the development of oral squamous cell carcinoma under oxidative stress
physiological function
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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
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
physiological function
hepatic SENP3 is upregulated in a nonalcoholic fatty liver disease model in vivo 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
physiological function
knockdown of SENP3 compromises tight junctions in Sertoli cells by destructing the permeability function with a concomitant decline in trans-epithelial electrical resistance in primary Sertoli cells. SENP3 knockdown disrupts F-actin architecture in Sertoli cells through intervening Rac1/CDC42-N-WASP-Arp2/3 signaling pathway and Profilin-1 abundance
physiological function
SENP3 is a pivotal regulator of regulatory T cells (Treg cells) that functions by controlling the SUMOylation and nuclear localization of transcription factor BACH2. Treg cell-specific deletion of Senp3 results in T cell activation, autoimmune symptoms and enhanced antitumor T cell responses. SENP3-mediated BACH2 deSUMOylation prevents the nuclear export of BACH2, thereby repressing the genes associated with CD4+ T effector cell differentiation and stabilizing Treg cell-specific gene signatures. SENP3 accumulation triggered by reactive oxygen species is involved in Treg cell-mediated tumor immunosuppression
physiological function
SENP3 enhances MDM2-mediated ubiquitination of PARIS/ZNF746 in HeLa cells. SENP3 enhances the ubiquitination of PARIS independently of its SUMOylation in HeLa cells
physiological function
SENP3 inhibits macrophage foam cell formation by deSUMOylating NLRP3 and regulating NLRP3 inflammasome activation
physiological function
SENP3 mediates vascular remodeling via de-SUMOylation of beta-catenin and regulation of its stability. SENP3 is strongly implicated in cancer development and progression
physiological function
SENP3 regulates mitochondrial autophagy mediated by Fis1. SENP3-mediated deSUMOylation facilitates Fis1 mitochondrial localization to underpin stress-induced mitophagy
physiological function
the effect of modification via SUMO and SENP3 is crucial to maintain the balance of SUMOylation and guarantee normal protein function and cellular activities. SENP3 acts as an oxidative stress-responsive molecule under physiological conditions. Critical role of SENP3 in autophagy. Critical roles of SENP3 in cell mitosis and cell cycle progression. SENP3 is increased in gastric cancer, and the increase in SENP3 increases deSUMOylation and enhances the tumorigenic activity of target proteins
physiological function
SENP3 mediates the activation of the Wnt/beta-catenin signaling pathway to accelerate the growth and metastasis of oesophagal squamous cell carcinoma
physiological function
SENP3-mediated TIP60 deSUMOylation is required for DNA-dependent kinase activity and DNA damage repair
physiological function
-
protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury. Cardiac ischemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischemia-reperfusion in heart
physiological function
the SENP3-IQGAP2 de-SUMOylation axis is a host defense mechanism of hepatocytes that restores host protein translation and suppresses HBV gene expression
physiological function
SENP3 promotes the expression of proinflammatory cytokines and chemokines in microglia
physiological function
SENP3 and SENP5 are required for proper mitotic spindle assembly and chromosome segregation. SUMO proteases SENP3 and SENP5 impact mitotic progression via deSUMOylating AurA and spatiotemporally controlling its kinase activity for precise spindle assembly and maintenance of genomic stability
physiological function
SENP3 mediates vascular remodeling via de-SUMOylation of beta-catenin and regulation of its stability. SENP3 is strongly implicated in cancer development and progression
physiological function
-
the enzyme SENP3 is critical for maintaining the level of SUMOylated and un-SUMOylated substrates required for normal physiology because of its isopeptidase activity, whereby it cleaves the isopeptide bond between SUMO and substrate proteins, as a result, SENP3 may weaken the neuroprotective effect of SUMO-2/3
-
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
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). G3V7S5_RAT
551
0
62566
TrEMBL
Secretory Pathway (Reliability: 1)
SENP3_HUMAN
574
0
65010
Swiss-Prot
other Location (Reliability: 2)
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
polyubiquitination
phosphoprotein
SENP3 is phosphorylated by the protein kinase CDK1 upon initiation of mitosis and is dephosphorylated by the protein phosphatase PP1alpha upon exit from mitosis. The mTOR kinase phosphorylates the N-terminal region of SENP3, leading to the translocation of SENP3 to the nucleolus and regulating the nucleolar targeting of SENP3
phosphoprotein
the p19Arf protein triggers the sequential phosphorylation, polyubiquitination and rapid proteasomal degradation of Senp3, and this ability of p19Arf to accelerate Senp3 turnover also depends on the presence of nucleophosmin
polyubiquitination
SUMO2/3 protease SENP3 is regulated by Hsc70-interacting protein (CHIP) and heat shock protein 90 (Hsp90)
polyubiquitination
the p19Arf protein triggers the sequential phosphorylation, polyubiquitination and rapid proteasomal degradation of Senp3, and this ability of p19Arf to accelerate Senp3 turnover also depends on the presence of nucleophosmin
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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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 destabilized in an nucleophosmin-dependent manner by a process involving sequential p19Arf-induced Senp3 phosphorylation, ubiquitination and proteasomal 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
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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
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
correlation between the clinicopathological features and SENP3 expression, overview
-
expression of SUMO2/3-specific protease, SENP3 increases after treatment with 50 mM H2O2, and this increase occurs in a dose-dependent manner
SENP3 expression is significantly reduced in ox-LDL-stimulated macrophages
SENP3 is increased in microglia after cerebral ischemia and reperfusion injury
SENP3 is over-accumulated in a variety of primary human cancers including colon adenocarcinoma
the enzyme is significantly upregulated in subarachnoid hemorrhage, the expression of SENP3 is increased in the brain cortex, in neurons, rather than astrocytes nor microglia
traumatic brain injury upregulates the enzyme expression in the brain, especially in the neurons and astrocytes
the enzyme is significantly upregulated in subarachnoid hemorrhage, the expression of SENP3 is increased in the brain cortex, in neurons, rather than astrocytes nor microglia
-
the enzyme is significantly upregulated in subarachnoid hemorrhage, the expression of SENP3 is increased in the brain cortex, in neurons, rather than astrocytes nor microglia
-
-
traumatic brain injury upregulates the enzyme expression in the brain, especially in the neurons and astrocytes
-
traumatic brain injury upregulates the enzyme expression in the brain, especially in the neurons and astrocytes
-
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
SENP3 plays a cardioprotective role during ischemia-reperfusion and promoting SENP3 levels in susceptible individuals, or maintaining the levels of SENP3 after ischemic infarct, may represent novel therapeutic strategies aimed at promoting cell survival and heart function after cardiac ischemia
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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
brenda
Kuo, M.L.; den Besten, W.; Thomas, M.C.; Sherr, C.J.
Arf-induced turnover of the nucleolar nucleophosmin-associated SUMO-2/3 protease Senp3
Cell Cycle
7
3378-3387
2008
Mus musculus (Q9EP97), Mus musculus
brenda
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)
brenda
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)
brenda
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
brenda
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
brenda
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)
brenda
Yang, Y.Q.; Li, H.; Zhang, X.; Wang, C.X.; Sun, Q.; Li, S.; Li, W.; Li, W.; Ding, K.; Liu, M.; Yu, Z.; Hang, C.H.
Expression and cell distribution of SENP3 in the cerebral cortex after experimental subarachnoid hemorrhage in rats: a pilot study
Cell. Mol. Neurobiol.
35
407-416
2015
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Yu, Z.; Li, H.; Yan, H.Y.; Yang, Y.Q.; Zhang, D.D.; Huang, L.T.; Xie, G.B.; Liu, M.; Tohti, M.; Hang, C.H.
Expression and cell distribution of SENP3 in brain tissue after traumatic brain injury in mice: a pilot study
Cell. Mol. Neurobiol.
35
733-740
2015
Mus musculus, Mus musculus ICR
brenda
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
brenda
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
brenda
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
brenda
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
brenda
Akiyama, H.; Nakadate, K.; Sakakibara, S.I.
Synaptic localization of the SUMOylation-regulating protease SENP5 in the adult mouse brain
J. Comp. Neurol.
526
990-1005
2018
Mus musculus (Q9EP97), Mus musculus
brenda
Yu, X.; Lao, Y.; Teng, X.L.; Li, S.; Zhou, Y.; Wang, F.; Guo, X.; Deng, S.; Chang, Y.; Wu, X.; Liu, Z.; Chen, L.; Lu, L.M.; Cheng, J.; Li, B.; Su, B.; Jiang, J.; Li, H.B.; Huang, C.; Yi, J.; Zou, Q.
SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation
Nat. Commun.
9
3157
2018
Mus musculus (Q9EP97)
brenda
Wu, D.; Huang, C.J.; Khan, F.A.; Jiao, X.F.; Liu, X.M.; Pandupuspitasari, N.S.; Brohi, R.D.; Huo, L.J.
SENP3 grants tight junction integrity and cytoskeleton architecture in mouse Sertoli cells
Oncotarget
8
58430-58442
2017
Mus musculus (Q9EP97), Mus musculus
brenda
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)
brenda
Nishida, T.
SUMO-specific protease SENP3 enhances MDM2-mediated ubiquitination of PARIS/ZNF746 in HeLa cells
Biochem. Biophys. Res. Commun.
615
150-156
2022
Homo sapiens (Q9H4L4)
brenda
Chen, J.; Sun, X.; Liu, Y.; Zhang, Y.; Zhao, M.; Shao, L.
SENP3 attenuates foam cell formation by deSUMOylating NLRP3 in macrophages stimulated with ox-LDL
Cell. Signal.
117
111092
2024
Homo sapiens (Q9H4L4)
brenda
Cai, Z.; Wang, Z.; Yuan, R.; Cui, M.; Lao, Y.; Wang, Y.; Nie, P.; Shen, L.; Yi, J.; He, B.
Redox-sensitive enzyme SENP3 mediates vascular remodeling via de-SUMOylation of beta-catenin and regulation of its stability
EBioMedicine
67
103386
2021
Mus musculus (Q9EP97), Homo sapiens (Q9H4L4)
brenda
Waters, E.; Wilkinson, K.A.; Harding, A.L.; Carmichael, R.E.; Robinson, D.; Colley, H.E.; Guo, C.
The SUMO protease SENP3 regulates mitochondrial autophagy mediated by Fis1
EMBO Rep.
23
e48754
2022
Homo sapiens (Q9H4L4)
brenda
Long, X.; Zhao, B.; Lu, W.; Chen, X.; Yang, X.; Huang, J.; Zhang, Y.; An, S.; Qin, Y.; Xing, Z.; Shen, Y.; Wu, H.; Qi, Y.
The critical roles of the SUMO-specific protease SENP3 in human diseases and clinical implications
Front. Physiol.
11
558220
2020
Homo sapiens (Q9H4L4)
brenda
Wang, P.; Yang, L.; Guo, Y.; Qi, S.; Liang, J.; Tian, G.; Tian, Z.
SENP3 mediates the activation of the Wnt/beta-catenin signaling pathway to accelerate the growth and metastasis of oesophagal squamous cell carcinoma in mice
Funct. Integr. Genomics
24
40
2024
Mus musculus (Q9EP97)
brenda
Xia, Q.; Mao, M.; Zhan, G.; Luo, Z.; Zhao, Y.; Li, X.
SENP3-mediated deSUMOylation of c-Jun facilitates microglia-induced neuroinflammation after cerebral ischemia and reperfusion injury
iScience
26
106953
2023
Mus musculus (Q9EP97)
brenda
Yu, B.; Lin, Q.; Huang, C.; Zhang, B.; Wang, Y.; Jiang, Q.; Zhang, C.; Yi, J.
SUMO proteases SENP3 and SENP5 spatiotemporally regulate the kinase activity of Aurora A
J. Cell Sci.
134
jcs249771
2021
Homo sapiens (Q9H4L4)
brenda
Han, Y.; Huang, X.; Cao, X.; Li, Y.; Gao, L.; Jia, J.; Li, G.; Guo, H.; Liu, X.; Zhao, H.; Guan, H.; Zhou, P.; Gao, S.
SENP3-mediated TIP60 deSUMOylation is required for DNA-PKcs activity and DNA damage repair
MedComm. (2020)
3
e123
2022
Homo sapiens (Q9H4L4)
brenda
Xi, R.; Kadur Lakshminarasimha Murthy, P.; Tung, K.L.; Guy, C.D.; Wan, J.; Li, F.; Wang, Z.; Li, X.; Varanko, A.; Rakhilin, N.; Xin, Y.; Liu, B.; Qian, S.B.; Su, L.; Han, Y.; Shen, X.
SENP3-mediated host defense response contains HBV replication and restores protein synthesis
PLoS ONE
14
e0209179
2019
Homo sapiens (Q9H4L4)
brenda
Rawlings, N.; Lee, L.; Nakamura, Y.; Wilkinson, K.A.; Henley, J.M.
Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury
PLoS ONE
14
e0213331
2019
Rattus norvegicus
brenda
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