Any feedback?
No. of entries
Information on EC 3.4.22.B73 - SENP5 peptidase
for references in articles please use BRENDA:EC3.4.22.B73
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Old data from external sources may still be available.
Please check here for current data: EC unknown
Please check here for current data: EC unknown
preliminary BRENDA-supplied EC number
EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.22 Cysteine endopeptidases
3.4.22.B73 SENP5 peptidase
The enzyme appears in viruses and cellular organisms
- 3.4.22.B73
-
senps
-
desumoylation
-
deconjugation
- isopeptidase
-
mitosis
-
fission
- nucleolus
-
regulator-related
- medicine
Reaction Schemes
showSENP5 more efficiently removes SUMO-2 and SUMO-3 than SUMO-1 from SUMO-modified target such as Ran GTPase-activating protein 1. Catalyzes desumoylation of mitochondrial fission GTPase DRP1.
Synonyms
senp5, sumo-specific protease 5, more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
SENP5
SUMO-specific protease 5
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
SENP5 more efficiently removes SUMO-2 and SUMO-3 than SUMO-1 from SUMO-modified target such as Ran GTPase-activating protein 1. Catalyzes desumoylation of mitochondrial fission GTPase DRP1.
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(SUMO-1)-mitochondrial fission GTPase DRP1 congugate + H2O
SUMO-1 + mitochondrial fission GTPase DRP1
(SUMO-1)-Ran GTPase-activating protein 1 conjugate + H2O
SUMO-1 + Ran GTPase-activating protein 1
Substrates: SENP5 more efficiently removes SUMO-2 and SUMO-3 than SUMO-1 from SUMO-modified Ran GTPase-activating protein 1 conjugate
Products: -
Products: -
?
(SUMO-2)-Ran GTPase-activating protein 1 conjugate + H2O
SUMO-2 + Ran GTPase-activating protein 1
Substrates: SENP5 more efficiently removes SUMO-2 and SUMO-3 than SUMO-1 from SUMO-modified Ran GTPase-activating protein 1 conjugate
Products: -
Products: -
?
(SUMO-3)-Ran GTPase-activating protein 1 conjugate + H2O
SUMO-3 + Ran GTPase-activating protein 1
Substrates: SENP5 more efficiently removes SUMO-2 and SUMO-3 than SUMO-1 from SUMO-modified Ran GTPase-activating protein 1 conjugate
Products: -
Products: -
?
SUMO-1 precursor + H2O
SUMO-1 + His-Ser-Thr-Val
Substrates: the catalytic domain of SENP5 shows higher efficiency for processing SUMO-3 over SUMO-1 precursors in vitro
Products: -
Products: -
?
SUMO-3 precursor + H2O
SUMO-3 + Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe
Substrates: the catalytic domain of SENP5 shows higher efficiency for processing SUMO-3 over SUMO-1 precursors in vitro
Products: -
Products: -
?
SUMOylated ATRIP + H2O
?
Substrates: ATRIP i.e regulator of ATR, ATM [ataxia telangiectasia-mutated]- and Rad3-related kinase
Products: -
Products: -
?
SUMOylated dynamin related protein + H2O
dynamin related protein + SUMO
-
Substrates: -
Products: -
Products: -
?
(SUMO-1)-mitochondrial fission GTPase DRP1 congugate + H2O
SUMO-1 + mitochondrial fission GTPase DRP1
Substrates: SENP5 catalyzes the cleavage of SUMO1 from a number of mitochondrial substrates. SENP5 is a new regulator of SUMO1 proteolysis from mitochondrial targets, impacting mitochondrial morphology and metabolism
Products: -
Products: -
?
(SUMO-1)-mitochondrial fission GTPase DRP1 congugate + H2O
SUMO-1 + mitochondrial fission GTPase DRP1
-
Substrates: -
Products: -
Products: -
?
(SUMO-1)-mitochondrial fission GTPase DRP1 congugate + H2O
SUMO-1 + mitochondrial fission GTPase DRP1
Substrates: SENP5 preferentially deSUMOylates SUMO2 and SUMO3 proteins
Products: -
Products: -
?
(SUMO-2)-AurA + H2O
SUMO-2 + AurA
Substrates: AurA is SUMOylated at K258
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(SUMO-1)-mitochondrial fission GTPase DRP1 congugate + H2O
SUMO-1 + mitochondrial fission GTPase DRP1
SUMOylated dynamin related protein + H2O
dynamin related protein + SUMO
-
Substrates: -
Products: -
Products: -
?
(SUMO-1)-mitochondrial fission GTPase DRP1 congugate + H2O
SUMO-1 + mitochondrial fission GTPase DRP1
Substrates: SENP5 catalyzes the cleavage of SUMO1 from a number of mitochondrial substrates. SENP5 is a new regulator of SUMO1 proteolysis from mitochondrial targets, impacting mitochondrial morphology and metabolism
Products: -
Products: -
?
(SUMO-1)-mitochondrial fission GTPase DRP1 congugate + H2O
SUMO-1 + mitochondrial fission GTPase DRP1
-
Substrates: -
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Breast Neoplasms
The SUMO-specific protease SENP5 controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma.
Carcinogenesis
The SUMO-specific protease SENP5 controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma.
Carcinoma
Inhibition of SENP5 suppresses cell growth and promotes apoptosis in osteosarcoma cells.
Carcinoma
Overexpression of SENP5 in oral squamous cell carcinoma and its association with differentiation.
Carcinoma
Sentrin/small ubiquitin-like modifier-specific protease 5 protects oral cancer cells from oxidative stress-induced apoptosis.
Carcinoma
The SUMO-specific protease SENP5 controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma.
Carcinoma, Hepatocellular
The SUMO-specific protease SENP5 controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma.
Epilepsy
SUMO proteases SENP3 and SENP5 spatiotemporally regulate the kinase activity of Aurora A.
Glioblastoma
SUMOylation Regulator-Related Molecules Can Be Used as Prognostic Biomarkers for Glioblastoma.
Neoplasms
The SUMO-specific protease SENP5 controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma.
Osteosarcoma
Inhibition of SENP5 suppresses cell growth and promotes apoptosis in osteosarcoma cells.
Osteosarcoma
The SUMO-specific protease SENP5 controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma.
Squamous Cell Carcinoma of Head and Neck
Inhibition of SENP5 suppresses cell growth and promotes apoptosis in osteosarcoma cells.
Squamous Cell Carcinoma of Head and Neck
Overexpression of SENP5 in oral squamous cell carcinoma and its association with differentiation.
Squamous Cell Carcinoma of Head and Neck
Sentrin/small ubiquitin-like modifier-specific protease 5 protects oral cancer cells from oxidative stress-induced apoptosis.
Squamous Cell Carcinoma of Head and Neck
The SUMO-specific protease SENP5 controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Senp5L is a dominant form in the early embryonic stages, E12-E14 when active neurogenesis occurs, whereas Senp5S becomes upregulated during the differentiation stage and becomes the dominant form in postnatal and adult
brenda
-
significant increase in the level of enzyme SENP5 in human idiopathic failing hearts
brenda
Senp5 is detected in the neuropil but not in cell bodies. Strong Senp5 immunoreactivity is observed in regions with high numbers of synapses such as the cerebellar glomeruli. Senp5 colocalizes with pre- and post-synaptic markers, as well as a mitochondrial marker. Senp5 is localized to presynaptic terminals, postsynaptic spines, and mitochondria in axon terminals
brenda
-
the SENP5 expression status is associated with differentiation of oral squamous cell carcinoma and not with any other clinicopathological parameters
brenda
-
enzyme SENP5 overexpression occurs in 31 OSCC tissue specimens
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
during anaphase, SENP5 quickly relocates back to the chromosomes while the nuclear envelope reassembles
brenda
a part of SENP5 is localized on the mitotic spindle
brenda
Senp5 is localized to presynaptic terminals, postsynaptic spines, and mitochondria in axon terminals
brenda
-
SENP5 expression is chiefly detected in the cytoplasm of tumor cells and in the cytoplasm and/or nucleus of normal epithelium cells
brenda
-
in interphase, SenP5 resides primarily within the nucleoli, in addition to a cytosolic pool. Relocalization of SenP5 from the nucleoli to the mitochondrial surface at G2/M transition prior to nuclear envelope breakdown
brenda
-
in interphase, SenP5 resides primarily within the nucleoli, in addition to a cytosolic pool. Relocalization of SenP5 from the nucleoli to the mitochondrial surface at G2/M transition prior to nuclear envelope breakdown. Transition of SenP5 to the mitochondria plays an important role in mitochondrial fragmentation during mitosis
brenda
Senp5 is localized to presynaptic terminals, postsynaptic spines, and mitochondria in axon terminals
brenda
-
SENP5 localizes within the granular component of the nucleolus, a subnucleolar compartment that contains B23/nucleophosmin
brenda
-
SENP5 expression is chiefly detected in the cytoplasm of tumor cells and in the cytoplasm and/or nucleus of normal epithelium cells
brenda
-
in interphase, SenP5 resides primarily within the nucleoli, in addition to a cytosolic pool. Relocalization of SenP5 from the nucleoli to the mitochondrial surface at G2/M transition prior to nuclear envelope breakdown
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
malfunction
metabolism
-
SUMO conjugation is a dynamic posttranslational modification that can be readily reversed by the activity of sentrin-specific proteases (SENPs). Elevated expression of SENP5 in the failing human hearts, development of cardiomyopathy, overview
physiological function
drug target
inhibiting SENP5 can alleviate brain injury following traumatic brain injury
drug target
SENP5 could be a critical target for overcoming radioresistance in colorectal cancer cells
malfunction
silencing of SENP5 results in a fragmented and altered morphology
malfunction
knockdown of SENP5 leads to an increase in cells with more than one nucleus or aberrant nuclear structure consistent with defects in mitosis and cytokinesis
malfunction
-
H2O2 alone enhances mitochondrial network formation, whereas the combination of H2O2 and enzyme SENP5 silencing leads to mitochondrial fragmentation in the CAL-27 cells
malfunction
-
SENP5 enzyme overexpression leads to cardiac dysfunction, accompanied by decreased cardiomyocyte proliferation and elevated apoptosis, overview. Transgenic SENP5-hearts, that are larger than wild-type, unveil a decrease in SUMO attachment to dynamin related protein (Drp1), a factor critical for mitochondrial fission, phenotype, overview
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
physiological function
SENP5 is a regulator of SUMO1 proteolysis from mitochondrial targets. SENP5 is required to maintain normal mitochondrial morphology and to control intracellular levels of reactive oxygen species. SENP5 expression affects the mitochondrial morphology by increasing the number of cells with elongated tubules
physiological function
SENP5 is required for cell division. SENP5 has nonredundant functions in vivo, likely due to distinct substrate specificities in SUMO maturation and deconjugation that are regulated by both the catalytic and noncatalytic domains of the enzyme
physiological function
-
enzyme SENP5 protects the oral squamous cell carcinoma cells from oxidative stress-induced apoptosis. Cell with higher enzyme content show a higher resistance to H2O2, overview
physiological function
-
SUMO isopeptidase SENP5 induces apoptosis and cardiomyopathy, which represents a major health issue and is a leading cause of heart failure. Significant increase in the level of enzyme SEN,P5 in human idiopathic failing hearts
physiological function
Senp5 is significantly repressed in clinical acute myeloid leukemia when compared to healthy neutrophil samples. SENP5 expression is induced during neutrophil differentiation of acute myeloid leukemia cells, and knocking down SENP5 results in significantly attenuated neutrophil differentiation
physiological function
Senp5 is overexpressed in hepatocellular carcinoma samples and required for hepatocellular carcinoma cells proliferation both in vitro and in vivo. SENP5-depleted Hep-G2 cells exhibit hypersensitivity to IR and etoposide treatment with defective checkpoint activation including decreased activation of ATM and Rad3-related kinases ATR and phosphorylation of ATR targets. Senp5 interacts with ATR regulator ATRIP and promotes ATRIP deSUMOylation
physiological function
NEDD4L/TCF3 axis can regulate the expression of SENP5 to affect the development of traumatic brain injury. However, SENP5 regulates downstream targets of traumatic brain injury
physiological function
SENP5 promotes homologous recombination-mediated DNA damage repair in colorectal cancer cells through H2AZ deSUMOylation
physiological function
Drp1 SUMO/deSUMOylation by Senp5 isoforms influences ER tubulation and mitochondrial dynamics to regulate brain development. Senp5L and Senp5S have opposite effects on SUMO conjugation to Drp1. Senp5L promotes deSUMOylation, whereas Senp5S facilitates SUMOylation. Splicing variant Senp5S, which lacks protease activity, promotes SUMOylation by competing with other Senps for the regulation of SUMOylation status. Balanced expression of Senp5L/S and Drp1 SUMOylation are required for corticogenesis
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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). Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C713S
no isopeptidase activity, no desumoylation of (SUMO-1)-Ran GTPase-activating protein 1 conjugate
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
transgenic overexpression of SENP5 in murine cardiomyocytes, overexpression of SENP5 leads to cardiac dysfunction, accompanied by decreased cardiomyocyte proliferation and elevated apoptosis
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Senp5L and Senp5S mRNAs are concurrently expressed during embryonic stages and are gradually upregulated throughout the brain development
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
the SENP5 expression status is associated with differentiation of oral squamous cell carcinoma and not with any other clinicopathological parameters. No detected correlation between SENP5 expression and the degree of epithelial dysplasia in the paracarcinoma epithelium. No expression difference between primary tumors and lymph node metastatic lesions. SENP5 expression is not associated with lymph node metastasis and cumulative survival
medicine
Senp5 is significantly repressed in clinical acute myeloid leukemia when compared to healthy neutrophil samples
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zunino, R.; Schauss, A.; Rippstein, P.; Andrade-Navarro, M.; McBride, H.M.
The SUMO protease SENP5 is required to maintain mitochondrial morphology and function
J. Cell Sci.
120
1178-1188
2007
Homo sapiens (Q96HI0)
brenda
Di Bacco, A.; Ouyang, J.; Lee, H.Y.; Catic, A.; Ploegh, H.; Gill, G.
The SUMO-specific protease SENP5 is required for cell division
Mol. Cell. Biol.
26
4489-4498
2006
Homo sapiens (Q96HI0)
brenda
Zunino, R.; Braschi, E.; Xu, L.; McBride, H.M.
Translocation of SenP5 from the nucleoli to the mitochondria modulates DRP1-dependent fission during mitosis
J. Biol. Chem.
284
17783-17795
2009
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
Ding, X.; Sun, J.; Wang, L.; Li, G.; Shen, Y.; Zhou, X.; Chen, W.
Overexpression of SENP5 in oral squamous cell carcinoma and its association with differentiation
Oncol. Rep.
20
1041-1045
2008
Homo sapiens
brenda
Kim, E.Y.; Zhang, Y.; Beketaev, I.; Segura, A.M.; Yu, W.; Xi, Y.; Chang, J.; Wang, J.
SENP5, a SUMO isopeptidase, induces apoptosis and cardiomyopathy
J. Mol. Cell. Cardiol.
78
154-164
2015
Homo sapiens
brenda
Cheng, Y.; Guo, X.; Gong, Y.; Ding, X.; Yu, Y.
Sentrin/small ubiquitin-like modifier-specific protease5 protects oral cancer cells from oxidative stress-induced apoptosis
Mol. Med. Rep.
12
2009-2014
2015
Homo sapiens
brenda
Jin, Z.L.; Pei, H.; Xu, Y.H.; Yu, J.; Deng, T.
The SUMO-specific protease SENP5 controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma
Eur. Rev. Med. Pharmacol. Sci.
20
3566-3573
2016
Homo sapiens (Q96HI0)
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 (Q6NXL6), Mus musculus
brenda
Federzoni, E.A.; Gloor, S.; Jin, J.; Shan-Krauer, D.; Fey, M.F.; Torbett, B.E.; Tschan, M.P.
Linking the SUMO protease SENP5 to neutrophil differentiation of AML cells
Leuk. Res. Rep.
4
32-35
2015
Homo sapiens (Q96HI0)
brenda
Zhang, C.Y.; Jiang, Z.M.; Ma, X.F.; Li, Y.; Liu, X.Z.; Li, L.L.; Wu, W.H.; Wang, T.
Saikosaponin-delta inhibits the hepatoma cells and enhances chemosensitivity through SENP5-dependent inhibition of Gli1 SUMOylation under hypoxia
Front. Pharmacol.
10
1039
2019
Homo sapiens (Q96HI0)
brenda
Wei, M.; Hong, T.; Liu, Y.; Luo, H.
Inhibition of SENP5 reduces brain injury in TBI rats by regulating NEDD4L/TCF3 axis
Int. J. Neurosci.
13
1-10
2024
Rattus norvegicus (D4A2S8)
brenda
Yamada, S.; Sato, A.; Ishihara, N.; Akiyama, H.; Sakakibara, S.I.
Drp1 SUMO/deSUMOylation by Senp5 isoforms influences ER tubulation and mitochondrial dynamics to regulate brain development
iScience
24
103484
2021
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 (Q96HI0)
brenda
Liu, T.; Wang, H.; Chen, Y.; Wan, Z.; Du, Z.; Shen, H.; Yu, Y.; Ma, S.; Xu, Y.; Li, Z.; Yu, N.; Zhang, F.; Cao, K.; Cai, J.; Zhang, W.; Gao, F.; Yang, Y.
SENP5 promotes homologous recombination-mediated DNA damage repair in colorectal cancer cells through H2AZ deSUMOylation
J. Exp. Clin. Cancer Res.
42
234
2023
Homo sapiens (Q96HI0)
brenda
EXTERNAL LINKS (specific for EC-Number 3.4.22.B73)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2026.1 (March 2026)
About BRENDA
Social media
Help
Survey
Download
Contribution
Legal
Curated at
Member of
![DSMZ Digital Diversity]()
![Global Core Biodata Resource]()
![ELIXIR Core Data Resource]()
![German Network for Bioinformatics Infrastructure]()
