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Information on EC 3.4.22.B75 - SENP7 peptidase and Organism(s) Homo sapiens and UniProt Accession Q9BQF6
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3.4.22.B75 SENP7 peptidaseSpecify your search results
Word Map
- 3.4.22.B75
- senp7s
- hp1
-
heterochromatin
- medicine
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deconjugation
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h3k9me3
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pericentric
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desumoylation
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
Protease that deconjugates SUMO2 and SUMO3 from targeted proteins, but not SUMO1. Catalyzes the deconjugation of poly-SUMO2 and poly-SUMO3 chains. Has very low efficiency in processing full-length SUMO proteins to their mature forms. SENP67 prefers the LRGG-/- sequence versus the QTGG-/- sequence.
Synonyms
sumo protease senp7, sumo/sentrin/smt3-specific peptidase, sentrin-specific protease 7, sumo-specific protease senp7, sumo-specific protease 7, 
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
(K335, K372, K382)-triSUMOyl-cyclic GMP-AMP synthase + 3 H2O
3 SUMO + cyclic GMP-AMP synthase
SUMO is conjugated onto the lysine residues 335, 372 and 382. SENP7 reverses this inhibition via catalyzing the deSUMOylation
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-
?
(SUMO-3)-Ran GTPase-activating protein 1 conjugate + H2O
SUMO-3 + Ran GTPase-activating protein 1
SENP6 and SENP7 prefer SUMO2 or SUMO3 in deconjugation reactions with rates comparable with those catalyzed by SENP2. In contrast to SENP2, SENP6 and SENP7 are less able to deconjugate SUMO1-RanGAP1, and products are only detected at enzyme concentrations 100 x higher than that observed for reactions containing SENP2
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-
?
SUMO-1 precursor + H2O
SUMO-1 + His-Ser-Thr-Val
SENP7 exhibits lower rates for processing pre-SUMO-1, pre-SUMO-2, or pre-SUMO-3 in comparison with SENP2
-
-
?
SUMO-2 precursor + H2O
SUMO-2 + Val-Tyr
SENP7 exhibits lower rates for processing pre-SUMO1, pre-SUMO-2, or pre-SUMO-3 in comparison with SENP2
-
-
?
SUMO-3 precursor + H2O
SUMO-3 + Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe
SENP7 exhibits lower rates for processing pre-SUMO1, pre-SUMO-2, or pre-SUMO-3 in comparison with SENP2
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?
(di-SUMO-2)-Ran GTPase-activating protein 1 conjugate + H2O
?
-
SENP7 displays isopeptidase activity against di-SUMO-2- and SUMO-2-modified Ran GTPase-activating protein 1 but has limited activity against SUMO-1-modified Ran GTPase-activating protein 1
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-
?
(SUMO-2)-Ran GTPase-activating protein 1 conjugate + H2O
?
-
SENP7 displays isopeptidase activity against di-SUMO-2- and SUMO-2-modified Ran GTPase-activating protein 1 but has limited activity against SUMO-1-modified Ran GTPase-activating protein 1
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-
?
acetyl-LRGG-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-LRGG + 7-amino-4-trifluoromethylcoumarin
-
SENP7 prefers the LRGG sequence, residues typical of Nedd8 or ubiquitin in the P3 and P4 positions
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-
?
acetyl-QTGG-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-QTGG + 7-amino-4-trifluoromethylcoumarin
-
very low activity
-
-
?
poly-SUMO-2 + H2O
?
-
the C-terminal catalytic domain of SENP7 efficiently depolymerized poly-SUMO-2 chains but has undetectable activity against poly-SUMO-1 chains
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-
?
polySUMO2 KRAB-associated protein 1 + H2O
KRAB-associated protein 1 + SUMO 2 + SUMO3
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enzyme SENP7 promotes the removal of SUMO2 from KRAB-associated protein 1
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-
?
SUMOylated KRAB-associated protein 1 + H2O
KRAB-associated protein 1 + SUMO 2 + SUMO3
-
enzyme SENP7 promotes the removal of SUMO2/3 from KRAB-associated protein 1
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-
?
SUMO2/3ylated HP1alpha + H2O
HP1alpha + SUMO3 + SUMO2
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HP1alpha localizes at the pericentric heterochromatin, importance of SUMOylation in directing HP1alphas subnuclear localization, SUMO deconjugation by enzyme SENP7
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-
?
SUMO2/3ylated HP1alpha + H2O
HP1alpha + SUMO3 + SUMO2
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SUMO deconjugation by enzyme SENP7
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?
additional information
?
-
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SENP7 has a restricted substrate specificity, being unable to process SUMO precursors and displaying paralogue-specific isopeptidase activity
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?
additional information
?
-
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SENP7 reveals no detectable endopeptidase activity on the precursors of ubiquitin, Nedd8 and ISG15
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-
?
additional information
?
-
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the enzyme SENP7 interacts with the chromatin repressive KRAB-associated protein 1 through heterochromatin protein 1 alpha, HP1alapha. Enzyme SENP7 contains a conserved HP1-box, PxVxL, required for interaction with HP1
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?
additional information
?
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isozyme SENP7 shows isoform specificity for SUMO2/3 over SUMO1
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?
additional information
?
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long enzyme variant SENP7L, but not short enzyme variant SENP7S, binds HP1alpha. This interaction does not require catalytic activity: both the active wild-type SENP7L and the catalytically inactive mutant (SENP7Lm) bind endogenous HP1alpha efficiently
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?
additional information
?
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SENP7 is a SUMO protease with a preference for deconjugating SUMO2 and SUMO3, particularly in a polymeric form. Precursor SUMO1, SUMO2 and SUMO3 and SUMO1 polymers are poorly processed by SENP7
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?
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
poly-SUMO-2 + H2O
?
-
the C-terminal catalytic domain of SENP7 efficiently depolymerized poly-SUMO-2 chains but has undetectable activity against poly-SUMO-1 chains
-
-
?
SUMO2/3ylated HP1alpha + H2O
HP1alpha + SUMO3 + SUMO2
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HP1alpha localizes at the pericentric heterochromatin, importance of SUMOylation in directing HP1alphas subnuclear localization, SUMO deconjugation by enzyme SENP7
-
-
?
SUMOylated KRAB-associated protein 1 + H2O
KRAB-associated protein 1 + SUMO 2 + SUMO3
-
enzyme SENP7 promotes the removal of SUMO2/3 from KRAB-associated protein 1
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-
?
additional information
?
-
-
the enzyme SENP7 interacts with the chromatin repressive KRAB-associated protein 1 through heterochromatin protein 1 alpha, HP1alapha. Enzyme SENP7 contains a conserved HP1-box, PxVxL, required for interaction with HP1
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-
?
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
truncated SUMO-2
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whereas truncated SUMO-2 and -3 can substantially enhance SENP6 activity, neither truncated SUMO-1 nor truncated Nedd8 nor ubiquitin has this ability
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truncated SUMO-3
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whereas truncated SUMO-2 and -3 can substantially enhance SENP6 activity, neither truncated SUMO-1 nor truncated Nedd8 nor ubiquitin has this ability
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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
-
two splicing variants, a short SENP7 splice variant SENP7S and a long transcript SENP7L
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
speckle-type POZ protein (SPOP) expression is significantly downregulated in hepatocellular carcinoma and is associated with tumor size, differentiation and metastasis. SPOP recognizes and binds SENP7 and promotes its degradation via ubiquitin-dependent proteolysis. Vimentin expression is correlated negatively with SPOP and positively with SENP7
physiological function
malfunction
metabolism
physiological function
additional information
physiological function
SENP7 interacted with and potentiated cyclic GMP-AMP synthase cGAS activation. The small ubiquitin-like modifier (SUMO) is conjugated onto the lysine residues 335, 372 and 382 of cGAS, which suppresses its DNA-binding, oligomerization and nucleotidyl-transferase activities. SENP7 reverses this inhibition via catalyzing the cGAS de-SUMOylation. Silencing of SENP7 markedly impaires the IRF3-responsive gene expression induced by cGAS-STING axis
physiological function
SUMOylated beta-catenin and Axin1 are both isoform SENP7S-substrates. With knockdown of SENP7S in mammary epithelial cells, Axin1-beta-catenin interaction is lost and beta-catenin escapes ubiquitylation-dependent proteasomal degradation. SUMOylated beta-catenin accumulates at the chromatin and activates multiple oncogenes. Nontumorigenic MCF10-2A cells with reduced SENP7S exhibit greater cell proliferation and anchorage-dependent growth. SENP7S depletion directly potentiates tumorigenic properties of MCF10-2A cells with induction of anchorage-independent growth and self-renewal in 3D-spheroid conditions
malfunction
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small interfering RNA-mediated ablation of SENP7 expression leads to the accumulation of high-molecular-mass SUMO-2 species and to the accumulation of promyelocytic leukaemia protein in subnuclear bodies
malfunction
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increased SUMOylation of c-Myc occurs upon knockdown of the SUMO protease SENP7
malfunction
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loss of SENP7LHP1alpha interaction causes HP1alpha hyperSUMOylation, an enrichment of HP1alpha at E2F-responsive and mesenchymal gene promoters, silences transcription of these genes, and elicits cellular senescence. Reducing all catalytically active SENP7 isoforms prompts a reduction in GILM2 cells' invasiveness. Lower mRNA of E2F-responsive genes and vimentin in tumor mass from GI101a-shSENP7 and GILM2-shSENP7 than their respective shNT control xenografts
metabolism
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oncogene c-Myc-driven tumours are strongly dependent on the SUMO pathway. c-Myc is a target protein for SUMOylation, and SUMOylated c-Myc is subsequently ubiquitylated and degraded by the proteasome.. SUMO protease SENP7 is involved in c-Myc SUMOylation and regulation. Multiple SUMO monomers conjugated to c-Myc could be sufficient to direct SUMOylated c-Myc to the ubiquitin-proteasome pathway. PIAS1 and SENP7 regulate reversible SUMOylation of c-Myc
physiological function
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SENP7 acts as a SUMO-2/3-specific protease that is likely to regulate the metabolism of poly-SUMO-2/3 rather than SUMO-1 conjugation in vivo
physiological function
-
enzyme SENP7 promotes the removal of SUMO2/3 from KRAB-associated protein 1 and regulates the interaction of the chromatin remodeler CHD3 with chromatin. In the presence of CHD3, SENP7 is required for chromatin relaxation in response to DNA damage, for homologous recombination repair and for cellular resistance to DNA-damaging agents. DeSUMOylation by SENP7 is required to promote a permissive chromatin environment for DNA repair. Enzyme SENP7 is required for localized euchromatin relaxation
physiological function
-
induction of SENP7L long variant maintains hypoSUMOylated HP1alpha, which relieves HP1alpha-mediated repression of proliferation promoting E2F-responsive genes as well as mesenchymal genes
physiological function
-
PIAS1 and SENP7 regulate reversible SUMOylation of c-Myc, SENP7 is responsible for removing SUMOs from c-Myc. Closely spaced SUMOs on c-Myc might be important for the regulation of SUMOylated c-Myc by SENP7 providing an alternative binding site for RNF4, a known regulator of SUMO polymers
additional information
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active site loop1 insertion is the determinant for the SUMO2/3 activity and specificity of SENP7, role of the SENP6/7-loop1 insertion in chain dismantling, loop1 structure of SENP7, overview
additional information
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the catalytic domain of SENP7 consists of two separate parts interrupted by a stretch of amino acids. This feature is thought to contribute to its specificity for SUMO chains
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). CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals of the SENP7 catalytic domain are obtained at 18°C by sitting drop vapor diffusion methods crystal structure of the SENP7 catalytic domain at a resolution of 2.4 A
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C745K
mutation does not alter deconjugation rates in comparison with wild-type SENP7
F709W
end point deconjugation reactions using di-SUMO2/3 or poly-SUMO2/3 reveales rates equivalent to or slightly greater than wild-type SENP7. Mutation results in a 2fold higher activity when di-SUMO2 deconjugation rates are measured
V713E
mutation elicits 65-fold reduction in deconjugation rate compared to wild-type activity
V713E/C745K
C745K substitution partially rescues defects observed for SENP7-V713E when present as a double point substitution (SENP7-V713E/C745K)
additional information
additional information
-
enzyme knockout by siRNA in HeLa cells, complementation of knockdown with siRNA-resistant Flag-SENP7
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of N-terminally FLAG-tagged wild-type and mutant enzymes in HEK-293 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
SENP7S is the predominant SENP transcript in human mammary epithelia but is significantly reduced in precancerous ductal carcinoma in situ and all breast cancer subtypes. Like other SENP family members, SENP7S has SUMO isopeptidase activity but unlike full-length SENP7L, SENP7S is localized in the cytosol
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
increased degradation of SENP7 by overexpression of SPOP decreases vimentin levels, which in turn may attenuate hepatocellular carcinoma cell metastasis
medicine
SENP7 is significantly up-regulated in patients with systemic lupus erythematosus
medicine
SENP7S is the predominant SENP transcript in human mammary epithelia but is significantly reduced in precancerous ductal carcinoma in situ and all breast cancer subtypes
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Drag, M.; Mikolajczyk, J.; Krishnakumar, I.M.; Huang, Z.; Salvesen, G.S.
Activity profiling of human deSUMOylating enzymes (SENPs) with synthetic substrates suggests an unexpected specificity of two newly characterized members of the family
Biochem. J.
409
461-469
2008
Homo sapiens
Shen, L.N.; Geoffroy, M.C.; Jaffray, E.G.; Hay, R.T.
Characterization of SENP7, a SUMO-2/3-specific isopeptidase
Biochem. J.
421
223-230
2009
Homo sapiens
Lima, C.D.; Reverter, D.
Structure of the human SENP7 catalytic domain and poly-SUMO deconjugation activities for SENP6 and SENP7
J. Biol. Chem.
283
32045-32055
2008
Homo sapiens (Q9BQF6)
Gonzalez-Prieto, R.; Cuijpers, S.A.; Kumar, R.; Hendriks, I.A.; Vertegaal, A.C.
c-Myc is targeted to the proteasome for degradation in a SUMOylation-dependent manner, regulated by PIAS1, SENP7 and RNF4
Cell Cycle
14
1859-1872
2015
Homo sapiens
Garvin, A.J.; Densham, R.M.; Blair-Reid, S.A.; Pratt, K.M.; Stone, H.R.; Weekes, D.; Lawrence, K.J.; Morris, J.R.
The deSUMOylase SENP7 promotes chromatin relaxation for homologous recombination DNA repair
EMBO Rep.
14
975-983
2013
Homo sapiens
Bawa-Khalfe, T.; Lu, L.S.; Zuo, Y.; Huang, C.; Dere, R.; Lin, F.M.; Yeh, E.T.
Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition
Proc. Natl. Acad. Sci. USA
109
17466-17471
2012
Homo sapiens
Alegre, K.O.; Reverter, D.
Structural insights into the SENP6 loop1 structure in complex with SUMO2
Protein Sci.
23
433-441
2014
Homo sapiens
Ji, P.; Liang, S.; Li, P.; Xie, C.; Li, J.; Zhang, K.; Zheng, X.; Feng, M.; Li, Q.; Jiao, H.; Chi, X.; Zhao, W.; Zhang, S.; Wang, X.
Speckle-type POZ protein suppresses hepatocellular carcinoma cell migration and invasion via ubiquitin-dependent proteolysis of SUMO1/sentrin specific peptidase 7
Biochem. Biophys. Res. Commun.
502
30-42
2018
Homo sapiens (Q9BQF6)
Cui, Y.; Yu, H.; Zheng, X.; Peng, R.; Wang, Q.; Zhou, Y.; Wang, R.; Wang, J.; Qu, B.; Shen, N.; Guo, Q.; Liu, X.; Wang, C.
SENP7 potentiates cGAS activation by relieving SUMO-mediated inhibition of cytosolic DNA sensing
PLoS Pathog.
13
e1006156
2017
Homo sapiens (Q9BQF6)
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