3.4.22.B75: SENP7 peptidase
This is an abbreviated version!
For detailed information about SENP7 peptidase, go to the full flat file.
Word Map on EC 3.4.22.B75
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3.4.22.B75
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senp7s
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hp1
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heterochromatin
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medicine
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deconjugation
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h3k9me3
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pericentric
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desumoylation
- 3.4.22.B75
- senp7s
- hp1
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heterochromatin
- medicine
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deconjugation
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h3k9me3
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pericentric
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desumoylation
Reaction
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
SENP7, SENP7 SUMO-protease, sentrin-specific protease 7, sentrin/small ubiquitin-like modifier-specific protease 7, SUMO protease SENP7, SUMO-specific protease 7, SUMO-specific protease SENP7, SUMO/sentrin/Smt3-specific peptidase
ECTree
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General Information
General Information on EC 3.4.22.B75 - SENP7 peptidase
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malfunction
metabolism
physiological function
additional information
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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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enzyme SENP7 depleted cells show reduced localization of HP1alpha at pericentric heterochromatin domains, while trimethylated histone H3 Lys9 (H3K9me3) remains present at these domains
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 SENP7 leads to an increased time spent in mitosis. Single PxVxL SENP7 mutants behave as dominant negatives
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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HP1 enrichment at pericentric heterochromatin is essential for proper chromosome segregation, the process requires H3K9me3 and the SUMO protease SENP7
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
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
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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
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a short module comprising two consecutive HP1 interaction motifs on SENP7 is the determinant for HP1 enrichment and acts by restricting HP1 mobility at pericentric domains. Mechanism for maintenance of HP1 enrichment determination in which this module functions on top of H3K9me3 to lock contiguous HP1 molecules already docked on H3K9me3-modified nucleosomes, overview
physiological function
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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
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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
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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
physiological function
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the SUMO-specific protease SENP7 in mouse is a maintenance factor for HP1alpha accumulation at pericentric heterochromatin. Enzyme SENP7 interacts directly with HP1alpha, localizes at HP1-enriched pericentric domain,s and can deconjugate SUMOylated HP1alpha in vivo. SUMOylation promotes targeting of HP1alpha to pericentric heterochromatin. DeSUMOylation event enables HP1alpha retention at these domains
physiological function
mouse oocytes deficient in SENP7 experienced meiotic arrest at prophase I and metaphase I stages. SENP7 depletion compromises oocyte meiosis. Aberrant epigenetic marks on histone H3 and disrupted expression of germinal vesicle breakdown-related proteins intervene M-phase entry in SENP7-depleted oocytes. SENP7-dependent microtubule organizing centers function is essential for spindle assembly. The resulting changes on histone H3 restrict Rad51C loading onto DNA lesions due to elevated HP1alpha euchromatic deposition, and reduced DNA 5hmC challenges the permissive status for zygotic DNA repair, which induce embryo death
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
strong upregulation of the Senp7 protease at both mRNA and protein levels is observed under differentiation conditions. Senp7 is required for neuronal differentiation in a model cell line, and also in the developing neural tube. Senp7 is transiently activated at early stages of neuronal differentiation
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
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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