Recombinant human SIRT7 protein

Specifications

Form

Liquid

Additional notes

Purity was determined to be >95% by densitometry. Affinity purified.

General info

Function

NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase, deglutarylase and dedecanoylase), depending on the context (PubMed : 22722849, PubMed : 26907567, PubMed : 30653310, PubMed : 31542297, PubMed : 35939806). Specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac) (PubMed : 22722849, PubMed : 30420520, PubMed : 35939806). In contrast to other histone deacetylases, displays strong preference for a specific histone mark, H3K18Ac, directly linked to control of gene expression (PubMed : 22722849, PubMed : 30653310). H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors; SIRT7 thereby acts as a transcription repressor (PubMed : 22722849). Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells (PubMed : 22722849). Also able to mediate deacetylation of histone H3 at 'Lys-36' (H3K36Ac) in the context of nucleosomes (PubMed : 30653310). Also mediates deacetylation of non-histone proteins, such as ATM, CDK9, DDX21, DDB1, FBL, FKBP5/FKBP51, GABPB1, RAN, RRP9/U3-55K and POLR1E/PAF53 (PubMed : 24207024, PubMed : 26867678, PubMed : 28147277, PubMed : 28426094, PubMed : 28790157, PubMed : 28886238, PubMed : 30540930, PubMed : 30944854, PubMed : 31075303). Enriched in nucleolus where it stimulates transcription activity of the RNA polymerase I complex (PubMed : 16618798, PubMed : 19174463, PubMed : 24207024). Acts by mediating the deacetylation of the RNA polymerase I subunit POLR1E/PAF53, thereby promoting the association of RNA polymerase I with the rDNA promoter region and coding region (PubMed : 16618798, PubMed : 19174463, PubMed : 24207024). In response to metabolic stress, SIRT7 is released from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased RNA polymerase I transcription (PubMed : 24207024). Required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis (PubMed : 19174463). Promotes pre-ribosomal RNA (pre-rRNA) cleavage at the 5'-terminal processing site by mediating deacetylation of RRP9/U3-55K, a core subunit of the U3 snoRNP complex (PubMed : 26867678). Mediates 'Lys-37' deacetylation of Ran, thereby regulating the nuclear export of NF-kappa-B subunit RELA/p65 (PubMed : 31075303). Acts as a regulator of DNA damage repair by mediating deacetylation of ATM during the late stages of DNA damage response, promoting ATM dephosphorylation and deactivation (PubMed : 30944854). Suppresses the activity of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes by mediating deacetylation of DDB1, which prevents the interaction between DDB1 and CUL4 (CUL4A or CUL4B) (PubMed : 28886238). Activates RNA polymerase II transcription by mediating deacetylation of CDK9, thereby promoting 'Ser-2' phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (PubMed : 28426094). Deacetylates FBL, promoting histone-glutamine methyltransferase activity of FBL (PubMed : 30540930). Acts as a regulator of mitochondrial function by catalyzing deacetylation of GABPB1 (By similarity). Regulates Akt/AKT1 activity by mediating deacetylation of FKBP5/FKBP51 (PubMed : 28147277). Required to prevent R-loop-associated DNA damage and transcription-associated genomic instability by mediating deacetylation and subsequent activation of DDX21, thereby overcoming R-loop-mediated stalling of RNA polymerases (PubMed : 28790157). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase (PubMed : 27436229, PubMed : 27997115, PubMed : 31542297). Acts as a protein depropionylase by mediating depropionylation of Osterix (SP7), thereby regulating bone formation by osteoblasts (By similarity). Acts as a histone deglutarylase by mediating deglutarylation of histone H4 on 'Lys-91' (H4K91glu); a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (PubMed : 31542297). Acts as a histone desuccinylase : in response to DNA damage, recruited to DNA double-strand breaks (DSBs) and catalyzes desuccinylation of histone H3 on 'Lys-122' (H3K122succ), thereby promoting chromatin condensation and DSB repair (PubMed : 27436229). Also promotes DSB repair by promoting H3K18Ac deacetylation, regulating non-homologous end joining (NHEJ) (By similarity). Along with its role in DNA repair, required for chromosome synapsis during prophase I of female meiosis by catalyzing H3K18Ac deacetylation (By similarity). Involved in transcriptional repression of LINE-1 retrotransposon via H3K18Ac deacetylation, and promotes their association with the nuclear lamina (PubMed : 31226208). Required to stabilize ribosomal DNA (rDNA) heterochromatin and prevent cellular senescence induced by rDNA instability (PubMed : 29728458). Acts as a negative regulator of SIRT1 by preventing autodeacetylation of SIRT1, restricting SIRT1 deacetylase activity (By similarity).

Sequence similarities

Belongs to the sirtuin family. Class IV subfamily.

Post-translational modifications

Phosphorylated during mitosis.. Methylation at Arg-388 by PRMT6 inhibits the H3K18Ac histone deacetylase activity, promoting mitochondria biogenesis and maintaining mitochondria respiration.. Ubiquitinated via 'Lys-63'-linked ubiquitin chains (PubMed:28655758). Deubiquitinated by USP7, inhibiting the H3K18Ac histone deacetylase activity and regulating gluconeogenesis (PubMed:28655758). Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO7; leading to proteasomal degradation.

Subcellular localisation

Nucleus