SIRT7

This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class IV of the sirtuin family. [provided by RefSeq, Jul 2008]

Sirtuin 7

NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase and deglutarylase), depending on the context (PubMed:22722849, PubMed:26907567, PubMed:30653310, PubMed:31542297).
Specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac) (PubMed:22722849, PubMed:30420520).
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:28886238, PubMed:28426094, PubMed:30540930, PubMed:31075303, PubMed:30944854, PubMed:28790157).
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 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).

Biological Process cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process chromatin organizationIEA:UniProtKB-KW
Biological Process DNA repairIEA:UniProtKB-KW
Biological Process histone glutamine methylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process histone H3 deacetylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process histone modificationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process homologous chromosome pairing at meiosisISS:UniProtKB
Biological Process negative regulation of protein ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of transpositionISS:UniProtKB
Biological Process osteoblast differentiationISS:UniProtKB
Biological Process peptidyl-lysine desuccinylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of rRNA processingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of transcription involved in exit from mitosisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein deacetylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein deglutarylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein depropionylationISS:UniProtKB
Biological Process R-loop disassemblyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of DNA repairManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of double-strand break repair via nonhomologous end joiningISS:UniProtKB
Biological Process regulation of gluconeogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of mitochondrion organizationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of protein export from nucleusISS:UniProtKB
Biological Process regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of transcription of nucleolar large rRNA by RNA polymerase IManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process rRNA transcriptionManual Assertion Based On ExperimentIMP:UniProtKB

Nucleus, nucleolus
Nucleus, nucleoplasm
Chromosome
Cytoplasm
Mainly localizes in the nucleolus and nucleoplasm (PubMed:24207024, PubMed:28886238, PubMed:28790157, PubMed:31075303).
Associated with rDNA promoter and transcribed region (PubMed:16079181, PubMed:19174463).
Associated with nucleolar organizer regions during mitosis (PubMed:16079181, PubMed:19174463).
In response to stress, released from nucleolus to nucleoplasm (PubMed:24207024).
Associated with chromatin (PubMed:22722849).
In response to DNA damage, recruited to DNA double-strand breaks (DSBs) sites (PubMed:27436229) (Probable). Located close to the nuclear membrane when in the cytoplasm (PubMed:11953824).

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).