Protein: NAD-dependent protein deacetylase sirtuin-7 (EC 2.3.1.286) (NAD-dependent protein deacylase sirtuin-7) (EC 2.3.1.-) (Regulatory protein SIR2 homolog 7) (SIR2-like protein 7) (Q8BKJ9)
Organism: Mus musculus (Mouse)
Function: NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase and deglutarylase), depending on the context. Also acts as a dedecanoylase (By similarity). Specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac) (By similarity). In contrast to other histone deacetylases, displays strong preference for a specific histone mark, H3K18Ac, directly linked to control of gene expression (By similarity). 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 (By similarity). Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells (By similarity). Also able to mediate deacetylation of histone H3 at 'Lys-36' (H3K36Ac) in the context of nucleosomes (By similarity). Also mediates deacetylation of non-histone proteins, such as ATM, CDK9, DDX21, DDB1, FBL, FKBP5/FKBP51, GABPB1, RAN, RRP9/U3-55K and POLR1E/PAF53 (By similarity). Enriched in nucleolus where it stimulates transcription activity of the RNA polymerase I complex. 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 (By similarity). In response to metabolic stress, SIRT7 is released from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased RNA polymerase I transcription (By similarity). Required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis. 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 (By similarity). Mediates 'Lys-37' deacetylation of Ran, thereby regulating the nuclear export of NF-kappa-B subunit RELA/p65. 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 (By similarity). May also deacetylate p53/TP53 and promotes cell survival, however such data need additional confirmation. 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) (By similarity). 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 (By similarity). Deacetylates FBL, promoting histone-glutamine methyltransferase activity of FBL (By similarity). Acts as a regulator of mitochondrial function by catalyzing deacetylation of GABPB1. Regulates Akt/AKT1 activity by mediating deacetylation of FKBP5/FKBP51 (By similarity). 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 (By similarity). In addition to protein deacetylase activity, also acts as protein-lysine deacylase (By similarity). Acts as a protein depropionylase by mediating depropionylation of Osterix (SP7), thereby regulating bone formation by osteoblasts. 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 (By similarity). 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 (By similarity). Also promotes DSB repair by promoting H3K18Ac deacetylation, regulating non-homologous end joining (NHEJ). Along with its role in DNA repair, required for chromosome synapsis during prophase I of female meiosis by catalyzing H3K18Ac deacetylation. Involved in transcriptional repression of LINE-1 retrotransposon via H3K18Ac deacetylation, and promotes their association with the nuclear lamina. Required to stabilize ribosomal DNA (rDNA) heterochromatin and prevent cellular senescence induced by rDNA instability. Acts as a negative regulator of SIRT1 by preventing autodeacetylation of SIRT1, restricting SIRT1 deacetylase activity.
Subcellular location: Nucleus, nucleolus {ECO:0000269|PubMed:16618798, ECO:0000269|PubMed:25200183}. Nucleus, nucleoplasm {ECO:0000269|PubMed:25200183}. Chromosome {ECO:0000269|PubMed:27225932, ECO:0000269|PubMed:31226208}. Cytoplasm {ECO:0000250|UniProtKB:Q9NRC8}. Note=Mainly localizes in the nucleolus and nucleoplasm (By similarity). Associated with rDNA promoter and transcribed region (By similarity). Associated with nucleolar organizer regions during mitosis (By similarity). In response to stress, released from nucleolus to nucleoplasm (By similarity). Associated with chromatin (By similarity). In response to DNA damage, recruited to DNA double-strand breaks (DSBs) sites (PubMed:27225932). Located close to the nuclear membrane when in the cytoplasm (By similarity). {ECO:0000250|UniProtKB:Q9NRC8, ECO:0000269|PubMed:27225932}.
InterPro domains:
- IPR003000: Sirtuin family (family) [142-274]
- IPR050134: NAD-dependent sirtuin protein deacylases (family) [76-335]
- IPR029035: DHS-like NAD/FAD-binding domain superfamily (homologous_superfamily) [63-364]
- IPR026590: Sirtuin family, catalytic core domain (domain) [83-330]
Sequence:
MAAGGGLSRSERKAAERVRRLREEQQRERLRQVSRILRKAAAERSAEEGRLLAESEDLVTELQGRSRRREGLKRRQEEVCDDPEELRRKVRELAGAVRSARHLVVYTGAGISTAASIPDYRGPNGVWTLLQKGRPVSAADLSEAEPTLTHMSITRLHEQKLVQHVVSQNCDGLHLRSGLPRTAISELHGNMYIEVCTSCIPNREYVRVFDVTERTALHRHLTGRTCHKCGTQLRDTIVHFGERGTLGQPLNWEAATEAASKADTILCLGSSLKVLKKYPRLWCMTKPPSRRPKLYIVNLQWTPKDDWAALKLHGKCDDVMQLLMNELGLEIPVYNRWQDPIFSLATPLRAGEEGSHSRKSLCRSREEAPPGDQSDPLASAPPILGGWFGRGCAKRAKRKKVA
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016787 (hydrolase activity), GO:0003682 (chromatin binding), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0016810 (hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds), GO:0033558 (protein lysine deacetylase activity), GO:0019213 (deacetylase activity), GO:0004407 (histone deacetylase activity), GO:0034979 (NAD-dependent protein deacetylase activity), GO:0016811 (hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides), GO:0017136 (NAD-dependent histone deacetylase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0019222 (regulation of metabolic process), GO:0022402 (cell cycle process), GO:0006807 (nitrogen compound metabolic process), GO:0007049 (cell cycle), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:1903047 (mitotic cell cycle process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0019538 (protein metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009891 (positive regulation of biosynthetic process), GO:0051726 (regulation of cell cycle), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0033554 (cellular response to stress), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0044770 (cell cycle phase transition), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0016043 (cellular component organization), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0000278 (mitotic cell cycle), GO:0000083 (regulation of transcription involved in G1/S transition of mitotic cell cycle), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0044843 (cell cycle G1/S phase transition), GO:0006974 (cellular response to DNA damage stimulus), GO:0051246 (regulation of protein metabolic process), GO:0051248 (negative regulation of protein metabolic process), GO:0006325 (chromatin organization), GO:0010468 (regulation of gene expression), GO:0036211 (protein modification process), GO:0044772 (mitotic cell cycle phase transition), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0043412 (macromolecule modification), GO:0090304 (nucleic acid metabolic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0006259 (DNA metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0006996 (organelle organization), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0031399 (regulation of protein modification process), GO:0031400 (negative regulation of protein modification process), GO:0098732 (macromolecule deacylation), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0006281 (DNA repair), GO:0035601 (protein deacylation), GO:0040029 (epigenetic regulation of gene expression), GO:0006338 (chromatin remodeling), GO:0006997 (nucleus organization), GO:0045814 (negative regulation of gene expression, epigenetic), GO:1902680 (positive regulation of RNA biosynthetic process), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0016570 (histone modification), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045893 (positive regulation of DNA-templated transcription), GO:0031057 (negative regulation of histone modification), GO:1990830 (cellular response to leukemia inhibitory factor), GO:0031507 (heterochromatin formation), GO:0006476 (protein deacetylation), GO:0045892 (negative regulation of DNA-templated transcription), GO:0070828 (heterochromatin organization), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0006302 (double-strand break repair), GO:0045944 (positive regulation of transcription by RNA polymerase II), GO:0070932 (histone H3 deacetylation), GO:0140718 (facultative heterochromatin formation), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0000785 (chromatin), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus), GO:0005694 (chromosome)