SIRT7
entrez
51547
canonical
uniprot
Q9NRC8
canonical
ensembl
ENSG00000187531
resolver
ensp
ENSP00000329466
resolver
ensp
ENSP00000579486
resolver
ensp
ENSP00000665609
resolver
ensp
ENSP00000665611
resolver
genesymbol
SIRT7
resolver
genesymbol_syn
SIR2L7
resolver
hgnc
HGNC:14935
resolver
uniprot
A8K2K0
resolver
uniprot
B3KSU8
resolver
uniprot
Q3MIK4
resolver
uniprot
Q9NSZ6
resolver
uniprot
Q9NUS6
resolver
uniprot_entry
SIR7_HUMAN
resolver
uniprot_sec
A8K2K0
resolver
uniprot_sec
B3KSU8
resolver
uniprot_sec
Q3MIK4
resolver
uniprot_sec
Q9NSZ6
resolver
uniprot_sec
Q9NUS6
resolver
activity_regulation
ACTIVITY REGULATION: NAD-dependent protein-lysine deacetylase and deacylase activities are activated by nucleic acids (PubMed:26907567, PubMed:27997115). Histone deacetylase activity is activated by DNA and nucleosomes (PubMed:27997115, PubMed:35939806). Protein-lysine deacylase activity is activated by RNA (PubMed:26907567). H3K18Ac histone deacetylase activity is inhibited by methylation at Arg-388 (PubMed:30420520). H3K18Ac histone deacetylase activity is inhibited by deubiquitination by USP7 (PubMed:28655758). {ECO:0000269|PubMed:26907567, ECO:0000269|PubMed:27997115, ECO:0000269|PubMed:28655758, ECO:0000269|PubMed:30420520, ECO:0000269|PubMed:35939806}.
uniprot
proteins
amino_acid_sequence
MAAGGLSRSERKAAERVRRLREEQQRERLRQVSRILRKAAAERSAEEGRLLAESADLVTELQGRSRRREGLKRRQEEVCDDPEELRGKVRELASAVRNAKYLVVYTGAGISTAASIPDYRGPNGVWTLLQKGRSVSAADLSEAEPTLTHMSITRLHEQKLVQHVVSQNCDGLHLRSGLPRTAISELHGNMYIEVCTSCVPNREYVRVFDVTERTALHRHQTGRTCHKCGTQLRDTIVHFGERGTLGQPLNWEAATEAASRADTILCLGSSLKVLKKYPRLWCMTKPPSRRPKLYIVNLQWTPKDDWAALKLHGKCDDVMRLLMAELGLEIPAYSRWQDPIFSLATPLRAGEEGSHSRKSLCRSREEAPPGDRGAPLSSAPILGGWFGRGCTKRTKRKKVT
uniprot
proteins
ec_number
2.3.1.-
uniprot
proteins
ec_number
2.3.1.286
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q8BKJ9, ECO:0000269|PubMed:16618798, ECO:0000269|PubMed:19174463, ECO:0000269|PubMed:22722849, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:26867678, ECO:0000269|PubMed:26907567, ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:27997115, ECO:0000269|PubMed:28147277, ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:29728458, ECO:0000269|PubMed:30420520, ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:30653310, ECO:0000269|PubMed:30944854, ECO:0000269|PubMed:31075303, ECO:0000269|PubMed:31226208, ECO:0000269|PubMed:31542297, ECO:0000269|PubMed:35939806}.
uniprot
proteins
mass_dalton
44898
uniprot
proteins
mutagenesis
MUTAGEN 111; /note="S->A: Catalytically inactive mutant; abolishes activation of pre-rRNA synthesis. Abolishes deacetylation of DDB1. Abolished histone desuccinylase activity; when associated with Y-187."; /evidence="ECO:0000269|PubMed:16618798, ECO:0000269|PubMed:22586326, ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:28886238"; MUTAGEN 187; /note="H->Y: Abolishes deacylase and deacetylase activities and activation of pre-rRNA synthesis. Abolished histone desuccinylase activity; when associated with A-111."; /evidence="ECO:0000269|PubMed:16618798, ECO:0000269|PubMed:22722849, ECO:0000269|PubMed:26867678, ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:30944854"; MUTAGEN 388; /note="R->F: Mimics methylation status; impaired histone deacetylase activity."; /evidence="ECO:0000269|PubMed:30420520"; MUTAGEN 388; /note="R->K: Decreased methylation; does not affect histone deacetylase activity."; /evidence="ECO:0000269|PubMed:30420520
uniprot
proteins
post_translational_modification
PTM: Phosphorylated during mitosis. {ECO:0000305|PubMed:19174463}.; PTM: Methylation at Arg-388 by PRMT6 inhibits the H3K18Ac histone deacetylase activity, promoting mitochondria biogenesis and maintaining mitochondria respiration. {ECO:0000269|PubMed:30420520}.; PTM: 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. {ECO:0000269|PubMed:28655758, ECO:0000269|PubMed:36646384}.
uniprot
proteins
protein_family
Class IV subfamily
uniprot
proteins
protein_family
Sirtuin family
uniprot
proteins
pubmed
10873683
uniprot
proteins
pubmed
11953824
uniprot
proteins
pubmed
12454780
uniprot
proteins
pubmed
12454781
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16079181
uniprot
proteins
pubmed
16618798
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19174463
uniprot
proteins
pubmed
22586326
uniprot
proteins
pubmed
22722849
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24207024
uniprot
proteins
pubmed
26867678
uniprot
proteins
pubmed
26907567
uniprot
proteins
pubmed
27287224
uniprot
proteins
pubmed
27436229
uniprot
proteins
pubmed
27997115
uniprot
proteins
pubmed
28147277
uniprot
proteins
pubmed
28426094
uniprot
proteins
pubmed
28655758
uniprot
proteins
pubmed
28790157
uniprot
proteins
pubmed
28886238
uniprot
proteins
pubmed
29728458
uniprot
proteins
pubmed
30420520
uniprot
proteins
pubmed
30540930
uniprot
proteins
pubmed
30653310
uniprot
proteins
pubmed
30944854
uniprot
proteins
pubmed
31075303
uniprot
proteins
pubmed
31226208
uniprot
proteins
pubmed
31542297
uniprot
proteins
pubmed
35939806
uniprot
proteins
pubmed
36646384
uniprot
proteins
sequence_length
400
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:16079181, ECO:0000269|PubMed:19174463, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:30420520}. Nucleus, nucleoplasm {ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:31075303}. Chromosome {ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:31226208}. Cytoplasm {ECO:0000269|PubMed:11953824}. Note=Mainly localizes in the nucleolus and nucleoplasm (PubMed:24207024, PubMed:28790157, PubMed:28886238, 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 (Probable) (PubMed:27436229). Located close to the nuclear membrane when in the cytoplasm (PubMed:11953824). {ECO:0000269|PubMed:11953824, ECO:0000269|PubMed:16079181, ECO:0000269|PubMed:19174463, ECO:0000269|PubMed:22722849, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:31075303, ECO:0000305|PubMed:30944854}.
uniprot
proteins