SIRT7

Summary

SIRT7 (sirtuin 7, HGNC:14935) is a protein-coding gene on chromosome 17q25.3, encoding NAD-dependent protein deacetylase sirtuin-7 (Q9NRC8). NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase, deglutarylase and dedecanoylase), depending on the context.

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.

Source: NCBI Gene 51547 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 57 total
• Druggable target: yes
• MANE Select transcript: NM_016538

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14935
Approved symbol	SIRT7
Name	sirtuin 7
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187531
Ensembl biotype	protein_coding
OMIM	606212
Entrez	51547

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 18 retained_intron, 8 protein_coding, 1 nonsense_mediated_decay

ENST00000328666, ENST00000536038, ENST00000570367, ENST00000571213, ENST00000571233, ENST00000571832, ENST00000571915, ENST00000572350, ENST00000572671, ENST00000572902, ENST00000572976, ENST00000573367, ENST00000573576, ENST00000574153, ENST00000574495, ENST00000574915, ENST00000574992, ENST00000575244, ENST00000575360, ENST00000576156, ENST00000577065, ENST00000909427, ENST00000909428, ENST00000909429, ENST00000934017, ENST00000934018, ENST00000966613

RefSeq mRNA: 1 — MANE Select: NM_016538 NM_016538

CCDS: CCDS11792

Canonical transcript exons

ENST00000328666 — 10 exons

Exon	Start	End
ENSE00002677156	81918039	81918176
ENSE00003513768	81917615	81917719
ENSE00003539255	81911939	81912614
ENSE00003595953	81915611	81915681
ENSE00003609574	81914604	81914702
ENSE00003615579	81914294	81914530
ENSE00003658152	81917830	81917967
ENSE00003672123	81913774	81913880
ENSE00003680970	81915440	81915512
ENSE00003786718	81914087	81914167

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 97.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4510 / max 90.7645, expressed in 1758 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168856	9.1500	1750
168855	0.3010	128

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.14	gold quality
mucosa of transverse colon	UBERON:0004991	96.35	gold quality
granulocyte	CL:0000094	96.04	gold quality
esophagus mucosa	UBERON:0002469	95.24	gold quality
monocyte	CL:0000576	94.35	gold quality
mononuclear cell	CL:0000842	94.12	gold quality
esophagus squamous epithelium	UBERON:0006920	94.00	gold quality
leukocyte	CL:0000738	93.85	gold quality
secondary oocyte	CL:0000655	93.66	gold quality
epithelium of esophagus	UBERON:0001976	93.44	gold quality
blood	UBERON:0000178	92.81	gold quality
oocyte	CL:0000023	92.42	gold quality
pharyngeal mucosa	UBERON:0000355	92.32	gold quality
transverse colon	UBERON:0001157	91.88	gold quality
body of stomach	UBERON:0001161	91.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.50	gold quality
spleen	UBERON:0002106	90.97	gold quality
esophagus	UBERON:0001043	90.85	gold quality
skin of leg	UBERON:0001511	90.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.45	gold quality
small intestine	UBERON:0002108	90.28	gold quality
squamous epithelium	UBERON:0006914	90.27	gold quality
gingival epithelium	UBERON:0001949	90.21	gold quality
cerebellar hemisphere	UBERON:0002245	90.17	gold quality
cerebellar cortex	UBERON:0002129	90.02	gold quality
lymph node	UBERON:0000029	89.91	gold quality
skin of abdomen	UBERON:0001416	89.88	gold quality
gingiva	UBERON:0001828	89.83	gold quality
penis	UBERON:0000989	89.70	gold quality
mouth mucosa	UBERON:0003729	89.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GTF2IRD1

miRNA regulators (miRDB)

30 targeting SIRT7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-4712-5P	97.24	67.79	775
HSA-MIR-770-5P	97.24	68.10	758
HSA-MIR-411-5P	97.11	66.82	601
HSA-MIR-6729-3P	96.91	66.79	703
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-7976	95.75	65.67	1186
HSA-MIR-433-5P	94.67	64.82	99

Literature-anchored findings (GeneRIF, showing 40)

• Fluorescence in situ hybridization analysis localized the Sirt7 gene to chromosome 17q25.3; a region which is frequently affected by chromosomal alterations in acute leukemias and lymphomas. (PMID:16525639)
• SIRT7 is a positive regulator of Pol I transcription and is required for cell viability in mammals. (PMID:16618798)
• Levels of SIRT7 expression were significantly increased in breast cancer (PMID:17003781)
• SIRT7 is required for the resumption of rDNA transcription at the exit from mitosis. (PMID:19174463)
• associated with NORs during mitosis,interacts with the rDNA transcription factor UBF,phosphorylated via the CDK1-cyclin B pathway during mitosis and dephosphorylated by a phosphatase sensitive to okadaic acid at exit from mitosis (PMID:19174463)
• SIRT7 plays a crucial role in connecting the function of chromatin remodeling complexes to RNA Pol I machinery during transcription (PMID:22586326)
• work establishes SIRT7 as a highly selective H3K18Ac deacetylase and demonstrates a pivotal role for SIRT7 in chromatin regulation, cellular transformation programs and tumour formation in vivo. (PMID:22722849)
• Our findings suggest the oncogenic potential of SIRT7 in hepatocarcinogenesis. (PMID:23079745)
• Idenitifcation of the nuclear localization sequence in human SIRT7 and an association between loss of nucleolar SIRT7 and replicative senescence. (PMID:23680022)
• Knockdown of Sirt7 led to an increase in HIF-1alpha and HIF-2alpha protein levels and an increase in HIF-1 and HIF-2 transcriptional activity. (PMID:23750001)
• We propose that SIRT7 is involved in multiple pathways involved in ribosome biogenesis, and we hypothesize that its down-regulation may contribute to an antitumor effect, partly through the inhibition of protein synthesis. (PMID:24113281)
• The results identify a nonhistone target of SIRT7 and uncover an RNA-mediated mechanism that adapts nucleolar transcription to stress signaling (PMID:24207024)
• Study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease. (PMID:24210820)
• These findings place SIRT7 at the crossroads of chromatin signaling, metabolic, and tumor-regulatory pathways. Thus, SIRT7 is a promising pharmacologic target for epigenetic cancer therapy. (PMID:24536059)
• Our findings suggest that Sirt7 plays an important role in the development and progression of human colorectal cancer and functions as a valuable marker of colorectal cancer prognosis. (PMID:24771643)
• Interactions of two highly acetylated proteins, nucleophosmin (NPM1) and nucleolin, with SIRT6 and SIRT7 were confirmed by co-immunoprecipitation. (PMID:24782448)
• stress-induced Sirt7 inhibition significantly increases stress resistance and modulates insulin/IGF-1 signaling pathways. (PMID:24885964)
• High Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response in osteosarcoma. (PMID:25445786)
• In the cancer group, the expression level of SIRT6 and SIRT7 were significantly up-regulated and are potential circulating prognostic markers for head and neck squamous cell carcinoma. (PMID:25503141)
• SIRT7 expression was reduced in aged hematopoietic stem cells (HSCs), and SIRT7 up-regulation improved the regenerative capacity of aged HSCs. (PMID:25792330)
• SIRT1 inhibition caused cell death, while SIRT2 inhibition resulted in cell cycle arrest. In conclusion, we report the overexpression of SIRT2 and SIRT7 proteins in cervical cancer (PMID:25794641)
• SIRT7 might play a role of oncogene in ovarian malignancy. Down-regulation of SIRT7 significantly reduced ovarian cancer cell growth, repressed colony formation and increased cancer cell apoptosis; up-regulation promoted the migration of cancer cells. (PMID:25921180)
• Sirt7 expression was implicated with high histological grade and independently predicted poor clinical outcome in patients with breast cancer, suggesting that Sirt7 might play a role in the malignant progression of breast cancer. (PMID:25973086)
• SIRT3 and SIRT7 possess tumour suppressor properties in the context of pancreatic cancer. (PMID:26121130)
• Novel interactions of TPPII, p53, and SIRT7 presented in this study might contribute to the knowledge of the regulatory effects of these proteins on apoptotic pathways and to the understanding mechanisms of aging and lifespan regulation. (PMID:26169984)
• SIRT7 trans-represses RPS7 gene in the presence of HBx protein.HBx enhances intracellular stability of SIRT7 protein. (PMID:26442981)
• Data indicate that compared to non-neoplastic endometria (NNE), endometrial cancer (EC) showed SIRT7 mRNA overexpression, whereas SIRT1, SIRT2, SIRT4 and SIRT5 were underexpressed, and no significant differences were observed for SIRT3 and SIRT6. (PMID:26701732)
• this is the first report on the regulation mechanism of SIRT7 gene, in which, HDAC3 collaborated with C/EBPalpha to occupy its responding element in the upstream region of SIRT7 gene and repressed its expression in human cells. (PMID:26704017)
• SIRT7 deacetylates U3-55k, enhancing U3-55k binding to U3 snoRNA, which is a prerequisite for pre-rRNA processing. (PMID:26867678)
• This study showed that SIRT7 can be activated by DNA to hydrolyze the acetyl group from lysine residues in vitro on histone peptides and histones in the chromatin context. (PMID:26907567)
• miR-152/SIRT7 axis plays a key role in the regulation of Human dental pulp stem cell senescence. (PMID:26991832)
• SIRT7-catalysed histone H3 lysine122 desuccinylation is critically implemented in DNA-damage response and cell survival. (PMID:27436229)
• We found a negative correlation between mRNA levels of SIRT1 in VAT of obese individuals and SIRT7 in VAT of the normal-weight subjects and expression of the relevant miRNAs. (PMID:27480132)
• our study suggests that SIRT7 functions as an oncogene in non-small cell lung cancer (NSCLC), and miR-3666 can target SIRT7 to inhibit NSCLC cell growth by promoting the pro-apoptotic signaling pathway (PMID:27599551)
• Energy stress strengthens SIRT7-mediated effects on Akt dephosphorylation. (PMID:28147277)
• the decline in SIRT7 in lung fibroblasts has a profibrotic effect, which is mediated by changes in Smad3 levels. (PMID:28385812)
• Authors evaluated the expression of known targets of miR-125a and found that sirtuin-7, matrix metalloproteinase-11, and c-Raf were up-regulated in tumor tissue by 2.2-, 3-, and 1.7-fold, respectively. Overall, these data support a tumor suppressor role for miR-125a. (PMID:28445974)
• SIRT7 inhibits TR4 degradation by deacetylation of DDB1. (PMID:28623141)
• Data suggest that SIRT7 undergoes Lys-63 polyubiquitination, later removed by USP7 to repress enzymatic activity of SIRT7; USP7 and SIRT7 regulate gluconeogenesis via expression of glucose-6-phosphatase catalytic subunit (G6PC); SIRT7 targets G6PC promoter through ELK4. (SIRT7 = sirtuin 7; USP7 = ubiquitin specific peptidase 7; G6PC = glucose-6-phosphatase catalytic subunit; ELK4 = transcription factor ELK4) (PMID:28655758)
• Knockdown of SIRT7 leads to the same phenotype as depletion of DDX21 (i.e., increased formation of R loops and DNA double-strand breaks), indicating that SIRT7 and DDX21 cooperate to prevent R-loop accumulation, thus safeguarding genome integrity. (PMID:28790157)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sirt7	ENSDARG00000060645
mus_musculus	Sirt7	ENSMUSG00000025138
rattus_norvegicus	Sirt7	ENSRNOG00000036683
drosophila_melanogaster	Sirt7	FBGN0039631

Paralogs (6): SIRT2 (ENSG00000068903), SIRT6 (ENSG00000077463), SIRT4 (ENSG00000089163), SIRT1 (ENSG00000096717), SIRT5 (ENSG00000124523), SIRT3 (ENSG00000142082)

Protein

Protein identifiers

NAD-dependent protein deacetylase sirtuin-7 — Q9NRC8 (reviewed: Q9NRC8)

Alternative names: NAD-dependent protein deacylase sirtuin-7, Regulatory protein SIR2 homolog 7, SIR2-like protein 7

All UniProt accessions (3): Q9NRC8, I3L2A4, I3L480

UniProt curated annotations — full annotation on UniProt →

Function. NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase, deglutarylase and dedecanoylase), depending on the context. Specifically mediates deacetylation of histone H3 at ‘Lys-18’ (H3K18Ac). In contrast to other histone deacetylases, displays strong preference for a specific histone mark, H3K18Ac, directly linked to control of gene expression. 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. Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells. Also able to mediate deacetylation of histone H3 at ‘Lys-36’ (H3K36Ac) in the context of nucleosomes. Also mediates deacetylation of non-histone proteins, such as ATM, CDK9, DDX21, DDB1, FBL, FKBP5/FKBP51, GABPB1, RAN, RRP9/U3-55K and POLR1E/PAF53. 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. In response to metabolic stress, SIRT7 is released from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased RNA polymerase I transcription. 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. 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. 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). 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. Deacetylates FBL, promoting histone-glutamine methyltransferase activity of FBL. Acts as a regulator of mitochondrial function by catalyzing deacetylation of GABPB1. Regulates Akt/AKT1 activity by mediating deacetylation of FKBP5/FKBP51. 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. In addition to protein deacetylase activity, also acts as a protein-lysine deacylase. 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. 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. 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.

Subunit / interactions. Interacts with UBTF and the RNA polymerase I complex. Interacts with components of the B-WICH complex, such as MYBBP1A, SMARCA5/SNF2H and BAZ1B/WSTF. Interacts with ELK4, leading to stabilization at target promoters for H3K18Ac deacetylation. Interacts with histone H2A and/or histone H2B. Interacts with DNMT1. Interacts with SIRT1.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Chromosome. Cytoplasm.

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. Deubiquitinated by USP7, inhibiting the H3K18Ac histone deacetylase activity and regulating gluconeogenesis. Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO7; leading to proteasomal degradation.

Activity regulation. NAD-dependent protein-lysine deacetylase and deacylase activities are activated by nucleic acids. Histone deacetylase activity is activated by DNA and nucleosomes. Protein-lysine deacylase activity is activated by RNA. H3K18Ac histone deacetylase activity is inhibited by methylation at Arg-388. H3K18Ac histone deacetylase activity is inhibited by deubiquitination by USP7.

Cofactor. Binds 1 zinc ion per subunit.

Induction. Overexpressed in thyroid carcinoma cell lines and tissues, but not in adenomas.

Similarity. Belongs to the sirtuin family. Class IV subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NRC8-1	1	yes
Q9NRC8-2	2
Q9NRC8-3	3

RefSeq proteins (1): NP_057622* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003000	Sirtuin	Family
IPR026590	Ssirtuin_cat_dom	Domain
IPR029035	DHS-like_NAD/FAD-binding_dom	Homologous_superfamily
IPR050134	NAD-dep_sirtuin_deacylases	Family

Pfam: PF02146

Catalyzed reactions (Rhea), 5 shown:

• N(6)-propanoyl-L-lysyl-[protein] + NAD(+) + H2O = 3’’-O-propanoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:23500)
• N(6)-acetyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-acetyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:43636)
• N(6)-glutaryl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-glutaryl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:47664)
• N(6)-succinyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-succinyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:47668)
• N(6)-decanoyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-decanoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:70631)

UniProt features (58 total): helix 14, strand 11, binding site 9, turn 6, splice variant 4, mutagenesis site 4, modified residue 2, region of interest 2, sequence conflict 2, chain 1, domain 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6G0S	X-RAY DIFFRACTION	1.48
5IQZ	X-RAY DIFFRACTION	2.33
9GMR	ELECTRON MICROSCOPY	2.8
9GMK	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRC8-F1	88.38	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 187 (proton acceptor)

Ligand- & substrate-binding residues (9): 225; 228; 268–270; 297–299; 315; 107–126; 167–170; 195; 198

Post-translational modifications (2): 388, 388

Mutagenesis-validated functional residues (4):

Position	Phenotype
111	catalytically inactive mutant; abolishes activation of pre-rrna synthesis. abolishes deacetylation of ddb1. abolished hi
187	abolishes deacylase and deacetylase activities and activation of pre-rrna synthesis. abolished histone desuccinylase act
388	mimics methylation status; impaired histone deacetylase activity.
388	decreased methylation; does not affect histone deacetylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 247 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, PID_HDAC_CLASSI_PATHWAY, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MACROMOLECULE_DEACYLATION, GOBP_REGULATION_OF_PROTEIN_EXPORT_FROM_NUCLEUS, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_RRNA_TRANSCRIPTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NUCLEAR_TRANSPORT, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (29): negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast differentiation (GO:0001649), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), regulation of transcription by RNA polymerase II (GO:0006357), protein deacetylation (GO:0006476), DNA damage response (GO:0006974), homologous chromosome pairing at meiosis (GO:0007129), rRNA transcription (GO:0009303), transposable element silencing (GO:0010526), regulation of mitochondrion organization (GO:0010821), negative regulation of protein ubiquitination (GO:0031397), positive regulation of gluconeogenesis (GO:0045722), negative regulation of gene expression, epigenetic (GO:0045814), transcription initiation-coupled chromatin remodeling (GO:0045815), positive regulation of transcription by RNA polymerase I (GO:0045943), regulation of protein export from nucleus (GO:0046825), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), protein deglutarylation (GO:0061698), R-loop processing (GO:0062176), protein depropionylation (GO:0106230), DNA repair-dependent chromatin remodeling (GO:0140861), regulation of transcription of nucleolar large rRNA by RNA polymerase I (GO:1901836), positive regulation of rRNA processing (GO:2000234), regulation of gluconeogenesis (GO:0006111), chromatin organization (GO:0006325), epigenetic regulation of gene expression (GO:0040029), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), regulation of macromolecule metabolic process (GO:0060255)

GO Molecular Function (12): chromatin binding (GO:0003682), protein methyltransferase activity (GO:0008276), hydrolase activity (GO:0016787), NAD-dependent protein lysine deacetylase activity (GO:0034979), protein-succinyllysine desuccinylase activity (GO:0036055), metal ion binding (GO:0046872), protein-glutaryllysine deglutarylase activity (GO:0061697), NAD+ binding (GO:0070403), histone H3K18 deacetylase activity, NAD-dependent (GO:0097372), NAD-dependent protein-lysine depropionylase activity (GO:0106231), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), nucleolus organizer region (GO:0005731), cytoplasm (GO:0005737), nuclear speck (GO:0016607), site of double-strand break (GO:0035861), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
NAD-dependent protein lysine deacylase activity	4
cellular anatomical structure	3
transcription by RNA polymerase II	2
protein deacylation	2
negative regulation of gene expression	2
binding	2
catalytic activity	2
nuclear lumen	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
ossification	1
cell differentiation	1
DNA metabolic process	1
DNA damage response	1
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
regulation of DNA-templated transcription	1
cellular response to stress	1
homologous chromosome segregation	1
chromosome organization involved in meiotic cell cycle	1
DNA-templated transcription	1
rRNA metabolic process	1
retrotransposition	1
mitochondrion organization	1
regulation of organelle organization	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
gluconeogenesis	1
regulation of gluconeogenesis	1
positive regulation of biosynthetic process	1
positive regulation of glucose metabolic process	1
epigenetic regulation of gene expression	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
regulation of transcription by RNA polymerase I	1
transcription by RNA polymerase I	1
positive regulation of DNA-templated transcription	1

Protein interactions and networks

STRING

2082 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIRT7	POLI	Q9UNA4	955
SIRT7	TP53	P04637	904
SIRT7	UBTF	P17480	903
SIRT7	EPAS1	Q99814	893
SIRT7	HIF1A	Q16665	858
SIRT7	MYBBP1A	Q9BQG0	784
SIRT7	MYC	P01106	778
SIRT7	SIRT1	Q96EB6	770
SIRT7	HDAC11	Q96DB2	745
SIRT7	DDX21	Q9NR30	729
SIRT7	DDX56	Q9NY93	720
SIRT7	SMARCA5	O60264	688
SIRT7	NRF1	Q16656	679
SIRT7	CDK2	P24941	664
SIRT7	ANKRD52	Q8NB46	653

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CBX1	KPNA3	psi-mi:“MI:0914”(association)	0.530
SIRT7	ELK4	psi-mi:“MI:0915”(physical association)	0.520
SIRT7	NRF1	psi-mi:“MI:0915”(physical association)	0.520
SIRT7		psi-mi:“MI:0197”(deacetylation reaction)	0.440
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SERF2	WDR46	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
RPS8		psi-mi:“MI:0914”(association)	0.350
MAGED1	SIRT7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (820): SIRT7 (Affinity Capture-MS), SIRT7 (Affinity Capture-MS), SIRT7 (Affinity Capture-MS), SIRT7 (Affinity Capture-MS), SIRT7 (Affinity Capture-MS), SIRT7 (Affinity Capture-Western), USP7 (Affinity Capture-MS), XRCC6 (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), SIRT1 (Affinity Capture-MS), DDB1 (Affinity Capture-MS), HERC5 (Affinity Capture-MS), PSME2 (Affinity Capture-MS), CDK9 (Affinity Capture-MS), USP7 (Affinity Capture-Western)

ESM2 similar proteins: A0A0J9UVG7, A0A250YGJ5, A0A2K5TU92, A8NWP2, A9UVV1, B0X4N8, B2RZ55, C8V3W5, E1BRE2, E2RDZ6, E9GD30, F4P804, F7DKV7, F7EZ75, J4W6X9, P16081, P17571, P22944, P27967, P27968, P27969, P36842, P38681, P43100, P49102, P59941, Q0P595, Q0UI56, Q1JQC6, Q3ZBQ0, Q4PEJ3, Q5AW69, Q5HZN8, Q5R6G3, Q5RBF1, Q5RJQ4, Q68FX9, Q6DHI5, Q7ZVK3, Q8BKJ9

Diamond homologs: A0A0J9UVG7, A0A250YGJ5, A0A2K5TU92, A8MBU4, B2RZ55, B5YJW3, B8ARK7, O07595, O28597, O58669, O67919, P59941, Q0P595, Q4JBN2, Q5JG47, Q5L014, Q6A5T5, Q6MJJ2, Q6N6U0, Q72IV5, Q73KE1, Q7XWV4, Q899G3, Q89LY4, Q8BKJ9, Q8ELR0, Q8N6T7, Q8R104, Q8R984, Q8R9N6, Q8TWG0, Q8U1Q1, Q8XNS6, Q8ZT00, Q8ZU41, Q95Q89, Q974M6, Q97VX5, Q9FE17, Q9I7I7

SIGNOR signaling

34 interactions.

A	Effect	B	Mechanism
SIRT7	down-regulates	TP53	deacetylation
SIRT7	“up-regulates activity”	SAR1A	deacetylation
SIRT7	“down-regulates activity”	RAN	deacetylation
PRKAA1	“down-regulates quantity by destabilization”	SIRT7	phosphorylation
AMPK	“down-regulates quantity by destabilization”	SIRT7	phosphorylation
PSME3	“down-regulates quantity by destabilization”	SIRT7	binding
SIRT7	“up-regulates activity”	H3-4	deacetylation
SIRT7	“up-regulates activity”	H3-2	deacetylation
SIRT7	“up-regulates activity”	H3-3A	deacetylation
SIRT7	“up-regulates activity”	H3-5	deacetylation
SIRT7	“up-regulates activity”	H3C1	deacetylation
SIRT7	“up-regulates activity”	H3C15	deacetylation
PRMT6	“down-regulates activity”	SIRT7	methylation
SIRT7	“down-regulates activity”	ATM	deacetylation
SIRT7	“up-regulates activity”	FBL	deacetylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

57 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1578 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81913769:CTCA:C	donor_gain	1.0000
17:81913770:TCA:T	donor_loss	1.0000
17:81913771:CA:C	donor_loss	1.0000
17:81913772:A:AC	donor_gain	1.0000
17:81913773:C:CC	donor_gain	1.0000
17:81913773:C:CG	donor_loss	1.0000
17:81913773:CCTG:C	donor_gain	1.0000
17:81913876:GTCCA:G	acceptor_gain	1.0000
17:81913877:TCCA:T	acceptor_gain	1.0000
17:81913878:CCA:C	acceptor_gain	1.0000
17:81913878:CCAC:C	acceptor_gain	1.0000
17:81913879:C:CT	acceptor_gain	1.0000
17:81913879:C:T	acceptor_gain	1.0000
17:81913879:CA:C	acceptor_gain	1.0000
17:81913881:C:CC	acceptor_gain	1.0000
17:81913888:C:CT	acceptor_gain	1.0000
17:81914082:GTTA:G	donor_loss	1.0000
17:81914083:TTACC:T	donor_loss	1.0000
17:81914084:TA:T	donor_loss	1.0000
17:81914085:A:AG	donor_loss	1.0000
17:81914086:CC:C	donor_loss	1.0000
17:81914164:GAAC:G	acceptor_gain	1.0000
17:81914165:AACC:A	acceptor_loss	1.0000
17:81914167:CCTG:C	acceptor_loss	1.0000
17:81914168:C:CC	acceptor_gain	1.0000
17:81914177:C:CT	acceptor_gain	1.0000
17:81914289:CGTA:C	donor_loss	1.0000
17:81914290:GTAC:G	donor_loss	1.0000
17:81914291:TACCT:T	donor_loss	1.0000
17:81914293:C:CA	donor_loss	1.0000

AlphaMissense

2571 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:81914393:A:C	F239L	1.000
17:81914393:A:T	F239L	1.000
17:81914395:A:G	F239L	1.000
17:81914616:G:C	N189K	1.000
17:81914616:G:T	N189K	1.000
17:81914620:C:A	G188V	1.000
17:81914620:C:T	G188E	1.000
17:81914621:C:A	G188W	1.000
17:81914624:G:C	H187D	1.000
17:81914674:T:A	D170V	1.000
17:81914679:G:C	N168K	1.000
17:81914679:G:T	N168K	1.000
17:81917618:G:C	S111R	1.000
17:81917618:G:T	S111R	1.000
17:81917620:T:G	S111R	1.000
17:81913833:A:C	C315W	0.999
17:81914093:G:C	N297K	0.999
17:81914093:G:T	N297K	0.999
17:81914307:C:T	G268E	0.999
17:81914308:C:A	G268W	0.999
17:81914312:A:C	C266W	0.999
17:81914314:A:G	C266R	0.999
17:81914395:A:T	F239I	0.999
17:81914403:A:T	I236N	0.999
17:81914409:T:A	D234V	0.999
17:81914409:T:G	D234A	0.999
17:81914410:C:G	D234H	0.999
17:81914455:G:C	H219D	0.999
17:81914486:G:C	F208L	0.999
17:81914486:G:T	F208L	0.999

dbSNP variants (sampled 300 via entrez): RS1000041849 (17:81919917 A>G), RS1000738479 (17:81911673 C>T), RS1001332798 (17:81916018 A>G), RS1001389602 (17:81915908 C>T), RS1002716626 (17:81916761 A>C,T), RS1003499393 (17:81917374 A>C), RS1003617104 (17:81913063 G>A), RS1004022827 (17:81912210 T>A), RS1004058397 (17:81915031 C>A,G,T), RS1004058543 (17:81917078 G>A), RS1005172379 (17:81918890 C>A,T), RS1005609279 (17:81912020 T>C,G), RS1005624018 (17:81912654 C>A,T), RS1005956050 (17:81911773 C>G), RS1006008425 (17:81911661 C>A,G,T)

Disease associations

OMIM: gene MIM:606212 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2163184 (SINGLE PROTEIN), CHEMBL5465223 (PROTEIN-PROTEIN INTERACTION)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 3.5.1.- Histone deacetylases (HDACs)

Binding affinities (BindingDB)

3 measured of 4 human assays (4 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
phenyl N-[1-anilino-6-(heptanethioylamino)-1-oxohexan-2-yl]carbamate	IC50	310 nM	US-9359293: Methods of treatment using modulators of SIRT2
phenyl N-[1-anilino-6-(butanethioylamino)-1-oxohexan-2-yl]carbamate	IC50	2400 nM	US-9359293: Methods of treatment using modulators of SIRT2
phenyl N-[1-anilino-6-(ethanethioylamino)-1-oxohexan-2-yl]carbamate	IC50	30000 nM	US-9359293: Methods of treatment using modulators of SIRT2

ChEMBL bioactivities

2 potent at pChembl≥5 of 5 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.49	IC50	325	nM	CHEMBL5723348
5.30	IC50	5000	nM	CHEMBL4438364

PubChem BioAssay actives

1 with measured affinity, of 99 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S,6S,23S)-6-[3-(diaminomethylideneamino)propyl]-3-[6-(dodecylamino)-6-oxohexyl]-2,5,8,11,14,17-hexaoxo-1,4,7,10,15,18-hexazacyclotricosane-23-carboxamide	1575165: Inhibition of tRNA-activated deacetylation activity of recombinant human full length N-terminal His6-tagged SIRT7 expressed in Escherichia coli using H2N-GGKAPR-[Nepsilon-acetyl-lysine]-QLATKA-CONH2 as substrate measured after 30 mins by HPLC analysis	ic50	5.0000	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Ozone	affects expression, affects cotreatment, decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	increases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases expression	1
cobaltous chloride	increases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
norcantharidin	increases phosphorylation, affects cotreatment, affects localization, decreases expression, increases reaction (+3 more)	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Atrazine	decreases expression	1
Curcumin	decreases expression	1
Quercetin	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	decreases reaction, increases expression, increases phosphorylation, increases splicing	1
Cyclosporine	increases expression	1
Paclitaxel	decreases reaction, increases cleavage, increases expression, increases phosphorylation, affects cotreatment (+3 more)	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

17 unique, capped per target: 15 binding, 1 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2166866	Binding	Activity of recombinant human SIRT7 assessed as deacylation of compound at 50 uM after 1 hr by trypsin developer-based fluorescence assay	Substrates for efficient fluorometric screening employing the NAD-dependent sirtuin 5 lysine deacylase (KDAC) enzyme. — J Med Chem
CHEMBL4683753	ADMET	Inhibition of SIRT7 (unknown origin) at 10 uM relative to control	Design, synthesis and biological evaluation of novel TRβ selective agonists sustained by ADME-toxicity analysis. — Eur J Med Chem
CHEMBL5723284	Functional	Affinity Biochemical interaction: (inhibition of deacetylase activity, luminescence measurement using the SIRT7 assay kit) EUB0002717a SIRT7	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8PH	Abcam HCT 116 SIRT7 KO	Cancer cell line	Male
CVCL_B9RW	Abcam A-549 SIRT7 KO	Cancer cell line	Male
CVCL_D8AC	Ubigene A-549 SIRT7 KO	Cancer cell line	Male
CVCL_E0TF	Ubigene HeLaS3 SIRT7 KO	Cancer cell line	Female
CVCL_E1EQ	Ubigene U-87 MG SIRT7 KO	Cancer cell line	Male
CVCL_TL37	HAP1 SIRT7 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.