SIRT2

Summary

SIRT2 (sirtuin 2, HGNC:10886) is a protein-coding gene on chromosome 19q13.2, encoding NAD-dependent protein deacetylase sirtuin-2 (Q8IXJ6). NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors.

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 I of the sirtuin family. Several transcript variants are resulted from alternative splicing of this gene.

Source: NCBI Gene 22933 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 88 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_012237

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10886
Approved symbol	SIRT2
Name	sirtuin 2
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000068903
Ensembl biotype	protein_coding
OMIM	604480
Entrez	22933

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 17 protein_coding, 5 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000249396, ENST00000358931, ENST00000381766, ENST00000392081, ENST00000407552, ENST00000414941, ENST00000420440, ENST00000423526, ENST00000437828, ENST00000443898, ENST00000447739, ENST00000451193, ENST00000462654, ENST00000476771, ENST00000479290, ENST00000481381, ENST00000491960, ENST00000496069, ENST00000851047, ENST00000872145, ENST00000872146, ENST00000872147, ENST00000872148, ENST00000872149, ENST00000872150, ENST00000872151, ENST00000941836, ENST00000941837

RefSeq mRNA: 3 — MANE Select: NM_012237 NM_001193286, NM_012237, NM_030593

CCDS: CCDS12523, CCDS46069, CCDS74361

Canonical transcript exons

ENST00000249396 — 16 exons

Exon	Start	End
ENSE00003458681	38883627	38883756
ENSE00003469686	38881432	38881491
ENSE00003499260	38879632	38879702
ENSE00003504070	38889689	38889745
ENSE00003505616	38889855	38889961
ENSE00003505833	38879434	38879500
ENSE00003508533	38881100	38881155
ENSE00003581685	38898379	38898425
ENSE00003586993	38899506	38899618
ENSE00003595239	38893414	38893527
ENSE00003633158	38893819	38893867
ENSE00003663776	38880685	38880736
ENSE00003686465	38890103	38890144
ENSE00003784271	38880821	38880897
ENSE00003791197	38889087	38889155
ENSE00003846341	38878560	38879310

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.1900 / max 866.2557, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180826	33.1668	1813
180825	8.4396	1667
180827	0.9615	638
180824	0.3900	172
180828	0.2321	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.79	gold quality
gastrocnemius	UBERON:0001388	98.57	gold quality
muscle of leg	UBERON:0001383	98.13	gold quality
right frontal lobe	UBERON:0002810	97.96	gold quality
spinal cord	UBERON:0002240	97.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.85	gold quality
anterior cingulate cortex	UBERON:0009835	97.64	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.28	gold quality
hypothalamus	UBERON:0001898	97.19	gold quality
cerebellar hemisphere	UBERON:0002245	96.98	gold quality
amygdala	UBERON:0001876	96.93	gold quality
cerebellar cortex	UBERON:0002129	96.91	gold quality
tibial nerve	UBERON:0001323	96.59	gold quality
apex of heart	UBERON:0002098	96.56	gold quality
prefrontal cortex	UBERON:0000451	96.54	gold quality
putamen	UBERON:0001874	96.48	gold quality
granulocyte	CL:0000094	96.10	gold quality
right testis	UBERON:0004534	95.93	gold quality
nucleus accumbens	UBERON:0001882	95.91	gold quality
left testis	UBERON:0004533	95.91	gold quality
cerebellum	UBERON:0002037	95.53	gold quality
left ovary	UBERON:0002119	95.38	gold quality
right ovary	UBERON:0002118	95.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.18	gold quality
lower esophagus	UBERON:0013473	95.17	gold quality
caudate nucleus	UBERON:0001873	95.16	gold quality
right atrium auricular region	UBERON:0006631	95.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.00	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.25
E-GEOD-93593	yes	5.13
E-CURD-97	no	315.09
E-GEOD-99795	no	56.82

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
AFP	Activation
CDKN1A	Repression
NEDD4	Repression

Upstream regulators (CollecTRI, top): ATF4, DDIT3, FOXO3, MYC, MYCN, NKX2-2, PLP1

miRNA regulators (miRDB)

50 targeting SIRT2, 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-4283	100.00	66.42	2097
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-4757-5P	99.12	64.51	981

Literature-anchored findings (GeneRIF, showing 40)

• Enzymatic analysis of recombinant SIRT2 in comparison to a yeast homolog of Sir2 protein (Hst2p) shows a striking preference of SIRT2 for acetylated tubulin peptide as a substrate relative to acetylated histone H3 peptide. (PMID:12620231)
• SIRT2 is phosphorylated late in G(2), during M, and into the period of cytokinesis. CDC14B may provoke exit from mitosis coincident with the loss of SIRT2 via ubiquitination and subsequent degradation by the 26S proteasome. (PMID:12697818)
• To inhibit myogenesis, Sir2 requires its NAD(+)-dependent deacetylase activity. Cells with reduced Sir2 levels are less sensitive to the inhibition imposed by an elevated [NAD(+)]/[NADH] ratio. (PMID:12887892)
• SIRT2 gene expression is down-regulated in gliomas. (PMID:12963026)
• Results show for the first time that SIRT2 interacts with the homeobox transcription factor, HOXA10. (PMID:15213244)
• SIRT2 can discriminate among various monoacetylated histone H3 and H4 peptide substrates of NAD+-dependent histone/protein deacetylase, as well as display differences in catalytic efficiency. (PMID:15274642)
• Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast (PMID:15328540)
• the absence of SIRT2, a potential tumor suppressor, could play a key role in the regulation of the cell-cycle within a multistep pathway that leads to full cellular transformation and, finally, the development of cellular malignancy (PMID:16211212)
• a SIR2 reaction metabolite modulates TRPM2 ion channel (PMID:16565078)
• SirT2 and its yeast counterpart Hst2 have a strong preference for histone H4K16Ac in their deacetylation activity in vitro and in vivo. (PMID:16648462)
• Expressed SIRT2 blocks the entry to chromosome condensation and subsequent hyperploid cell formation in glioma cell lines. (PMID:16909107)
• Mutations in SIRT2 deacetylase which regulate enzymatic activity but not its interaction with HDAC6 and tubulin (PMID:17516032)
• Human silent information regulator 2 NAD (+)-dependent protein deacetylase, SIRT2, protect against alpha-synuclein-mediated toxicity in cellular models of Parkinson’s disease. [SIRT2] (PMID:17708669)
• a novel mechanism of regulating SIRT2 function by nucleo-cytoplasmic shuttling, as well as a role for SIRT2 in the nucleus during interphase and throughout mitosis (PMID:17726514)
• reviewe emerging role of SIR2 as regulators of metabolism (PMID:18249170)
• Therefore, our results suggest that the interaction between Sirt2 and 14-3-3 beta/gamma is a novel mechanism for the negative regulation of p53 beside the well-characterized Mdm2-mediated repression. (PMID:18249187)
• Collectively, our findings identify a posttranslational mechanism that controls SIRT2 function, and they provide evidence for a novel regulatory circuitry involving Cdks, SIRT2, and microtubules. (PMID:18332217)
• These observations demonstrate that p300 can inactivate Sirt2 by acetylation and that p300 may regulate the activity of p53 indirectly through Sirt2 in addition to its direct modification of p53. (PMID:18722353)
• p300 undergoes a dynamic cycle of autoacetylation and deacetylation regulated by SIRT2. (PMID:18995842)
• The effects of SIRT2 downregulation on sensitivity to microtubule inhibitors using HCT116 cells, was investigated. (PMID:19282667)
• identified a common GXG signature nucleotide-binding site shared by the gamma-secretase subunit presenilin-1 C-terminal fragment (PS1-CTF), SIRT2, and Janus kinase 3 (PMID:20237298)
• SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis in a model of Huntington’s disease. (PMID:20378838)
• In response to stress, FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2), a NAD(+)-dependent histone deacetylase, and the acetylated FoxO1 bound to Atg7. (PMID:20543840)
• This study has replicated associations to chronic obstructive pulmonary disease phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings. (PMID:20562129)
• SIRT2 inhibition rescues alpha-synuclein (SYN)-mediated oligodendroglial apoptotic cell death accompanied by increased number of intracellular inclusions in a model of multiple system atrophy (PMID:20849899)
• This study suggested that altered SIRT1, 2 and 6 expression is state-dependent and might be associated with the pathogenesis and/or pathophysiology of mood disorders. (PMID:21349544)
• By using SIRT2-specific siRNA combined with tubacin treatment, the cell migratory and invasive abilities were dramatically suppressed. (PMID:22089141)
• SIRT2 activity plays a key role in maintaining the survival of glioma cells; reduced SIRT2 activity can induce both necrosis and caspase-3-dependent apoptosis of C6 glioma cells. (PMID:22166219)
• visceral adipose tissue from human obese subjects is characterized by high levels of HIF1alpha and low levels of SIRT2 (PMID:22302938)
• The study found some evidence of an association between SIRT2 rs10410544 T allele and increased risk of Alzheimer’s disease in patients who did not carry the APOE epsilon4 gene. (PMID:22651940)
• SIRT2-nuclear localization was indicative of glioma malignancy, and it may be predictive of glioblastoma patient survival. (PMID:22735931)
• SIRT2 is upregulated in postmortem amyotrophic lateral sclerosis tissue and is associated with toxicity to neural cells. (PMID:22796962)
• report that SIRT2 increases protein accumulation in murine cholinergic SN56 cells and human neuroblastoma SH-SY5Y cells under proteasome inhibition (PMID:22819792)
• SIRT2 gene polymorphisms were associated with height in healthy, elderly Japanese subjects (PMID:22857867)
• It may be SIRT2 rather than HADAC6 that is responsible for tumour occurrence and the progression of prostate cancer. (PMID:22944623)
• SIRT2 repressed NEDD4 gene expression by directly binding to the NEDD4 gene core promoter and deacetylating histone H4 lysine 16. (PMID:23175188)
• Suppression of SIRT2 expression in hepatocellular carcinoma cell lines revealed significant inhibition of motility and invasiveness. (PMID:23348706)
• K8 acetylation at Lys-207, a highly conserved residue among type II keratins, is up-regulated upon hyperglycemia and down-regulated by SIRT2. (PMID:23358244)
• These findings from this study provide insights to elucidate the binding pattern of SIRT2 inhibitors and help in the rational structure-based design of novel SIRT2 inhibitors with improved potency and better resistance profile. (PMID:23382805)
• Modulation of p53 C-terminal acetylation by mdm2, p14ARF, and cytoplasmic SirT2. (PMID:23416275)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sirt2	ENSDARG00000011488
mus_musculus	Sirt2	ENSMUSG00000015149
rattus_norvegicus	Sirt2	ENSRNOG00000020102
drosophila_melanogaster	Sirt2	FBGN0038788

Paralogs (6): SIRT6 (ENSG00000077463), SIRT4 (ENSG00000089163), SIRT1 (ENSG00000096717), SIRT5 (ENSG00000124523), SIRT3 (ENSG00000142082), SIRT7 (ENSG00000187531)

Protein

Protein identifiers

NAD-dependent protein deacetylase sirtuin-2 — Q8IXJ6 (reviewed: Q8IXJ6)

Alternative names: NAD-dependent protein deacylase sirtuin-2, NAD-dependent protein defatty-acylase sirtuin-2, Regulatory protein SIR2 homolog 2, SIR2-like protein 2

All UniProt accessions (11): Q8IXJ6, A0A0A0MRF5, B5MCS1, C9J3U7, C9JR33, C9JZQ0, E7EWX6, F8WBT6, F8WCF4, F8WDM4, F8WF57

UniProt curated annotations — full annotation on UniProt →

Function. NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 ‘Lys-20’ methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at ‘Lys-16’ (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response. Also deacetylates histone H3 at ‘Lys-57’ (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates ‘Lys-18’ of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection. During oocyte meiosis progression, may deacetylate histone H4 at ‘Lys-16’ (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates histone H4 at ‘Lys-16’ (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis. Deacetylates alpha-tubulin at ‘Lys-40’ and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy. Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation. Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Also deacetylates EIF5A. In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of N(6)-benzoyl (benzoyl) and N(6)-methacryl (methacryl) acyl groups from lysine residues, leading to histone debenzoylation and demethacrylation, respectively. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor. In addition to protein deacetylase activity, also has activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as ARF6 and KRAS, thereby regulating their association with membranes. Deacetylates EP300, alpha-tubulin and histone H3 and H4. Deacetylates EP300, alpha-tubulin and histone H3 and H4. Lacks deacetylation activity, at least toward known SIRT2 targets.

Subunit / interactions. Interacts with CDC20, FOXO3 and FZR1. Associates with microtubules in primary cortical mature neurons. Homotrimer. Isoform 1 and isoform 2 interact (via both phosphorylated, unphosphorylated, active or inactive forms) with HDAC6; the interaction is necessary for the complex to interact with alpha-tubulin, suggesting that these proteins belong to a large complex that deacetylates the cytoskeleton. Interacts with FOXO1; the interaction is disrupted upon serum-starvation or oxidative stress, leading to increased level of acetylated FOXO1 and induction of autophagy. Interacts with RELA; the interaction occurs in the cytoplasm and is increased in a TNF-dependent manner. Interacts with HOXA10; the interaction is direct. Interacts with YWHAB and YWHAG; the interactions occur in a AKT-dependent manner and increase SIRT2-dependent TP53 deacetylation. Interacts with MAPK1/ERK2 and MAPK3/ERK1; the interactions increase SIRT2 stability and deacetylation activity. Interacts (phosphorylated form) with KMT5A isoform 2; the interaction is direct, stimulates KMT5A-mediated methyltransferase activity on histone at ‘Lys-20’ (H4K20me1) and is increased in a H(2)O(2)-induced oxidative stress-dependent manner. Interacts with G6PD; the interaction is enhanced by H(2)O(2) treatment. Interacts with a G1/S-specific cyclin E-CDK2 complex. Interacts with AURKA, CDK5R1 (p35 form) and CDK5 and HIF1A. Isoform 1, isoform 2 and isoform 5 interact (via C-terminus region) with EP300. Interacts with the tRNA ligase SARS1; recruited to the VEGFA promoter via interaction with SARS1. Interacts with BEX4; negatively regulates alpha-tubulin deacetylation by SIRT2.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Spindle. Midbody. Chromosome. Perikaryon. Cell projection. Growth cone. Myelin membrane Cytoplasm. Nucleus Cytoplasm.

Tissue specificity. Isoform 1 is expressed in heart, liver and skeletal muscle, weakly expressed in the cortex. Isoform 2 is strongly expressed in the cortex, weakly expressed in heart and liver. Weakly expressed in several malignancies including breast, liver, brain, kidney and prostate cancers compared to normal tissues. Weakly expressed in glioma cell lines compared to normal brain tissues (at protein level). Widely expressed. Highly expressed in heart, brain and skeletal muscle, while it is weakly expressed in placenta and lung. Down-regulated in many gliomas suggesting that it may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network.

Post-translational modifications. Phosphorylated at phosphoserine and phosphothreonine. Phosphorylated at Ser-368 by a mitotic kinase CDK1/cyclin B at the G2/M transition; phosphorylation regulates the delay in cell-cycle progression. Phosphorylated at Ser-368 by a mitotic kinase G1/S-specific cyclin E/Cdk2 complex; phosphorylation inactivates SIRT2-mediated alpha-tubulin deacetylation and thereby negatively regulates cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Phosphorylated by cyclin A/Cdk2 and p35-Cdk5 complexes and to a lesser extent by the cyclin D3/Cdk4 and cyclin B/Cdk1, in vitro. Dephosphorylated at Ser-368 by CDC14A and CDC14B around early anaphase. Acetylated by EP300; acetylation leads both to the decreased of SIRT2-mediated alpha-tubulin deacetylase activity and SIRT2-mediated down-regulation of TP53 transcriptional activity. Ubiquitinated.

Activity regulation. Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide. Inhibited by a macrocyclic peptide inhibitor S2iL5. Inhibited by EP300-induced acetylation.

Cofactor. Binds 1 zinc ion per subunit.

Induction. Up-regulated in response to low levels of glucose and anoxia-reoxygenation stress. Up-regulated by trichostatin A. Down-regulated in response to high levels of glucose. Down-regulated by histone deacetylation in several tumors.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q8IXJ6-1	1	yes
Q8IXJ6-2	2
Q8IXJ6-3	3
Q8IXJ6-4	4
Q8IXJ6-5	5

RefSeq proteins (3): NP_001180215, NP_036369, NP_085096 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003000	Sirtuin	Family
IPR017328	Sirtuin_class_I	Family
IPR026590	Ssirtuin_cat_dom	Domain
IPR026591	Sirtuin_cat_small_dom_sf	Homologous_superfamily
IPR029035	DHS-like_NAD/FAD-binding_dom	Homologous_superfamily
IPR050134	NAD-dep_sirtuin_deacylases	Family

Pfam: PF02146

Enzyme classification (BRENDA):

• EC 2.3.1.286 — protein acetyllysine N-acetyltransferase (BRENDA: 13 organisms, 147 substrates, 140 inhibitors, 18 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.0161–0.4535	4
NICOTINAMIDE	0.037–0.16	3
[HISTONE H3]-N6-ACETYL-L-LYSINE9	0.019–0.039	2
[HISTONE H3]-N6-MYRISTOYL-L-LYSINE9	0.0002–0.001	2
K382AZAKAC-CONTAINING P53 PEPTIDE	0.0109	1
K382KAC-CONTAINING P53 PEPTIDE	0.0718	1
[HISTONE H3]-N6-ACETYL-L-LYSINE	0.372	1
[HISTONE H3]-N6-BUTYRYL-L-LYSINE9	0.008	1
[HISTONE H3]-N6-OCTANOYL-L-LYSINE9	0.0012	1
[HISTONE H4]-N6-ACETYL-L-LYSINE	0.176	1
[PEPTIDE P300]-N6-ACETYL-L-LYSINE	0.085	1

Catalyzed reactions (Rhea), 5 shown:

• N(6)-acetyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-acetyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:43636)
• N(6)-hexadecanoyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-hexadecanoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:70563)
• N(6)-tetradecanoyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-tetradecanoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:70567)
• N(6)-benzoyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-benzoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:83535)
• N(6)-methacrylyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-methacrylyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:85159)

UniProt features (96 total): mutagenesis site 23, helix 19, strand 15, binding site 10, modified residue 9, splice variant 5, turn 4, region of interest 2, sequence conflict 2, compositionally biased region 2, initiator methionine 1, chain 1, domain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

78 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9S1Z	X-RAY DIFFRACTION	1.1
9FDR	X-RAY DIFFRACTION	1.25
9FDS	X-RAY DIFFRACTION	1.4
4RMH	X-RAY DIFFRACTION	1.42
4RMI	X-RAY DIFFRACTION	1.45
9S46	X-RAY DIFFRACTION	1.45
9S48	X-RAY DIFFRACTION	1.45
5YQO	X-RAY DIFFRACTION	1.48
4X3O	X-RAY DIFFRACTION	1.5
9S20	X-RAY DIFFRACTION	1.5
8QOO	X-RAY DIFFRACTION	1.55
8QT1	X-RAY DIFFRACTION	1.55
8QT3	X-RAY DIFFRACTION	1.55
8QT4	X-RAY DIFFRACTION	1.55
9FDU	X-RAY DIFFRACTION	1.55
9FDX	X-RAY DIFFRACTION	1.55
9S21	X-RAY DIFFRACTION	1.55
4Y6L	X-RAY DIFFRACTION	1.6
4Y6O	X-RAY DIFFRACTION	1.6
5YQN	X-RAY DIFFRACTION	1.6
9FDT	X-RAY DIFFRACTION	1.6
9FDW	X-RAY DIFFRACTION	1.6
5YQL	X-RAY DIFFRACTION	1.6
9VG0	X-RAY DIFFRACTION	1.61
3ZGO	X-RAY DIFFRACTION	1.63
5D7O	X-RAY DIFFRACTION	1.63
8OWZ	X-RAY DIFFRACTION	1.65
8PY3	X-RAY DIFFRACTION	1.65
8QT2	X-RAY DIFFRACTION	1.65
8QT8	X-RAY DIFFRACTION	1.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXJ6-F1	82.70	0.62

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 (10): 95–97; 167–170; 195; 200; 221; 224; 262–263; 286–288; 324; 85–89

Post-translational modifications (9): 2, 23, 25, 27, 53, 100, 207, 368, 372

Mutagenesis-validated functional residues (23):

Position	Phenotype
53	reduces deacetylase activity.
97	no effect on deacetylase activity.
98	inhibits deacetylase activity.
100	reduces deacetylase activity.
116	reduces binding for the peptide inhibitor s2il5.
120	reduces binding for the peptide inhibitor s2il5.
167	reduces deacetylase activity. inhibits the block of entry to chromosome condensation and subsequent hyperploidy cell for
168	abolishes deacetylation of alpha-tubulin. inhibits deacetylation of histone h3 at ’lys-18’. inhibits the block of entry
170	reduces deacetylase activity.
187	inhibits deacetylase activity toward histone, alpha-tubulin, fzr1 and cdc20. no effect on cdk2-dependent phosphorylation
244	strongly reduces binding for the peptide inhibitor s2il5.
265	reduces binding for the peptide inhibitor s2il5.
271	reduces binding for the peptide inhibitor s2il5.
279	reduces deacetylase activity.
280	reduces deacetylase activity.
294	reduces binding for the peptide inhibitor s2il5.
311	reduces deacetylase activity.
315	reduces deacetylase activity.
364	abolishes cdk2-dependent phosphorylation.
368	does not affect deacetylase activity. abolishes cdk2-dependent phosphorylation. inhibits cellular proliferation delay in
368	abolishes cdk2-dependent phosphorylation. inhibits interaction with a cyclin e-cdk2 complex. reduces strongly histone de
368	abolishes cdk2-dependent phosphorylation.
372	reduces phosphorylation. does not inhibit interaction with hdac6, ubiquitination and deacetylase activity. inhibits deac

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation
R-HSA-1640170	Cell Cycle
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2995410	Nuclear Envelope (NE) Reassembly
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 482 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, PID_HDAC_CLASSI_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GCM_MAP4K4, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_NUCLEAR_MEMBRANE_REASSEMBLY, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_MATURATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION

GO Biological Process (61): negative regulation of transcription by RNA polymerase II (GO:0000122), rDNA heterochromatin formation (GO:0000183), protein deacetylation (GO:0006476), autophagy (GO:0006914), mitotic nuclear membrane reassembly (GO:0007084), regulation of exit from mitosis (GO:0007096), negative regulation of autophagy (GO:0010507), negative regulation of peptidyl-threonine phosphorylation (GO:0010801), lipid catabolic process (GO:0016042), substantia nigra development (GO:0021762), myelination in peripheral nervous system (GO:0022011), heterochromatin formation (GO:0031507), subtelomeric heterochromatin formation (GO:0031509), regulation of myelination (GO:0031641), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), cellular response to oxidative stress (GO:0034599), peptidyl-lysine deacetylation (GO:0034983), epigenetic regulation of gene expression (GO:0040029), negative regulation of protein catabolic process (GO:0042177), regulation of phosphorylation (GO:0042325), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of DNA binding (GO:0043388), NLRP3 inflammasome complex assembly (GO:0044546), innate immune response (GO:0045087), negative regulation of fat cell differentiation (GO:0045599), positive regulation of fatty acid biosynthetic process (GO:0045723), positive regulation of meiotic nuclear division (GO:0045836), negative regulation of striated muscle tissue development (GO:0045843), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), cell division (GO:0051301), meiotic cell cycle (GO:0051321), regulation of cell cycle (GO:0051726), response to redox state (GO:0051775), positive regulation of cell division (GO:0051781), positive regulation of attachment of spindle microtubules to kinetochore (GO:0051987), cellular response to caloric restriction (GO:0061433), negative regulation of oligodendrocyte progenitor proliferation (GO:0070446), cellular response to hypoxia (GO:0071456), cellular response to epinephrine stimulus (GO:0071872)

GO Molecular Function (23): chromatin binding (GO:0003682), NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), histone deacetylase activity (GO:0004407), zinc ion binding (GO:0008270), histone deacetylase activity, NAD-dependent (GO:0017136), protein lysine deacetylase activity (GO:0033558), NAD-dependent protein lysine deacetylase activity (GO:0034979), histone acetyltransferase binding (GO:0035035), histone deacetylase binding (GO:0042826), tubulin deacetylase activity (GO:0042903), ubiquitin binding (GO:0043130), histone H4K16 deacetylase activity, NAD-dependent (GO:0046970), NAD+ binding (GO:0070403), histone methacryllysine demethacrylase activity (GO:0140219), histone benzoyllysine debenzoylase activity (GO:0140228), DNA-binding transcription factor binding (GO:0140297), NAD-dependent protein demyristoylase activity (GO:0140773), NAD-dependent protein depalmitoylase activity (GO:0140774), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747), metal ion binding (GO:0046872), NAD binding (GO:0051287)

GO Cellular Component (30): chromosome, telomeric region (GO:0000781), heterochromatin (GO:0000792), nucleus (GO:0005634), chromatin silencing complex (GO:0005677), chromosome (GO:0005694), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), centrosome (GO:0005813), centriole (GO:0005814), spindle (GO:0005819), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), growth cone (GO:0030426), midbody (GO:0030496), paranodal junction (GO:0033010), paranode region of axon (GO:0033270), perikaryon (GO:0043204), myelin sheath (GO:0043209), lateral loop (GO:0043219), Schmidt-Lanterman incisure (GO:0043220), juxtaparanode region of axon (GO:0044224), perinuclear region of cytoplasm (GO:0048471), mitotic spindle (GO:0072686), meiotic spindle (GO:0072687), glial cell projection (GO:0097386), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Nuclear Envelope (NE) Reassembly	1
M Phase	1
Mitotic Anaphase	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
intracellular membraneless organelle	4
histone modifying activity	3
catabolic process	2
negative regulation of catabolic process	2
myelination	2
binding	2
protein lysine deacetylase activity	2
enzyme binding	2
acyltransferase activity, transferring groups other than amino-acyl groups	2
post-translational protein modification	2
intracellular membrane-bounded organelle	2
cytoplasm	2
microtubule organizing center	2
microtubule cytoskeleton	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
facultative heterochromatin formation	1
nucleolar chromatin organization	1
protein deacylation	1
transmembrane transport	1
process utilizing autophagic mechanism	1
mitotic cell cycle	1
nuclear membrane reassembly	1
mitotic nuclear membrane organization	1
exit from mitosis	1
regulation of mitotic cell cycle phase transition	1
autophagy	1
regulation of autophagy	1
negative regulation of protein phosphorylation	1
regulation of peptidyl-threonine phosphorylation	1
peptidyl-threonine phosphorylation	1
lipid metabolic process	1
midbrain development	1
neural nucleus development	1
Schwann cell development	1
peripheral nervous system axon ensheathment	1
cellular component assembly	1
heterochromatin boundary formation	1

Protein interactions and networks

STRING

2932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIRT2	CDC14A	Q9UNH5	990
SIRT2	CTNNB1	P35222	899
SIRT2	FOXO1	Q12778	896
SIRT2	HDAC8	Q9BY41	874
SIRT2	HDAC6	Q9UBN7	872
SIRT2	H3C1	P02295	856
SIRT2	H3-3A	P06351	855
SIRT2	H3-4	Q16695	851
SIRT2	H3-7	Q5TEC6	851
SIRT2	H3-5	Q6NXT2	850
SIRT2	H3C14	Q71DI3	850
SIRT2	HDAC1	Q13547	843
SIRT2	HDAC2	Q92769	823
SIRT2	HDAC3	O15379	814
SIRT2	ATAT1	Q5SQI0	806

IntAct

71 interactions, top by confidence:

A	B	Type	Score
CDC20	CDC27	psi-mi:“MI:0914”(association)	0.950
CDC27	CDC20	psi-mi:“MI:0915”(physical association)	0.950
FZR1	CDC27	psi-mi:“MI:0914”(association)	0.910
SNAI1	KDM1A	psi-mi:“MI:0914”(association)	0.830
SIRT2	KAT2B	psi-mi:“MI:0915”(physical association)	0.580
KAT2B	SIRT2	psi-mi:“MI:0915”(physical association)	0.580
SIRT2	BUB1B	psi-mi:“MI:0915”(physical association)	0.580
BUB1B	SIRT2	psi-mi:“MI:0915”(physical association)	0.580
SIRT2	RELA	psi-mi:“MI:0197”(deacetylation reaction)	0.540
SIRT2	RELA	psi-mi:“MI:0915”(physical association)	0.540
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
GSTT1	MID1	psi-mi:“MI:0914”(association)	0.530
KIAA0930	ATG7	psi-mi:“MI:0914”(association)	0.530
DMD	UTRN	psi-mi:“MI:0914”(association)	0.530
MOAP1	PNMA8A	psi-mi:“MI:0914”(association)	0.530
CDC14B	SIRT2	psi-mi:“MI:0915”(physical association)	0.520
SIRT2	G6PD	psi-mi:“MI:0915”(physical association)	0.520
G6PD	SIRT2	psi-mi:“MI:0915”(physical association)	0.520
SIRT2	SHANK3	psi-mi:“MI:0915”(physical association)	0.510
FZR1	Cdc27	psi-mi:“MI:0914”(association)	0.500
BUB1B	Crebbp	psi-mi:“MI:0914”(association)	0.500
SIRT2	MYOD1	psi-mi:“MI:0914”(association)	0.460
MYOD1	SIRT2	psi-mi:“MI:0914”(association)	0.460
SIRT2	HDAC6	psi-mi:“MI:0915”(physical association)	0.460
HDAC6	SIRT2	psi-mi:“MI:0403”(colocalization)	0.460
AHI1	OFD1	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (247): SIRT2 (Affinity Capture-Western), SIRT2 (Affinity Capture-Western), SIRT2 (Affinity Capture-Western), FOXO1 (Affinity Capture-Western), EP300 (Biochemical Activity), HIST1H3A (Biochemical Activity), SIRT2 (Affinity Capture-MS), RAB3GAP2 (Affinity Capture-MS), GPAM (Affinity Capture-MS), RAB3GAP1 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), SARS (Affinity Capture-MS), FADS1 (Affinity Capture-MS), MTDH (Affinity Capture-MS), DEGS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9UVG7, A0A250YGJ5, A0A2K5TU92, A8NWP2, A9UVV1, B0X4N8, B2RZ55, E1BRE2, E2RDZ6, E9GD30, F4P804, F7DKV7, F7EZ75, O54747, P16081, P27967, P27968, P27969, P38681, P43100, P49102, P59941, Q0P595, Q0UI56, Q1JQC6, Q3ZBQ0, Q4PEJ3, Q5AW69, Q5HZN8, Q5R6G3, Q5RBF1, Q5RJQ4, Q68FX9, Q6DHI5, Q7ZVK3, Q8BKJ9, Q8IRR5, Q8IXJ6, Q8K2C6, Q8N6T7

Diamond homologs: A0A0G2JZ79, A8MBU4, B0RM75, B5YJW3, C1DBX3, C6A243, C8V3W5, E9GD30, O07595, O28597, O30124, O58669, O59923, O94640, P06700, P0CS88, P33294, P53685, P53686, P53687, Q21921, Q25337, Q4JBN2, Q4R834, Q4UZX0, Q54GV7, Q54LF0, Q54P49, Q54QE6, Q57V41, Q5A985, Q5AQ47, Q5AW69, Q5HM33, Q5KZE8, Q5L014, Q5RBF1, Q5RJQ4, Q5V4Q5, Q607X6

SIGNOR signaling

24 interactions.

A	Effect	B	Mechanism
SIRT2	down-regulates	KAT2B	binding
SIRT2	down-regulates	MYOD1	deacetylation
CDK1	down-regulates	SIRT2	phosphorylation
CDK2	down-regulates	SIRT2	phosphorylation
CyclinE/CDK2	down-regulates	SIRT2	phosphorylation
CDC14B	unknown	SIRT2	dephosphorylation
CDC14A	unknown	SIRT2	dephosphorylation
SIRT2	“down-regulates quantity by repression”	CDKN1A	“transcriptional regulation”
ING1	“down-regulates activity”	SIRT2	binding
SIRT2	“up-regulates quantity by expression”	AFP	“transcriptional regulation”
SIRT2	“down-regulates quantity by repression”	NEDD4	“transcriptional regulation”
MYCN	“up-regulates quantity by expression”	SIRT2	“transcriptional regulation”
MYC	“up-regulates quantity by expression”	SIRT2	“transcriptional regulation”
SIRT2	“up-regulates quantity by stabilization”	MYCN
SIRT2	“up-regulates quantity by stabilization”	MYC
SRC	“down-regulates quantity by destabilization”	SIRT2	phosphorylation
SIRT2	“up-regulates activity”	PGAM1	deacetylation
SIRT2	“up-regulates activity”	PGAM2	deacetylation
SIRT2	“up-regulates activity”	PGAM	deacetylation
SIRT2	“up-regulates quantity by stabilization”	PCK1	deacetylation
CDK5	“up-regulates activity”	SIRT2	phosphorylation
DYRK1A	“up-regulates activity”	SIRT2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Anchoring of the basal body to the plasma membrane	7	16.1×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
cilium assembly	10	11.9×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	1
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2137 predictions. Top by Δscore:

Variant	Effect	Δscore
19:38879308:CTT:C	acceptor_gain	1.0000
19:38879311:C:CA	acceptor_loss	1.0000
19:38879311:C:CC	acceptor_gain	1.0000
19:38879320:C:CT	acceptor_gain	1.0000
19:38879688:C:CT	acceptor_gain	1.0000
19:38879688:C:T	acceptor_gain	1.0000
19:38879699:CCGA:C	acceptor_gain	1.0000
19:38879700:CGA:C	acceptor_gain	1.0000
19:38879700:CGAC:C	acceptor_gain	1.0000
19:38879703:C:CC	acceptor_gain	1.0000
19:38880679:TCTTA:T	donor_loss	1.0000
19:38880680:CTTA:C	donor_loss	1.0000
19:38880681:TTAC:T	donor_loss	1.0000
19:38880682:TACC:T	donor_loss	1.0000
19:38880683:A:AC	donor_gain	1.0000
19:38880683:A:C	donor_loss	1.0000
19:38880684:C:CC	donor_gain	1.0000
19:38880684:CCTGG:C	donor_gain	1.0000
19:38880735:CC:C	acceptor_gain	1.0000
19:38880736:CC:C	acceptor_gain	1.0000
19:38880736:CCTG:C	acceptor_loss	1.0000
19:38880737:C:CC	acceptor_gain	1.0000
19:38880819:A:AC	donor_gain	1.0000
19:38880820:C:CC	donor_gain	1.0000
19:38880820:CTTG:C	donor_gain	1.0000
19:38881098:A:AC	donor_gain	1.0000
19:38881099:C:CC	donor_gain	1.0000
19:38881099:CTGA:C	donor_gain	1.0000
19:38881431:CCAGG:C	donor_gain	1.0000
19:38881487:CTTCT:C	acceptor_gain	1.0000

AlphaMissense

2548 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:38889087:C:A	Q167H	1.000
19:38889087:C:G	Q167H	1.000
19:38889942:A:C	F96L	1.000
19:38889942:A:T	F96L	1.000
19:38889944:A:G	F96L	1.000
19:38880710:A:G	L284P	0.999
19:38880713:A:G	L283P	0.999
19:38880864:C:G	G261R	0.999
19:38880878:A:G	L256P	0.999
19:38881142:A:C	F235L	0.999
19:38881142:A:T	F235L	0.999
19:38881144:A:G	F235L	0.999
19:38881436:C:A	K229N	0.999
19:38881436:C:G	K229N	0.999
19:38883673:G:C	C195W	0.999
19:38883695:C:A	G188V	0.999
19:38883695:C:T	G188D	0.999
19:38883754:G:C	N168K	0.999
19:38883754:G:T	N168K	0.999
19:38889873:A:C	F119L	0.999
19:38889873:A:T	F119L	0.999
19:38889875:A:G	F119L	0.999
19:38889881:C:G	A117P	0.999
19:38889943:A:C	F96C	0.999
19:38880716:C:G	R282P	0.998
19:38880863:C:A	G261V	0.998
19:38880875:A:G	L257P	0.998
19:38881438:T:C	K229E	0.998
19:38883674:C:G	C195S	0.998
19:38883674:C:T	C195Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000180561 (19:38893735 TGAG>T), RS1000255777 (19:38893992 G>A), RS1000538826 (19:38882844 A>C,G), RS1000582023 (19:38879506 G>A), RS1000611679 (19:38885656 T>C), RS1000808894 (19:38888413 T>A), RS1000819844 (19:38890614 C>A,G,T), RS1001124173 (19:38892229 C>T), RS1001415776 (19:38898168 G>T), RS1001488288 (19:38882303 C>G), RS1001507894 (19:38897934 G>A), RS1001519456 (19:38899331 C>T), RS1001617499 (19:38893100 G>A), RS1001645083 (19:38897647 C>T), RS1001733536 (19:38893439 C>T)

Disease associations

OMIM: gene MIM:604480 | 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): CHEMBL4296131 (PROTEIN-PROTEIN INTERACTION), CHEMBL4462 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 280,091 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1140	NIACINAMIDE	4	231,688
CHEMBL252556	IDEBENONE	4	8,581
CHEMBL265502	SURAMIN	3	36,848
CHEMBL413376	SURAMIN HEXASODIUM	3	2,743
CHEMBL382277	EX-527	2	231

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2053071	Toxicity	3	gefitinib	Toxic liver disease

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2053071	NFKBIB, SIRT2	3	2.00	1	gefitinib

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 17 [PMID: 23570514]	Inhibition	8.74	pIC50
compound 86 [PMID: 26982234]	Inhibition	7.14	pKi
AGK2	Inhibition	5.81	pIC50

Binding affinities (BindingDB)

33 measured of 57 human assays (57 total across all organisms); most potent 33 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
3-bromo-2-[[5-(4-chlorophenyl)-4-phenyl-1,2,4-triazol-3-yl]sulfanyl]-5-nitropyridine	IC50	750 nM	US-9737525: Small molecule activators of NRF2 pathway
5-nitro-8-[[5-(phenoxymethyl)-4-phenyl-1,2,4-triazol-3-yl]sulfanyl]quinoline	IC50	1700 nM	US-9737525: Small molecule activators of NRF2 pathway
phenyl N-[1-anilino-6-(butanethioylamino)-1-oxohexan-2-yl]carbamate	IC50	2400 nM	US-9359293: Methods of treatment using modulators of SIRT2
3-benzylsulfanyl-5-(naphthalen-1-yloxymethyl)-4-phenyl-1,2,4-triazole	IC50	4500 nM	US-9737525: Small molecule activators of NRF2 pathway
3-[(3-bromophenyl)methylsulfanyl]-5-(phenoxymethyl)-4-phenyl-1,2,4-triazole	IC50	5000 nM	US-9737525: Small molecule activators of NRF2 pathway
4-benzyl-3-benzylsulfanyl-5-(naphthalen-1-yloxymethyl)-1,2,4-triazole	IC50	6000 nM	US-9737525: Small molecule activators of NRF2 pathway
3-benzylsulfanyl-5-(phenoxymethyl)-4-phenyl-1,2,4-triazole	IC50	7000 nM	US-9737525: Small molecule activators of NRF2 pathway
8-[(4,5-diphenyl-1,2,4-triazol-3-yl)sulfanyl]-5-nitroquinoline	IC50	7500 nM	US-9737525: Small molecule activators of NRF2 pathway
2-[[5-(4-chlorophenyl)-4-phenyl-1,2,4-triazol-3-yl]sulfanyl]-5-nitropyridine	IC50	7500 nM	US-9737525: Small molecule activators of NRF2 pathway
8-[(5-benzylsulfanyl-4-phenyl-1,2,4-triazol-3-yl)methoxy]quinoline	IC50	9000 nM	US-9737525: Small molecule activators of NRF2 pathway
4-benzyl-3-[(4-methoxyphenyl)methylsulfanyl]-5-(naphthalen-1-yloxymethyl)-1,2,4-triazole	IC50	9000 nM	US-9737525: Small molecule activators of NRF2 pathway
3-[(4-nitrophenyl)methylsulfanyl]-5-(phenoxymethyl)-4-phenyl-1,2,4-triazole	IC50	10000 nM	US-9737525: Small molecule activators of NRF2 pathway
3-benzylsulfanyl-4-(4-chlorophenyl)-5-(naphthalen-1-yloxymethyl)-1,2,4-triazole	IC50	12000 nM	US-9737525: Small molecule activators of NRF2 pathway
cambinol analog, 6b	IC50	12700 nM
3-bromo-4-tert-butyl-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide	IC50	18300 nM	US-9365508: Aroyl thiourea derivatives
4-butoxy-3,5-dichloro-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide	IC50	22500 nM	US-9365508: Aroyl thiourea derivatives
3,5-dichloro-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-ethoxybenzamide	IC50	29300 nM	US-9365508: Aroyl thiourea derivatives
phenyl N-[1-anilino-6-(ethanethioylamino)-1-oxohexan-2-yl]carbamate	IC50	30000 nM	US-9359293: Methods of treatment using modulators of SIRT2
cambinol analog, 6xi	IC50	38300 nM
3-bromo-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide	IC50	39900 nM	US-9365508: Aroyl thiourea derivatives
cambinol	IC50	40700 nM
cambinol analog, 6i	IC50	43000 nM
3-bromo-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-methylbenzamide	IC50	43900 nM	US-9365508: Aroyl thiourea derivatives
cambinol analog, 6ii	IC50	44200 nM
cambinol analog, 6iii	IC50	44500 nM
3,5-dibromo-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-methoxybenzamide	IC50	47200 nM	US-9365508: Aroyl thiourea derivatives
cambinol analog, 6x	IC50	50000 nM
N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-methoxy-3-(trifluoromethyl)benzamide	IC50	51700 nM	US-9365508: Aroyl thiourea derivatives
4-bromo-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide	IC50	62100 nM	US-9365508: Aroyl thiourea derivatives
3,5-dichloro-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-methoxybenzamide	IC50	62500 nM	US-9365508: Aroyl thiourea derivatives
N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-propan-2-ylbenzamide	IC50	64800 nM	US-9365508: Aroyl thiourea derivatives
3,4-dichloro-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide	IC50	70900 nM	US-9365508: Aroyl thiourea derivatives

ChEMBL bioactivities

809 potent at pChembl≥5 of 1294 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL3769432
8.96	IC50	1.1	nM	CHEMBL2338810
8.89	IC50	1.3	nM	CHEMBL2332037
8.74	IC50	1.8	nM	CHEMBL2332041
8.57	IC50	2.7	nM	CHEMBL2332039
8.57	IC50	2.7	nM	CHEMBL5614132
8.49	IC50	3.2	nM	CHEMBL3779989
8.36	IC50	4.4	nM	CHEMBL2332042
8.32	IC50	4.8	nM	CHEMBL2332040
8.27	IC50	5.4	nM	CHEMBL2332044
8.19	IC50	6.5	nM	CHEMBL2332043
8.15	IC50	7	nM	CHEMBL4446458
8.00	IC50	10	nM	CHEMBL2332055
8.00	IC50	10	nM	CHEMBL2332038
8.00	IC50	10.1	nM	CHEMBL3781485
7.92	IC50	12	nM	CHEMBL5594203
7.87	IC50	13.5	nM	CHEMBL3805001
7.85	IC50	14	nM	CHEMBL5556672
7.80	IC50	16	nM	CHEMBL2338808
7.80	IC50	15.7	nM	CHEMBL3805929
7.78	IC50	16.7	nM	CHEMBL3805692
7.77	IC50	17	nM	CHEMBL2338809
7.75	IC50	18	nM	CHEMBL5595847
7.72	IC50	19	nM	CHEMBL3804834
7.72	IC50	19	nM	CHEMBL4446458
7.72	IC50	19	nM	CHEMBL4447813
7.70	IC50	20	nM	CHEMBL4638983
7.70	IC50	20	nM	CHEMBL5592172
7.66	IC50	22	nM	CHEMBL4438193
7.65	IC50	22.4	nM	CHEMBL3805063
7.64	IC50	23	nM	CHEMBL2332045
7.64	IC50	22.7	nM	CHEMBL3805835
7.64	IC50	22.9	nM	CHEMBL3806268
7.63	IC50	23.4	nM	CHEMBL3805112
7.60	IC50	25	nM	CHEMBL5592160
7.58	IC50	26.3	nM	CHEMBL3805479
7.57	IC50	26.7	nM	CHEMBL3805070
7.57	IC50	27	nM	CHEMBL5590798
7.55	IC50	28	nM	CHEMBL2338816
7.55	IC50	28.1	nM	CHEMBL3805847
7.55	IC50	28.1	nM	CHEMBL3805072
7.55	IC50	28	nM	CHEMBL4129995
7.55	IC50	28	nM	CHEMBL4638983
7.54	IC50	29	nM	CHEMBL2338814
7.54	IC50	28.9	nM	CHEMBL3805639
7.53	IC50	29.3	nM	CHEMBL3805586
7.53	IC50	29.7	nM	CHEMBL3805934
7.52	IC50	30	nM	CHEMBL2332052
7.52	IC50	30	nM	CHEMBL5556672
7.52	IC50	30	nM	CHEMBL5592898

PubChem BioAssay actives

741 with measured affinity, of 4057 total; 50 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
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42S)-12-(2-amino-2-oxoethyl)-18,21-bis(3-carbamimidamidopropyl)-15,36-bis[(1R)-1-hydroxyethyl]-6,9,33,42-tetrakis[(4-hydroxyphenyl)methyl]-30,39-bis(1H-imidazol-4-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-27-propan-2-yl-24-[4-[(2,2,2-trifluoroacetyl)amino]butyl]-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	1280432: Inhibition of human SIRT2	ic50	0.0010	uM
4-[4-[2-(methanesulfonamido)ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0011	uM
3-N-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethyl]-1-N-ethylbenzene-1,3-dicarboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0013	uM
tert-butyl 5-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethylcarbamoyl]thiophene-2-carboxylate	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0018	uM
4-[4-[2-[[5-(ethylcarbamothioyl)thiophene-2-carbonyl]amino]ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide	2125909: Inhibition of SIRT2 (unknown origin)	ic50	0.0027	uM
2-N-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethyl]-5-N-ethylthiophene-2,5-dicarboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0027	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39R,42S)-12,36-bis(2-amino-2-oxoethyl)-33-benzyl-27-[(2S)-butan-2-yl]-21,30-bis(3-carbamimidamidopropyl)-6,9,15,39-tetrakis(hydroxymethyl)-18,42-bis[(4-hydroxyphenyl)methyl]-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-24-[4-[(2,2,2-trifluoroacetyl)amino]butyl]-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	1286969: Inhibition of human SIRT2	ic50	0.0032	uM
5-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethylcarbamoyl]thiophene-2-carboxylic acid	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0044	uM
2-N-[2-[4-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl]ethyl]-5-N-ethylthiophene-2,5-dicarboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0048	uM
tert-butyl N-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethyl]carbamate	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0054	uM
4-[4-[2-(thiophene-2-carbonylamino)ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0065	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[[2-[4-[(4-hydroxyphenyl)diazenyl]phenyl]acetyl]amino]hexanamide	1709693: Inhibition of 5-(3-((1r,4r)-4-((5S,8S,11S,14S,17S,20S,29S)-11-((1H-imidazol-4-yl)methyl)-1,33-diamino-5-carbamoyl-17-(4-(4-(4-((4-(dimethylamino)phenyl)diazenyl)phenyl)butanamido)butyl)-8,14-bis(3-guanidinopropyl)-20-methyl-7,10,13,16,19,22,25,28-octaoxo-6,9,12,15,18,21,24,27-octaazatritriacontan-29-ylcarbamoyl)cyclohexyl)thioureido)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid binding to SIRT2 (unknown origin) measured after 2 hrs in presence of NAD+ by fluorometric method	ic50	0.0070	uM
4-[4-[2-(2,2-dimethylpropanoylamino)ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0100	uM
3-N-[2-[4-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl]ethyl]-1-N-ethylbenzene-1,3-dicarboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0100	uM
(2S,5S,8S,23S)-23-acetamido-2-(4-aminobutyl)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-5-[4-(ethanethioylamino)butyl]-3,6,14,17,24-pentaoxo-1,4,7,13,18-pentazacyclotetracosane-8-carboxamide	1286978: Inhibition of recombinant His6 tagged human SIRT2 using 0.39 mM H2N-HK-[N(epsilon)-acetyl-lysine]-LM-COOH as substrate measured after 12 mins HPLC analysis in presence of 0.5 mM beta-NAD+	ic50	0.0101	uM
(2S)-2-(phenylmethoxycarbonylamino)-6-(tetradecanethioylamino)hexanoic acid	2117959: Inhibition of human SIRT2 preincubated for 15 mins followed by H3K9Ac (KQTARK(Ac)STGGWW) peptide addition and measured after 5 mins	ic50	0.0120	uM
5-[[3-[(4-phenylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0135	uM
benzyl N-[(2S)-1-(3-hydroxyanilino)-1-oxo-6-(tetradecanethioylamino)hexan-2-yl]carbamate	2117959: Inhibition of human SIRT2 preincubated for 15 mins followed by H3K9Ac (KQTARK(Ac)STGGWW) peptide addition and measured after 5 mins	ic50	0.0140	uM
N-[3-[(5-carbamoyl-3-pyridinyl)oxymethyl]phenyl]-1H-indazole-6-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0157	uM
4-[4-[3-(2,2-dimethylpropanoylamino)propyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0160	uM
5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0167	uM
4-[4-[2-(2,2-dimethylpropanoylamino)ethyl]piperazin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0170	uM
methyl (2S)-2-(phenylmethoxycarbonylamino)-6-(tetradecanethioylamino)hexanoate	2117959: Inhibition of human SIRT2 preincubated for 15 mins followed by H3K9Ac (KQTARK(Ac)STGGWW) peptide addition and measured after 5 mins	ic50	0.0180	uM
5-[[3-[[4-(1,2,4-triazol-4-yl)benzoyl]amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0190	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[[2-(4-phenyldiazenylphenyl)acetyl]amino]hexanamide	1509494: Inhibition of recombinant human SIRT2 defatty-acylase activity using SFP3 as substrate measured at 5 mins interval for 60 mins in presence of NAD+ by fluorescence assay	ic50	0.0190	uM
benzyl N-[1-anilino-1-oxo-6-(tetradecanethioylamino)hexan-2-yl]carbamate	1652961: Inhibition of sirtuin 2 (unknown origin)	ic50	0.0200	uM
triethyl-[3-[[(2S)-2-(phenylmethoxycarbonylamino)-6-(tetradecanethioylamino)hexanoyl]amino]propyl]azanium bromide	2117959: Inhibition of human SIRT2 preincubated for 15 mins followed by H3K9Ac (KQTARK(Ac)STGGWW) peptide addition and measured after 5 mins	ic50	0.0200	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-(tetradecanethioylamino)hexanamide	1509494: Inhibition of recombinant human SIRT2 defatty-acylase activity using SFP3 as substrate measured at 5 mins interval for 60 mins in presence of NAD+ by fluorescence assay	ic50	0.0220	uM
N-[3-[(5-carbamoyl-3-pyridinyl)oxymethyl]phenyl]-6-pyrrol-1-ylpyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0224	uM
5-[[3-[(4-pyridin-2-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0227	uM
5-[[3-[(4-pyridin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0229	uM
4-[4-(2-acetamidoethyl)piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0230	uM
5-[[3-(naphthalene-2-carbonylamino)phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0234	uM
triethyl-[[3-[[(2S)-2-(phenylmethoxycarbonylamino)-6-(tetradecanethioylamino)hexanoyl]amino]phenyl]methyl]azanium bromide	2117959: Inhibition of human SIRT2 preincubated for 15 mins followed by H3K9Ac (KQTARK(Ac)STGGWW) peptide addition and measured after 5 mins	ic50	0.0250	uM
5-[[3-[(4-thiophen-2-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0263	uM
5-[[3-[[4-(dimethylamino)benzoyl]amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0267	uM
benzyl N-[(2S)-1-amino-1-oxo-6-(tetradecanethioylamino)hexan-2-yl]carbamate	2117959: Inhibition of human SIRT2 preincubated for 15 mins followed by H3K9Ac (KQTARK(Ac)STGGWW) peptide addition and measured after 5 mins	ic50	0.0270	uM
benzyl N-[(2S)-1-anilino-1-oxo-6-(tetradecanethioylamino)hexan-2-yl]carbamate	1498677: Inhibition of human N-terminal His6-SUMO-tagged SIRT2 (38 to 356 residues) expressed in Escherichia coli BL21 using H3K9AcWW as substrate preincubated for 15 mins followed by substrate addition measured after 1 hr by HPLC analysis	ic50	0.0280	uM
7-[4-[2-(2,2-dimethylpropanoylamino)ethyl]piperidin-1-yl]thieno[3,2-b]pyridine-2-carboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0280	uM
5-[[3-[(4-pyridin-3-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0281	uM
4-N-[3-[(5-carbamoyl-3-pyridinyl)oxymethyl]phenyl]-1-N-methylbenzene-1,4-dicarboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0281	uM
N-[3-[(5-carbamoyl-3-pyridinyl)oxymethyl]phenyl]-6-(furan-2-yl)pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0289	uM
4-[4-(2-pyrrolidin-1-ylethyl)piperazin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0290	uM
5-[[3-[(3-fluoro-4-phenylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0293	uM
5-[[3-[(3-fluoro-4-pyridin-3-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0297	uM
triethyl-[5-[[(2S)-2-(phenylmethoxycarbonylamino)-6-(tetradecanethioylamino)hexanoyl]amino]pentyl]azanium bromide	2117959: Inhibition of human SIRT2 preincubated for 15 mins followed by H3K9Ac (KQTARK(Ac)STGGWW) peptide addition and measured after 5 mins	ic50	0.0300	uM
4-[4-[2-(ethanethioylamino)ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide	735749: Inhibition of His-tagged SIRT2 (1 to 389) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate incubated for 20 mins prior to substrate addition measured after 30 mins by mass spectrophotometric analysis	ic50	0.0300	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[(2,2,2-trifluoroacetyl)amino]hexanamide	1509532: Inhibition of recombinant human SIRT2 deacylation activity expressed in Escherichia coli Rosetta2 using Fluor-de-Lys-SIRT2 deacetylase substrate measured after 2 hrs by fluorescence assay	ic50	0.0310	uM
5-[[3-(1-benzothiophene-2-carbonylamino)phenyl]methoxy]pyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0331	uM
N-[3-[(5-carbamoyl-3-pyridinyl)oxymethyl]phenyl]-6-pyrazol-1-ylpyridine-3-carboxamide	1299770: Inhibition of recombinant human C-terminal His-tagged SIRT2 (50 to 389 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate incubated for 2 hrs by fluorescence analysis	ic50	0.0333	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide	decreases activity, decreases expression	3
bisphenol A	decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
sirtinol	decreases activity	2
Resveratrol	decreases reaction, increases reaction, decreases expression, affects binding	2
Estradiol	increases reaction, decreases expression, affects binding, decreases reaction	2
Niacinamide	affects cotreatment, decreases expression, decreases activity	2
aristolochic acid I	increases expression	1
urushiol	decreases activity	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
polymarcine	decreases activity	1
decabromobiphenyl ether	decreases expression	1
diisononyl phthalate	decreases expression	1
mancozeb	decreases activity	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases expression	1
cerous chloride	affects cotreatment, increases expression, decreases expression	1
lanthanum chloride	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
ceric oxide	affects cotreatment, decreases expression, increases abundance	1
norcantharidin	decreases expression	1
pterostilbene	affects reaction, increases acetylation, increases expression, decreases expression, decreases reaction	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
vosaroxin	affects reaction, increases activity	1
abrine	increases expression	1
cambinol	decreases expression	1

ChEMBL screening assays

570 unique, capped per target: 554 binding, 15 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4219424	Binding	Induction of cereblon-mediated Sirt2 degradation in human HeLa cells at 10 uM after 1 to 6 hrs by Western blot method	Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals). — J Med Chem
CHEMBL4305686	ADMET	Drug metabolism assessed as recombinant human SIRT2-mediated deacylation by measuring dabcyl formation at 20 uM measured up to 4 hrs in presence of NAD+ by HPLC analysis	Development of Peptide-Based Sirtuin Defatty-Acylase Inhibitors Identified by the Fluorescence Probe, SFP3, That Can Efficiently Measure Defatty-Acylase Activity of Sirtuin. — J Med Chem
CHEMBL906599	Functional	Inhibition of recombinant SIRT2 assessed as increase in tubulin acetylation relative to control	Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson’s disease. — Science

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B8PD	Abcam HCT 116 SIRT2 KO	Cancer cell line	Male
CVCL_B9RR	Abcam A-549 SIRT2 KO	Cancer cell line	Male
CVCL_D2H9	Abcam MCF-7 SIRT2 KO	Cancer cell line	Female
CVCL_D8AA	Ubigene A-549 SIRT2 KO	Cancer cell line	Male
CVCL_D8GE	Ubigene H9 SIRT2 KO	Embryonic stem cell	Female
CVCL_TL27	HAP1 SIRT2 (-) 1	Cancer cell line	Male
CVCL_TL28	HAP1 SIRT2 (-) 2	Cancer cell line	Male
CVCL_TL29	HAP1 SIRT2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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