NAD-dependent protein deacetylase and defatty-acylase that functions primarily in the cytoplasm but shuttles to the nucleus during G2/M transition. SIRT2 deacetylates histones (H4K16, H3K18, H3K56), alpha-tubulin (K40), and numerous non-histone substrates including transcription factors (FOXO1, FOXO3, HIF1A, RELA/p65), metabolic enzymes (ACLY, G6PD, PCK1), and cell cycle regulators (CDC20, BubR1). Also possesses efficient demyristoylase and depalmitoylase activities. Key roles include regulation of cell cycle progression, chromatin condensation during mitosis, metabolic regulation, and peripheral nerve myelination. SIRT2 also restricts bacterial infection by stripping lysine fatty-acylation installed by effectors such as Shigella IcsB. In viral infection its effect is virus-specific and predominantly permissive: across hepatitis B, dengue, HIV-1 and herpes simplex, inhibiting or depleting SIRT2 reduces viral replication, and SIRT2 deacetylates G3BP1 to dampen cGAS-STING signalling. Antiviral effects reported for influenza and for a minor spliced isoform run the other way.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT2 localizes to the nucleus, particularly during G2/M transition and mitosis. North and Verdin (PMID:17726514) demonstrated that SIRT2 undergoes nucleo-cytoplasmic shuttling via CRM1-dependent nuclear export, with nuclear accumulation during mitosis. Reason: Well-supported by multiple experimental studies. SIRT2 shuttles between cytoplasm and nucleus, with nuclear enrichment during mitosis where it associates with chromatin and deacetylates H4K16. Supporting Evidence: PMID:17726514 During the cell cycle, SIRT2 becomes enriched in the nucleus and is associated with mitotic structures, beginning with the centrosome during prophase, the mitotic spindle during metaphase, and the midbody during cytokinesis. PMID:17726514 Here we report that SIRT2 maintains a largely cytoplasmic localization during interphase by active nuclear export in a Crm1-dependent manner. PMID:23908241 during infection with the bacterium Listeria monocytogenes, the host deacetylase sirtuin 2 (SIRT2) translocates to the nucleus file:human/SIRT2/SIRT2-deep-research-falcon.md See deep research file for comprehensive analysis |
| GO:0017136 histone deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT2 is a well-established NAD-dependent histone deacetylase. Crystal structure (PMID:11427894) reveals NAD-binding domain and catalytic mechanism. Deacetylates H4K16 preferentially (PMID:16648462), as well as H3K18 and H3K56. High-resolution human Sirt2 structures including a complex with the cosubstrate NAD+ (PDB 4RMG) and a product-analogue form (PDB 4RMJ, the ADPR-NCA complex) resolve the NAD+/cofactor pocket and the catalytic active site (PMID:25672491). Reason: Core molecular function of SIRT2 confirmed by structural and biochemical studies. The NAD-dependent deacetylase activity is fundamental to all sirtuin functions. Supporting Evidence: PMID:11427894 Sir2 is an NAD-dependent histone deacetylase... The 1.7 A crystal structure of the 323 amino acid catalytic core of human SIRT2 PMID:16648462 SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis PMID:25672491 Sirtuins are a highly conserved class of NAD(+)-dependent lysine deacylases. PMID:25672491 However, only a kinked conformation where the NCA moiety of NAD+ occupies the C-pocket is considered productive for catalytic deacylation. |
| GO:0000183 rDNA heterochromatin formation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: This annotation is based on yeast Sir2 function. While SIRT2 has chromatin-related functions, direct evidence for human SIRT2 involvement in rDNA heterochromatin formation is limited. Reason: Inferred from yeast Sir2 function. Human SIRT2 is primarily cytoplasmic and its chromatin functions are more related to mitotic H4K16 deacetylation than rDNA silencing. The IBA annotation may be conservative but represents possible ancestral function. |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000108 | UNDECIDED | Summary: Automated annotation based on inter-ontology links. While yeast Sir2 functions in telomeric silencing, direct evidence for human SIRT2 at telomeres is limited. Reason: Lacks direct experimental evidence for human SIRT2. This may be extrapolated from yeast Sir2 telomeric functions. SIRT2 does associate with chromatin during mitosis but telomeric localization specifically is not well documented. |
| GO:0002376 immune system process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT2 has been implicated in immune responses, particularly through its role in NF-kB regulation (PMID:21081649) and bacterial infection response (PMID:23908241). Reason: While SIRT2 deacetylates p65/RELA and modulates NF-kB signaling, this represents a downstream consequence of its deacetylase activity rather than a core function. The term is also quite broad. Supporting Evidence: PMID:21081649 SIRT2 interacts with p65 in the cytoplasm and deacetylates p65 in vitro and in vivo at Lys310 |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. Nuclear localization is well-supported experimentally. Reason: Consistent with IBA annotation and experimental evidence showing SIRT2 nuclear shuttling and enrichment during mitosis. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: SIRT2 associates with chromosomes during mitosis, where it deacetylates H4K16 to promote chromatin condensation. Reason: Supported by experimental evidence showing SIRT2 association with mitotic chromatin and its role in H4K16 deacetylation during cell cycle. Supporting Evidence: PMID:16648462 SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: SIRT2 is predominantly cytoplasmic during interphase, maintained by active CRM1-dependent nuclear export. Reason: Well-established primary localization of SIRT2. Multiple studies confirm cytoplasmic residence during interphase where it functions as tubulin deacetylase. Supporting Evidence: PMID:17726514 SIRT2 was exclusively cytoplasmic in 99.5% of cells and pancellular in 0.5% PMID:17726514 SIRT2 often appears distinctly localized in the cytoplasm |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: SIRT2 localizes to centrosomes during prophase, colocalizing with Aurora A kinase. Reason: Well-supported by immunofluorescence studies showing SIRT2 enrichment at centrosomes during early mitosis. Supporting Evidence: PMID:17726514 During early prophase, endogenous SIRT2 became enriched at the centrosome demonstrated by its colocalization with Aurora A |
| GO:0005814 centriole | IEA GO_REF:0000044 | ACCEPT | Summary: SIRT2 localizes to centrioles during metaphase. Reason: Experimentally supported localization during mitosis. Supporting Evidence: PMID:17726514 At metaphase, SIRT2 remained concentrated in the centrioles and spread along the spindle fibers |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: SIRT2 localizes along spindle fibers during metaphase. Reason: Well-documented localization pattern during mitosis, consistent with SIRT2's role in cell cycle regulation. Supporting Evidence: PMID:17726514 At metaphase, SIRT2 remained concentrated in the centrioles and spread along the spindle fibers |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: SIRT2 associates with microtubule cytoskeleton as tubulin deacetylase. Reason: Consistent with SIRT2's well-established role as alpha-tubulin K40 deacetylase. |
| GO:0005874 microtubule | IEA GO_REF:0000043 | ACCEPT | Summary: SIRT2 associates with microtubules as the primary tubulin deacetylase. Reason: Core localization related to tubulin deacetylase function. SIRT2 deacetylates alpha-tubulin at K40. |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT2 regulates transcription through histone deacetylation and deacetylation of transcription factors (FOXO, p65, HIF1A). Reason: This is an indirect/downstream effect of SIRT2's deacetylase activity on chromatin and transcription factors, not a direct transcriptional function. |
| GO:0006914 autophagy | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT2 regulates autophagy through deacetylation of FOXO1 (PMID:20543840). Acetylated FOXO1 binds ATG7 to induce autophagy. Reason: SIRT2 negatively regulates autophagy by deacetylating FOXO1. This is a documented but not core function. Supporting Evidence: PMID:20543840 In response to stress, FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2)... the acetylated FoxO1 bound to Atg7 |
| GO:0007399 nervous system development | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT2 is involved in peripheral nerve myelination through Par-3/aPKC signaling (PMID:21949390). Reason: Documented role in Schwann cell myelination but this is a tissue-specific function rather than a core molecular function. Supporting Evidence: PMID:21949390 Sirt2 deacetylates Par-3, a master regulator of cell polarity |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: SIRT2 has been reported to possess ADP-ribosyltransferase activity (PMID:10381378). Reason: While sirtuins can exhibit weak ADP-ribosyltransferase activity, this is not considered a major physiological function of SIRT2. The term is also very general and uninformative. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate annotation - core molecular function of SIRT2. Reason: Fundamental enzymatic activity confirmed by structural and biochemical studies. |
| GO:0030154 cell differentiation | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT2 has been implicated in differentiation of various cell types including muscle (PMID:12887892), adipocytes, and oligodendrocytes. Reason: Very broad term. SIRT2 affects differentiation through its deacetylase activity on various substrates, but this is not a core molecular function. |
| GO:0030426 growth cone | IEA GO_REF:0000044 | UNDECIDED | Summary: Localization based on UniProt subcellular location annotation. Reason: Limited direct experimental evidence for SIRT2 localization to growth cones. May be inferred from neuronal expression and microtubule association. |
| GO:0030496 midbody | IEA GO_REF:0000120 | ACCEPT | Summary: SIRT2 localizes to the midbody during cytokinesis, colocalizing with Aurora B. Reason: Well-documented localization during cytokinesis. Supporting Evidence: PMID:17726514 However, during cytokinesis, SIRT2 associated with the midbody, a structure formed by the bundled microtubules originating from polar microtubules after metaphase. PMID:17726514 We observed that SIRT2 colocalized with Aurora B, a midbody-localized protein |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core molecular function - SIRT2 deacetylates numerous protein substrates including histones, tubulin, and transcription factors in an NAD-dependent manner. Reason: Fundamental enzymatic activity of SIRT2 supported by extensive biochemical evidence. |
| GO:0042995 cell projection | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: General localization potentially related to microtubule association in neuronal projections. Reason: Broad term that may be inferred from SIRT2's microtubule association and expression in neurons. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT2 promotes proteasomal degradation of substrates like HIF1A by deacetylating them, which increases their ubiquitination (PMID:24681946). Reason: Indirect effect - SIRT2 deacetylates substrates, which can then be ubiquitinated and degraded. This is a downstream consequence of deacetylase activity. Supporting Evidence: PMID:24681946 Deacetylation of HIF-1alpha by SIRT2 resulted in increased binding affinity for prolyl hydroxylase 2... and increased HIF-1alpha hydroxylation and ubiquitination |
| GO:0043204 perikaryon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Neuronal cell body localization based on expression in neurons. Reason: Consistent with SIRT2 expression in neurons but represents tissue-specific rather than core localization. |
| GO:0043209 myelin sheath | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: SIRT2 is highly expressed in myelin and functions in peripheral myelination (PMID:21949390). Reason: Tissue-specific localization in Schwann cells related to myelination function. Supporting Evidence: PMID:21949390 Sirt2 expression in SCs is correlated with that of structural myelin components during both developmental myelination and remyelination |
| GO:0043687 post-translational protein modification | IEA GO_REF:0000120 | ACCEPT | Summary: SIRT2 performs deacetylation and defatty-acylation, both post-translational modifications. Reason: Accurate but very broad description of SIRT2's enzymatic function. |
| GO:0045087 innate immune response | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT2 modulates innate immunity through NF-kB regulation and response to bacterial infection (PMID:23908241). Reason: Downstream effect of deacetylase activity on immune signaling pathways. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MODIFY | Summary: SIRT2 contains a zinc-binding domain essential for structure and function. High-resolution human Sirt2 crystal structures (e.g. PDB 4RMG) confirm the two-domain architecture with a smaller zinc-binding domain adjacent to the Rossmann-fold cofactor domain (PMID:25672491). Reason: Should be more specific - SIRT2 binds zinc ion, not general metal ions. Proposed replacements: zinc ion binding Supporting Evidence: PMID:11427894 a smaller domain composed of a helical module and a zinc-binding module PMID:25672491 the two-domain structure typical for sirtuins-a larger domain with a Rossmann fold and a smaller zinc-binding domain that are separated through a large groove that constitutes the active site |
| GO:0046890 regulation of lipid biosynthetic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT2 regulates lipid biosynthesis by deacetylating and destabilizing ACLY (PMID:23932781). Reason: Documented role in lipid metabolism through ACLY regulation, but this is a downstream metabolic consequence of deacetylase activity. Supporting Evidence: PMID:23932781 the protein deacetylase sirtuin 2 (SIRT2) deacetylates and destabilizes ACLY |
| GO:0046970 histone H4K16 deacetylase activity, NAD-dependent | IEA GO_REF:0000117 | ACCEPT | Summary: SIRT2 preferentially deacetylates H4K16, particularly during mitosis, promoting chromatin condensation (PMID:16648462). Reason: Well-established specific substrate preference of SIRT2. H4K16 is the preferred histone substrate. Supporting Evidence: PMID:16648462 SirT2 is a histone deacetylase with preference for histone H4 Lys 16 |
| GO:0051093 negative regulation of developmental process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Very broad term - SIRT2 affects various developmental processes including muscle differentiation and adipogenesis. Reason: Too broad and vague. More specific terms should be used for SIRT2's roles in specific developmental contexts. |
| GO:0051239 regulation of multicellular organismal process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Extremely broad term reflecting SIRT2's pleiotropic effects. Reason: Too general to be informative. More specific process terms are appropriate. |
| GO:0051287 NAD binding | IEA GO_REF:0000002 | ACCEPT | Summary: SIRT2 requires NAD+ as a cofactor for its deacetylase/defatty-acylase activity. Reason: Confirmed by crystal structure showing NAD-binding Rossmann fold domain. Supporting Evidence: PMID:11427894 reveals an NAD-binding domain, which is a variant of the Rossmann fold |
| GO:0051301 cell division | IEA GO_REF:0000043 | ACCEPT | Summary: SIRT2 regulates cell division through multiple mechanisms including chromatin condensation, spindle checkpoint, and cytokinesis. Reason: Core biological process for SIRT2. Well-supported by localization studies and functional analyses. Supporting Evidence: PMID:17726514 SIRT2 contributes to the proper progression through mitosis PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit |
| GO:0051321 meiotic cell cycle | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT2 has been implicated in oocyte maturation and meiosis regulation. Reason: Evidence for meiotic roles exists but is less extensive than mitotic functions. |
| GO:0062013 positive regulation of small molecule metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Broad term reflecting SIRT2's metabolic regulatory functions. Reason: Too general. More specific metabolic process terms are more informative. |
| GO:0070403 NAD+ binding | IEA GO_REF:0000002 | ACCEPT | Summary: SIRT2 binds NAD+ as essential cofactor for catalysis. A high-resolution human Sirt2 structure with the cosubstrate NAD+ (PDB 4RMG) resolves the NAD+ pocket, with the A- and B-pockets binding the ADP-ribose moiety and the C-pocket binding the nicotinamide (PMID:25672491). Reason: Core requirement for SIRT2 enzymatic activity confirmed structurally. Supporting Evidence: PMID:11427894 Sir2 is an NAD-dependent histone deacetylase PMID:25672491 The A- and B-pocket, respectively, bind the ADPR moiety, whereas the C-pocket binds the NCA of NAD+. NAD+ is able to adopt different conformations |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT2 regulates hypoxia response by deacetylating HIF1A, promoting its hydroxylation and degradation (PMID:24681946). Reason: Well-documented role through HIF1A regulation but represents downstream effect of deacetylase activity. Supporting Evidence: PMID:24681946 SIRT2-mediated deacetylation of HIF-1alpha regulates its stability in tumour cells |
| GO:0140773 NAD-dependent protein demyristoylase activity | IEA GO_REF:0000116 | ACCEPT | Summary: SIRT2 possesses efficient demyristoylase activity with kcat/Km higher than deacetylase activity (PMID:25704306). Reason: Well-characterized enzymatic activity supported by kinetic and structural studies. Supporting Evidence: PMID:25704306 The catalytic efficiency (kcat/Km) for the removal of a myristoyl group is slightly higher than that for the removal of an acetyl group |
| GO:0140774 NAD-dependent protein depalmitoylase activity | IEA GO_REF:0000116 | ACCEPT | Summary: SIRT2 can remove palmitoyl groups from lysine residues, though less efficiently than myristoyl groups. Reason: Documented defatty-acylase activity, though myristoyl substrates are preferred. Supporting Evidence: PMID:25704306 the defatty-acylase activity toward palmitoyl groups is not efficient, which may result from the limited depth of the active site |
| GO:0005515 protein binding | IPI PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in c... | MODIFY | Summary: General protein binding based on interaction with CDC14B and other cell cycle regulators. Reason: Protein binding is uninformative. The referenced paper shows SIRT2 interacts with CDC14B phosphatase in context of mitotic regulation. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. |
| GO:0005515 protein binding | IPI PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potentia... | MODIFY | Summary: Interaction with MyoD transcription factor in context of muscle differentiation. Reason: Should be more specific - SIRT2 binds transcription factors to regulate their activity. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. |
| GO:0005515 protein binding | IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by... | REMOVE | Summary: Large-scale protein interaction mapping study. Reason: Generic protein binding annotation from high-throughput screen is uninformative. More specific interaction terms should be used. Supporting Evidence: PMID:17353931 Large-scale mapping of human protein-protein interactions by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:21081649 SIRT2 regulates NF-ΞΊB dependent gene expression through deac... | MODIFY | Summary: Interaction with p65/RELA subunit of NF-kB. Reason: Should be annotated with more specific term for transcription factor binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:21081649 SIRT2 interacts with p65 in the cytoplasm and deacetylates p65 in vitro and in vivo |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | REMOVE | Summary: Protein interactome study for autism-related pathways. Reason: Generic protein binding from interaction screen is uninformative. Supporting Evidence: PMID:21653829 Protein interactome reveals converging molecular pathways among autism disorders. |
| GO:0005515 protein binding | IPI PMID:24769394 Regulation of G6PD acetylation by SIRT2 and KAT9 modulates N... | KEEP AS NON CORE | Summary: Interaction with G6PD (glucose-6-phosphate dehydrogenase). Reason: Represents a specific substrate interaction. SIRT2 deacetylates G6PD to regulate pentose phosphate pathway. Supporting Evidence: PMID:24769394 Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. |
| GO:0005515 protein binding | IPI PMID:24825348 SIRT2 induces the checkpoint kinase BubR1 to increase lifesp... | MODIFY | Summary: Interaction with BubR1 checkpoint kinase. Reason: Should use more specific term. SIRT2 deacetylates BubR1 in spindle checkpoint. Proposed replacements: protein kinase binding Supporting Evidence: PMID:24825348 SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput proteome-scale interaction study. Reason: Generic protein binding from large-scale screen is uninformative. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:15213244 Human histone deacetylase SIRT2 interacts with the homeobox ... | MODIFY | Summary: Interaction with HOXA10 homeobox transcription factor. Reason: Should be more specific - transcription factor binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:15213244 Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10. |
| GO:0005515 protein binding | IPI PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | MODIFY | Summary: Interaction with FOXO1 transcription factor. Reason: SIRT2 binds and deacetylates FOXO1. Should be transcription factor binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:20543840 FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2) |
| GO:0005515 protein binding | IPI PMID:27512957 Oncogenic microtubule hyperacetylation through BEX4-mediated... | KEEP AS NON CORE | Summary: Interaction with BEX4 which inhibits SIRT2 tubulin deacetylase activity. Reason: Documents regulatory interaction but protein binding term is too general. Supporting Evidence: PMID:27512957 Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2 inhibition. |
| GO:0005515 protein binding | IPI PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± ... | MODIFY | Summary: Interaction with HIF1A. Reason: SIRT2 binds and deacetylates HIF1A transcription factor. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:24681946 SIRT2 directly interacted with HIF-1alpha and deacetylated Lys709 of HIF-1alpha |
| GO:0005515 protein binding | IPI PMID:18722353 Acetylation of Sirt2 by p300 attenuates its deacetylase acti... | MODIFY | Summary: Interaction with p300 acetyltransferase. Reason: SIRT2 is acetylated and regulated by p300. Should use histone acetyltransferase binding. Proposed replacements: histone acetyltransferase binding Supporting Evidence: PMID:18722353 p300 interacts with Sirt2... and triggers the acetylation |
| GO:0005515 protein binding | IPI PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination t... | KEEP AS NON CORE | Summary: Interaction with Par-3 polarity protein. Reason: Specific substrate interaction in context of myelination. Supporting Evidence: PMID:21949390 Sirt2 deacetylates Par-3, a master regulator of cell polarity |
| GO:0005515 protein binding | IPI PMID:23932781 Acetylation stabilizes ATP-citrate lyase to promote lipid bi... | KEEP AS NON CORE | Summary: Interaction with ACLY (ATP-citrate lyase). Reason: Specific substrate interaction. SIRT2 deacetylates ACLY to regulate lipid metabolism. Supporting Evidence: PMID:23932781 the protein deacetylase sirtuin 2 (SIRT2) deacetylates and destabilizes ACLY |
| GO:0005515 protein binding | IPI PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of ... | MODIFY | Summary: Interaction with Aurora A and Aurora B kinases. Reason: SIRT2 interacts with Aurora kinases during mitosis. Should be protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:17726514 coimmunoprecipitation experiments with FLAG-tagged SIRT2 and Myc-tagged Aurora A indicate that these two proteins interact |
| GO:0005515 protein binding | IPI PMID:17172643 Multiple histone deacetylases and the CREB-binding protein r... | MODIFY | Summary: Interaction with CBP in context of pre-mRNA 3-end processing. Reason: CBP is a histone acetyltransferase. Should use more specific term. Proposed replacements: histone acetyltransferase binding Supporting Evidence: PMID:17172643 2006 Dec 17. Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 represses transcription through histone deacetylation and transcription factor modification. Reason: Indirect effect through substrate modification. |
| GO:0004407 histone deacetylase activity | IEA GO_REF:0000107 | MODIFY | Summary: General HDAC activity - should be NAD-dependent specific term. Reason: SIRT2 is a class III NAD-dependent HDAC, not a Zn-dependent HDAC. Proposed replacements: histone deacetylase activity, NAD-dependent |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | REMOVE | Summary: SIRT2 is primarily cytoplasmic, not mitochondrial. Reason: SIRT2 is the cytoplasmic sirtuin. SIRT3-5 are the mitochondrial sirtuins. Any mitochondrial detection likely represents contamination. |
| GO:0016042 lipid catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 affects lipid metabolism through multiple substrates. Reason: Metabolic consequence of deacetylase activity. |
| GO:0022011 myelination in peripheral nervous system | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 regulates peripheral myelination. Reason: Tissue-specific function documented in mouse studies. |
| GO:0031641 regulation of myelination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 regulates myelination through Par-3/aPKC pathway. Reason: Tissue-specific function. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: SIRT2 promotes substrate degradation through deacetylation. Reason: Indirect effect. |
| GO:0033010 paranodal junction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 localization in myelin structures. Reason: Tissue-specific localization. |
| GO:0033558 protein lysine deacetylase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Broad deacetylase activity on non-histone substrates. Reason: Core enzymatic function - SIRT2 deacetylates many protein substrates. |
| GO:0034599 cellular response to oxidative stress | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 involved in oxidative stress response. Reason: Pleiotropic effect through various substrates. |
| GO:0040029 epigenetic regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: SIRT2 affects gene expression through histone deacetylation. Reason: Direct epigenetic function through H4K16 and H3K18 deacetylation. |
| GO:0042903 tubulin deacetylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: SIRT2 is the primary tubulin deacetylase. Reason: Core enzymatic function. |
| GO:0043220 Schmidt-Lanterman incisure | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 localization in myelin structures. Reason: Tissue-specific localization. |
| GO:0045599 negative regulation of fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 inhibits adipogenesis. Reason: Tissue-specific developmental function. |
| GO:0045836 positive regulation of meiotic nuclear division | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 role in meiosis from ortholog data. Reason: Less characterized than mitotic functions. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Context-dependent positive transcriptional regulation. Reason: Indirect effect - SIRT2 effects on transcription are substrate-dependent. |
| GO:0051781 positive regulation of cell division | IEA GO_REF:0000107 | ACCEPT | Summary: SIRT2 promotes proper cell division. Reason: Consistent with cell cycle functions. |
| GO:0051987 positive regulation of attachment of spindle microtubules to kinetochore | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 role in spindle checkpoint. Reason: Related to cell cycle function. |
| GO:0061433 cellular response to caloric restriction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sirtuins involved in metabolic adaptation. Reason: General sirtuin function. |
| GO:0071872 cellular response to epinephrine stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 involved in hormonal metabolic responses. Reason: Physiological context. |
| GO:1900119 positive regulation of execution phase of apoptosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 can promote apoptosis in certain contexts. Reason: Context-dependent effect. |
| GO:1900195 positive regulation of oocyte maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 role in oocyte maturation. Reason: Tissue-specific function. |
| GO:2000378 negative regulation of reactive oxygen species metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT2 affects ROS through multiple pathways. Reason: Indirect effect. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nuclear localization confirmed by immunofluorescence in HPA/Cell Atlas. Reason: Consistent with SIRT2 nuclear shuttling and chromatin association. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | REMOVE | Summary: Interestingly, SIRT2 appears to be excluded from nucleoli when nuclear. Reason: Contradicts published data showing SIRT2 is excluded from nucleoli. Supporting Evidence: PMID:17726514 Upon LMB treatment, SIRT2-FLAG was sequestered in the nucleus but was excluded from the nucleoli |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic localization confirmed by immunofluorescence. Reason: Primary localization of SIRT2 during interphase. |
| GO:0007084 mitotic nuclear membrane reassembly | TAS Reactome:R-HSA-2995410 | KEEP AS NON CORE | Summary: SIRT2 involved in nuclear envelope reassembly pathway via ANKLE2 deacetylation. Reason: Documented Reactome pathway but represents specific mitotic function. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | TAS Reactome:R-HSA-9667952 | ACCEPT | Summary: SIRT2 deacetylates ANKLE2 in Reactome pathway. Reason: Core enzymatic function in curated pathway. |
| GO:0140219 histone methacryllysine demethacrylase activity | IDA PMID:34961760 Histone lysine methacrylation is a dynamic post-translationa... | ACCEPT | Summary: SIRT2 can remove methacryl modification from histone lysines. Reason: Newly characterized enzymatic activity extending SIRT2's substrate range. Supporting Evidence: PMID:34961760 Histone lysine methacrylation is a dynamic post-translational modification regulated by HAT1 and SIRT2. |
| GO:0140228 histone benzoyllysine debenzoylase activity | IDA PMID:30154464 Lysine benzoylation is a histone mark regulated by SIRT2. | ACCEPT | Summary: SIRT2 regulates histone lysine benzoylation by removing benzoyl groups. Reason: Experimentally validated enzymatic activity. Supporting Evidence: PMID:30154464 Lysine benzoylation is a histone mark regulated by SIRT2. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | REMOVE | Summary: Mitochondrial localization from high-throughput proteomics. Reason: SIRT2 is primarily cytoplasmic. Mitochondrial detection likely reflects cytoplasmic contamination or non-specific association. SIRT3-5 are the established mitochondrial sirtuins. Supporting Evidence: PMID:34800366 Epub 2021 Nov 19. Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:23932781 Acetylation stabilizes ATP-citrate lyase to promote lipid bi... | ACCEPT | Summary: Direct demonstration of NAD-dependent deacetylase activity on ACLY substrate. Reason: Core enzymatic function confirmed with specific substrate. Supporting Evidence: PMID:23932781 the protein deacetylase sirtuin 2 (SIRT2) deacetylates and destabilizes ACLY |
| GO:1902725 negative regulation of satellite cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Inferred from mouse Sirt2 function in muscle. Reason: Supported by mouse studies but represents tissue-specific function. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IMP PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± ... | KEEP AS NON CORE | Summary: SIRT2 promotes HIF1A degradation by deacetylation leading to ubiquitination. Reason: Downstream effect of SIRT2 deacetylase activity on specific substrates. Supporting Evidence: PMID:24681946 Deacetylation of HIF-1alpha by SIRT2 resulted in... increased HIF-1alpha hydroxylation and ubiquitination |
| GO:0040029 epigenetic regulation of gene expression | IMP PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in ba... | ACCEPT | Summary: SIRT2 H3K18 deacetylation affects gene expression during infection. Reason: Direct epigenetic function through histone modification. Supporting Evidence: PMID:23908241 SIRT2 associates with the transcription start site of a subset of genes repressed during infection and deacetylates histone H3 on lysine 18 |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | TAS NOT PMID:17456799 Sirtuin functions in health and disease. | ACCEPT | Summary: This is a NOT annotation indicating SIRT2 does not have NAD+-protein mono-ADP-ribosyltransferase activity per the cited review. Reason: The GOA record uses a NOT qualifier for this activity; we accept the negated annotation as the current curation position for SIRT2. Supporting Evidence: PMID:17456799 Apr 24. Sirtuin functions in health and disease. |
| GO:0045723 positive regulation of fatty acid biosynthetic process | IDA PMID:23932781 Acetylation stabilizes ATP-citrate lyase to promote lipid bi... | REMOVE | Summary: Counter-intuitive annotation - SIRT2 actually destabilizes ACLY and should inhibit fatty acid synthesis. This annotation appears to be an error. Reason: SIRT2 deacetylates and destabilizes ACLY, which should NEGATIVELY regulate fatty acid synthesis, not positively. The referenced paper states SIRT2 deacetylates and destabilizes ACLY - stabilization of ACLY promotes lipid synthesis. Supporting Evidence: PMID:23932781 the protein deacetylase sirtuin 2 (SIRT2) deacetylates and destabilizes ACLY |
| GO:0140773 NAD-dependent protein demyristoylase activity | IDA PMID:25704306 Efficient demyristoylase activity of SIRT2 revealed by kinet... | ACCEPT | Summary: Kinetic and structural characterization of SIRT2 demyristoylase activity. Reason: Core enzymatic function with higher catalytic efficiency than deacetylation. Supporting Evidence: PMID:25704306 The catalytic efficiency (kcat/Km) for the removal of a myristoyl group is slightly higher than that for the removal of an acetyl group |
| GO:0140773 NAD-dependent protein demyristoylase activity | IDA PMID:32103017 NMT1 and NMT2 are lysine myristoyltransferases regulating th... | ACCEPT | Summary: Demyristoylase activity demonstrated in cellular context. Reason: Additional experimental support for demyristoylase activity. Supporting Evidence: PMID:32103017 NMT1 and NMT2 are lysine myristoyltransferases regulating the ARF6 GTPase cycle. |
| GO:0140774 NAD-dependent protein depalmitoylase activity | IDA PMID:32103017 NMT1 and NMT2 are lysine myristoyltransferases regulating th... | ACCEPT | Summary: Depalmitoylase activity demonstrated experimentally. Reason: Documented enzymatic activity though less efficient than demyristoylation. Supporting Evidence: PMID:32103017 NMT1 and NMT2 are lysine myristoyltransferases regulating the ARF6 GTPase cycle. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potentia... | ACCEPT | Summary: SIRT2 interacts with MyoD transcription factor. Reason: More specific than generic protein binding. Supporting Evidence: PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:15126506 FOXO4 is acetylated upon peroxide stress and deacetylated by... | REMOVE | Summary: Referenced paper is about SIRT1/FOXO4 interaction, not SIRT2. Reason: Incorrect gene - this paper describes SIRT1, not SIRT2, interacting with FOXO4. Supporting Evidence: PMID:15126506 2004 May 4. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:10381378 Characterization of five human cDNAs with homology to the ye... | REMOVE | Summary: Early study suggesting ADP-ribosyltransferase activity based on NAD labeling. Reason: The activity described was mono-ADP-ribosylation, not poly-ADP-ribosylation. SIRT2 does not have poly-ADP-ribosyltransferase activity. Annotation should be to GO:1990404 (NAD+-protein mono-ADP-ribosyltransferase activity) instead. Proposed replacements: NAD+-protein mono-ADP-ribosyltransferase activity Supporting Evidence: PMID:10381378 Recombinant E. coli cobB and human SIRT2 sirtuin proteins were able to cause radioactivity to be transferred from [32P]NAD to bovine serum albumin |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9667952 | ACCEPT | Summary: Cytosolic SIRT2 in Reactome pathway. Reason: Consistent with primary localization. |
| GO:0042903 tubulin deacetylase activity | IDA PMID:23886946 Furry promotes acetylation of microtubules in the mitotic sp... | ACCEPT | Summary: SIRT2 tubulin deacetylase activity demonstrated in mitotic spindle context. Reason: Well-established core function of SIRT2 on alpha-tubulin K40. Supporting Evidence: PMID:23886946 Jul 25. Furry promotes acetylation of microtubules in the mitotic spindle by inhibition of SIRT2 tubulin deacetylase. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± ... | KEEP AS NON CORE | Summary: SIRT2 negatively regulates HIF1A-dependent transcription by destabilizing HIF1A. Reason: Indirect transcriptional effect through substrate modification. Supporting Evidence: PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± hydroxylation. |
| GO:0005829 cytosol | IDA PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± ... | ACCEPT | Summary: Cytosolic SIRT2 deacetylates HIF1A. Reason: Confirms cytosolic function. Supporting Evidence: PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± hydroxylation. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Conserved function from ortholog data. Reason: Downstream effect of deacetylase activity. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IMP PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± ... | ACCEPT | Summary: NAD-dependent deacetylation of HIF1A demonstrated by mutant analysis. Reason: Core function confirmed. Supporting Evidence: PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± hydroxylation. |
| GO:0071456 cellular response to hypoxia | IDA PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± ... | KEEP AS NON CORE | Summary: SIRT2 modulates hypoxia response through HIF1A regulation. Reason: Specific physiological context for SIRT2 function. Supporting Evidence: PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± hydroxylation. |
| GO:0005737 cytoplasm | IDA PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | ACCEPT | Summary: Cytoplasmic localization where SIRT2 deacetylates FOXO1. Reason: Confirms cytoplasmic function. Supporting Evidence: PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. |
| GO:0006476 protein deacetylation | IDA PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | ACCEPT | Summary: SIRT2 deacetylates FOXO1 transcription factor. Reason: Core biological process for SIRT2. Supporting Evidence: PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. |
| GO:0010507 negative regulation of autophagy | IMP PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | KEEP AS NON CORE | Summary: SIRT2 inhibits autophagy by deacetylating FOXO1. Reason: Documented but not core function. Supporting Evidence: PMID:20543840 FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2)... the acetylated FoxO1 bound to Atg7... to influence the autophagic process |
| GO:0033558 protein lysine deacetylase activity | IDA PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | ACCEPT | Summary: SIRT2 deacetylates FOXO1. Reason: Confirms broad substrate specificity beyond histones. Supporting Evidence: PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. |
| GO:0034599 cellular response to oxidative stress | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 involved in oxidative stress response through multiple substrates. Reason: Pleiotropic effect through various substrates including FOXO factors. |
| GO:0042177 negative regulation of protein catabolic process | IMP PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | KEEP AS NON CORE | Summary: SIRT2 inhibits autophagy-mediated protein degradation. Reason: Indirect effect through autophagy regulation. Supporting Evidence: PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. |
| GO:0043388 positive regulation of DNA binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Inferred from ortholog - SIRT2 affects transcription factor DNA binding. Reason: Indirect effect through deacetylation of transcription factors. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Context-dependent transcriptional regulation. Reason: Indirect effect - SIRT2 can both activate and repress transcription depending on substrate. |
| GO:0061433 cellular response to caloric restriction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sirtuins involved in metabolic adaptation to caloric restriction. Reason: General sirtuin function but not uniquely characteristic of SIRT2. |
| GO:1900119 positive regulation of execution phase of apoptosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 can promote apoptosis in certain contexts. Reason: Context-dependent effect, not core function. |
| GO:2000378 negative regulation of reactive oxygen species metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 affects ROS through multiple pathways including FOXO factors. Reason: Indirect effect through substrate modification. |
| GO:0045836 positive regulation of meiotic nuclear division | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 role in meiosis inferred from orthologs. Reason: Less well-characterized than mitotic functions. |
| GO:0051781 positive regulation of cell division | ISS GO_REF:0000024 | ACCEPT | Summary: SIRT2 promotes proper cell division. Reason: Consistent with well-documented mitotic functions. |
| GO:0051987 positive regulation of attachment of spindle microtubules to kinetochore | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 role in spindle checkpoint. Reason: Related to cell cycle function but specific mechanism unclear. |
| GO:1900195 positive regulation of oocyte maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 role in oocyte maturation from ortholog data. Reason: Tissue-specific developmental function. |
| GO:0006476 protein deacetylation | IDA PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination t... | ACCEPT | Summary: SIRT2 deacetylates Par-3 in Schwann cells. Reason: Core biological process demonstrated with specific substrate. Supporting Evidence: PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. |
| GO:0010801 negative regulation of peptidyl-threonine phosphorylation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 affects phosphorylation through aPKC regulation in myelination. Reason: Specific to Schwann cell function. |
| GO:0022011 myelination in peripheral nervous system | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 regulates peripheral myelination through Par-3/aPKC. Reason: Tissue-specific function well-documented in mouse. Supporting Evidence: PMID:21949390 Sirt2 deacetylates Par-3, a master regulator of cell polarity |
| GO:0031641 regulation of myelination | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 regulates Schwann cell myelination. Reason: Tissue-specific function. |
| GO:0033010 paranodal junction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 localization in myelin structures from mouse studies. Reason: Tissue-specific localization in myelinating cells. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination t... | ACCEPT | Summary: NAD-dependent deacetylation of Par-3. Reason: Core enzymatic function. Supporting Evidence: PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. |
| GO:0043219 lateral loop | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 localization in myelin structures. Reason: Tissue-specific localization. |
| GO:0043220 Schmidt-Lanterman incisure | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 localization in myelin structures. Reason: Tissue-specific localization. |
| GO:0003682 chromatin binding | IDA PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in ba... | ACCEPT | Summary: SIRT2 associates with transcription start sites during bacterial infection. Reason: Demonstrated by ChIP showing SIRT2 at gene promoters. Supporting Evidence: PMID:23908241 SIRT2 associates with the transcription start site of a subset of genes repressed during infection |
| GO:0005634 nucleus | IDA PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in ba... | ACCEPT | Summary: SIRT2 translocates to nucleus during bacterial infection. Reason: Demonstrates stimulus-induced nuclear translocation. Supporting Evidence: PMID:23908241 the host deacetylase sirtuin 2 (SIRT2) translocates to the nucleus |
| GO:0005737 cytoplasm | IDA PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in ba... | ACCEPT | Summary: SIRT2 is cytoplasmic under basal conditions. Reason: Primary localization confirmed. Supporting Evidence: PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. |
| GO:0016042 lipid catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 affects lipid metabolism through ACLY and other substrates. Reason: Metabolic consequence of deacetylase activity. |
| GO:0033558 protein lysine deacetylase activity | IMP PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in ba... | ACCEPT | Summary: SIRT2 deacetylase activity required for H3K18 deacetylation during infection. Reason: Confirms deacetylase function in physiological context. Supporting Evidence: PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. |
| GO:0071872 cellular response to epinephrine stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 involved in metabolic responses to hormonal stimuli. Reason: Physiological context for metabolic regulation. |
| GO:0045599 negative regulation of fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 inhibits adipocyte differentiation. Reason: Tissue-specific developmental function. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:18722353 Acetylation of Sirt2 by p300 attenuates its deacetylase acti... | KEEP AS NON CORE | Summary: SIRT2 inhibits p53-dependent transcription when active. Reason: Indirect transcriptional effect. Supporting Evidence: PMID:18722353 the acetylation of Sirt2 by p300 relieves the inhibitory effect of Sirt2 on the transcriptional activity of p53 |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:18722353 Acetylation of Sirt2 by p300 attenuates its deacetylase acti... | ACCEPT | Summary: SIRT2 NAD-dependent deacetylase activity regulated by p300 acetylation. Reason: Core function with regulatory mechanism characterized. Supporting Evidence: PMID:18722353 Acetylation of Sirt2 by p300 attenuates its deacetylase activity. |
| GO:0042903 tubulin deacetylase activity | IDA PMID:18722353 Acetylation of Sirt2 by p300 attenuates its deacetylase acti... | ACCEPT | Summary: SIRT2 deacetylates tubulin. Reason: Duplicate of well-supported core function. Supporting Evidence: PMID:18722353 Acetylation of Sirt2 by p300 attenuates its deacetylase activity. |
| GO:0090042 tubulin deacetylation | IDA PMID:18722353 Acetylation of Sirt2 by p300 attenuates its deacetylase acti... | ACCEPT | Summary: SIRT2 deacetylates tubulin. Reason: Core biological process for cytoplasmic SIRT2. Supporting Evidence: PMID:18722353 Acetylation of Sirt2 by p300 attenuates its deacetylase activity. |
| GO:0000792 heterochromatin | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 associates with heterochromatin, inferred from Sir2 function. Reason: Chromatin association during mitosis is documented, but constitutive heterochromatin localization is less clear. |
| GO:0005634 nucleus | IDA PMID:16648462 SirT2 is a histone deacetylase with preference for histone H... | ACCEPT | Summary: SIRT2 enters nucleus during mitosis for H4K16 deacetylation. Reason: Cell cycle-dependent nuclear localization. Supporting Evidence: PMID:16648462 SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. |
| GO:0005694 chromosome | IDA PMID:16648462 SirT2 is a histone deacetylase with preference for histone H... | ACCEPT | Summary: SIRT2 associates with chromosomes during mitosis. Reason: Consistent with H4K16 deacetylation function during mitosis. Supporting Evidence: PMID:16648462 SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. |
| GO:0005737 cytoplasm | IDA PMID:16648462 SirT2 is a histone deacetylase with preference for histone H... | ACCEPT | Summary: Primary cytoplasmic localization during interphase. Reason: Well-established localization pattern. Supporting Evidence: PMID:16648462 SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. |
| GO:0033270 paranode region of axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 in myelin structures from mouse data. Reason: Tissue-specific localization. |
| GO:0043204 perikaryon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuronal cell body localization. Reason: Tissue-specific localization. |
| GO:0043209 myelin sheath | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 in myelin from mouse studies. Reason: Tissue-specific localization. |
| GO:0044224 juxtaparanode region of axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 in axonal structures from mouse data. Reason: Tissue-specific localization. |
| GO:0046970 histone H4K16 deacetylase activity, NAD-dependent | IDA PMID:16648462 SirT2 is a histone deacetylase with preference for histone H... | ACCEPT | Summary: SIRT2 shows preference for H4K16 deacetylation during mitosis. Reason: Specific substrate preference established by biochemical studies. Supporting Evidence: PMID:16648462 SirT2 is a histone deacetylase with preference for histone H4 Lys 16 |
| GO:0070446 negative regulation of oligodendrocyte progenitor proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT2 role in CNS myelination from mouse studies. Reason: Tissue-specific function. |
| GO:0090042 tubulin deacetylation | ISS GO_REF:0000024 | ACCEPT | Summary: Conserved tubulin deacetylation function. Reason: Core biological process for SIRT2. |
| GO:0004407 histone deacetylase activity | IDA PMID:17488717 Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dep... | MODIFY | Summary: SIRT2 histone deacetylase activity regulated by CDK1 phosphorylation. Reason: Should be the more specific NAD-dependent term since SIRT2 is a class III HDAC. Proposed replacements: histone deacetylase activity, NAD-dependent Supporting Evidence: PMID:17488717 2007 May 8. Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent phosphorylation. |
| GO:0005634 nucleus | IDA PMID:15213244 Human histone deacetylase SIRT2 interacts with the homeobox ... | ACCEPT | Summary: Nuclear SIRT2 interacts with HOXA10 transcription factor. Reason: Confirms nuclear functions of SIRT2. Supporting Evidence: PMID:15213244 Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10. |
| GO:0005634 nucleus | IDA PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of ... | ACCEPT | Summary: SIRT2 accumulates in nucleus upon LMB treatment or during mitosis. Reason: Key study on nuclear shuttling. Supporting Evidence: PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis. |
| GO:0005737 cytoplasm | IDA PMID:15213244 Human histone deacetylase SIRT2 interacts with the homeobox ... | ACCEPT | Summary: Cytoplasmic localization observed. Reason: Consistent with other studies. Supporting Evidence: PMID:15213244 Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10. |
| GO:0005737 cytoplasm | IDA PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of ... | ACCEPT | Summary: SIRT2 predominantly cytoplasmic during interphase due to active nuclear export. Reason: Key study characterizing SIRT2 localization dynamics. Supporting Evidence: PMID:17726514 SIRT2 was exclusively cytoplasmic in 99.5% of cells |
| GO:0005813 centrosome | IDA PMID:17488717 Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dep... | ACCEPT | Summary: SIRT2 localizes to centrosome, phosphorylated by CDK1. Reason: Mitotic localization confirmed. Supporting Evidence: PMID:17488717 2007 May 8. Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent phosphorylation. |
| GO:0005813 centrosome | IDA PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of ... | ACCEPT | Summary: SIRT2 enriched at centrosome during prophase. Reason: Well-documented mitotic localization. Supporting Evidence: PMID:17726514 During early prophase, endogenous SIRT2 became enriched at the centrosome |
| GO:0005814 centriole | IDA PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of ... | ACCEPT | Summary: SIRT2 concentrated at centrioles during metaphase. Reason: Detailed mitotic localization study. Supporting Evidence: PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis. |
| GO:0005819 spindle | IDA PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of ... | ACCEPT | Summary: SIRT2 spreads along spindle fibers during metaphase. Reason: Consistent with tubulin deacetylase function. Supporting Evidence: PMID:17726514 At metaphase, SIRT2 remained concentrated in the centrioles and spread along the spindle fibers |
| GO:0030496 midbody | IDA PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of ... | ACCEPT | Summary: SIRT2 localizes to midbody during cytokinesis, colocalizing with Aurora B. Reason: Critical localization for cytokinesis function. Supporting Evidence: PMID:17726514 during cytokinesis, SIRT2 associated with the midbody |
| GO:0048471 perinuclear region of cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Perinuclear localization pattern. Reason: May reflect centrosomal/MTOC association. |
| GO:0051726 regulation of cell cycle | IMP PMID:17726514 Interphase nucleo-cytoplasmic shuttling and localization of ... | ACCEPT | Summary: SIRT2 overexpression affects mitotic progression and causes multinucleation. Reason: Core function of SIRT2 in cell cycle regulation. Supporting Evidence: PMID:17726514 Overexpression of wild-type GFP-SIRT2 increased by 3-fold, while overexpression of catalytically inactive GFP-SIRT2 resulted in a 5.5-fold in the number of cells containing 2 or more nuclei, suggesting that SIRT2 contributes to the proper progression through mitosis. |
| GO:0021762 substantia nigra development | HEP PMID:22926577 Quantitative proteomic analysis of human substantia nigra in... | UNDECIDED | Summary: SIRT2 detected in substantia nigra proteomics study comparing neurodegenerative diseases. Reason: Expression-based annotation from disease study. Does not demonstrate direct role in substantia nigra development. Supporting Evidence: PMID:22926577 2012 Aug 28. Quantitative proteomic analysis of human substantia nigra in Alzheimer's disease, Huntington's disease and Multiple sclerosis. |
| GO:0034983 peptidyl-lysine deacetylation | IDA PMID:23932781 Acetylation stabilizes ATP-citrate lyase to promote lipid bi... | ACCEPT | Summary: SIRT2 deacetylates ACLY at specific lysine residues. Reason: Core biological process with specific substrate. Supporting Evidence: PMID:23932781 2013 Aug 8. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IMP PMID:21841822 Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-media... | KEEP AS NON CORE | Summary: SIRT2 deacetylates FOXO3, leading to its ubiquitination and degradation. Reason: Indirect effect on protein stability through deacetylation. Supporting Evidence: PMID:21841822 Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. |
| GO:0008270 zinc ion binding | IDA PMID:11427894 Structure of the histone deacetylase SIRT2 | ACCEPT | Summary: Crystal structure reveals zinc-binding module essential for SIRT2 structure. Reason: Structurally confirmed - zinc binding is required for proper folding. Supporting Evidence: PMID:11427894 a smaller domain composed of a helical module and a zinc-binding module |
| GO:0017136 histone deacetylase activity, NAD-dependent | IDA PMID:11427894 Structure of the histone deacetylase SIRT2 | ACCEPT | Summary: Crystal structure and mutagenesis confirm NAD-dependent histone deacetylase activity. Reason: Foundational structural study establishing SIRT2 enzymatic mechanism. Supporting Evidence: PMID:11427894 Structure of the histone deacetylase SIRT2. |
| GO:0070403 NAD+ binding | IDA PMID:11427894 Structure of the histone deacetylase SIRT2 | ACCEPT | Summary: NAD-binding domain structurally characterized in SIRT2. Reason: Essential cofactor binding confirmed by crystal structure. Supporting Evidence: PMID:11427894 Structure of the histone deacetylase SIRT2. |
| GO:0005737 cytoplasm | IDA PMID:16079181 Evolutionarily conserved and nonconserved cellular localizat... | ACCEPT | Summary: Comparative study confirming SIRT2 cytoplasmic localization. Reason: Systematic characterization of sirtuin localization. Supporting Evidence: PMID:16079181 2005 Aug 3. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. |
| GO:0033558 protein lysine deacetylase activity | IDA PMID:17172643 Multiple histone deacetylases and the CREB-binding protein r... | ACCEPT | Summary: Broad protein deacetylase activity demonstrated. Reason: SIRT2 deacetylates many non-histone substrates, making this general term appropriate. Supporting Evidence: PMID:17172643 2006 Dec 17. Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | TAS NOT PMID:17456799 Sirtuin functions in health and disease. | ACCEPT | Summary: This is a NOT annotation indicating SIRT2 does not have NAD+ poly-ADP- ribosyltransferase activity. Reason: The GOA record uses a NOT qualifier for this activity; we accept the negated annotation. Supporting Evidence: PMID:17456799 Apr 24. Sirtuin functions in health and disease. |
| GO:0005737 cytoplasm | IDA PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in c... | ACCEPT | Summary: Cytoplasmic SIRT2 interacts with cell cycle regulators. Reason: Functional cytoplasmic localization. Supporting Evidence: PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. |
| GO:0005874 microtubule | IDA PMID:12620231 The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin... | ACCEPT | Summary: SIRT2 associates with microtubules as tubulin deacetylase. Reason: Foundational study on SIRT2-microtubule association. Supporting Evidence: PMID:12620231 The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. |
| GO:0007096 regulation of exit from mitosis | NAS PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in c... | ACCEPT | Summary: SIRT2 regulates mitotic exit through CDC14B interaction. Reason: Core cell cycle function of SIRT2. Supporting Evidence: PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IDA PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in c... | ACCEPT | Summary: SIRT2 histone deacetylase activity in context of cell cycle regulation. Reason: Core function confirmed with cellular substrates. Supporting Evidence: PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. |
| GO:0035035 histone acetyltransferase binding | IPI PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potentia... | ACCEPT | Summary: SIRT2 interacts with PCAF acetyltransferase. Reason: Documented regulatory interaction with opposing enzyme. Supporting Evidence: PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. |
| GO:0042325 regulation of phosphorylation | NAS PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in c... | KEEP AS NON CORE | Summary: SIRT2 affects phosphorylation through phosphatase interactions. Reason: Indirect effect through CDC14B interaction. Supporting Evidence: PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. |
| GO:0042826 histone deacetylase binding | IPI PMID:12620231 The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin... | ACCEPT | Summary: SIRT2 interacts with HDAC6 in tubulin deacetylation complex. Reason: Documented interaction with class II HDAC. Supporting Evidence: PMID:12620231 The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. |
| GO:0042903 tubulin deacetylase activity | IDA PMID:12620231 The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin... | ACCEPT | Summary: Original demonstration of SIRT2 tubulin deacetylase activity. Reason: Foundational paper establishing SIRT2 as major tubulin deacetylase. Supporting Evidence: PMID:12620231 The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. |
| GO:0043130 ubiquitin binding | IDA PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in c... | KEEP AS NON CORE | Summary: SIRT2 interacts with polyubiquitinated proteins. Reason: Documented but functional significance unclear. Supporting Evidence: PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. |
| GO:0045843 negative regulation of striated muscle tissue development | IDA PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potentia... | KEEP AS NON CORE | Summary: SIRT2 inhibits muscle differentiation through MyoD deacetylation. Reason: Tissue-specific developmental function. Supporting Evidence: PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potentia... | KEEP AS NON CORE | Summary: SIRT2 represses MyoD-dependent transcription. Reason: Indirect transcriptional effect through substrate deacetylation. Supporting Evidence: PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. |
| GO:0051775 response to redox state | NAS PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potentia... | ACCEPT | Summary: SIRT2 activity influenced by cellular NAD+/NADH ratio. Reason: NAD-dependent activity inherently links SIRT2 to cellular redox state. Supporting Evidence: PMID:12887892 Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. |
| GO:0000183 rDNA heterochromatin formation | NAS PMID:11427894 Structure of the histone deacetylase SIRT2 | KEEP AS NON CORE | Summary: Extrapolated from yeast Sir2 function mentioned in structural paper. Reason: Based on yeast homolog function. Human SIRT2 is primarily cytoplasmic. Supporting Evidence: PMID:11427894 Structure of the histone deacetylase SIRT2. |
| GO:0031507 heterochromatin formation | NAS PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in c... | KEEP AS NON CORE | Summary: SIRT2 role in heterochromatin from H4K16 deacetylation. Reason: Related to chromatin function but primary role is during mitosis. Supporting Evidence: PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. |
| GO:0031509 subtelomeric heterochromatin formation | NAS PMID:11427894 Structure of the histone deacetylase SIRT2 | UNDECIDED | Summary: Extrapolated from yeast Sir2 telomeric silencing function. Reason: Limited direct evidence for human SIRT2 in telomeric silencing. Supporting Evidence: PMID:11427894 Structure of the histone deacetylase SIRT2. |
| GO:0031115 negative regulation of microtubule polymerization | IDA PMID:23886946 Furry promotes acetylation of microtubules in the mitotic sp... | NEW | Summary: SIRT2 deacetylates alpha-tubulin at K40, which destabilizes microtubules. Reason: Direct consequence of SIRT2 tubulin deacetylase activity - deacetylation promotes microtubule depolymerization. Supporting Evidence: PMID:23886946 AGK2, a specific inhibitor of SIRT2, increased the level of MT acetylation in the mitotic spindle, indicating that SIRT2 is involved in the deacetylation of spindle MTs |
| GO:0016192 vesicle-mediated transport | IMP PMID:32103017 NMT1 and NMT2 are lysine myristoyltransferases regulating th... | NEW | Summary: SIRT2 demyristoylates ARF6 to regulate vesicle trafficking. Reason: Demyristoylation of ARF6 by SIRT2 affects membrane trafficking and vesicle formation. Supporting Evidence: PMID:32103017 We demonstrate that the NAD+-dependent deacylase SIRT2 removes the myristoyl group |
| GO:0030261 chromosome condensation | IMP PMID:12697818 Role for human SIRT2 NAD-dependent deacetylase activity in c... | NEW | Summary: SIRT2 deacetylates H4K16 during G2/M transition for chromosome condensation. Reason: H4K16 deacetylation by SIRT2 is required for proper chromosome condensation during mitosis. Supporting Evidence: PMID:12697818 The SIRT2 protein is a NAD-dependent deacetylase (NDAC), the abundance of which increases dramatically during mitosis and is multiply phosphorylated at the G(2)/M transition of the cell cycle |
| GO:0042742 defense response to bacterium | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. SIRT2 defatty-acylates substrates modified by the Shigella effector IcsB, and Sirt2-null mice are more susceptible to Shigella, so the gene product itself performs a step that restricts the pathogen (DOI:10.1038/s41467-022-32227-x). The allosteric-inhibitor paper DOI:10.1172/jci158978 was previously cited here; it concerns viruses, not bacteria, and has been dropped from this annotation. Supporting Evidence: DOI:10.1038/s41467-022-32227-x SIRT2 in turn removes the lysine fatty acylation introduced by Shigella virulence factor IcsB to enhance host innate immunity. DOI:10.1038/s41467-022-32227-x SIRT2 knockout mice are more susceptible to Shigella infection than wildtype mice, demonstrating the importance of SIRT2 to counteract Shigella infection. |
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Q: What are the key physiological substrates for SIRT2 demyristoylase activity?
Q: How is SIRT2 nuclear translocation regulated during the cell cycle and stress responses?
Experiment: Proteomics to identify SIRT2 demyristoylation substrates in cells
Experiment: Live-cell imaging to characterize SIRT2 localization dynamics during cell cycle
Experiment: Structure-function studies to separate deacetylase and defatty-acylase activities
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