NAD-dependent protein deacetylase and defatty-acylase (EC 2.3.1.286) that functions primarily in the cytoplasm but shuttles to the nucleus during G2/M transition and mitosis. Sirt2 deacetylates histones (preferentially H4K16, also H3K18), alpha-tubulin (K40), and numerous non-histone substrates including transcription factors (FOXO1, FOXO3), cell cycle regulators (CDC20, FZR1), and polarity proteins (Par-3). Also possesses efficient demyristoylase and depalmitoylase activities. Key roles include regulation of cell cycle progression through APC/C activity, chromatin condensation during mitosis, metabolic regulation, adipocyte differentiation, and peripheral nerve myelination in Schwann cells. Loss of Sirt2 leads to genomic instability and gender-specific tumorigenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0017136 histone deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | ACCEPT | Summary: Core enzymatic activity of Sirt2. NAD-dependent deacetylation mechanism confirmed by crystal structure and biochemical studies on human ortholog. Reason: Fundamental enzymatic function of all class I sirtuins. Confirmed by multiple studies on human SIRT2 and conserved in mouse. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate annotation from automated method. Core function. Reason: Consistent with IBA annotation and experimental evidence. |
| GO:0017136 histone deacetylase activity, NAD-dependent | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human SIRT2. Core function. Reason: Highly conserved enzymatic activity. |
| GO:0017136 histone deacetylase activity, NAD-dependent | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Core function. Reason: Core molecular function. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:34059674 Acetylation of PAX7 controls muscle stem cell self-renewal a... | ACCEPT | Summary: Direct experimental evidence for NAD-dependent protein lysine deacetylase activity in mouse. This study demonstrated Sirt2 deacetylates PAX7 to regulate muscle stem cell self-renewal. Reason: High quality experimental evidence from mouse directly. Supporting Evidence: PMID:34059674 Acetylation of PAX7 controls muscle stem cell self-renewal and differentiation potential in mice. file:mouse/Sirt2/Sirt2-deep-research-falcon.md The target gene/protein is **Mus musculus Sirt2** (UniProt **Q8VDQ8**), a **class I sirtuin** that functions as an **NAD+-dependent lysine deacylase** (class III HDAC family) with prominent **cytosolic localization** and stimulus-dependent **nuclear shuttling**. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation. Core function. Reason: Consistent with IDA evidence. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat ortholog. Core function. Reason: Core molecular function conserved in mammals. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human ortholog. Core function. Reason: Core molecular function conserved. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Core function. Reason: Core molecular function. |
| GO:0004407 histone deacetylase activity | IMP PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | ACCEPT | Summary: Demonstrated in mouse oocyte meiosis. Sirt2 functions in spindle organization and chromosome alignment. Reason: Direct mouse experimental evidence. Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. |
| GO:0004407 histone deacetylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation. Parent term of NAD-dependent activity. Reason: Consistent with experimental evidence. |
| GO:0004407 histone deacetylase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Core function. Reason: Core molecular function. |
| GO:0004407 histone deacetylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Core molecular function. |
| GO:0046970 histone H4K16 deacetylase activity, NAD-dependent | IEA GO_REF:0000107 | ACCEPT | Summary: Specific substrate activity. Sirt2 preferentially deacetylates H4K16 during mitosis, which is critical for chromatin condensation. Reason: Well-documented substrate specificity from human studies, conserved in mouse. |
| GO:0046970 histone H4K16 deacetylase activity, NAD-dependent | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Well-characterized substrate. Reason: Core substrate specificity. |
| GO:0046970 histone H4K16 deacetylase activity, NAD-dependent | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Core substrate specificity. |
| GO:0042903 tubulin deacetylase activity | IMP PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | ACCEPT | Summary: Direct mouse experimental evidence from oocyte studies. Sirt2 deacetylates alpha-tubulin at K40. Reason: Core function with direct experimental evidence in mouse. Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. file:mouse/Sirt2/Sirt2-deep-research-falcon.md SIRT2 is explicitly described as deacetylating **tubulin at lysine 40** and co-localizing with microtubules primarily in the cytoplasm. |
| GO:0042903 tubulin deacetylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation. Core function. Reason: Consistent with IMP evidence. |
| GO:0042903 tubulin deacetylase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat. Core function. Reason: Core function conserved. |
| GO:0042903 tubulin deacetylase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Core function. Reason: Core function conserved. |
| GO:0042903 tubulin deacetylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Core function. |
| GO:0033558 protein lysine deacetylase activity | IMP PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | ACCEPT | Summary: Demonstrated Sirt2 deacetylates FOXO3a in response to oxidative stress and caloric restriction in mouse cells. Reason: Direct experimental evidence on mouse cells. Parent term of NAD-dependent activity. Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0033558 protein lysine deacetylase activity | IDA PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acet... | ACCEPT | Summary: Direct activity assay in adipocyte differentiation context. Reason: Direct experimental evidence. Supporting Evidence: PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. |
| GO:0033558 protein lysine deacetylase activity | IMP PMID:19037106 SIRT2 suppresses adipocyte differentiation by deacetylating ... | ACCEPT | Summary: Demonstrated in adipocyte context. Reason: Experimental evidence. Supporting Evidence: PMID:19037106 Nov 26. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. |
| GO:0033558 protein lysine deacetylase activity | IMP PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in ba... | ACCEPT | Summary: Demonstrated in bacterial infection context. Sirt2 deacetylates H3K18. Reason: Experimental evidence from infection studies. Supporting Evidence: PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. |
| GO:0033558 protein lysine deacetylase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Automated transfer. Parent term. Reason: Consistent with experimental evidence. |
| GO:0033558 protein lysine deacetylase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Core function. |
| GO:0140773 NAD-dependent protein demyristoylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Sirt2 has efficient defatty-acylase activities in addition to deacetylase activity. Demyristoylase activity removes myristoyl groups from lysine residues. Falcon deep research confirms demyristoylation is a distinct, pharmacologically separable activity used as a primary screening endpoint for SIRT2. Reason: Documented activity for SIRT2 family, conserved from human. Supporting Evidence: file:mouse/Sirt2/Sirt2-deep-research-falcon.md Modern understanding emphasizes that SIRT2 (and SIRT1β3 more broadly) can remove multiple lysine acyl modifications, and that **deacetylation and defatty-acylation can be pharmacologically separable activities**. |
| GO:0140773 NAD-dependent protein demyristoylase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human SIRT2. Reason: Conserved enzymatic activity. |
| GO:0140773 NAD-dependent protein demyristoylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Conserved enzymatic activity. |
| GO:0140774 NAD-dependent protein depalmitoylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Depalmitoylase activity removes palmitoyl groups from lysine residues. Reason: Documented activity for SIRT2 family. |
| GO:0140774 NAD-dependent protein depalmitoylase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human SIRT2. Reason: Conserved enzymatic activity. |
| GO:0140774 NAD-dependent protein depalmitoylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Conserved enzymatic activity. |
| GO:0140219 histone methacryllysine demethacrylase activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Extended substrate scope - removal of methacryl modifications from histones. Reason: Less well-characterized activity compared to deacetylation. |
| GO:0140219 histone methacryllysine demethacrylase activity | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: Less well-characterized activity. |
| GO:0140219 histone methacryllysine demethacrylase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Less well-characterized activity. |
| GO:0140228 histone benzoyllysine debenzoylase activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Extended substrate scope - removal of benzoyl modifications. Reason: Less well-characterized activity. |
| GO:0140228 histone benzoyllysine debenzoylase activity | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: Less well-characterized activity. |
| GO:0140228 histone benzoyllysine debenzoylase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Less well-characterized activity. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Weak ADP-ribosyltransferase activity reported for sirtuins but not considered a major physiological function. Reason: Weak activity not considered physiologically relevant for Sirt2. |
| GO:0070403 NAD+ binding | IEA GO_REF:0000120 | ACCEPT | Summary: Essential for enzymatic activity. NAD+ is a cofactor for deacetylase reaction. Reason: Required for enzymatic mechanism. Well-supported by structural data. |
| GO:0070403 NAD+ binding | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Essential binding activity. |
| GO:0051287 NAD binding | IEA GO_REF:0000002 | ACCEPT | Summary: Parent term. NAD binding essential for activity. Reason: Essential for enzymatic mechanism. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000107 | ACCEPT | Summary: Sirt2 contains a zinc-binding domain with four cysteine residues coordinating zinc ion, important for structural stability. Reason: Structural feature confirmed by sequence analysis. |
| GO:0008270 zinc ion binding | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Structural feature conserved. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: Parent term of zinc ion binding. Reason: Consistent with zinc binding. |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Sirt2 associates with chromatin during mitosis for H4K16 deacetylation. Reason: Supported by localization and functional data. |
| GO:0003682 chromatin binding | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Functional requirement for chromatin-associated activity. |
| GO:0003682 chromatin binding | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Functional requirement. |
| GO:0043130 ubiquitin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Sirt2 binds ubiquitin chains and promotes proteasomal degradation of substrates. Reason: Related to function in protein quality control. |
| GO:0043130 ubiquitin binding | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Consistent with proteasome regulation function. |
| GO:0043130 ubiquitin binding | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Consistent function. |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Sirt2 binds and deacetylates transcription factors including FOXO1 and FOXO3. Reason: Well-supported by substrate interaction studies. |
| GO:0140297 DNA-binding transcription factor binding | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Well-documented interactions. |
| GO:0140297 DNA-binding transcription factor binding | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Documented interactions. |
| GO:0035035 histone acetyltransferase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Functional interaction with HATs for opposing regulation. Reason: Indirect functional relationship. |
| GO:0035035 histone acetyltransferase binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: Indirect relationship. |
| GO:0035035 histone acetyltransferase binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Indirect relationship. |
| GO:0042826 histone deacetylase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: May form complexes with other HDACs. Reason: Interaction with HDAC6 documented. |
| GO:0042826 histone deacetylase binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: HDAC6 interaction documented. |
| GO:0042826 histone deacetylase binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Documented interaction. |
| GO:0005515 protein binding | IPI PMID:22014574 SIRT2 maintains genome integrity and suppresses tumorigenesi... | MARK AS OVER ANNOTATED | Summary: Protein interactions with APC/C subunits demonstrated. Sirt2 regulates APC/C activity for genome stability. Reason: Too general. More specific binding terms are available. Supporting Evidence: PMID:22014574 SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. |
| GO:0005515 protein binding | IPI PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | MARK AS OVER ANNOTATED | Summary: Interaction with FOXO3 demonstrated. Reason: Too general. More specific terms are available (transcription factor binding). Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0005515 protein binding | IPI PMID:19037106 SIRT2 suppresses adipocyte differentiation by deacetylating ... | MARK AS OVER ANNOTATED | Summary: Interaction with FOXO1 demonstrated. Reason: Too general. More specific terms are available. Supporting Evidence: PMID:19037106 Nov 26. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Very general term. More specific deacetylase terms are available. Reason: Uninformative general term. Deacetylase is technically a transferase but this term does not capture the specific activity. |
| GO:0005737 cytoplasm | IDA PMID:11056054 Cloning and characterization of two mouse genes with homolog... | ACCEPT | Summary: Original cloning paper demonstrated cytoplasmic localization in mouse. Reason: Primary localization during interphase. Multiple experimental confirmations. Supporting Evidence: PMID:11056054 Cloning and characterization of two mouse genes with homology to the yeast Sir2 gene. file:mouse/Sirt2/Sirt2-deep-research-falcon.md SIRT2 is repeatedly described as **predominantly cytoplasmic**, with ability to shuttle to the nucleus under specific conditions (e.g., stress, cell cycle states, infection, ischemic injury). |
| GO:0005737 cytoplasm | IDA PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | ACCEPT | Summary: Cytoplasmic localization confirmed in FOXO3 deacetylation studies. Reason: Consistent with multiple studies. Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0005737 cytoplasm | IDA PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acet... | ACCEPT | Summary: Cytoplasmic localization in adipocyte studies. Reason: Consistent experimental evidence. Supporting Evidence: PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. |
| GO:0005737 cytoplasm | IDA PMID:19037106 SIRT2 suppresses adipocyte differentiation by deacetylating ... | ACCEPT | Summary: Cytoplasmic localization in adipocyte differentiation context. Reason: Consistent experimental evidence. Supporting Evidence: PMID:19037106 Nov 26. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. |
| GO:0005737 cytoplasm | IDA PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | ACCEPT | Summary: Cytoplasmic localization in oocyte studies. Reason: Consistent experimental evidence. Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. |
| GO:0005737 cytoplasm | HDA PMID:17634366 Proteolipid protein is required for transport of sirtuin 2 i... | ACCEPT | Summary: High-throughput data confirms cytoplasmic localization. Reason: Consistent with other evidence. Supporting Evidence: PMID:17634366 Proteolipid protein is required for transport of sirtuin 2 into CNS myelin. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation. Reason: Consistent with experimental evidence. |
| GO:0005737 cytoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Primary localization conserved. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Primary localization. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Soluble cytoplasmic protein. Reason: More specific localization within cytoplasm. |
| GO:0005829 cytosol | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Consistent localization. |
| GO:0005829 cytosol | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Consistent localization. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Sirt2 shuttles to nucleus during G2/M transition and mitosis. Nuclear localization is transient and regulated. Reason: Well-documented nucleo-cytoplasmic shuttling. |
| GO:0005634 nucleus | IDA PMID:19037106 SIRT2 suppresses adipocyte differentiation by deacetylating ... | ACCEPT | Summary: Nuclear localization demonstrated in adipocyte context. Reason: Direct experimental evidence. Supporting Evidence: PMID:19037106 Nov 26. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. |
| GO:0005634 nucleus | IDA PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | ACCEPT | Summary: Nuclear localization in oocyte meiosis. Reason: Direct experimental evidence in mouse. Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation. Reason: Consistent with experimental evidence. |
| GO:0005634 nucleus | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Conserved shuttling behavior. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Conserved shuttling behavior. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: When in nucleus, localizes to nucleoplasm. Reason: More specific nuclear localization. |
| GO:0005654 nucleoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Consistent localization. |
| GO:0005730 nucleolus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Some nucleolar localization reported. Reason: Minor localization. |
| GO:0005730 nucleolus | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: Minor localization. |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: Sirt2 localizes to centrosomes during prophase in mitosis. Reason: Well-documented localization during mitosis. |
| GO:0005813 centrosome | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Mitotic localization conserved. |
| GO:0005813 centrosome | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Mitotic localization. |
| GO:0005814 centriole | IEA GO_REF:0000120 | ACCEPT | Summary: Sirt2 localizes to centrioles during metaphase. Reason: Documented localization during mitosis. |
| GO:0005814 centriole | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Mitotic localization conserved. |
| GO:0005814 centriole | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Mitotic localization. |
| GO:0005819 spindle | IEA GO_REF:0000120 | ACCEPT | Summary: Sirt2 spreads along spindle fibers during metaphase. Reason: Documented localization during mitosis. |
| GO:0005819 spindle | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Mitotic localization conserved. |
| GO:0005819 spindle | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Mitotic localization. |
| GO:0072686 mitotic spindle | IEA GO_REF:0000107 | ACCEPT | Summary: More specific spindle term. Reason: Documented localization. |
| GO:0072686 mitotic spindle | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Mitotic localization. |
| GO:0072686 mitotic spindle | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Mitotic localization. |
| GO:0072687 meiotic spindle | IDA PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | ACCEPT | Summary: Direct experimental evidence from mouse oocyte studies. Sirt2 localizes to meiotic spindle. Reason: High quality mouse-specific evidence. Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. |
| GO:0030496 midbody | IDA PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | ACCEPT | Summary: Sirt2 localizes to midbody during cytokinesis in mouse oocytes. Reason: Direct experimental evidence. Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. |
| GO:0030496 midbody | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation. Reason: Consistent with IDA evidence. |
| GO:0030496 midbody | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Cytokinesis localization conserved. |
| GO:0030496 midbody | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Cytokinesis localization. |
| GO:0005874 microtubule | IEA GO_REF:0000120 | ACCEPT | Summary: Sirt2 associates with microtubules as tubulin deacetylase. Reason: Consistent with core tubulin deacetylase function. |
| GO:0005874 microtubule | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Core localization for tubulin function. |
| GO:0005874 microtubule | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Core localization. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Parent term of microtubule. Reason: Consistent with microtubule localization. |
| GO:0005694 chromosome | IEA GO_REF:0000120 | ACCEPT | Summary: Sirt2 associates with chromosomes during mitosis for H4K16 deacetylation. Reason: Mitotic chromatin association documented. |
| GO:0005694 chromosome | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Mitotic chromatin association conserved. |
| GO:0005694 chromosome | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Mitotic chromatin association. |
| GO:0000792 heterochromatin | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Some heterochromatin association reported. Reason: Less well-characterized localization. |
| GO:0000792 heterochromatin | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Less well-characterized. |
| GO:0043209 myelin sheath | IDA PMID:16933150 Microtubule deacetylases, SirT2 and HDAC6, in the nervous sy... | ACCEPT | Summary: Direct experimental evidence for myelin sheath localization in mouse nervous system. Sirt2 is highly expressed in Schwann cells. Reason: Well-documented localization in peripheral nervous system. Supporting Evidence: PMID:16933150 2006 Aug 25. Microtubule deacetylases, SirT2 and HDAC6, in the nervous system. |
| GO:0043209 myelin sheath | HDA PMID:17634366 Proteolipid protein is required for transport of sirtuin 2 i... | ACCEPT | Summary: High-throughput proteomics confirms myelin sheath localization. Reason: Consistent with IDA evidence. Supporting Evidence: PMID:17634366 Proteolipid protein is required for transport of sirtuin 2 into CNS myelin. |
| GO:0043209 myelin sheath | IEA GO_REF:0000044 | ACCEPT | Summary: Automated annotation from subcellular location. Reason: Consistent with experimental evidence. |
| GO:0043209 myelin sheath | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat. Reason: Nervous system localization conserved. |
| GO:0035748 myelin sheath abaxonal region | ISO GO_REF:0000096 | ACCEPT | Summary: Specific myelin region localization. Reason: More specific localization within myelin sheath. |
| GO:0033010 paranodal junction | IDA PMID:16933150 Microtubule deacetylases, SirT2 and HDAC6, in the nervous sy... | ACCEPT | Summary: Direct experimental evidence for paranodal junction localization in mouse. Reason: Specific localization in myelinated axons. Supporting Evidence: PMID:16933150 2006 Aug 25. Microtubule deacetylases, SirT2 and HDAC6, in the nervous system. |
| GO:0033010 paranodal junction | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA annotation. Reason: Consistent with IDA evidence. |
| GO:0033010 paranodal junction | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat. Reason: Consistent localization. |
| GO:0043220 Schmidt-Lanterman incisure | IDA PMID:16933150 Microtubule deacetylases, SirT2 and HDAC6, in the nervous sy... | ACCEPT | Summary: Direct experimental evidence for Schmidt-Lanterman incisure localization. Reason: Specific localization in Schwann cells. Supporting Evidence: PMID:16933150 2006 Aug 25. Microtubule deacetylases, SirT2 and HDAC6, in the nervous system. |
| GO:0043220 Schmidt-Lanterman incisure | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA annotation. Reason: Consistent with IDA evidence. |
| GO:0043220 Schmidt-Lanterman incisure | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat. Reason: Consistent localization. |
| GO:0043219 lateral loop | ISO GO_REF:0000096 | ACCEPT | Summary: Localization in lateral loops of myelin. Reason: Specific myelin structure localization. |
| GO:0043219 lateral loop | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Consistent localization. |
| GO:0097456 terminal loop | ISO GO_REF:0000096 | ACCEPT | Summary: Terminal loop localization in myelin. Reason: Specific myelin structure. |
| GO:0033270 paranode region of axon | ISO GO_REF:0000096 | ACCEPT | Summary: Paranode localization. Reason: Consistent with paranodal junction localization. |
| GO:0033270 paranode region of axon | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Consistent localization. |
| GO:0044224 juxtaparanode region of axon | ISO GO_REF:0000096 | ACCEPT | Summary: Juxtaparanode localization. Reason: Related to paranodal localization. |
| GO:0044224 juxtaparanode region of axon | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Consistent localization. |
| GO:0097386 glial cell projection | ISO GO_REF:0000096 | ACCEPT | Summary: Glial cell projection localization. Reason: Consistent with Schwann cell function. |
| GO:0097386 glial cell projection | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Consistent localization. |
| GO:0043204 perikaryon | IDA PMID:16933150 Microtubule deacetylases, SirT2 and HDAC6, in the nervous sy... | ACCEPT | Summary: Perikaryon (neuronal cell body) localization. Reason: Direct experimental evidence. Supporting Evidence: PMID:16933150 2006 Aug 25. Microtubule deacetylases, SirT2 and HDAC6, in the nervous system. |
| GO:0043204 perikaryon | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation. Reason: Consistent with IDA evidence. |
| GO:0043204 perikaryon | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat. Reason: Consistent localization. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:16933150 Microtubule deacetylases, SirT2 and HDAC6, in the nervous sy... | ACCEPT | Summary: Perinuclear localization. Reason: Direct experimental evidence. Supporting Evidence: PMID:16933150 2006 Aug 25. Microtubule deacetylases, SirT2 and HDAC6, in the nervous system. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Automated annotation. Reason: Consistent with experimental evidence. |
| GO:0098978 glutamatergic synapse | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Synaptic localization. Reason: Minor localization in neurons. |
| GO:0005739 mitochondrion | IDA PMID:26767982 Nutritional stress exacerbates hepatic steatosis induced by ... | MARK AS OVER ANNOTATED | Summary: Mitochondrial localization was annotated from PMID:26767982, but that paper is primarily about the Hint2 mitochondrial protein and provides only weak, indirect support for a resident mitochondrial Sirt2 pool. Falcon deep research summarizing direct mouse-liver fractionation (Schmidt et al. 2024) found Sirt2 isoforms in nuclear and cytosolic fractions but NO detectable Sirt2 antigen in purified mitochondria (or peroxisomes), even though many hyperacetylated sites in Sirt2-/- liver map to mitochondria. This argues that Sirt2 controls mitochondrial protein acetylation from outside the organelle (e.g. cytosolic pre-import deacylation or indirect signaling) rather than as a mitochondrial resident protein. Reason: Direct mouse-liver fractionation found no detectable Sirt2 antigen in purified mitochondria; the supporting reference (a Hint2 paper) does not establish a genuine resident mitochondrial pool. Sirt2 is overwhelmingly a cytoplasmic and nuclear-shuttling enzyme, and any mitochondrial metabolic effects appear to be exerted from outside the organelle. Supporting Evidence: PMID:26767982 Nutritional stress exacerbates hepatic steatosis induced by deletion of the histidine nucleotide-binding (Hint2) mitochondrial protein. file:mouse/Sirt2/Sirt2-deep-research-falcon.md In wild-type mouse liver fractionation, Sirt2 isoforms were detected in nuclear/cytosolic fractions; purified mitochondria and peroxisomes lacked detectable Sirt2 antigen (N=3). file:mouse/Sirt2/Sirt2-deep-research-falcon.md This supports an emerging annotation nuance: in some tissues Sirt2 may exert metabolic control **from outside the organelle** (e.g., cytosolic deacylation before import, signaling-mediated indirect effects, or regulation of carrier proteins). |
| GO:0005886 plasma membrane | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Plasma membrane localization reported. Reason: Minor localization. |
| GO:0042995 cell projection | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: General cell projection term. Reason: Broad term, more specific terms available. |
| GO:0030426 growth cone | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Growth cone localization. Reason: Minor localization. |
| GO:0051301 cell division | IEA GO_REF:0000043 | ACCEPT | Summary: Sirt2 regulates cell division through multiple mechanisms including APC/C regulation and chromatin condensation. Reason: Well-documented role in cell cycle. |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000107 | ACCEPT | Summary: Sirt2 regulates cell cycle through deacetylation of CDC20 and FZR1, controlling APC/C activity. Reason: Core regulatory function. |
| GO:0051726 regulation of cell cycle | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Core regulatory function conserved. |
| GO:0051726 regulation of cell cycle | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Core regulatory function. |
| GO:0051321 meiotic cell cycle | IEA GO_REF:0000043 | ACCEPT | Summary: Sirt2 functions in meiotic cell cycle in oocytes. Reason: Documented in mouse oocyte studies. |
| GO:0051781 positive regulation of cell division | IMP PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | KEEP AS NON CORE | Summary: Sirt2 promotes cell division in oocytes. Reason: Real but non-core: regulation of cell division is downstream of Sirt2's core NAD-dependent deacetylase / defatty-acylase activity (e.g. mitotic substrate deacetylation during the G2/M shuttle), not a core function in its own right. Direct mouse IMP evidence supports the role. Surfaced by the ASSAY_TO_FUNCTION analysis (proliferation/division readout). Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. |
| GO:0045836 positive regulation of meiotic nuclear division | IMP PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | ACCEPT | Summary: Sirt2 promotes meiotic nuclear division in oocytes. Reason: Direct mouse experimental evidence. Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. |
| GO:1900195 positive regulation of oocyte maturation | IMP PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | ACCEPT | Summary: Sirt2 promotes oocyte maturation. Reason: Direct mouse experimental evidence. Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. |
| GO:0051987 positive regulation of attachment of spindle microtubules to kinetochore | IMP PMID:24334550 Sirt2 functions in spindle organization and chromosome align... | ACCEPT | Summary: Sirt2 promotes proper kinetochore-microtubule attachments in oocyte meiosis. Reason: Direct mouse experimental evidence. Important for chromosome segregation. Supporting Evidence: PMID:24334550 Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis. |
| GO:0006476 protein deacetylation | IMP PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | ACCEPT | Summary: Demonstrated Sirt2 deacetylates FOXO3a in response to oxidative stress. Reason: Core process directly related to enzymatic function. Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0006476 protein deacetylation | IDA PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acet... | ACCEPT | Summary: Direct demonstration of protein deacetylation. Reason: Core process. Supporting Evidence: PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. |
| GO:0006476 protein deacetylation | IMP PMID:19037106 SIRT2 suppresses adipocyte differentiation by deacetylating ... | ACCEPT | Summary: Protein deacetylation in adipocyte context. Reason: Core process. Supporting Evidence: PMID:19037106 Nov 26. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. |
| GO:0006476 protein deacetylation | IMP PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination t... | ACCEPT | Summary: Deacetylation of Par-3 for myelination. Reason: Core process in myelination context. Supporting Evidence: PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. |
| GO:0006476 protein deacetylation | IMP PMID:30655546 Tip60- and sirtuin 2-regulated MARCKS acetylation and phosph... | ACCEPT | Summary: Deacetylation of MARCKS in diabetic embryopathy. Reason: Core process. Supporting Evidence: PMID:30655546 Tip60- and sirtuin 2-regulated MARCKS acetylation and phosphorylation are required for diabetic embryopathy. |
| GO:0006476 protein deacetylation | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat. Reason: Core process. |
| GO:0006476 protein deacetylation | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Core process. |
| GO:0034983 peptidyl-lysine deacetylation | ISO GO_REF:0000119 | ACCEPT | Summary: More specific term for lysine deacetylation. Reason: Core process. |
| GO:0034983 peptidyl-lysine deacetylation | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Core process. |
| GO:0090042 tubulin deacetylation | IMP PMID:23126280 Regulation of adipogenesis by cytoskeleton remodelling is fa... | ACCEPT | Summary: Tubulin deacetylation in adipogenesis context. Reason: Core process for tubulin function. Supporting Evidence: PMID:23126280 Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of Ξ±-tubulin. |
| GO:0090042 tubulin deacetylation | IMP PMID:23502856 Microtubule-driven spatial arrangement of mitochondria promo... | ACCEPT | Summary: Tubulin deacetylation in inflammasome context. Reason: Core process. Supporting Evidence: PMID:23502856 Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. |
| GO:0090042 tubulin deacetylation | IGI PMID:20562830 The ATAC acetyl transferase complex controls mitotic progres... | ACCEPT | Summary: Genetic interaction evidence for tubulin deacetylation. Reason: Genetic evidence supports function. Supporting Evidence: PMID:20562830 The ATAC acetyl transferase complex controls mitotic progression by targeting non-histone substrates. |
| GO:0090042 tubulin deacetylation | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat. Reason: Core process conserved. |
| GO:0090042 tubulin deacetylation | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Core process conserved. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acet... | ACCEPT | Summary: Sirt2 negatively regulates transcription through deacetylation of FOXO1. Reason: Well-documented regulatory function. Supporting Evidence: PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:19037106 SIRT2 suppresses adipocyte differentiation by deacetylating ... | ACCEPT | Summary: Transcriptional regulation in adipocyte context. Reason: Documented regulatory function. Supporting Evidence: PMID:19037106 Nov 26. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± ... | ACCEPT | Summary: HIF-1alpha regulation context. Reason: Documented regulatory function. Supporting Evidence: PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± hydroxylation. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Automated transfer. Reason: Consistent with experimental evidence. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Regulatory function conserved. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Regulatory function. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | ACCEPT | Summary: Sirt2 can also positively regulate transcription through FOXO3 activation. Reason: Context-dependent transcriptional regulation. Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: General transcription regulation term. Reason: Parent term consistent with specific annotation. |
| GO:0045892 negative regulation of DNA-templated transcription | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Regulatory function. |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Regulatory function. |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: General transcription term. Reason: Very broad term. Sirt2 regulates transcription indirectly through deacetylation. |
| GO:0040029 epigenetic regulation of gene expression | IMP PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in ba... | ACCEPT | Summary: Sirt2 regulates gene expression epigenetically through H3K18 deacetylation during bacterial infection. Reason: Direct experimental evidence. Supporting Evidence: PMID:23908241 A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. |
| GO:0040029 epigenetic regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: Automated transfer. Reason: Consistent with IMP evidence. |
| GO:0040029 epigenetic regulation of gene expression | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Epigenetic function conserved. |
| GO:0043388 positive regulation of DNA binding | IDA PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | ACCEPT | Summary: Sirt2 promotes FOXO3 DNA binding through deacetylation. Reason: Direct experimental evidence. Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0006325 chromatin organization | IGI PMID:20562830 The ATAC acetyl transferase complex controls mitotic progres... | ACCEPT | Summary: Sirt2 involved in chromatin organization through genetic interaction with ATAC complex. Reason: Genetic evidence supports chromatin function. Supporting Evidence: PMID:20562830 The ATAC acetyl transferase complex controls mitotic progression by targeting non-histone substrates. |
| GO:0000183 rDNA heterochromatin formation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Based on yeast Sir2 function. Human/mouse SIRT2 role in rDNA silencing less well characterized than yeast. Reason: Inferred from yeast. More relevant for yeast Sir2 than mammalian SIRT2. |
| GO:0045599 negative regulation of fat cell differentiation | IMP PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acet... | ACCEPT | Summary: Sirt2 negatively regulates adipocyte differentiation through FOXO1 deacetylation. Reason: Well-documented function with multiple experimental papers. Supporting Evidence: PMID:17681146 SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. |
| GO:0045599 negative regulation of fat cell differentiation | IMP PMID:19037106 SIRT2 suppresses adipocyte differentiation by deacetylating ... | ACCEPT | Summary: Confirmed negative regulation of adipogenesis. Reason: Consistent experimental evidence. Supporting Evidence: PMID:19037106 Nov 26. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. |
| GO:0045599 negative regulation of fat cell differentiation | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA annotation. Reason: Consistent with experimental evidence. |
| GO:0045598 regulation of fat cell differentiation | IMP PMID:23126280 Regulation of adipogenesis by cytoskeleton remodelling is fa... | ACCEPT | Summary: Regulation of fat cell differentiation through tubulin deacetylation. Reason: More general term. Supporting Evidence: PMID:23126280 Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of Ξ±-tubulin. |
| GO:0030154 cell differentiation | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Very broad term. Reason: More specific terms available. |
| GO:0022011 myelination in peripheral nervous system | IMP PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination t... | ACCEPT | Summary: Sirt2 modulates peripheral myelination through Par-3/aPKC signaling in Schwann cells. Reason: Well-documented function with direct experimental evidence. Supporting Evidence: PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. |
| GO:0022011 myelination in peripheral nervous system | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA annotation. Reason: Consistent with IMP evidence. |
| GO:0022011 myelination in peripheral nervous system | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat. Reason: Myelination function conserved. |
| GO:0031641 regulation of myelination | IMP PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination t... | ACCEPT | Summary: Direct regulation of myelination process. Reason: Core function in Schwann cells. Supporting Evidence: PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. |
| GO:0031641 regulation of myelination | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA annotation. Reason: Consistent with IMP evidence. |
| GO:0031641 regulation of myelination | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat. Reason: Myelination regulation conserved. |
| GO:0007399 nervous system development | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Parent term of myelination. Reason: More specific terms available. |
| GO:0070446 negative regulation of oligodendrocyte progenitor proliferation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Regulation of oligodendrocyte development. Reason: Less well-characterized than Schwann cell function. |
| GO:0070446 negative regulation of oligodendrocyte progenitor proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Less well-characterized. |
| GO:0048715 negative regulation of oligodendrocyte differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Regulation of oligodendrocyte differentiation. Reason: Less well-characterized. |
| GO:0006914 autophagy | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Sirt2 regulates autophagy through FOXO1 deacetylation. Reason: Indirect regulation through FOXO1. |
| GO:0010507 negative regulation of autophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sirt2 negatively regulates autophagy by deacetylating FOXO1, preventing its interaction with ATG7. Reason: Regulatory function but not core activity. Supporting Evidence: file:mouse/Sirt2/Sirt2-deep-research-falcon.md **Autophagy regulation:** SIRT2 binds and deacetylates **FOXO1**, with reported context dependence (basal vs oxidative stress) affecting autophagy induction. |
| GO:0010507 negative regulation of autophagy | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: Regulatory function. |
| GO:0010507 negative regulation of autophagy | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Regulatory function. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Sirt2 modulates apoptosis through FOXO transcription factors. Reason: Indirect regulatory function. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Anti-apoptotic function. Reason: Context-dependent function. |
| GO:1900119 positive regulation of execution phase of apoptosis | IMP PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | KEEP AS NON CORE | Summary: Pro-apoptotic function under certain conditions through FOXO3 activation. Reason: Context-dependent, through FOXO3. Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0034599 cellular response to oxidative stress | IDA PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | ACCEPT | Summary: Sirt2 responds to oxidative stress by deacetylating FOXO3. Reason: Direct experimental evidence. Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0061433 cellular response to caloric restriction | IDA PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | ACCEPT | Summary: Sirt2 responds to caloric restriction. Reason: Direct experimental evidence. Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sirt2 regulates HIF-1alpha in hypoxia response. Reason: Regulatory function through HIF-1alpha. |
| GO:0071456 cellular response to hypoxia | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: Regulatory function. |
| GO:0071456 cellular response to hypoxia | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Regulatory function. |
| GO:0071872 cellular response to epinephrine stimulus | IDA PMID:19037106 SIRT2 suppresses adipocyte differentiation by deacetylating ... | KEEP AS NON CORE | Summary: Sirt2 responds to epinephrine in adipocytes. Reason: Tissue-specific response. Supporting Evidence: PMID:19037106 Nov 26. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. |
| GO:2000378 negative regulation of reactive oxygen species metabolic process | IMP PMID:17521387 SIRT2 deacetylates FOXO3a in response to oxidative stress an... | KEEP AS NON CORE | Summary: Sirt2 reduces ROS through FOXO-mediated antioxidant gene expression. Reason: Indirect effect through FOXO transcription factors. Supporting Evidence: PMID:17521387 2007 May 23. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IMP PMID:24681946 SIRT2 regulates tumour hypoxia response by promoting HIF-1Ξ± ... | ACCEPT | Summary: Sirt2 promotes proteasomal degradation of substrates like HIF-1alpha. Reason: Direct experimental evidence. 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 | IEA GO_REF:0000107 | ACCEPT | Summary: Automated transfer. Reason: Consistent with IMP evidence. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Degradation function conserved. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Degradation function. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Parent process. Reason: Consistent with positive regulation term. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human. Reason: Consistent function. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity transfer. Reason: Consistent function. |
| GO:0006511 ubiquitin-dependent protein catabolic process | ISO GO_REF:0000119 | ACCEPT | Summary: Parent process. Reason: Consistent function. |
| GO:0042177 negative regulation of protein catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Context-dependent regulation. Reason: May reflect substrate-specific effects. |
| GO:0042177 negative regulation of protein catabolic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: Context-dependent. |
| GO:0042177 negative regulation of protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Context-dependent. |
| GO:0016042 lipid catabolic process | IMP PMID:19037106 SIRT2 suppresses adipocyte differentiation by deacetylating ... | KEEP AS NON CORE | Summary: Sirt2 promotes lipolysis in adipocytes through FOXO1 activation. Reason: Indirect effect through transcription factor deacetylation. Supporting Evidence: PMID:19037106 Nov 26. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. |
| GO:0045723 positive regulation of fatty acid biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Fatty acid metabolism regulation. Reason: Indirect metabolic effect. |
| GO:0045723 positive regulation of fatty acid biosynthetic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: Indirect metabolic effect. |
| GO:0045717 negative regulation of fatty acid biosynthetic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Context-dependent fatty acid regulation. Reason: Indirect metabolic effect. |
| GO:0006633 fatty acid biosynthetic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Parent process. Reason: Indirect involvement. |
| GO:1900226 negative regulation of NLRP3 inflammasome complex assembly | IMP PMID:23502856 Microtubule-driven spatial arrangement of mitochondria promo... | ACCEPT | Summary: Sirt2 negatively regulates NLRP3 inflammasome through microtubule deacetylation. Reason: Direct experimental evidence. Supporting Evidence: PMID:23502856 Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. file:mouse/Sirt2/Sirt2-deep-research-falcon.md **Inflammation/innate immunity:** SIRT2 deacetylates **NF-ΞΊB** and **NLRP3**, positioning it at the interface of acetylation control and inflammasome/NF-ΞΊB signaling. |
| GO:0010801 negative regulation of peptidyl-threonine phosphorylation | IMP PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination t... | KEEP AS NON CORE | Summary: Sirt2 deacetylation of Par-3 affects aPKC phosphorylation. Reason: Indirect regulatory effect through Par-3. Supporting Evidence: PMID:21949390 Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. |
| GO:0043687 post-translational protein modification | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Very general term. Deacetylation is a PTM. Reason: More specific terms available. |
| GO:0045843 negative regulation of striated muscle tissue development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Muscle development regulation. Reason: Less well-characterized in mouse. |
| GO:0045843 negative regulation of striated muscle tissue development | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Transferred from human. Reason: Less well-characterized. |
| GO:0045843 negative regulation of striated muscle tissue development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity transfer. Reason: Less well-characterized. |
| GO:0099149 regulation of postsynaptic neurotransmitter receptor internalization | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Synaptic function regulation. Reason: Less well-characterized. |
| GO:0000226 microtubule cytoskeleton organization | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. |
| GO:0007049 cell cycle | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. |
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