NAD-dependent protein deacetylase that catalyzes removal of acetyl groups from lysine residues of histones (preferentially H4K16, H3K9, H3K14) and numerous non-histone proteins including p53, NF-kB RelA/p65, FOXO factors, HIF1alpha/HIF2alpha, and PGC-1alpha. The core enzymatic function couples NAD+ cleavage to lysine deacetylation, producing nicotinamide and 2-O-acetyl-ADP-ribose. Functions in transcriptional regulation through heterochromatin formation and as a transcription corepressor. Has broad pleiotropic effects on metabolism, stress responses, DNA damage response, and aging through deacetylation of diverse substrates.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 is predominantly nuclear with regulated nucleo-cytoplasmic shuttling. Contains an N-terminal nuclear localization signal. Nuclear enrichment is well-established through multiple IDA studies (PMID:11672523, PMID:20167603, PMID:20955178). Reason: Core localization supported by phylogenetic inference and extensive experimental evidence. SIRT1 functions primarily in the nucleus for chromatin regulation and transcription factor deacetylation. Supporting Evidence: PMID:12006491 SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. file:human/SIRT1/SIRT1-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0003714 transcription corepressor activity | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 functions as a transcriptional corepressor through histone deacetylation and deacetylation of transcription factors. Experimentally demonstrated through IDA evidence (PMID:12535671, PMID:20955178). Reason: Core molecular function well-supported by phylogenetic inference and experimental evidence. SIRT1 mediates transcriptional repression through heterochromatin formation and deacetylation of transcription factors. Supporting Evidence: PMID:15469825 We propose a model for SirT1-mediated heterochromatin formation that includes deacetylation of histone tails, recruitment and deacetylation of histone H1, and spreading of hypomethylated H3-K79 with resultant silencing. |
| GO:0006974 DNA damage response | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 participates in DNA damage response through deacetylation of p53, Ku70, NBS1, and other DNA repair proteins. Well-supported by multiple experimental studies (PMID:18203716, PMID:19934257, PMID:20100829). Reason: Core biological process supported by phylogenetic inference and extensive experimental evidence. SIRT1 modulates DNA damage response through deacetylation of key repair proteins. Supporting Evidence: PMID:12006491 SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation. |
| GO:0031509 subtelomeric heterochromatin formation | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 promotes heterochromatin formation through histone deacetylation. Phylogenetically conserved from yeast Sir2p which is required for telomeric silencing. Reason: Core biological process supported by phylogenetic inference. SIRT1 promotes facultative heterochromatin formation through deacetylation of H4K16 and H3K9. Supporting Evidence: PMID:15469825 We propose a model for SirT1-mediated heterochromatin formation that includes deacetylation of histone tails, recruitment and deacetylation of histone H1, and spreading of hypomethylated H3-K79 with resultant silencing. |
| GO:0032041 histone H3K14 deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 has NAD-dependent histone H3K14 deacetylase activity. Demonstrated experimentally (PMID:15469825). Reason: Core molecular function. SIRT1 deacetylates H3K14 among other histone lysines in an NAD-dependent manner. This is the primary enzymatic activity of SIRT1. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0046969 histone H3K9 deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 has NAD-dependent histone H3K9 deacetylase activity. Directly demonstrated experimentally (PMID:15469825). Reason: Core molecular function. H3K9 deacetylation is a major activity of SIRT1 linked to heterochromatin formation. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0046970 histone H4K16 deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 has NAD-dependent histone H4K16 deacetylase activity as its preferential histone substrate. Directly demonstrated experimentally (PMID:15469825). Reason: Core molecular function. H4K16 is the preferred histone substrate of SIRT1 and its deacetylation is critical for heterochromatin formation. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0045892 negative regulation of DNA-templated transcription | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: SIRT1 negatively regulates transcription through histone deacetylation and heterochromatin formation. Reason: Transcriptional repression is a downstream effect of chromatin modification rather than a singular core function. Supporting Evidence: PMID:15469825 Gal4-SirT1 expression resulted in the deacetylation of H4-K16 and H3-K9, recruitment of H1 within the promoter vicinity, drastically reduced reporter expression |
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 localizes to the nucleoplasm. Supported by multiple IDA studies and subcellular fractionation. Reason: Core localization supported by phylogenetic inference and experimental evidence. Supporting Evidence: PMID:15469825 We characterized human SirT1, one of the human homologs of the budding yeast Sir2p, an NAD+-dependent histone deacetylase involved in establishing repressive chromatin |
| GO:0005637 nuclear inner membrane | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 has been reported at the nuclear envelope/inner membrane (PMID:15469825). May reflect association with heterochromatin at the nuclear periphery. Reason: Localization supported by phylogenetic inference and experimental evidence. Association with nuclear envelope is consistent with heterochromatin regulation at nuclear periphery. |
| GO:0033553 rDNA heterochromatin | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT1 localizes to rDNA heterochromatin as part of the eNoSC complex that regulates rRNA transcription in response to energy status (PMID:18485871). Reason: Core localization supported by phylogenetic inference and experimental evidence. SIRT1 is a key component of the eNoSC complex at rDNA loci. Supporting Evidence: PMID:18485871 eNoSC contains Nucleomethylin, which binds histone H3 dimethylated Lys9 in the rDNA locus, in a complex with SIRT1 and SUV39H1. |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000108 | ACCEPT | Summary: SIRT1 localizes to telomeric regions, consistent with its role in subtelomeric heterochromatin formation inherited from yeast Sir2. Reason: Localization consistent with phylogenetically conserved function in telomeric silencing. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization of SIRT1 is well-established through multiple experimental studies. Reason: Core localization. Duplicate of IBA annotation; IEA provides broader automated coverage. |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT1 modulates apoptosis through deacetylation of p53 and other pro-apoptotic factors. This is a downstream consequence of its deacetylase activity. Reason: SIRT1 affects apoptosis through its primary deacetylase function on substrates like p53 and FOXO, but apoptosis regulation is not the core function of the enzyme. This is a pleiotropic effect. |
| GO:0007517 muscle organ development | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT1 has been implicated in muscle differentiation through deacetylation of MyoD and other myogenic factors. Reason: Downstream pleiotropic effect of SIRT1 deacetylase activity. Not the core function. |
| GO:0016605 PML body | IEA GO_REF:0000044 | ACCEPT | Summary: SIRT1 is recruited to PML nuclear bodies upon PML overexpression where it co-localizes with p53 (PMID:12006491). Reason: Well-established localization. PML body recruitment is relevant to SIRT1 function in p53 deacetylation. Supporting Evidence: PMID:12006491 SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MODIFY | Summary: SIRT1 is classified as a transferase (EC 2.3.1.286) because the deacetylation reaction transfers the acetyl group to ADP-ribose. Reason: This is too general. SIRT1 has NAD-dependent protein deacetylase activity which is more specific. Proposed replacements: NAD-dependent protein lysine deacetylase activity |
| GO:0030154 cell differentiation | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: SIRT1 affects various differentiation processes through deacetylation of transcription factors. Reason: Downstream pleiotropic effect. SIRT1 impacts differentiation in multiple cell types but this is not its core function. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT1 deacetylation can promote proteasomal degradation of some substrates, including through effects on ubiquitination. Reason: Downstream effect of SIRT1 deacetylase activity on protein stability. Not the core function. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: NAD-dependent protein lysine deacetylase activity is the core enzymatic function of SIRT1. Reason: Core molecular function. This is the primary enzymatic activity of SIRT1. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT1 deacetylation can affect protein stability and degradation of some substrates. Reason: Downstream effect of SIRT1 deacetylase activity. Not the core function. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: SIRT1 contains a zinc-finger motif in its catalytic domain that coordinates zinc ions for structural stability. Reason: SIRT1 contains a conserved zinc-binding domain that is essential for its structure and function. |
| GO:0046890 regulation of lipid biosynthetic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT1 regulates lipid metabolism through deacetylation of SREBP and other metabolic transcription factors. Reason: Downstream metabolic effect of SIRT1 deacetylase activity. Part of SIRT1 pleiotropic metabolic functions. |
| GO:0046970 histone H4K16 deacetylase activity, NAD-dependent | IEA GO_REF:0000117 | ACCEPT | Summary: SIRT1 preferentially deacetylates H4K16 among histone substrates (PMID:15469825). Reason: Core molecular function. H4K16 is the preferred histone substrate of SIRT1. |
| GO:0048511 rhythmic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: SIRT1 can deacetylate circadian clock components BMAL1 and PER2 (PMID:18662546), but this is one of many substrates. SIRT1 core function is NAD-dependent deacetylation with broad substrate specificity including p53, NF-kB, FOXO, HIF, PGC-1alpha, and histones. Clock component deacetylation is a downstream effect of the enzymatic activity, not an evolved rhythmic function. Reason: SIRT1 has broad substrate specificity as an NAD-dependent deacetylase. While it can deacetylate clock proteins, this is one of many substrates. The core function is the NAD-dependent deacetylase activity, not rhythm generation. This represents an over-annotation based on one particular substrate class. |
| GO:0050793 regulation of developmental process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT1 affects various developmental processes through deacetylation of developmental transcription factors. Reason: Downstream pleiotropic effect. SIRT1 has broad effects on gene regulation but developmental regulation is not its core function. |
| GO:0051239 regulation of multicellular organismal process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT1 affects various organismal processes through its broad deacetylase activity. Reason: Downstream pleiotropic effect. This is too broad and vague to be informative about SIRT1 core function. |
| GO:0062013 positive regulation of small molecule metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT1 regulates metabolism through deacetylation of PGC-1alpha and other metabolic regulators. Reason: Downstream metabolic effect. SIRT1 affects metabolism broadly but this is not its core function. |
| GO:0070403 NAD+ binding | IEA GO_REF:0000002 | ACCEPT | Summary: SIRT1 binds NAD+ as an essential cofactor for its deacetylase reaction. The NAD-binding Rossmann-like fold is conserved in all sirtuins. Reason: Core molecular function. NAD+ binding is essential for SIRT1 catalytic activity. |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SIRT1 deacetylates HIF1alpha and HIF2alpha to modulate hypoxia responses. Reason: Downstream effect through deacetylation of HIF transcription factors. One of many substrates of SIRT1. |
| GO:0141208 NAD-dependent protein lysine delactylase activity | IEA GO_REF:0000116 | ACCEPT | Summary: SIRT1 may have delactylase activity in addition to its primary deacetylase function. IDA evidence from PMID:38512451. Reason: Molecular function consistent with the broad deacylase activity of sirtuins. |
| GO:0160011 NAD-dependent protein decrotonylase activity | IEA GO_REF:0000116 | ACCEPT | Summary: SIRT1 has decrotonylase activity in addition to deacetylase activity. IDA evidence from PMID:28497810. Reason: Molecular function consistent with the broad deacylase activity of sirtuins. SIRT1 can remove various acyl modifications. |
| GO:0005515 protein binding | IPI PMID:11672523 hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. | REMOVE | Summary: SIRT1 binds p53 (PMID:11672523). This protein binding annotation is uninformative - the specific interaction with p53 is better captured by the p53 binding annotation (GO:0002039). Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions (e.g. p53 binding, transcription factor binding). Supporting Evidence: PMID:11672523 hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. |
| GO:0005515 protein binding | IPI PMID:12006491 Human SIR2 deacetylates p53 and antagonizes PML/p53-induced ... | REMOVE | Summary: SIRT1 binds PML and p53 at PML nuclear bodies (PMID:12006491). Generic protein binding is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:12006491 Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. |
| GO:0005515 protein binding | IPI PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH re... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression. |
| GO:0005515 protein binding | IPI PMID:14976264 Stress-dependent regulation of FOXO transcription factors by... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:14976264 Feb 19. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. |
| GO:0005515 protein binding | IPI PMID:15126506 FOXO4 is acetylated upon peroxide stress and deacetylated by... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:15126506 2004 May 4. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). |
| GO:0005515 protein binding | IPI PMID:15152190 Modulation of NF-kappaB-dependent transcription and cell sur... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:15152190 May 20. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. |
| GO:0005515 protein binding | IPI PMID:15175761 Sirt1 promotes fat mobilization in white adipocytes by repre... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:15175761 Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. |
| GO:0005515 protein binding | IPI PMID:15205477 Calorie restriction promotes mammalian cell survival by indu... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:15205477 Jun 17. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. |
| GO:0005515 protein binding | IPI PMID:15220471 Silent information regulator 2 potentiates Foxo1-mediated tr... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:15220471 Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. |
| GO:0005515 protein binding | IPI PMID:15632193 SIRT1 deacetylation and repression of p300 involves lysine r... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:15632193 2005 Jan 4. SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. |
| GO:0005515 protein binding | IPI PMID:15692560 Suppression of FOXO1 activity by FHL2 through SIRT1-mediated... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:15692560 Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. |
| GO:0005515 protein binding | IPI PMID:16892051 Interactions between E2F1 and SirT1 regulate apoptotic respo... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:16892051 Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. |
| GO:0005515 protein binding | IPI PMID:16998810 SIRT1 interacts with p73 and suppresses p73-dependent transc... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:16998810 SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity. |
| GO:0005515 protein binding | IPI PMID:17334224 SIRT1 promotes DNA repair activity and deacetylation of Ku70... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:17334224 SIRT1 promotes DNA repair activity and deacetylation of Ku70. |
| GO:0005515 protein binding | IPI PMID:17612497 SIRT1 regulates the function of the Nijmegen breakage syndro... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:17612497 SIRT1 regulates the function of the Nijmegen breakage syndrome protein. |
| GO:0005515 protein binding | IPI PMID:17680780 Sirt1 interacts with transducin-like enhancer of split-1 to ... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:17680780 Sirt1 interacts with transducin-like enhancer of split-1 to inhibit nuclear factor kappaB-mediated transcription. |
| GO:0005515 protein binding | IPI PMID:17901049 The direct involvement of SirT1 in insulin-induced insulin r... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:17901049 2007 Sep 27. The direct involvement of SirT1 in insulin-induced insulin receptor substrate-2 tyrosine phosphorylation. |
| GO:0005515 protein binding | IPI PMID:17936707 SIRT1 deacetylates and positively regulates the nuclear rece... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:17936707 SIRT1 deacetylates and positively regulates the nuclear receptor LXR. |
| GO:0005515 protein binding | IPI PMID:17964266 Active regulator of SIRT1 cooperates with SIRT1 and facilita... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:17964266 Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity. |
| GO:0005515 protein binding | IPI PMID:18004385 SIRT1 regulates the histone methyl-transferase SUV39H1 durin... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:18004385 SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. |
| GO:0005515 protein binding | IPI PMID:18203716 Regulation of WRN protein cellular localization and enzymati... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:18203716 2008 Jan 17. Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation. |
| GO:0005515 protein binding | IPI PMID:18235501 DBC1 is a negative regulator of SIRT1. | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:18235501 DBC1 is a negative regulator of SIRT1. |
| GO:0005515 protein binding | IPI PMID:18235502 Negative regulation of the deacetylase SIRT1 by DBC1. | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:18235502 Negative regulation of the deacetylase SIRT1 by DBC1. |
| GO:0005515 protein binding | IPI PMID:18296641 A role for the NAD-dependent deacetylase Sirt1 in the regula... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:18296641 A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. |
| GO:0005515 protein binding | IPI PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:18485871 Epigenetic control of rDNA loci in response to intracellular energy status. |
| GO:0005515 protein binding | IPI PMID:19047049 Hyaluronan-mediated CD44 interaction with p300 and SIRT1 reg... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:19047049 2008 Dec 1. Hyaluronan-mediated CD44 interaction with p300 and SIRT1 regulates beta-catenin signaling and NFkappaB-specific transcription activity leading to MDR1 and Bcl-xL gene expression and chemoresistance in breast tumor cells. |
| GO:0005515 protein binding | IPI PMID:19188449 hSirT1-dependent regulation of the PCAF-E2F1-p73 apoptotic p... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:19188449 Feb 2. hSirT1-dependent regulation of the PCAF-E2F1-p73 apoptotic pathway in response to DNA damage. |
| GO:0005515 protein binding | IPI PMID:19236849 Carboxy-terminal phosphorylation of SIRT1 by protein kinase ... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:19236849 Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2. |
| GO:0005515 protein binding | IPI PMID:19343720 Identification and characterization of proteins interacting ... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:19343720 Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the anti-aging and metabolic effects of sirtuins. |
| GO:0005515 protein binding | IPI PMID:19478080 Enzymes in the NAD+ salvage pathway regulate SIRT1 activity ... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:19478080 2009 May 28. Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters. |
| GO:0005515 protein binding | IPI PMID:19680552 CK2 is the regulator of SIRT1 substrate-binding affinity, de... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:19680552 CK2 is the regulator of SIRT1 substrate-binding affinity, deacetylase activity and cellular response to DNA-damage. |
| GO:0005515 protein binding | IPI PMID:19690166 Transcriptional corepressor SMILE recruits SIRT1 to inhibit ... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:19690166 2009 Aug 18. Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear receptor estrogen receptor-related receptor gamma transactivation. |
| GO:0005515 protein binding | IPI PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:19934257 Nov 24. SIRT1 deacetylates APE1 and regulates cellular base excision repair. |
| GO:0005515 protein binding | IPI PMID:19934264 Reciprocal roles of SIRT1 and SKIP in the regulation of RAR ... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:19934264 Nov 24. Reciprocal roles of SIRT1 and SKIP in the regulation of RAR activity: implication in the retinoic acid-induced neuronal differentiation of P19 cells. |
| GO:0005515 protein binding | IPI PMID:20169165 SIRT1 negatively regulates the mammalian target of rapamycin... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:20169165 SIRT1 negatively regulates the mammalian target of rapamycin. |
| GO:0005515 protein binding | IPI PMID:20375098 Transcriptional corepressor SHP recruits SIRT1 histone deace... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:20375098 Apr 7. Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation. |
| GO:0005515 protein binding | IPI PMID:20439735 SIRT1 regulates Dishevelled proteins and promotes transient ... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:20439735 SIRT1 regulates Dishevelled proteins and promotes transient and constitutive Wnt signaling. |
| GO:0005515 protein binding | IPI PMID:20660480 SIRT1 is regulated by a PPAR{Ξ³}-SIRT1 negative feedback loop... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:20660480 Jul 25. SIRT1 is regulated by a PPAR{Ξ³}-SIRT1 negative feedback loop associated with senescence. |
| GO:0005515 protein binding | IPI PMID:20670893 SIRT1 regulates UV-induced DNA repair through deacetylating ... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:20670893 SIRT1 regulates UV-induced DNA repair through deacetylating XPA. |
| GO:0005515 protein binding | IPI PMID:20817729 SIRT1 deacetylates and inhibits SREBP-1C activity in regulat... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:20817729 2010 Sep 3. SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. |
| GO:0005515 protein binding | IPI PMID:21081649 SIRT2 regulates NF-ΞΊB dependent gene expression through deac... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21081649 Nov 16. SIRT2 regulates NF-ΞΊB dependent gene expression through deacetylation of p65 Lys310. |
| GO:0005515 protein binding | IPI PMID:21241768 Phosphoinositide 3-kinase as a novel functional target for t... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21241768 Phosphoinositide 3-kinase as a novel functional target for the regulation of the insulin signaling pathway by SIRT1. |
| GO:0005515 protein binding | IPI PMID:21245319 Methyltransferase Set7/9 regulates p53 activity by interacti... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21245319 Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1). |
| GO:0005515 protein binding | IPI PMID:21471201 Cancer cell survival following DNA damage-mediated premature... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21471201 2011 Apr 6. Cancer cell survival following DNA damage-mediated premature senescence is regulated by mammalian target of rapamycin (mTOR)-dependent Inhibition of sirtuin 1. |
| GO:0005515 protein binding | IPI PMID:21555002 EVI1 up-regulates the stress responsive gene SIRT1 which tri... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21555002 EVI1 up-regulates the stress responsive gene SIRT1 which triggers deacetylation and degradation of EVI1. |
| GO:0005515 protein binding | IPI PMID:21698133 SIRT1 promotes N-Myc oncogenesis through a positive feedback... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21698133 2011 Jun 16. SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability. |
| GO:0005515 protein binding | IPI PMID:21775285 The deacetylase SIRT1 promotes membrane localization and act... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21775285 The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy. |
| GO:0005515 protein binding | IPI PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. |
| GO:0005515 protein binding | IPI PMID:21890893 SIRT1 links CIITA deacetylation to MHC II activation. | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21890893 Sep 2. SIRT1 links CIITA deacetylation to MHC II activation. |
| GO:0005515 protein binding | IPI PMID:21909281 The evolutionarily conserved longevity determinants HCF-1 an... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21909281 2011 Sep 1. The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. |
| GO:0005515 protein binding | IPI PMID:21947282 SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) prote... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21947282 Sep 26. SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities. |
| GO:0005515 protein binding | IPI PMID:21968188 p53 deacetylation by SIRT1 decreases during protein kinase C... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21968188 2011 Sep 29. p53 deacetylation by SIRT1 decreases during protein kinase CKII downregulation-mediated cellular senescence. |
| GO:0005515 protein binding | IPI PMID:22094255 Oxidative damage targets complexes containing DNA methyltran... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:22094255 Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands. |
| GO:0005515 protein binding | IPI PMID:22169038 SIRT1 activates MAO-A in the brain to mediate anxiety and ex... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:22169038 Dec 8. SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive. |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes. | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:22190034 Global landscape of HIV-human protein complexes. |
| GO:0005515 protein binding | IPI PMID:22510882 Novel repressor regulates insulin sensitivity through intera... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:22510882 Novel repressor regulates insulin sensitivity through interaction with Foxo1. |
| GO:0005515 protein binding | IPI PMID:22863012 Brown remodeling of white adipose tissue by SirT1-dependent ... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:22863012 Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of PparΞ³. |
| GO:0005515 protein binding | IPI PMID:24681097 AROS has a context-dependent effect on SIRT1. | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:24681097 2014 Mar 26. AROS has a context-dependent effect on SIRT1. |
| GO:0005515 protein binding | IPI PMID:25751424 NAD(+)-SIRT1 control of H3K4 trimethylation through circadia... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:25751424 Mar 9. NAD(+)-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:31403225 The interactome of KRAB zinc finger proteins reveals the evo... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:31403225 Aug 12. The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification. |
| GO:0005515 protein binding | IPI PMID:32761762 CSAG2 is a cancer-specific activator of SIRT1. | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:32761762 CSAG2 is a cancer-specific activator of SIRT1. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 represses RNA Pol II transcription through histone deacetylation and deacetylation of transcription factors. Reason: Represents downstream transcriptional regulation rather than a singular core function. Supporting Evidence: PMID:15469825 Gal4-SirT1 expression resulted in the deacetylation of H4-K16 and H3-K9, recruitment of H1 within the promoter vicinity, drastically reduced reporter expression |
| GO:0000720 pyrimidine dimer repair by nucleotide-excision repair | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 participates in DNA repair processes through deacetylation of repair proteins. This is one of many DNA damage response roles mediated by SIRT1 deacetylase activity. Reason: Downstream effect of SIRT1 deacetylase activity on DNA repair proteins. SIRT1 contributes to DNA repair but this specific pathway is not its core function. |
| GO:0000731 DNA synthesis involved in DNA repair | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 participates in DNA repair processes through deacetylation of repair proteins. This is one of many DNA damage response roles mediated by SIRT1 deacetylase activity. Reason: Downstream effect of SIRT1 deacetylase activity on DNA repair proteins. SIRT1 contributes to DNA repair but this specific pathway is not its core function. |
| GO:0000785 chromatin | IEA GO_REF:0000107 | ACCEPT | Summary: SIRT1 localizes to chromatin where it functions as a histone deacetylase. Core localization consistent with its primary enzymatic function. Reason: Core localization. SIRT1 functions at chromatin to deacetylate histones and regulate transcription. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0000792 heterochromatin | IEA GO_REF:0000107 | ACCEPT | Summary: SIRT1 promotes heterochromatin formation through histone deacetylation. Core localization consistent with its primary function in chromatin silencing. Reason: Core localization. SIRT1 promotes facultative heterochromatin formation through deacetylation of H4K16 and H3K9. Supporting Evidence: PMID:15469825 We propose a model for SirT1-mediated heterochromatin formation that includes deacetylation of histone tails, recruitment and deacetylation of histone H1, and spreading of hypomethylated H3-K79 with resultant silencing. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | REMOVE | Summary: SIRT1 does not have intrinsic sequence-specific DNA binding activity. It is recruited to promoters through interactions with transcription factors rather than direct DNA sequence recognition. Reason: SIRT1 lacks intrinsic sequence-specific DNA binding. It is a deacetylase that is recruited to chromatin through protein-protein interactions, not DNA sequence recognition. |
| GO:0001525 angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 affects angiogenesis through deacetylation of HIF and FOXO transcription factors. This is a downstream pleiotropic effect of its broad deacetylase activity. Reason: Downstream pleiotropic effect. SIRT1 modulates angiogenesis through its effects on transcription factors but this is not its core function. |
| GO:0001678 intracellular glucose homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates glucose homeostasis through deacetylation of PGC-1alpha, FOXO factors, and other metabolic regulators. NAD+ dependence links SIRT1 activity to metabolic state. Reason: Important downstream metabolic effect of SIRT1 deacetylase activity. SIRT1 functions as a metabolic sensor through NAD+ dependence but glucose homeostasis per se is not its core function. |
| GO:0002039 p53 binding | IEA GO_REF:0000107 | ACCEPT | Summary: SIRT1 directly binds p53 and deacetylates its C-terminal K382 residue. Well-established substrate interaction demonstrated in multiple studies (PMID:11672523, PMID:12006491). Reason: Core substrate interaction. p53 is a major non-histone substrate of SIRT1. Binding is required for deacetylation of p53 K382. Supporting Evidence: PMID:11672523 the protein product of the gene hSIR2(SIRT1), the human homolog of the S. cerevisiae Sir2 protein known to be involved in cell aging and in the response to DNA damage, binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue PMID:12006491 SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation. |
| GO:0003713 transcription coactivator activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 is primarily a transcriptional corepressor through histone deacetylation. However, in some contexts deacetylation of specific transcription factors can enhance their activity. This is a minor function compared to corepressor activity. Reason: Context-dependent function. SIRT1 is predominantly a corepressor but can have coactivator effects in specific contexts. Not the core function. |
| GO:0003714 transcription corepressor activity | IEA GO_REF:0000107 | ACCEPT | Summary: SIRT1 functions as a transcriptional corepressor through histone deacetylation and deacetylation of transcription factors. Core molecular function well-supported by phylogenetic inference and experimental evidence (PMID:15469825, PMID:20955178). Reason: Core molecular function. SIRT1 mediates transcriptional repression through heterochromatin formation and deacetylation of transcription factors. Supporting Evidence: PMID:15469825 We propose a model for SirT1-mediated heterochromatin formation that includes deacetylation of histone tails, recruitment and deacetylation of histone H1, and spreading of hypomethylated H3-K79 with resultant silencing. |
| GO:0004857 enzyme inhibitor activity | IEA GO_REF:0000107 | REMOVE | Summary: SIRT1 is an enzyme (deacetylase) itself, not primarily an enzyme inhibitor. While deacetylation can modulate enzyme activity, this is an indirect effect. This annotation is misleading. Reason: Misleading annotation. SIRT1 is a deacetylase enzyme, not an enzyme inhibitor. Any effects on other enzyme activities are indirect consequences of its deacetylation activity. |
| GO:0006642 triglyceride mobilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates lipid metabolism through deacetylation of SREBP and other lipid metabolism transcription factors. This is a downstream pleiotropic effect. Reason: Downstream metabolic effect. SIRT1 modulates lipid metabolism through transcription factor deacetylation but this is not its core function. |
| GO:0007623 circadian rhythm | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: SIRT1 can deacetylate circadian clock components but this is one of many substrates. Clock regulation is not the core function. Reason: SIRT1 deacetylates many transcription factors including clock proteins. This represents an over-annotation based on one substrate class rather than the core NAD-dependent deacetylase function. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 modulates DNA damage-induced apoptosis primarily through deacetylation of p53, suppressing its pro-apoptotic activity (PMID:11672523). This is a downstream effect of SIRT1 deacetylase activity. Reason: Downstream effect of SIRT1 deacetylase activity on p53 and other apoptotic regulators. Apoptosis regulation is not SIRT1's core function. Supporting Evidence: PMID:11672523 Expression of wild-type hSir2 in human cells reduces the transcriptional activity of p53. In contrast, expression of a catalytically inactive hSir2 protein potentiates p53-dependent apoptosis and radiosensitivity. |
| GO:0009267 cellular response to starvation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 is activated by increased NAD+/NADH ratio during starvation and mediates metabolic adaptations through deacetylation of PGC-1alpha, FOXO, and other metabolic regulators (PMID:18485871). This is an important metabolic sensor function. Reason: Downstream metabolic response. SIRT1 NAD+ dependence makes it a metabolic sensor but starvation response per se is not its core function. Supporting Evidence: PMID:18485871 a change in the NAD(+)/NADH ratio induced by reduction of energy status could activate SIRT1, leading to deacetylation of histone H3 and dimethylation at Lys9 by SUV39H1, thus establishing silent chromatin |
| GO:0010875 positive regulation of cholesterol efflux | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates cholesterol metabolism through deacetylation of LXR and other cholesterol metabolism regulators. This is a downstream pleiotropic metabolic effect. Reason: Downstream metabolic effect. SIRT1 modulates cholesterol metabolism through transcription factor deacetylation but this is not its core function. |
| GO:0010883 regulation of lipid storage | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates lipid storage through deacetylation of SREBP and other lipid metabolism transcription factors. This is a downstream pleiotropic metabolic effect. Reason: Downstream metabolic effect. SIRT1 modulates lipid storage through transcription factor deacetylation but this is not its core function. |
| GO:0010906 regulation of glucose metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates glucose metabolism through deacetylation of PGC-1alpha, FOXO factors, and other metabolic regulators. NAD+ dependence links SIRT1 activity to metabolic state. Reason: Important downstream metabolic effect of SIRT1 deacetylase activity but glucose metabolism per se is not its core function. |
| GO:0016239 positive regulation of macroautophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates autophagy through deacetylation of autophagy-related proteins and FOXO transcription factors. This is a downstream effect of SIRT1 deacetylase activity. Reason: Downstream effect. SIRT1 modulates autophagy through protein deacetylation but autophagy regulation is not its core function. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IEA GO_REF:0000107 | ACCEPT | Summary: NAD-dependent histone deacetylase activity is the core enzymatic function of SIRT1. Well-demonstrated through multiple experimental studies (PMID:15469825, PMID:12006491). Reason: Core molecular function. This is the primary enzymatic activity of SIRT1 on histones. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0019213 deacetylase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Deacetylase activity is the core enzymatic function of SIRT1. This is a broader parent term; more specific NAD-dependent protein lysine deacetylase activity annotations are preferred. Reason: Core molecular function. SIRT1 is an NAD-dependent deacetylase. This general term is correct but less informative than more specific deacetylase annotations. |
| GO:0019899 enzyme binding | IEA GO_REF:0000107 | ACCEPT | Summary: SIRT1 binds multiple enzymes and enzyme complexes. Reason: Enzyme binding is supported by multiple interaction studies. |
| GO:0019904 protein domain specific binding | IEA GO_REF:0000107 | REMOVE | Summary: SIRT1 interacts with specific protein domains but this generic annotation is not informative about the specific interactions. Reason: Generic protein domain binding annotation is uninformative. More specific annotations for particular domain interactions are preferred. |
| GO:0030225 macrophage differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 affects macrophage differentiation through deacetylation of transcription factors. This is a downstream pleiotropic effect. Reason: Downstream pleiotropic effect on immune cell differentiation. Not the core function of SIRT1. |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can modulate TGF-beta signaling through deacetylation of SMAD proteins. This is a downstream pleiotropic effect. Reason: Downstream signaling effect through transcription factor deacetylation. Not the core function of SIRT1. |
| GO:0030968 endoplasmic reticulum unfolded protein response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 deacetylates XBP1s and modulates the UPR (PMID:20955178). This is a downstream effect of SIRT1 deacetylase activity. Reason: Downstream effect through XBP1s deacetylation. UPR regulation is not the core function of SIRT1. Supporting Evidence: PMID:20955178 SIRT1 deacetylates XBP1s and inhibits its transcriptional activity. |
| GO:0031393 negative regulation of prostaglandin biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can affect prostaglandin biosynthesis through deacetylation of inflammatory regulators like NF-kB. This is a downstream pleiotropic effect. Reason: Downstream anti-inflammatory effect through transcription factor deacetylation. Not the core function of SIRT1. |
| GO:0031648 protein destabilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 deacetylation can promote protein destabilization and degradation of some substrates (e.g., PER2). This is a downstream effect of deacetylase activity. Reason: Downstream effect on specific substrates. Protein destabilization per se is not SIRT1's core function. |
| GO:0032007 negative regulation of TOR signaling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can modulate mTOR signaling through deacetylation of pathway components. This is a downstream metabolic signaling effect. Reason: Downstream signaling effect. mTOR regulation is not the core function of SIRT1. |
| GO:0032868 response to insulin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 modulates insulin sensitivity through deacetylation of IRS proteins and insulin signaling components. Downstream metabolic effect. Reason: Downstream metabolic effect. Insulin response is not the core function of SIRT1. |
| GO:0032922 circadian regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 modulates circadian clock components through deacetylation. Reason: Circadian regulation is a downstream outcome of SIRT1 activity. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | ACCEPT | Summary: SIRT1 functions in various protein complexes including the eNoSC complex at rDNA loci (PMID:18485871). This is a generic localization annotation. Reason: SIRT1 functions within protein complexes. This generic annotation is consistent with its participation in eNoSC and other chromatin regulatory complexes. |
| GO:0033210 leptin-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can modulate leptin signaling in the hypothalamus. This is a downstream metabolic signaling effect. Reason: Downstream signaling effect in specific tissues. Leptin signaling is not the core function of SIRT1. |
| GO:0033558 protein lysine deacetylase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Protein lysine deacetylase activity is the core enzymatic function of SIRT1. SIRT1 deacetylates histones and many non-histone proteins at lysine residues (PMID:15469825, PMID:11672523). Reason: Core molecular function. This is the primary enzymatic activity of SIRT1. Supporting Evidence: PMID:11672523 the protein product of the gene hSIR2(SIRT1)...binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue |
| GO:0034391 regulation of smooth muscle cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can modulate smooth muscle cell apoptosis through deacetylation of p53 and other apoptotic regulators. This is a downstream pleiotropic effect in specific cell types. Reason: Downstream cell type-specific effect. Smooth muscle cell apoptosis regulation is not the core function of SIRT1. |
| GO:0035356 intracellular triglyceride homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates triglyceride metabolism through deacetylation of SREBP and other metabolic transcription factors. Downstream metabolic effect. Reason: Downstream metabolic effect. Triglyceride homeostasis is not the core function of SIRT1. |
| GO:0035358 regulation of peroxisome proliferator activated receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can modulate PPAR signaling through deacetylation of PPAR coactivators like PGC-1alpha. Downstream metabolic signaling effect. Reason: Downstream metabolic signaling effect. PPAR signaling regulation is not the core function of SIRT1. |
| GO:0042632 cholesterol homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates cholesterol metabolism through deacetylation of LXR and other cholesterol metabolism regulators. Downstream metabolic effect. Reason: Downstream metabolic effect. Cholesterol homeostasis is not the core function of SIRT1. |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 generally suppresses apoptosis through p53 deacetylation but can have context-dependent pro-apoptotic effects. Downstream effect. Reason: Downstream context-dependent effect on apoptosis. Apoptosis regulation is not the core function of SIRT1. |
| GO:0044321 response to leptin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can modulate leptin signaling in the hypothalamus. Downstream metabolic signaling effect. Reason: Downstream metabolic signaling effect. Leptin response is not the core function of SIRT1. |
| GO:0045599 negative regulation of fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 inhibits adipogenesis through deacetylation of PPAR-gamma and other adipogenic transcription factors. Downstream metabolic effect. Reason: Downstream metabolic effect on adipocyte differentiation. Not the core function of SIRT1. |
| GO:0045722 positive regulation of gluconeogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 promotes gluconeogenesis through deacetylation and activation of PGC-1alpha and FOXO1. Well-supported metabolic function. Reason: Important downstream metabolic effect through PGC-1alpha/FOXO1 deacetylation. Not the core function but a well-established metabolic role. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 is predominantly a transcriptional corepressor but can positively regulate transcription of some genes through effects on specific transcription factors. Context-dependent effect. Reason: Secondary function. SIRT1 is primarily a corepressor but has context-dependent coactivator effects on some promoters. |
| GO:0046969 histone H3K9 deacetylase activity, NAD-dependent | IEA GO_REF:0000107 | ACCEPT | Summary: H3K9 deacetylation is a core histone modification activity of SIRT1. Well-demonstrated in PMID:15469825. Reason: Core molecular function. H3K9 deacetylation is one of SIRT1's primary histone substrate specificities. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0050872 white fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 inhibits white adipocyte differentiation through effects on PPAR-gamma and other adipogenic regulators. Downstream metabolic effect. Reason: Downstream metabolic effect on adipocyte differentiation. Not the core function of SIRT1. |
| GO:0051152 positive regulation of smooth muscle cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 affects smooth muscle cell differentiation through transcription factor deacetylation. Downstream pleiotropic effect. Reason: Downstream cell type-specific effect. Not the core function of SIRT1. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can modulate PI3K/AKT signaling through effects on insulin signaling and other pathways. Downstream signaling effect. Reason: Downstream signaling effect. PI3K/AKT regulation is not the core function of SIRT1. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can negatively modulate PI3K/AKT signaling in some contexts. Context-dependent downstream signaling effect. Reason: Downstream context-dependent signaling effect. PI3K/AKT regulation is not the core function of SIRT1. |
| GO:0055089 fatty acid homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates fatty acid metabolism through deacetylation of SREBP and other lipid metabolism transcription factors. Downstream metabolic effect. Reason: Downstream metabolic effect. Fatty acid homeostasis is not the core function of SIRT1. |
| GO:0060907 positive regulation of macrophage cytokine production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 modulates macrophage cytokine production through NF-kB deacetylation and other inflammatory regulators. Downstream immune effect. Reason: Downstream immune/inflammatory effect. Macrophage cytokine regulation is not the core function of SIRT1. |
| GO:0070857 regulation of bile acid biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 regulates bile acid metabolism through deacetylation of FXR and other bile acid metabolism regulators. Downstream metabolic effect. Reason: Downstream metabolic effect. Bile acid regulation is not the core function of SIRT1. |
| GO:0071479 cellular response to ionizing radiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 modulates DNA damage response through deacetylation of p53 and other DNA repair/checkpoint proteins. Downstream stress response effect. Reason: Downstream stress response effect through p53 and DNA repair protein deacetylation. Not the core function of SIRT1. |
| GO:0090335 regulation of brown fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 affects brown adipocyte differentiation through effects on PGC-1alpha and other thermogenic regulators. Downstream metabolic effect. Reason: Downstream metabolic effect on adipocyte differentiation. Not the core function of SIRT1. |
| GO:0106231 NAD-dependent protein-lysine depropionylase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: SIRT1 can remove propionyl groups from lysine residues in addition to acetyl groups. Minor enzymatic activity compared to deacetylation. Reason: Secondary enzymatic activity. Depropionylation is a minor activity compared to the primary deacetylase function. |
| GO:1902166 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 suppresses p53-mediated apoptosis through deacetylation of p53 K382 (PMID:11672523). Well-established downstream effect. Reason: Downstream effect of SIRT1 deacetylase activity on p53. Apoptosis regulation is not SIRT1's core function but this is a well-supported effect. Supporting Evidence: PMID:11672523 Expression of wild-type hSir2 in human cells reduces the transcriptional activity of p53. In contrast, expression of a catalytically inactive hSir2 protein potentiates p53-dependent apoptosis and radiosensitivity. |
| GO:1902237 positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 can modulate ER stress-induced apoptosis through effects on XBP1s and other UPR regulators (PMID:20955178). Context-dependent effect. Reason: Downstream context-dependent effect on ER stress apoptosis. Not the core function of SIRT1. Supporting Evidence: PMID:20955178 Sirt1-/- MEFs display a greater resistance to ER-stress-induced apoptotic cell death compared with Sirt1+/+ MEFs. |
| GO:1904179 positive regulation of adipose tissue development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SIRT1 affects adipose tissue development through effects on PPAR-gamma and other adipogenic regulators. Context-dependent downstream metabolic effect. Reason: Downstream metabolic effect on adipose development. Not the core function of SIRT1. |
| GO:1990841 promoter-specific chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: SIRT1 is recruited to specific promoters through interactions with transcription factors. Core localization related to its transcriptional regulatory function. Reason: Core localization. SIRT1 binds chromatin at specific promoters to regulate transcription through histone deacetylation. |
| GO:2000111 positive regulation of macrophage apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Annotation indicates SIRT1 can influence macrophage apoptosis through deacetylation of regulatory factors in immune contexts. Reason: Downstream immune regulation rather than a core function; keep as non-core despite indirect support. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: SIRT1 localizes to nuclear compartments including the nucleoplasm. Reason: Consistent with nuclear localization shown in immunostaining studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | UNDECIDED | Summary: Mitochondrial localization for full-length SIRT1 is not clearly supported here. Reason: Evidence may be context- or isoform-specific; requires confirmation. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: SIRT1 localizes to the cytosol as well as the nucleus. Reason: Immunostaining shows cytoplasmic localization. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0000183 rDNA heterochromatin formation | TAS Reactome:R-HSA-427359 | ACCEPT | Summary: SIRT1 in eNoSC promotes rRNA gene silencing via histone modification. Reason: Reactome summary describes eNoSC-mediated repression of rRNA genes. Supporting Evidence: Reactome:R-HSA-427359 Deacetylation and methylation of histone H3 in the chromatin of a rRNA gene by eNoSC causes reduced expression of the gene. Reactome:R-HSA-427359 eNoSC comprises Nucleomethylin (NML), SIRT1, and the histone methylase SUV39H1 (Murayama et al. 2008). |
| GO:1900034 regulation of cellular response to heat | TAS Reactome:R-HSA-3371453 | KEEP AS NON CORE | Summary: SIRT1 participates in heat shock response regulation via HSF1 deacetylation. Reason: Pathway-level regulatory effect rather than core function. Supporting Evidence: Reactome:R-HSA-3371467 Sirtuin 1 (SIRT1) functions as a NAD(+)-dependent deacetylase, which regulates the heat shock response through deacetylation of HSF1 at Lys80. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | TAS Reactome:R-HSA-3371467 | ACCEPT | Summary: SIRT1 functions as a NAD-dependent deacetylase in the HSF1 heat shock pathway. Reason: Core enzymatic activity supported in Reactome summary. Supporting Evidence: Reactome:R-HSA-3371467 Sirtuin 1 (SIRT1) functions as a NAD(+)-dependent deacetylase, which regulates the heat shock response through deacetylation of HSF1 at Lys80. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | TAS Reactome:R-HSA-9620532 | ACCEPT | Summary: SIRT1 deacetylates FOXO3 as an NAD-dependent histone deacetylase. Reason: Reactome summary documents FOXO3 deacetylation by SIRT1. Supporting Evidence: Reactome:R-HSA-9620532 SIRT1, an NAD-dependent histone deacetylase, deacetylates FOXO3. |
| GO:0000183 rDNA heterochromatin formation | IMP PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | ACCEPT | Summary: eNoSC containing SIRT1 establishes silent chromatin at rDNA loci. Reason: Supported by the eNoSC complex and rDNA chromatin silencing. Supporting Evidence: PMID:18485871 eNoSC contains Nucleomethylin, which binds histone H3 dimethylated Lys9 in the rDNA locus, in a complex with SIRT1 and SUV39H1. PMID:18485871 thus establishing silent chromatin in the rDNA locus. |
| GO:0005730 nucleolus | IDA PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | KEEP AS NON CORE | Summary: SIRT1 participates in rDNA locus regulation within the nucleolar context. Reason: Context-specific localization associated with rDNA regulation. Supporting Evidence: PMID:18485871 eNoSC contains Nucleomethylin, which binds histone H3 dimethylated Lys9 in the rDNA locus, in a complex with SIRT1 and SUV39H1. |
| GO:0042149 cellular response to glucose starvation | IMP PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | MARK AS OVER ANNOTATED | Summary: This study links energy status to rRNA transcription, but glucose-specific starvation is not explicit. Reason: The term is too specific relative to the evidence presented. Supporting Evidence: PMID:18485871 Furthermore, eNoSC promotes restoration of energy balance by limiting rRNA transcription, thus protecting cells from energy deprivation-dependent apoptosis. |
| GO:0045786 negative regulation of cell cycle | IMP PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | UNDECIDED | Summary: Negative regulation of cell cycle is not described in the PMID:18485871 abstract. Reason: Insufficient evidence in this reference for cell cycle regulation. Supporting Evidence: PMID:18485871 SIRT1 and SUV39H1 are required for energy-dependent transcriptional repression |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | KEEP AS NON CORE | Summary: SIRT1 and SUV39H1 are required for energy-dependent transcriptional repression at rDNA loci. Reason: Represents context-specific repression of rRNA transcription. Supporting Evidence: PMID:18485871 SIRT1 and SUV39H1 are required for energy-dependent transcriptional repression |
| GO:0046015 regulation of transcription by glucose | IMP PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | MARK AS OVER ANNOTATED | Summary: The evidence discusses energy status broadly rather than glucose-specific transcriptional control. Reason: Glucose-specific regulation is not explicit in the abstract. Supporting Evidence: PMID:18485871 Furthermore, eNoSC promotes restoration of energy balance by limiting rRNA transcription, thus protecting cells from energy deprivation-dependent apoptosis. |
| GO:0097009 energy homeostasis | IMP PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | KEEP AS NON CORE | Summary: eNoSC limits rRNA transcription to restore energy balance. Reason: Energy homeostasis is a downstream consequence of rDNA repression. Supporting Evidence: PMID:18485871 Furthermore, eNoSC promotes restoration of energy balance by limiting rRNA transcription, thus protecting cells from energy deprivation-dependent apoptosis. |
| GO:0003714 transcription corepressor activity | IDA PMID:20955178 Regulation of unfolded protein response modulator XBP1s by a... | ACCEPT | Summary: SIRT1 represses XBP1s transcriptional activity via deacetylation. Reason: Corepressor activity is supported by inhibition of XBP1s. Supporting Evidence: PMID:20955178 SIRT1 deacetylates XBP1s and inhibits its transcriptional activity |
| GO:0030968 endoplasmic reticulum unfolded protein response | IDA PMID:20955178 Regulation of unfolded protein response modulator XBP1s by a... | KEEP AS NON CORE | Summary: SIRT1 modulates the unfolded protein response through XBP1s deacetylation. Reason: Represents a pathway-specific regulatory role. Supporting Evidence: PMID:20955178 Deficiency of SIRT1 enhances XBP1s-mediated luciferase reporter activity in HEK (human embryonic kidney)-293 cells |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:20955178 Regulation of unfolded protein response modulator XBP1s by a... | ACCEPT | Summary: SIRT1 deacetylates XBP1s as a lysine deacetylase. Reason: Direct deacetylation of XBP1s supports this activity. Supporting Evidence: PMID:20955178 In the present study, we demonstrate that XBP1s is a target of acetylation and deacetylation mediated by p300 and SIRT1 (sirtuin 1) respectively |
| GO:0004407 histone deacetylase activity | EXP PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | ACCEPT | Summary: SIRT1 contributes to histone deacetylation during rDNA silencing. Reason: Core enzymatic activity within the eNoSC complex. Supporting Evidence: PMID:18485871 SIRT1 and SUV39H1 are required for energy-dependent transcriptional repression |
| GO:0033558 protein lysine deacetylase activity | TAS Reactome:R-HSA-9825772 | ACCEPT | Summary: SIRT1 deacetylates HINT1, consistent with protein lysine deacetylase activity. Reason: Reactome summary documents SIRT1-dependent deacetylation. Supporting Evidence: Reactome:R-HSA-9825772 Deacetylation at these sites by SIRT1 promotes the interaction between MITF and HINT1 |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:11672523 hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. | KEEP AS NON CORE | Summary: SIRT1 reduces p53 transcriptional activity via deacetylation. Reason: Represents a downstream regulatory effect on p53 target genes. Supporting Evidence: PMID:11672523 Expression of wild-type hSir2 in human cells reduces the transcriptional activity of p53 |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IMP PMID:11672523 hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. | ACCEPT | Summary: SIRT1 deacetylates p53 in an NAD-dependent manner. Reason: Core enzymatic activity supported by direct deacetylation of p53. Supporting Evidence: PMID:11672523 binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue |
| GO:0140416 transcription regulator inhibitor activity | IDA PMID:11672523 hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. | MODIFY | Summary: SIRT1 represses p53-mediated transcription; a corepressor term better captures this activity. Reason: Use transcription corepressor activity for this function instead of a generic inhibitor term. Proposed replacements: transcription corepressor activity Supporting Evidence: PMID:11672523 Expression of wild-type hSir2 in human cells reduces the transcriptional activity of p53 |
| GO:0008047 enzyme activator activity | IDA PMID:18203716 Regulation of WRN protein cellular localization and enzymati... | MARK AS OVER ANNOTATED | Summary: SIRT1 reverses WRN acetylation effects on enzymatic activities via deacetylation rather than acting as a classical enzyme activator. Reason: The mechanism is deacetylation, not direct enzyme activation. Supporting Evidence: PMID:18203716 WRN acetylation decreases its helicase and exonuclease activities, and SIRT1 can reverse this effect. |
| GO:0035331 negative regulation of hippo signaling | IDA PMID:38512451 The alanyl-tRNA synthetase AARS1 moonlights as a lactyltrans... | KEEP AS NON CORE | Summary: SIRT1 delactylates YAP, counteracting lactylation-linked Hippo pathway activation. Reason: Context-specific modulation of YAP activity rather than a core SIRT1 function. Supporting Evidence: PMID:38512451 overexpression of SIRT1, but not of other members of this family, substantially reduced the lactylation levels of YAP |
| GO:0141208 NAD-dependent protein lysine delactylase activity | IDA PMID:38512451 The alanyl-tRNA synthetase AARS1 moonlights as a lactyltrans... | ACCEPT | Summary: SIRT1 removes lactylation from YAP and TEAD1 peptides in vitro. Reason: Direct delactylation activity is demonstrated with purified enzyme. Supporting Evidence: PMID:38512451 purified SIRT1, but not the H363Y mutant, eliminated lactylation of synthetic peptides of both YAP K90lac and TEAD1 K108lac |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:20203304 SIRT1 promotes proliferation and prevents senescence through... | KEEP AS NON CORE | Summary: SIRT1 can repress RNA polymerase II transcription through deacetylation of transcription factors; this is a downstream effect. Reason: Transcriptional repression is a contextual outcome of SIRT1 deacetylase activity rather than a core function. Supporting Evidence: PMID:11672523 Expression of wild-type hSir2 in human cells reduces the transcriptional activity of p53 |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IMP PMID:20203304 SIRT1 promotes proliferation and prevents senescence through... | KEEP AS NON CORE | Summary: SIRT1 promotes proteasome-mediated degradation of LKB1. Reason: Represents substrate-specific regulation of protein stability. Supporting Evidence: PMID:20203304 SIRT1 antagonized LKB1-dependent AMPK activation through promoting the deacetylation, ubiquitination and proteasome-mediated degradation of LKB1. |
| GO:0033558 protein lysine deacetylase activity | IMP PMID:20203304 SIRT1 promotes proliferation and prevents senescence through... | ACCEPT | Summary: SIRT1 deacetylates LKB1 as a protein lysine deacetylase. Reason: Direct deacetylation is reported. Supporting Evidence: PMID:20203304 SIRT1 antagonized LKB1-dependent AMPK activation through promoting the deacetylation, ubiquitination and proteasome-mediated degradation of LKB1. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:22918831 Autoacetylation of the MYST lysine acetyltransferase MOF pro... | ACCEPT | Summary: NAD-dependent protein lysine deacetylase activity is the core enzymatic function of SIRT1. Reason: Core molecular function supported by multiple experimental studies. Supporting Evidence: PMID:22918831 Autoacetylation of the MYST lysine acetyltransferase MOF protein. PMID:15692560 SIRT1, a mammalian homolog of yeast Sir2, bound to and deacetylated FOXO1 and inhibited its transcriptional activity. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:17505061 Sirtuin 1 is required for antagonist-induced transcriptional... | KEEP AS NON CORE | Summary: SIRT1 is required for androgen antagonist-mediated transcriptional repression. Reason: Context-specific repression in androgen receptor signaling. Supporting Evidence: PMID:17505061 is required for androgen antagonist-mediated transcriptional repression and growth suppression |
| GO:0003714 transcription corepressor activity | IMP PMID:17505061 Sirtuin 1 is required for antagonist-induced transcriptional... | ACCEPT | Summary: SIRT1 acts as a transcriptional corepressor in AR antagonist responses. Reason: Direct evidence for corepressor function at AR-responsive promoters. Supporting Evidence: PMID:17505061 androgen receptor (AR) recruits SIRT1 and nuclear receptor corepressor to AR-responsive promoters and deacetylates histone H3 locally |
| GO:0017136 histone deacetylase activity, NAD-dependent | IDA PMID:12006491 Human SIR2 deacetylates p53 and antagonizes PML/p53-induced ... | ACCEPT | Summary: SIRT1 is an NAD-dependent histone deacetylase. Reason: Histone deacetylase activity is supported by multiple SIRT1 studies. Supporting Evidence: PMID:12006491 SIRT1 binds and deacetylates p53 PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | ACCEPT | Summary: SIRT1 is an NAD-dependent histone deacetylase that deacetylates H4K16 and H3K9. Reason: Core enzymatic activity in chromatin regulation. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0032041 histone H3K14 deacetylase activity, NAD-dependent | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | ACCEPT | Summary: SIRT1 is an NAD-dependent histone deacetylase with H3-directed activity. Reason: Histone deacetylase activity is well supported and H3K14 specificity is consistent with SIRT1 histone targeting. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0033558 protein lysine deacetylase activity | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: SIRT1 is an NAD-dependent protein deacetylase. Reason: Core molecular function supported by this study. Supporting Evidence: PMID:20027304 SIRT1 is a NAD-dependent deacetylase that regulates a variety of pathways |
| GO:0046969 histone H3K9 deacetylase activity, NAD-dependent | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | ACCEPT | Summary: SIRT1 deacetylates histone H3K9 in vitro. Reason: Core histone substrate supported by biochemical evidence. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0046970 histone H4K16 deacetylase activity, NAD-dependent | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | ACCEPT | Summary: SIRT1 deacetylates histone H4K16 in vitro. Reason: Core histone substrate supported by biochemical evidence. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0140937 histone H4K12 deacetylase activity, hydrolytic mechanism | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | UNDECIDED | Summary: H4K12 deacetylation is not described in the PMID:15469825 abstract. Reason: Additional evidence is required to support H4K12 specificity. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0141050 histone H3K deacetylase activity | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: SIRT1 deacetylates histone H3 in cells. Reason: Histone H3 is a demonstrated substrate in this study. Supporting Evidence: PMID:20027304 resulting in selective activation of SIRT1, as measured by deacetylation of histone H3 |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:29681526 A Designed Peptide Targets Two Types of Modifications of p53... | ACCEPT | Summary: Sirtuin deacetylase recruitment supports NAD-dependent protein lysine deacetylase activity. Reason: The study references sirtuin deacetylase activity in the p53 modification complex. Supporting Evidence: PMID:29681526 Morn3, a cancer-testis antigen, recruits different PTM enzymes, such as sirtuin deacetylase and ubiquitin ligase, to confer composite modifications on p53. |
| GO:1901797 negative regulation of signal transduction by p53 class mediator | IDA PMID:29681526 A Designed Peptide Targets Two Types of Modifications of p53... | UNDECIDED | Summary: p53 suppression is described but the specific SIRT1-dependent mechanism is not explicit. Reason: The abstract does not directly attribute p53 signal suppression to SIRT1. Supporting Evidence: PMID:29681526 We found that Morn3, a cancer-testis antigen, recruits different PTM enzymes, such as sirtuin deacetylase and ubiquitin ligase, to confer composite modifications on p53. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IDA PMID:16079181 Evolutionarily conserved and nonconserved cellular localizat... | ACCEPT | Summary: SIRT1 shows in vitro deacetylase activity on histone H4 peptides. Reason: The study reports SIRT1-specific histone deacetylase activity. Supporting Evidence: PMID:16079181 SIRT1, but not the other two nuclear SIRT proteins, shows an in vitro deacetylase activity on histone H4 and p53 peptides |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | TAS NOT PMID:17456799 Sirtuin functions in health and disease. | UNDECIDED | Summary: Review notes that some sirtuins have ADP-ribosyltransferase activity but does not specify SIRT1. Reason: The reference does not provide SIRT1-specific evidence to support or refute this activity. Supporting Evidence: PMID:17456799 Certain sirtuins have in addition an ADP-ribosyltransferase activity. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:32538779 Synergy between SIRT1 and SIRT6 helps recognize DNA breaks a... | ACCEPT | Summary: SIRT1 deacetylates SIRT6 at K33 in the DNA damage response. Reason: Direct deacetylation of a protein substrate is reported. Supporting Evidence: PMID:32538779 SIRT1 deacetylates SIRT6 at residue K33 |
| GO:2000781 positive regulation of double-strand break repair | IDA PMID:32538779 Synergy between SIRT1 and SIRT6 helps recognize DNA breaks a... | KEEP AS NON CORE | Summary: SIRT1 supports repair signaling by enabling SIRT6 recruitment to DNA breaks. Reason: DNA repair promotion is a downstream effect of SIRT1 activity. Supporting Evidence: PMID:32538779 Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice. |
| GO:0005829 cytosol | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: SIRT1 localizes to cytoplasmic compartments. Reason: Direct immunostaining shows cytoplasmic localization. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:30193097 Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Tog... | ACCEPT | Summary: SIRT1 deacetylates PCK1, supporting NAD-dependent protein lysine deacetylase activity. Reason: The abstract directly states SIRT1 deacetylates a protein substrate (PCK1). Supporting Evidence: PMID:30193097 SIRT1 deacetylates PCK1 |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:15692560 Suppression of FOXO1 activity by FHL2 through SIRT1-mediated... | ACCEPT | Summary: SIRT1 deacetylates FOXO1 as an NAD-dependent protein lysine deacetylase. Reason: Direct deacetylation of a protein substrate is reported. Supporting Evidence: PMID:15692560 SIRT1, a mammalian homolog of yeast Sir2, bound to and deacetylated FOXO1 and inhibited its transcriptional activity. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:23142079 The deacetylase Sirt6 activates the acetyltransferase GCN5 a... | ACCEPT | Summary: SIRT1 is noted as a deacetylase controlling PGC-1Ξ± acetylation. Reason: The abstract describes SIRT1 as the deacetylase that controls PGC-1Ξ± acetylation state. Supporting Evidence: PMID:23142079 PGC-1Ξ±'s activation of gluconeogenic gene expression is dependent upon its acetylation state, which is controlled by the acetyltransferase GCN5 and the deacetylase Sirt1. |
| GO:0045722 positive regulation of gluconeogenesis | IDA PMID:15692560 Suppression of FOXO1 activity by FHL2 through SIRT1-mediated... | KEEP AS NON CORE | Summary: SIRT1 influences gluconeogenic gene expression via FOXO1. Reason: Gluconeogenesis regulation is a downstream metabolic effect. Supporting Evidence: PMID:15692560 SIRT1, a mammalian homolog of yeast Sir2, bound to and deacetylated FOXO1 and inhibited its transcriptional activity. |
| GO:0045722 positive regulation of gluconeogenesis | IDA PMID:23142079 The deacetylase Sirt6 activates the acetyltransferase GCN5 a... | KEEP AS NON CORE | Summary: SIRT1 regulates gluconeogenic gene expression via PGC-1Ξ± acetylation control. Reason: Gluconeogenesis regulation is a downstream metabolic effect. Supporting Evidence: PMID:23142079 PGC-1Ξ±'s activation of gluconeogenic gene expression is dependent upon its acetylation state, which is controlled by the acetyltransferase GCN5 and the deacetylase Sirt1. |
| GO:0051658 maintenance of nucleus location | IDA PMID:15692560 Suppression of FOXO1 activity by FHL2 through SIRT1-mediated... | REMOVE | Summary: Maintenance of nucleus location is not described in this study. Reason: No evidence for nuclear positioning in the FOXO1 deacetylation study. Supporting Evidence: PMID:15692560 SIRT1, a mammalian homolog of yeast Sir2, bound to and deacetylated FOXO1 and inhibited its transcriptional activity. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IDA PMID:28497810 Class I histone deacetylases are major histone decrotonylase... | ACCEPT | Summary: SIRT1 is an NAD-dependent histone deacetylase. Reason: Histone deacetylase activity is supported by multiple SIRT1 studies. Supporting Evidence: PMID:28497810 class I histone deacetylases (HDACs) rather than sirtuin family deacetylases (SIRTs) are the major histone decrotonylases PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:29765047 Tip60-mediated lipin 1 acetylation and ER translocation dete... | ACCEPT | Summary: SIRT1 is described as a deacetylase in this study, supporting NAD-dependent protein lysine deacetylase activity. Reason: The abstract explicitly identifies Sirt1 as the deacetylase repressing TAG synthesis. Supporting Evidence: PMID:29765047 repressed by deacetylase Sirt1. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:30409912 Dynamic acetylation of the kinetochore-associated protein HE... | ACCEPT | Summary: SIRT1 reverses TIP60-mediated HEC1 acetylation, supporting NAD-dependent protein lysine deacetylase activity. Reason: The abstract notes SIRT1 specifically reverses HEC1 acetylation. Supporting Evidence: PMID:30409912 TIP60-mediated acetylation was specifically reversed by sirtuin 1 (SIRT1). |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:32034146 Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex as... | ACCEPT | Summary: NAD-dependent protein lysine deacetylase activity is the core enzymatic function of SIRT1. Reason: Core molecular function supported by multiple experimental studies. Supporting Evidence: PMID:32034146 TIP60, also known as KAT5, a haplo-insufficient tumor suppressor, directly acetylates XPF PMID:15692560 SIRT1, a mammalian homolog of yeast Sir2, bound to and deacetylated FOXO1 and inhibited its transcriptional activity. |
| GO:0160012 histone decrotonylase activity, NAD-dependent | IDA PMID:28497810 Class I histone deacetylases are major histone decrotonylase... | REMOVE | Summary: This study indicates sirtuins are not the major histone decrotonylases. Reason: Evidence points to class I HDACs, not SIRT1, as major decrotonylases. Supporting Evidence: PMID:28497810 class I histone deacetylases (HDACs) rather than sirtuin family deacetylases (SIRTs) are the major histone decrotonylases |
| GO:0010868 negative regulation of triglyceride biosynthetic process | IDA PMID:29765047 Tip60-mediated lipin 1 acetylation and ER translocation dete... | KEEP AS NON CORE | Summary: SIRT1 represses TAG synthesis in this system. Reason: The study reports repression of TAG synthesis by SIRT1, a metabolic regulation role rather than a core function. Supporting Evidence: PMID:29765047 synthesis, which is repressed by deacetylase Sirt1. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:20100829 SIRT1 regulates autoacetylation and histone acetyltransferas... | ACCEPT | Summary: SIRT1 deacetylates TIP60 as an NAD-dependent protein lysine deacetylase. Reason: Direct deacetylation of TIP60 is reported. Supporting Evidence: PMID:20100829 we identified SIRT1 that specifically deacetylates TIP60 and negatively regulates TIP60 activity in vivo. |
| GO:0140861 DNA repair-dependent chromatin remodeling | IDA PMID:20100829 SIRT1 regulates autoacetylation and histone acetyltransferas... | UNDECIDED | Summary: DNA repair-dependent chromatin remodeling is not directly demonstrated here. Reason: The abstract focuses on TIP60 autoacetylation and SIRT1 deacetylation, not chromatin remodeling. Supporting Evidence: PMID:20100829 TIP60 is autoacetylated in response to UV damage |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:20955178 Regulation of unfolded protein response modulator XBP1s by a... | KEEP AS NON CORE | Summary: SIRT1 binds the transcription factor XBP1s for deacetylation. Reason: Represents a context-specific transcription factor interaction. Supporting Evidence: PMID:20955178 In the present study, we demonstrate that XBP1s is a target of acetylation and deacetylation mediated by p300 and SIRT1 (sirtuin 1) respectively |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:23382074 A high-confidence interaction map identifies SIRT1 as a medi... | KEEP AS NON CORE | Summary: SIRT1 interacts with transcription factors in specific contexts. Reason: Represents a context-specific transcription factor interaction. Supporting Evidence: PMID:23382074 Feb 4. A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex. |
| GO:0005515 protein binding | IPI PMID:31722219 CCDC84 Acetylation Oscillation Regulates Centrosome Duplicat... | REMOVE | Summary: Generic protein binding from this study is not informative for SIRT1 function. Reason: Specific interactions and enzymatic activity are more informative than a generic binding term. Supporting Evidence: PMID:31722219 the acetylation state of CCDC84 at lysine 31 is regulated by the deacetylase SIRT1 |
| GO:0006476 protein deacetylation | IDA PMID:31722219 CCDC84 Acetylation Oscillation Regulates Centrosome Duplicat... | ACCEPT | Summary: SIRT1 deacetylates CCDC84 as a protein deacetylase. Reason: Direct evidence that SIRT1 regulates acetylation state of a substrate. Supporting Evidence: PMID:31722219 the acetylation state of CCDC84 at lysine 31 is regulated by the deacetylase SIRT1 |
| GO:0010824 regulation of centrosome duplication | IDA PMID:31722219 CCDC84 Acetylation Oscillation Regulates Centrosome Duplicat... | KEEP AS NON CORE | Summary: CCDC84 acetylation state affects centrosome duplication, with SIRT1 as the deacetylase. Reason: Centrosome duplication effects are downstream of SIRT1 deacetylation activity. Supporting Evidence: PMID:31722219 CCDC84 Acetylation Oscillation Regulates Centrosome Duplication by Modulating HsSAS-6 Degradation |
| GO:0106230 protein depropionylation | ISS GO_REF:0000024 | UNDECIDED | Summary: Evidence for SIRT1 depropionylation activity is not specified in this reference. Reason: GO_REF:0000024 does not provide direct experimental support here. |
| GO:0106231 NAD-dependent protein-lysine depropionylase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 exhibits NAD-dependent deacylase activities including depropionylation in some contexts. Reason: Downstream enzymatic activity beyond core deacetylation. |
| GO:0045722 positive regulation of gluconeogenesis | IDA PMID:30193097 Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Tog... | KEEP AS NON CORE | Summary: SIRT1 promotes gluconeogenic activity via PCK1 deacetylation. Reason: Gluconeogenesis regulation is a downstream metabolic effect. Supporting Evidence: PMID:30193097 Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity between Gluconeogenic and Anaplerotic Reactions. |
| GO:0005515 protein binding | IPI PMID:29656858 A Recurrent De Novo PACS2 Heterozygous Missense Variant Caus... | REMOVE | Summary: This paper is about PACS2 variants and does not provide SIRT1 binding evidence. Reason: No SIRT1 interactions are described. Supporting Evidence: PMID:29656858 A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar Dysgenesis. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:23960241 MicroRNA-mediated epigenetic silencing of sirtuin1 contribut... | REMOVE | Summary: This study links TGF-Ξ² signaling to Sirt1 silencing, but does not place SIRT1 within the receptor signaling pathway. Reason: SIRT1 is a downstream target rather than a component of TGF-Ξ² receptor signaling. Supporting Evidence: PMID:23960241 MeCP2 inhibited endothelial angiogenic characteristics partly by epigenetic silencing of Sirt1. |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | IDA PMID:23960241 MicroRNA-mediated epigenetic silencing of sirtuin1 contribut... | KEEP AS NON CORE | Summary: Sirt1 influences endothelial angiogenic functions affected by TGF-Ξ²/MeCP2. Reason: Context-specific effect on endothelial migration/angiogenic function. Supporting Evidence: PMID:23960241 involvement of MeCP2/Sirt1 in the regulation of angiogenic functions of endothelial cells. |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:23960241 MicroRNA-mediated epigenetic silencing of sirtuin1 contribut... | KEEP AS NON CORE | Summary: Sirt1 contributes to angiogenic functions in endothelial cells. Reason: Represents downstream functional impact rather than core enzymatic role. Supporting Evidence: PMID:23960241 involvement of MeCP2/Sirt1 in the regulation of angiogenic functions of endothelial cells. |
| GO:0033558 protein lysine deacetylase activity | IMP PMID:20424141 MicroRNA-34a induces endothelial progenitor cell senescence ... | ACCEPT | Summary: Sirt1 modulation affects acetylation status of FOXO1, consistent with protein lysine deacetylase activity. Reason: Changes in Sirt1 levels alter acetylated FOXO1. Supporting Evidence: PMID:20424141 overexpression of miR-34a increased the level of Sirt1 effector-acetylated forkhead box O transcription factors 1 (FoxO1) |
| GO:0045766 positive regulation of angiogenesis | IMP PMID:20424141 MicroRNA-34a induces endothelial progenitor cell senescence ... | KEEP AS NON CORE | Summary: Sirt1 suppression impairs EPC-mediated angiogenesis. Reason: Angiogenesis phenotype is downstream of Sirt1 regulation. Supporting Evidence: PMID:20424141 miR-34a inhibits EPC-mediated angiogenesis by inducing senescence via suppressing Sirt1. |
| GO:2000773 negative regulation of cellular senescence | IMP PMID:20424141 MicroRNA-34a induces endothelial progenitor cell senescence ... | KEEP AS NON CORE | Summary: Sirt1 suppression induces senescence in EPCs. Reason: Senescence regulation is context-specific. Supporting Evidence: PMID:20424141 miR-34a inhibits EPC-mediated angiogenesis by inducing senescence via suppressing Sirt1. |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:25217442 Vascular importance of the miR-212/132 cluster. | KEEP AS NON CORE | Summary: The study links miR-212/132 effects to suppression of SIRT1 and impaired endothelial function, but does not directly show SIRT1 driving angiogenesis. Reason: Evidence is indirect but supports a context-specific role in angiogenic regulation. Supporting Evidence: PMID:25217442 suppression of important endothelial genes such as GAB1 and SIRT1 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:12837246 Multiple tumor suppressor pathways negatively regulate telom... | KEEP AS NON CORE | Summary: SIRT1 influences transcriptional regulation in specific contexts. Reason: Context-specific transcriptional modulation rather than a core function. Supporting Evidence: PMID:12837246 Multiple tumor suppressor pathways negatively regulate telomerase. |
| GO:0042981 regulation of apoptotic process | IMP PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | KEEP AS NON CORE | Summary: SIRT1 influences apoptosis during genotoxic stress via APE1 regulation. Reason: Apoptosis effects are downstream of DNA repair modulation. Supporting Evidence: PMID:19934257 sensitizing cells to death induced by genotoxic stress |
| GO:0005634 nucleus | IDA PMID:20167603 DYRK1A and DYRK3 promote cell survival through phosphorylati... | ACCEPT | Summary: SIRT1 localizes to the nucleus. Reason: Nuclear localization is well supported in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0010883 regulation of lipid storage | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences regulation of lipid storage. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0030225 macrophage differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 modulates macrophage differentiation in broader immune contexts. Reason: Downstream immune regulation rather than a core function. |
| GO:0060907 positive regulation of macrophage cytokine production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 modulates macrophage cytokine production. Reason: Downstream immune regulation rather than a core function. |
| GO:1904179 positive regulation of adipose tissue development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences adipose tissue development. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0045766 positive regulation of angiogenesis | IMP PMID:24048733 Antidicer RNAse activity of monocyte chemotactic protein-ind... | KEEP AS NON CORE | Summary: SIRT1 induction is reported as part of MCPIP-driven angiogenic signaling. Reason: This reflects a context-specific angiogenic pathway rather than a core SIRT1 function. Supporting Evidence: PMID:24048733 MCPIP-induced angiogenesis is mediated via hypoxia-inducible factor (HIF-1Ξ±), vascular endothelial growth factor (VEGF), and silent information regulator (SIRT-1) induction |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 positively modulates PI3K/AKT signaling in some contexts. Reason: Downstream signaling modulation rather than a core function. |
| GO:0090335 regulation of brown fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences brown fat cell differentiation. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0033210 leptin-mediated signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences leptin-mediated signaling. Reason: Downstream metabolic signaling role rather than a core function. |
| GO:0044321 response to leptin | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 participates in leptin response contexts. Reason: Downstream metabolic signaling role rather than a core function. |
| GO:0001938 positive regulation of endothelial cell proliferation | IMP PMID:20203304 SIRT1 promotes proliferation and prevents senescence through... | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:20203304 2010 Mar 4. SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells. |
| GO:0005515 protein binding | IPI PMID:21030595 HDAC3 is negatively regulated by the nuclear protein DBC1. | REMOVE | Summary: Generic protein binding annotation is uninformative. Reason: Generic protein binding annotation is uninformative. More specific annotations capture the biologically relevant interactions. Supporting Evidence: PMID:21030595 2010 Oct 28. HDAC3 is negatively regulated by the nuclear protein DBC1. |
| GO:0005515 protein binding | IPI PMID:25661920 CCAR2 negatively regulates nuclear receptor LXRΞ± by competin... | REMOVE | Summary: The study focuses on CCAR2 competition with SIRT1; generic protein binding is uninformative. Reason: A specific SIRT1 interaction context is described, making the generic binding term unhelpful. Supporting Evidence: PMID:25661920 CCAR2 negatively regulates nuclear receptor LXRΞ± by competing with SIRT1 deacetylase. |
| GO:0006476 protein deacetylation | IMP PMID:24824780 MCC inhibits beta-catenin transcriptional activity by seques... | ACCEPT | Summary: SIRT1 inhibition reverses MCC-induced deacetylation of Ξ²-catenin. Reason: Direct deacetylation effect is supported in this context. Supporting Evidence: PMID:24824780 Treatment of cells with the SIRT1 inhibitor Nicotinamide reverses MCC-induced deacetylation of Ξ²-cat K49. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:20074560 Repression of estrogen receptor beta function by putative tu... | KEEP AS NON CORE | Summary: DBC1 modulation implicates SIRT1 in transcriptional repression contexts. Reason: Represents context-specific transcriptional repression rather than a core function. Supporting Evidence: PMID:20074560 depletion of the endogenous DBC1 negatively regulates p53-dependent apoptosis through its specific inhibition of SIRT1. |
| GO:0016922 nuclear receptor binding | IPI PMID:24043310 SIRT4 represses peroxisome proliferator-activated receptor Ξ±... | REMOVE | Summary: This paper is about SIRT4 and PPARΞ±, not SIRT1. Reason: No SIRT1 nuclear receptor binding evidence is provided. Supporting Evidence: PMID:24043310 SIRT4 represses peroxisome proliferator-activated receptor Ξ± activity to suppress hepatic fat oxidation. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:20955178 Regulation of unfolded protein response modulator XBP1s by a... | KEEP AS NON CORE | Summary: SIRT1 inhibits XBP1s-dependent transcription. Reason: Downstream effect of deacetylating a specific transcription factor. Supporting Evidence: PMID:20955178 SIRT1 deacetylates XBP1s and inhibits its transcriptional activity |
| GO:0005634 nucleus | IDA PMID:20955178 Regulation of unfolded protein response modulator XBP1s by a... | ACCEPT | Summary: SIRT1 is nuclear in studies of XBP1s regulation. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0032922 circadian regulation of gene expression | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 modulates circadian clock components through deacetylation. Reason: Circadian regulation is a downstream outcome of SIRT1 activity. |
| GO:0006476 protein deacetylation | IDA PMID:18662546 SIRT1 regulates circadian clock gene expression through PER2... | ACCEPT | Summary: SIRT1 promotes PER2 deacetylation, supporting protein deacetylation activity. Reason: The abstract reports SIRT1 deacetylation of PER2. Supporting Evidence: PMID:18662546 SIRT1 regulates circadian clock gene expression through PER2 deacetylation. |
| GO:0032922 circadian regulation of gene expression | IMP PMID:18662546 SIRT1 regulates circadian clock gene expression through PER2... | KEEP AS NON CORE | Summary: SIRT1 regulates circadian clock gene expression through PER2 deacetylation (PMID:18662546). While the experimental evidence supports clock regulation, SIRT1 has broad substrate specificity and clock proteins are just one of many targets. Reason: The IMP evidence from PMID:18662546 specifically demonstrates SIRT1 involvement in circadian regulation. However, this is one of many downstream effects of SIRT1 deacetylase activity on diverse substrates. Not a core function. Supporting Evidence: PMID:18662546 SIRT1, an NAD(+)-dependent protein deacetylase, is required for high-magnitude circadian transcription of several core clock genes, including Bmal1, Rorgamma, Per2, and Cry1. |
| GO:0005515 protein binding | IPI PMID:23382074 A high-confidence interaction map identifies SIRT1 as a medi... | REMOVE | Summary: Generic protein binding is uninformative relative to specific interaction terms. Reason: Specific enzyme-binding interaction is more informative. Supporting Evidence: PMID:23382074 as a SIRT1-interacting partner |
| GO:0019899 enzyme binding | IPI PMID:23382074 A high-confidence interaction map identifies SIRT1 as a medi... | ACCEPT | Summary: SIRT1 interacts with the deubiquitinating enzyme USP22. Reason: Direct interaction with an enzyme partner is reported. Supporting Evidence: PMID:23382074 as a SIRT1-interacting partner |
| GO:1990254 keratin filament binding | IPI PMID:23382074 A high-confidence interaction map identifies SIRT1 as a medi... | REMOVE | Summary: Keratin filament binding is not described in this study. Reason: No evidence for keratin filament binding. Supporting Evidence: PMID:23382074 as a SIRT1-interacting partner |
| GO:0000785 chromatin | IDA PMID:22956909 Dynamic distribution of linker histone H1.5 in cellular diff... | ACCEPT | Summary: SIRT1 binds chromatin at H1.5 target loci in differentiated cells. Reason: SIRT1 binding is required for chromatin compaction at H1.5 targets. Supporting Evidence: PMID:22956909 H1.5 binding is associated with gene repression and is required for SIRT1 binding, H3K9me2 enrichment, and chromatin compaction. |
| GO:0006325 chromatin organization | IMP PMID:22956909 Dynamic distribution of linker histone H1.5 in cellular diff... | KEEP AS NON CORE | Summary: SIRT1 contributes to chromatin compaction at H1.5 target loci. Reason: Represents context-specific chromatin organization effects. Supporting Evidence: PMID:22956909 H1.5 binding is associated with gene repression and is required for SIRT1 binding, H3K9me2 enrichment, and chromatin compaction. |
| GO:0042393 histone binding | IPI PMID:22956909 Dynamic distribution of linker histone H1.5 in cellular diff... | ACCEPT | Summary: SIRT1 associates with histone H1.5-containing chromatin. Reason: Histone association supports histone binding. Supporting Evidence: PMID:22956909 H1.5 binding is associated with gene repression and is required for SIRT1 binding, H3K9me2 enrichment, and chromatin compaction. |
| GO:0010629 negative regulation of gene expression | IMP PMID:17916362 Sirt1 modulates premature senescence-like phenotype in human... | MARK AS OVER ANNOTATED | Summary: Gene expression changes are specific (PAI-1 and eNOS), not a broad repression program. Reason: The term is too general for the evidence provided. Supporting Evidence: PMID:17916362 increased PAI-1 expression and decreased both protein expression and activity of eNOS. |
| GO:0090400 stress-induced premature senescence | IMP PMID:17916362 Sirt1 modulates premature senescence-like phenotype in human... | KEEP AS NON CORE | Summary: Sirt1 inhibition induces premature senescence-like phenotype in endothelial cells. Reason: Senescence effects are downstream of Sirt1 activity. Supporting Evidence: PMID:17916362 Sirt1 inhibition increased p53 acetylation and induced premature senescence-like phenotype |
| GO:1901984 negative regulation of protein acetylation | IMP PMID:17916362 Sirt1 modulates premature senescence-like phenotype in human... | ACCEPT | Summary: Sirt1 normally counteracts protein acetylation, as inhibition increases p53 acetylation. Reason: Direct evidence of increased acetylation upon Sirt1 inhibition. Supporting Evidence: PMID:17916362 Treatment with sirtinol or Sirt1 siRNA increased acetylation of p53 |
| GO:0042542 response to hydrogen peroxide | IDA PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | KEEP AS NON CORE | Summary: Genotoxic stress including H2O2 affects APE1 acetylation regulated by SIRT1. Reason: Represents stress-context regulation rather than a core function. Supporting Evidence: PMID:19934257 H2O2 led to an increase in acetylation of APE1 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3371467 | ACCEPT | Summary: SIRT1 is nuclear in contexts including HSF1 regulation. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3371518 | ACCEPT | Summary: SIRT1 is nuclear in HSF1 regulatory contexts. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3371537 | ACCEPT | Summary: SIRT1 is nuclear in DBC1 regulatory contexts. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-427514 | ACCEPT | Summary: SIRT1 is nuclear in eNoSC chromatin regulation contexts. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-427527 | ACCEPT | Summary: SIRT1 is nuclear in eNoSC chromatin regulation contexts. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-427528 | ACCEPT | Summary: SIRT1 is nuclear in eNoSC complex contexts. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9620532 | ACCEPT | Summary: SIRT1 is nuclear in FOXO3 regulation contexts. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9765850 | ACCEPT | Summary: SIRT1 is nuclear in transcriptional regulation contexts. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825772 | ACCEPT | Summary: SIRT1 is nuclear in HINT1-related regulatory contexts. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9854916 | ACCEPT | Summary: SIRT1 is nuclear in transcriptional regulation contexts. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:1902166 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | ISS PMID:11672522 Negative control of p53 by Sir2alpha promotes cell survival ... | KEEP AS NON CORE | Summary: Sir2alpha represses p53-dependent apoptosis under DNA damage stress. Reason: The effect is context-specific p53-dependent apoptosis modulation rather than a core SIRT1 function. Supporting Evidence: PMID:11672522 Sir2alpha represses p53-dependent apoptosis in response to DNA damage and oxidative stress |
| GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway | IMP PMID:17317627 Phosphorylation of HuR by Chk2 regulates SIRT1 expression. | REMOVE | Summary: This paper focuses on HuR regulation of SIRT1 expression under oxidative stress, not direct apoptosis pathway regulation. Reason: No direct evidence for negative regulation of oxidative stress-induced intrinsic apoptosis by SIRT1 is provided. Supporting Evidence: PMID:17317627 SIRT1 mRNA decay, reducing SIRT1 abundance, and lowering cell survival. |
| GO:0033558 protein lysine deacetylase activity | IDA PMID:23056314 Angiogenesis inhibitor vasohibin-1 enhances stress resistanc... | ACCEPT | Summary: Protein lysine deacetylase activity is a core function of SIRT1. Reason: Core molecular function supported by multiple SIRT1 studies. Supporting Evidence: PMID:23056314 VASH1 augmented the synthesis of sirtuin 1 (SIRT1) |
| GO:0033558 protein lysine deacetylase activity | IMP PMID:20670893 SIRT1 regulates UV-induced DNA repair through deacetylating ... | ACCEPT | Summary: SIRT1 deacetylates XPA, supporting protein lysine deacetylase activity. Reason: The study reports direct deacetylation of XPA by SIRT1. Supporting Evidence: PMID:20670893 SIRT1 deacetylates XPA |
| GO:0070914 UV-damage excision repair | IMP PMID:20670893 SIRT1 regulates UV-induced DNA repair through deacetylating ... | KEEP AS NON CORE | Summary: SIRT1 regulates the NER pathway in UV-damage excision repair contexts. Reason: SIRT1 modulates NER via XPA deacetylation, but this is a specific downstream process rather than a core function. Supporting Evidence: PMID:20670893 SIRT1 regulates NER pathway |
| GO:0035358 regulation of peroxisome proliferator activated receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 modulates PPAR signaling in metabolic contexts. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0010875 positive regulation of cholesterol efflux | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences cholesterol efflux. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0031648 protein destabilization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 can influence protein stability in specific contexts. Reason: Downstream regulatory effect rather than a core function. |
| GO:0035356 intracellular triglyceride homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 contributes to intracellular triglyceride homeostasis. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0042632 cholesterol homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 contributes to cholesterol homeostasis. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0031393 negative regulation of prostaglandin biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 modulates prostaglandin biosynthesis in specific contexts. Reason: Downstream regulatory effect rather than a core function. |
| GO:0070857 regulation of bile acid biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences bile acid biosynthesis regulation. Reason: Downstream metabolic regulation rather than a core function. |
| GO:2000111 positive regulation of macrophage apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 modulates macrophage apoptotic processes. Reason: Downstream immune regulation rather than a core function. |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 modulates TGF-beta signaling in specific contexts. Reason: Downstream signaling regulation rather than a core function. |
| GO:0034391 regulation of smooth muscle cell apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences smooth muscle cell apoptotic processes. Reason: Downstream cell-type-specific regulation rather than a core function. |
| GO:2000481 positive regulation of cAMP-dependent protein kinase activity | IMP PMID:18687677 SIRT1 modulation of the acetylation status, cytosolic locali... | REMOVE | Summary: The study addresses LKB1/AMPK activation, not cAMP-dependent protein kinase activity. Reason: The abstract discusses AMP-activated protein kinase signaling rather than cAMP-dependent protein kinase regulation. Supporting Evidence: PMID:18687677 AMP-activated protein kinase (AMPK) |
| GO:2000773 negative regulation of cellular senescence | IDA PMID:20203304 SIRT1 promotes proliferation and prevents senescence through... | KEEP AS NON CORE | Summary: Increasing SIRT1 levels blocks LKB1-induced cellular senescence. Reason: Senescence regulation is context-specific downstream biology. Supporting Evidence: PMID:20203304 Overexpression of LKB1 promoted cellular senescence and retarded endothelial proliferation, which could be blocked by increasing SIRT1 levels. |
| GO:2000774 positive regulation of cellular senescence | IDA PMID:18687677 SIRT1 modulation of the acetylation status, cytosolic locali... | REMOVE | Summary: This paper focuses on LKB1 deacetylation and AMPK activation, not cellular senescence. Reason: There is no reported senescence phenotype in the abstract; the evidence centers on AMPK signaling. Supporting Evidence: PMID:18687677 AMP-activated protein kinase (AMPK) |
| GO:0032007 negative regulation of TOR signaling | IMP PMID:20169165 SIRT1 negatively regulates the mammalian target of rapamycin... | KEEP AS NON CORE | Summary: SIRT1 negatively regulates mTOR signaling via TSC2. Reason: mTOR pathway regulation is a downstream signaling role rather than a core enzymatic function. Supporting Evidence: PMID:20169165 SIRT1 negatively regulates the mammalian target of rapamycin. |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IDA PMID:17680780 Sirt1 interacts with transducin-like enhancer of split-1 to ... | KEEP AS NON CORE | Summary: Sirt1 and TLE1 repress NF-kappaB activity. Reason: NF-kappaB repression is a specific downstream regulatory effect of SIRT1. Supporting Evidence: PMID:17680780 Sirt1 and TLE1 repress NF-kappaB activity. |
| GO:0001934 positive regulation of protein phosphorylation | ISS GO_REF:0000024 | UNDECIDED | Summary: No direct evidence for SIRT1 in positive regulation of protein phosphorylation is provided here. Reason: GO_REF:0000024 does not provide direct experimental support. |
| GO:0032868 response to insulin | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 modulates insulin response through deacetylation of insulin signaling regulators. Reason: Downstream signaling modulation rather than a core function. |
| GO:0046628 positive regulation of insulin receptor signaling pathway | IDA PMID:21241768 Phosphoinositide 3-kinase as a novel functional target for t... | KEEP AS NON CORE | Summary: SIRT1 positively modulates insulin signaling via PI3K in muscle cells. Reason: This is a context-specific signaling modulation downstream of SIRT1 activity. Supporting Evidence: PMID:21241768 SIRT1 as a positive modulator of insulin signaling in muscle cells through PI3K |
| GO:0002821 positive regulation of adaptive immune response | IDA PMID:21890893 SIRT1 links CIITA deacetylation to MHC II activation. | MARK AS OVER ANNOTATED | Summary: The evidence supports SIRT1-enhanced MHC II transcription, a specific step within adaptive immunity. Reason: The study demonstrates MHC II transactivation rather than broad positive regulation of the adaptive immune response. Supporting Evidence: PMID:21890893 SIRT1 activation augments MHC II transcription |
| GO:0045348 positive regulation of MHC class II biosynthetic process | IDA PMID:21890893 SIRT1 links CIITA deacetylation to MHC II activation. | KEEP AS NON CORE | Summary: SIRT1 activation augments MHC II transcription via CIITA. Reason: This reflects immune regulation downstream of SIRT1 activity rather than a core enzymatic function. Supporting Evidence: PMID:21890893 SIRT1 activation augments MHC II transcription |
| GO:0035098 ESC/E(Z) complex | IDA PMID:15684044 Composition and histone substrates of polycomb repressive gr... | KEEP AS NON CORE | Summary: SirT1 is reported as a component of a PRC4 polycomb complex. Reason: The study describes SIRT1 in a polycomb complex context, which is not a core function. Supporting Evidence: PMID:15684044 PRC4, that contains the NAD+-dependent histone deacetylase SirT1 |
| GO:0000012 single strand break repair | IMP PMID:20097625 Role of SIRT1 in homologous recombination. | REMOVE | Summary: This study demonstrates SIRT1 promotion of homologous recombination, not single-strand break repair. Reason: The evidence is specific to double-strand break repair via HR. Supporting Evidence: PMID:20097625 SIRT1 activity promotes homologous recombination (HR) in human cells. |
| GO:0001678 intracellular glucose homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 participates in glucose homeostasis regulation. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0010906 regulation of glucose metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 modulates glucose metabolic processes. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0055089 fatty acid homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences fatty acid homeostasis. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0016239 positive regulation of macroautophagy | IDA PMID:18296641 A role for the NAD-dependent deacetylase Sirt1 in the regula... | KEEP AS NON CORE | Summary: Increased Sirt1 expression stimulates autophagy and Sirt1 deficiency impairs autophagy activation. Reason: Autophagy regulation is a downstream process rather than the core deacetylase activity. Supporting Evidence: PMID:18296641 transient increased expression of Sirt1 is sufficient to stimulate basal rates of autophagy. |
| GO:0000720 pyrimidine dimer repair by nucleotide-excision repair | IMP PMID:21149730 Regulation of global genome nucleotide excision repair by SI... | KEEP AS NON CORE | Summary: SIRT1 regulates global genome nucleotide excision repair via XPC. Reason: The paper supports NER involvement but this is a specific downstream DNA repair role. Supporting Evidence: PMID:21149730 SIRT1 impairs global genome NER |
| GO:0000731 DNA synthesis involved in DNA repair | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 participates in DNA repair-related synthesis contexts. Reason: Downstream DNA repair role rather than a core function. |
| GO:0042326 negative regulation of phosphorylation | IMP PMID:17612497 SIRT1 regulates the function of the Nijmegen breakage syndro... | REMOVE | Summary: The study indicates SIRT1 is required for NBS1 phosphorylation, not negative regulation of phosphorylation. Reason: Evidence shows SIRT1 supports phosphorylation rather than suppressing it. Supporting Evidence: PMID:17612497 required for ionizing radiation-induced NBS1 Ser343 phosphorylation. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:21149730 Regulation of global genome nucleotide excision repair by SI... | KEEP AS NON CORE | Summary: SIRT1 modulates an AKT-dependent localization step but direct negative regulation of PI3K/AKT signaling is not shown. Reason: The evidence is indirect but indicates a regulatory role in this signaling context. Supporting Evidence: PMID:21149730 reducing AKT-dependent nuclear localization |
| GO:0071479 cellular response to ionizing radiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 participates in responses to ionizing radiation. Reason: Downstream stress-response role rather than a core function. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:15152190 Modulation of NF-kappaB-dependent transcription and cell sur... | KEEP AS NON CORE | Summary: SIRT1 activity augments TNFalpha-induced apoptosis. Reason: The apoptotic effect is stimulus-specific and not a core function. Supporting Evidence: PMID:15152190 augments apoptosis in response to TNFalpha |
| GO:0071356 cellular response to tumor necrosis factor | IDA PMID:15152190 Modulation of NF-kappaB-dependent transcription and cell sur... | KEEP AS NON CORE | Summary: SIRT1 sensitizes cells to TNFalpha-induced apoptosis. Reason: This reflects a context-specific TNF response rather than a core SIRT1 function. Supporting Evidence: PMID:15152190 sensitization of cells to TNFalpha-induced apoptosis. |
| GO:0007346 regulation of mitotic cell cycle | IDA PMID:15692560 Suppression of FOXO1 activity by FHL2 through SIRT1-mediated... | REMOVE | Summary: Mitotic cell cycle regulation is not described in this study. Reason: No evidence for mitotic cell cycle regulation in this FOXO1 study. Supporting Evidence: PMID:15692560 SIRT1, a mammalian homolog of yeast Sir2, bound to and deacetylated FOXO1 and inhibited its transcriptional activity. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:16892051 Interactions between E2F1 and SirT1 regulate apoptotic respo... | KEEP AS NON CORE | Summary: SirT1 knockdown increases E2F1 apoptotic functions, indicating SirT1 suppresses apoptosis in this context. Reason: The effect is context-specific regulation of E2F1-mediated apoptosis. Supporting Evidence: PMID:16892051 Knockdown of SirT1 by small interference RNA (siRNA) increases E2F1 transcriptional and apoptotic functions. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:15692560 Suppression of FOXO1 activity by FHL2 through SIRT1-mediated... | KEEP AS NON CORE | Summary: SIRT1 inhibits FOXO1 transcriptional activity via deacetylation. Reason: Downstream effect on a specific transcription factor, not core function. Supporting Evidence: PMID:15692560 SIRT1, a mammalian homolog of yeast Sir2, bound to and deacetylated FOXO1 and inhibited its transcriptional activity. |
| GO:0001525 angiogenesis | IDA PMID:20620956 Sirtuin 1 modulates cellular responses to hypoxia by deacety... | KEEP AS NON CORE | Summary: SIRT1 negatively affects angiogenesis in vivo. Reason: The study reports an effect on angiogenesis downstream of SIRT1 regulation of HIF-1alpha, which is not a core function. Supporting Evidence: PMID:20620956 SIRT1 has negative effects on tumor growth and angiogenesis. |
| GO:0006979 response to oxidative stress | IDA PMID:14976264 Stress-dependent regulation of FOXO transcription factors by... | KEEP AS NON CORE | Summary: SIRT1 shifts FOXO3 responses toward resistance to oxidative stress. Reason: This is a downstream stress-response outcome of SIRT1 activity. Supporting Evidence: PMID:14976264 SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress |
| GO:0016567 protein ubiquitination | IDA PMID:21841822 Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-media... | KEEP AS NON CORE | Summary: SIRT1 deacetylation of FOXO3 promotes ubiquitination and degradation. Reason: The evidence reflects a specific regulatory mechanism rather than a core SIRT1 function. Supporting Evidence: PMID:21841822 Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IMP PMID:20100829 SIRT1 regulates autoacetylation and histone acetyltransferas... | MARK AS OVER ANNOTATED | Summary: This study links TIP60 to UV damage responses, but intrinsic apoptotic signaling is not directly demonstrated. Reason: Apoptotic pathway specificity is beyond the presented evidence. Supporting Evidence: PMID:20100829 TIP60 is autoacetylated in response to UV damage |
| 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: SIRT1-driven FOXO3 degradation is proteasome dependent. Reason: The study demonstrates a proteasome-dependent outcome for FOXO3 turnover downstream of SIRT1. Supporting Evidence: PMID:21841822 process is proteasome dependent. |
| GO:0071456 cellular response to hypoxia | IMP PMID:20620956 Sirtuin 1 modulates cellular responses to hypoxia by deacety... | KEEP AS NON CORE | Summary: SIRT1 modulates cellular responses to hypoxia via HIF-1alpha deacetylation. Reason: Hypoxia response is a context-specific downstream process of SIRT1 activity. Supporting Evidence: PMID:20620956 Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. |
| GO:2000757 negative regulation of peptidyl-lysine acetylation | IDA PMID:20100829 SIRT1 regulates autoacetylation and histone acetyltransferas... | ACCEPT | Summary: SIRT1 deacetylates TIP60, negatively regulating lysine acetylation. Reason: Direct deacetylation supports negative regulation of lysine acetylation. Supporting Evidence: PMID:20100829 we identified SIRT1 that specifically deacetylates TIP60 and negatively regulates TIP60 activity in vivo. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:21947282 SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) prote... | KEEP AS NON CORE | Summary: SIRT1-mediated deacetylation of DNMT1 supports gene silencing. Reason: The evidence indicates transcriptional silencing via DNMT1 regulation, a downstream effect rather than a core SIRT1 function. Supporting Evidence: PMID:21947282 SIRT1-mediated deacetylation of DNMT1 is crucial for DNMT1's multiple effects in gene silencing. |
| GO:0006346 DNA methylation-dependent constitutive heterochromatin formation | TAS PMID:21947282 SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) prote... | MARK AS OVER ANNOTATED | Summary: The study links SIRT1 to DNMT1-mediated gene silencing but does not demonstrate constitutive heterochromatin formation. Reason: Evidence supports DNMT1 activity and gene silencing, not heterochromatin formation specifically. Supporting Evidence: PMID:21947282 SIRT1-mediated deacetylation of DNMT1 is crucial for DNMT1's multiple effects in gene silencing. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. | KEEP AS NON CORE | Summary: Sirt1 supports proliferation in K562 cells via c-Myc activity. Reason: Proliferation effects are context-specific downstream outcomes. Supporting Evidence: PMID:21807113 suppress cell proliferation and arrest cell cycle at G1/S phase |
| GO:0033558 protein lysine deacetylase activity | IDA PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. | ACCEPT | Summary: Sirt1 deacetylates c-Myc in vitro and in vivo. Reason: Direct substrate deacetylation is reported. Supporting Evidence: PMID:21807113 deacetylates c-Myc both in vitro and in vivo |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:19047049 Hyaluronan-mediated CD44 interaction with p300 and SIRT1 reg... | KEEP AS NON CORE | Summary: SIRT1 activation in this context leads to caspase-3 activation and apoptosis. Reason: Apoptotic effects are context-specific in breast tumor cells. Supporting Evidence: PMID:19047049 lead to an activation of caspase-3 |
| GO:0043425 bHLH transcription factor binding | IPI PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. | ACCEPT | Summary: Sirt1 physically interacts with c-Myc, a bHLH transcription factor. Reason: Direct physical interaction is reported. Supporting Evidence: PMID:21807113 Sirt1 interacts physically with the C-terminus of c-Myc |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. | KEEP AS NON CORE | Summary: Sirt1 enhances c-Myc/Max transcriptional activity. Reason: Context-specific transcriptional modulation rather than a core function. Supporting Evidence: PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. |
| GO:0005515 protein binding | IPI PMID:21212262 MST1 promotes apoptosis through regulating Sirt1-dependent p... | REMOVE | Summary: Generic protein binding is uninformative relative to specific mechanistic interactions. Reason: The study focuses on MST1 regulation of SIRT1 activity rather than a specific binding annotation. Supporting Evidence: PMID:21212262 Sirt1 can be phosphorylated by MST1 leading to the inhibition of Sirt1 activity. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IDA PMID:21775285 The deacetylase SIRT1 promotes membrane localization and act... | ACCEPT | Summary: SIRT1 deacetylates Akt and PDK1, supporting NAD-dependent protein lysine deacetylase activity. Reason: The abstract reports deacetylation by SIRT1 that enables Akt/PDK1 activation. Supporting Evidence: PMID:21775285 Deacetylation by SIRT1 enhanced binding of Akt and PDK1 to PIP(3) |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:21775285 The deacetylase SIRT1 promotes membrane localization and act... | KEEP AS NON CORE | Summary: Akt/PDK1 activation by SIRT1 can influence cell survival. Reason: Represents a context-specific survival signaling effect. Supporting Evidence: PMID:21775285 Deacetylation by SIRT1 enhanced binding of Akt and PDK1 to PIP(3) |
| GO:2000655 negative regulation of cellular response to testosterone stimulus | IMP PMID:17505061 Sirtuin 1 is required for antagonist-induced transcriptional... | KEEP AS NON CORE | Summary: SIRT1 dampens androgen-response transcription under antagonist conditions. Reason: Specific to androgen receptor signaling context. Supporting Evidence: PMID:17505061 is required for androgen antagonist-mediated transcriptional repression and growth suppression |
| GO:0000785 chromatin | IDA PMID:17505061 Sirtuin 1 is required for antagonist-induced transcriptional... | ACCEPT | Summary: SIRT1 is recruited to chromatin at AR-responsive promoters. Reason: Promoter-localized deacetylation supports chromatin association. Supporting Evidence: PMID:17505061 androgen receptor (AR) recruits SIRT1 and nuclear receptor corepressor to AR-responsive promoters and deacetylates histone H3 locally |
| GO:0060766 negative regulation of androgen receptor signaling pathway | IMP PMID:17505061 Sirtuin 1 is required for antagonist-induced transcriptional... | KEEP AS NON CORE | Summary: SIRT1 negatively regulates androgen receptor signaling under antagonist conditions. Reason: Specific signaling-context effect rather than core function. Supporting Evidence: PMID:17505061 is required for androgen antagonist-mediated transcriptional repression and growth suppression |
| GO:0005634 nucleus | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: SIRT1 localizes to the nucleus. Reason: Direct immunostaining shows nuclear localization. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005737 cytoplasm | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: SIRT1 localizes to the cytoplasm. Reason: Direct immunostaining shows cytoplasmic localization. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0051019 mitogen-activated protein kinase binding | IPI PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: SIRT1 physically interacts with the MAPK JNK1. Reason: Coimmunoprecipitation demonstrates JNK1 interaction. Supporting Evidence: PMID:20027304 We identified a functional interaction between cJUN N-terminal kinase (JNK1) and SIRT1 |
| GO:0070301 cellular response to hydrogen peroxide | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | KEEP AS NON CORE | Summary: SIRT1 responds to oxidative stress by changing nuclear localization. Reason: Stress-responsive localization is a context-specific regulatory effect. Supporting Evidence: PMID:20027304 Treatment with H2O2 increased nuclear localization of SIRT1 |
| GO:0018394 peptidyl-lysine acetylation | IMP PMID:18004385 SIRT1 regulates the histone methyl-transferase SUV39H1 durin... | REMOVE | Summary: SIRT1 deacetylates SUV39H1; this is deacetylation rather than acetylation. Reason: The evidence supports deacetylation activity, not acetylation. Supporting Evidence: PMID:18004385 SIRT1 interacts directly with, recruits and deacetylates SUV39H1 |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH re... | KEEP AS NON CORE | Summary: SIRT1 contributes to transcriptional repression mediated by HES1/HEY2. Reason: Context-specific repression via bHLH factors. Supporting Evidence: PMID:12535671 SIRT1-dependent and -independent deacetylase pathways are involved in the transcriptional repressions |
| GO:0003714 transcription corepressor activity | IDA PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH re... | ACCEPT | Summary: SIRT1 functions as a transcriptional corepressor with HES1/HEY2. Reason: Corepressor activity is directly supported. Supporting Evidence: PMID:12535671 SIRT1-dependent and -independent deacetylase pathways are involved in the transcriptional repressions |
| GO:0043398 HLH domain binding | IPI PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH re... | ACCEPT | Summary: SIRT1 associates with HLH/bHLH repressors HES1 and HEY2. Reason: Physical association with bHLH proteins is reported. Supporting Evidence: PMID:12535671 SIRT1, also physically associates with the human bHLH repressor proteins, hHES1 and hHEY2 |
| GO:0043425 bHLH transcription factor binding | IPI PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH re... | ACCEPT | Summary: SIRT1 binds bHLH transcription factors HES1 and HEY2. Reason: Direct interaction with bHLH factors is reported. Supporting Evidence: PMID:12535671 SIRT1, also physically associates with the human bHLH repressor proteins, hHES1 and hHEY2 |
| GO:0000791 euchromatin | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | KEEP AS NON CORE | Summary: SIRT1 was targeted to a reporter integrated in euchromatin in this study. Reason: Represents context-specific targeting rather than core localization. Supporting Evidence: PMID:15469825 a Gal4-reporter integrated in euchromatin |
| GO:0000792 heterochromatin | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | ACCEPT | Summary: SIRT1 promotes heterochromatin formation via histone deacetylation. Reason: Core chromatin silencing function in this reference. Supporting Evidence: PMID:15469825 SirT1-mediated heterochromatin formation that includes deacetylation of histone tails |
| GO:0005637 nuclear inner membrane | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | ACCEPT | Summary: Nuclear inner membrane localization is supported by broader SIRT1 localization evidence. Reason: Consistent with curated localization annotations for SIRT1. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0046969 histone H3K9 deacetylase activity, NAD-dependent | ISS GO_REF:0000024 | ACCEPT | Summary: SIRT1 deacetylates histone H3K9 as part of its core activity. Reason: Supported by multiple SIRT1 histone deacetylase studies. |
| GO:0005634 nucleus | IDA PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | ACCEPT | Summary: SIRT1 is nuclear in studies of APE1 regulation. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0032071 regulation of endodeoxyribonuclease activity | IMP PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | ACCEPT | Summary: SIRT1 deacetylates APE1, modulating its endonuclease activity. Reason: APE1 is a direct SIRT1 substrate in base excision repair. Supporting Evidence: PMID:19934257 SIRT1 deacetylates APE1 in vitro and in vivo targeting lysines 6 and 7 |
| GO:0033558 protein lysine deacetylase activity | IDA PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | ACCEPT | Summary: APE1 is a target of the SIRT1 protein deacetylase. Reason: Direct substrate deacetylation supports this activity. Supporting Evidence: PMID:19934257 APE1 is a target of the SIRTUIN1 (SIRT1) protein deacetylase |
| GO:0045739 positive regulation of DNA repair | IMP PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | ACCEPT | Summary: SIRT1 promotes base excision repair and genomic integrity. Reason: Evidence supports a positive role in DNA repair pathways. Supporting Evidence: PMID:19934257 SIRT1 plays a vital role in maintaining genomic integrity through regulation of the BER pathway |
| GO:0006476 protein deacetylation | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: SIRT1 catalyzes protein deacetylation. Reason: Core biochemical process of SIRT1 activity. Supporting Evidence: PMID:20027304 SIRT1 is a NAD-dependent deacetylase that regulates a variety of pathways |
| GO:0000183 rDNA heterochromatin formation | IDA PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | ACCEPT | Summary: eNoSC containing SIRT1 establishes silent chromatin at rDNA loci. Reason: Supported by the eNoSC complex and rDNA chromatin silencing. Supporting Evidence: PMID:18485871 eNoSC contains Nucleomethylin, which binds histone H3 dimethylated Lys9 in the rDNA locus, in a complex with SIRT1 and SUV39H1. PMID:18485871 thus establishing silent chromatin in the rDNA locus. |
| GO:0005677 chromatin silencing complex | IDA PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | ACCEPT | Summary: SIRT1 is part of the eNoSC chromatin silencing complex. Reason: Complex membership is explicitly described. Supporting Evidence: PMID:18485871 eNoSC contains Nucleomethylin, which binds histone H3 dimethylated Lys9 in the rDNA locus, in a complex with SIRT1 and SUV39H1. |
| GO:0033553 rDNA heterochromatin | IDA PMID:18485871 Epigenetic control of rDNA loci in response to intracellular... | ACCEPT | Summary: Silent chromatin is established at rDNA loci by eNoSC. Reason: Supports rDNA heterochromatin at the locus. Supporting Evidence: PMID:18485871 thus establishing silent chromatin in the rDNA locus. |
| GO:0005654 nucleoplasm | IDA PMID:16079181 Evolutionarily conserved and nonconserved cellular localizat... | ACCEPT | Summary: SIRT1 is among the nuclear sirtuins with distinct subnuclear localizations. Reason: The study identifies SIRT1 as a nuclear SIRT protein. Supporting Evidence: PMID:16079181 three nuclear SIRT proteins (SIRT1, SIRT6, and SIRT7) show different subnuclear localizations |
| GO:0005730 nucleolus | IDA NOT PMID:16079181 Evolutionarily conserved and nonconserved cellular localizat... | KEEP AS NON CORE | Summary: SIRT1 is not reported as nucleolar in this study. Reason: Subnuclear localization is context-specific; NOT annotation kept as non-core. Supporting Evidence: PMID:16079181 2005 Aug 3. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. |
| GO:0005515 protein binding | IPI PMID:17172643 Multiple histone deacetylases and the CREB-binding protein r... | REMOVE | Summary: Generic protein binding is uninformative in this context. Reason: The study focuses on deacetylation by multiple HDACs rather than a specific binding interaction. Supporting Evidence: PMID:17172643 HDAC1, HDAC3, HDAC10, SIRT1, and SIRT2 were involved in in vivo deacetylation. |
| GO:0003714 transcription corepressor activity | ISS GO_REF:0000024 | ACCEPT | Summary: SIRT1 functions as a transcriptional corepressor in multiple contexts. Reason: Supported by multiple experimental studies of SIRT1 corepressor roles. |
| GO:0006642 triglyceride mobilization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 can influence triglyceride mobilization through deacetylation of metabolic regulators. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0009267 cellular response to starvation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 responds to nutrient status via NAD+-dependent deacetylase activity and influences starvation responses. Reason: Downstream metabolic response rather than a core function. |
| GO:0031507 heterochromatin formation | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | ACCEPT | Summary: SirT1-mediated deacetylation supports heterochromatin formation. Reason: Core chromatin silencing activity in this study. Supporting Evidence: PMID:15469825 SirT1-mediated heterochromatin formation that includes deacetylation of histone tails |
| GO:0042393 histone binding | IPI PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | ACCEPT | Summary: SIRT1 interacts with histone H1. Reason: Histone interaction is part of the core chromatin regulation mechanism. Supporting Evidence: PMID:15469825 SirT1 interacts with and deacetylates histone H1 at lysine 26. |
| GO:0042802 identical protein binding | IPI PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | UNDECIDED | Summary: Identical protein binding is not described in the PMID:15469825 abstract. Reason: Need direct evidence for homomeric binding. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0045599 negative regulation of fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences fat cell differentiation. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0050872 white fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SIRT1 influences white fat cell differentiation. Reason: Downstream metabolic regulation rather than a core function. |
| GO:0002039 p53 binding | IPI PMID:11672523 hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. | ACCEPT | Summary: SIRT1 binds p53 as a deacetylation substrate. Reason: Direct p53 binding is reported. Supporting Evidence: PMID:11672523 binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | TAS NOT PMID:17456799 Sirtuin functions in health and disease. | UNDECIDED | Summary: Review notes that some sirtuins have ADP-ribosyltransferase activity but does not specify SIRT1. Reason: The reference does not provide SIRT1-specific evidence to support or refute this activity. Supporting Evidence: PMID:17456799 Certain sirtuins have in addition an ADP-ribosyltransferase activity. |
| GO:0005634 nucleus | IDA PMID:11672523 hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. | ACCEPT | Summary: SIRT1 is nuclear in cells where p53 deacetylation occurs. Reason: Consistent with nuclear localization in SIRT1 studies. Supporting Evidence: PMID:20027304 SIRT1 was localized both in cytoplasmic and nuclear compartments |
| GO:0005635 nuclear envelope | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | UNDECIDED | Summary: Nuclear envelope localization is not described in the PMID:15469825 abstract. Reason: Insufficient evidence in this reference for nuclear envelope localization. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0005730 nucleolus | IDA PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | KEEP AS NON CORE | Summary: Nucleolar localization is context-specific and not central to SIRT1 function. Reason: Subnuclear localization is a downstream/context-specific aspect. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0005737 cytoplasm | IDA NOT PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | ACCEPT | Summary: This study does not report cytoplasmic localization; the NOT annotation is acceptable. Reason: Consistent with the lack of cytoplasmic localization evidence in this reference. Supporting Evidence: PMID:15469825 SirT1 deacetylates histone polypeptides with a preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in vitro. |
| GO:0016605 PML body | IDA PMID:12006491 Human SIR2 deacetylates p53 and antagonizes PML/p53-induced ... | ACCEPT | Summary: SIRT1 localizes to PML nuclear bodies. Reason: Direct localization to PML bodies is reported. Supporting Evidence: PMID:12006491 SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies |
| GO:0042127 regulation of cell population proliferation | IMP PMID:12006491 Human SIR2 deacetylates p53 and antagonizes PML/p53-induced ... | KEEP AS NON CORE | Summary: SIRT1 rescues PML-induced premature senescence, indicating effects on cell proliferation state. Reason: Senescence modulation is downstream and context-specific. Supporting Evidence: PMID:12006491 rescues PML-mediated premature cellular senescence |
| GO:0043518 negative regulation of DNA damage response, signal transduction by p53 class mediator | IDA PMID:11672523 hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. | KEEP AS NON CORE | Summary: SIRT1 modulates p53-mediated DNA damage responses via deacetylation. Reason: Downstream consequence of p53 regulation rather than core function. Supporting Evidence: PMID:11672523 binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue |
| GO:0006476 protein deacetylation | IDA PMID:18203716 Regulation of WRN protein cellular localization and enzymati... | ACCEPT | Summary: SIRT1 deacetylates protein substrates such as WRN. Reason: Direct deacetylation activity is reported. Supporting Evidence: PMID:18203716 SIRT1 can deacetylate WRN both in vitro and in vivo. |
| GO:0006974 DNA damage response | IDA PMID:18203716 Regulation of WRN protein cellular localization and enzymati... | ACCEPT | Summary: SIRT1 regulates WRN-mediated responses to DNA damage. Reason: DNA damage response is a supported functional role for SIRT1. Supporting Evidence: PMID:18203716 SIRT1 regulates WRN-mediated cellular responses to DNA damage through deacetylation of WRN. |
| GO:0019213 deacetylase activity | IDA PMID:18203716 Regulation of WRN protein cellular localization and enzymati... | ACCEPT | Summary: SIRT1 deacetylates WRN. Reason: Deacetylase activity is supported by direct substrate deacetylation. Supporting Evidence: PMID:18203716 SIRT1 can deacetylate WRN both in vitro and in vivo. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IDA PMID:16959573 SIRT4 inhibits glutamate dehydrogenase and opposes the effec... | ACCEPT | Summary: Core NAD-dependent histone deacetylase activity demonstrated experimentally. Reason: Core molecular function. SIRT1 is a well-established NAD-dependent histone deacetylase. Supporting Evidence: PMID:16959573 SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. |
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