SIRT5 is an NAD-dependent protein lysine deacylase that efficiently removes succinyl, malonyl and glutaryl groups. Its mitochondrial and extramitochondrial substrates connect deacylation to nitrogen metabolism, redox control and other metabolic pathways. Protein deacetylation is comparatively weak and does not define its principal substrate preference.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000050 urea cycle | TAS Reactome:R-HSA-70635 | ACCEPT | Summary: SIRT5 deacylates CPS1 and thereby regulates urea-cycle capacity; participation does not imply it catalyzes a urea-cycle small-molecule reaction. Reason: SIRT5 deacylates CPS1 and thereby regulates urea-cycle capacity; participation does not imply it catalyzes a urea-cycle small-molecule reaction. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | TAS NOT PMID:17456799 Sirtuin functions in health and disease. | UNDECIDED | Summary: The family-level sirtuin review does not isolate the experimental basis for the target-specific absence of poly-ADP-ribosyltransferase activity. Reason: The family-level sirtuin review does not isolate the experimental basis for the target-specific absence of poly-ADP-ribosyltransferase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A nuclear SIRT5 pool is retained as a secondary localization rather than overriding the principal mitochondrial deacylase role. Reason: A nuclear SIRT5 pool is retained as a secondary localization rather than overriding the principal mitochondrial deacylase role. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A nuclear SIRT5 pool is retained as a secondary localization rather than overriding the principal mitochondrial deacylase role. Reason: A nuclear SIRT5 pool is retained as a secondary localization rather than overriding the principal mitochondrial deacylase role. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005634 nucleus | TAS PMID:23806337 SIRT5-mediated lysine desuccinylation impacts diverse metabo... | UNDECIDED | Summary: A nuclear SIRT5 pool is retained as a secondary localization rather than overriding the principal mitochondrial deacylase role. The target-specific support in PMID:23806337 still requires detailed assessment of the experimental results. Reason: A nuclear SIRT5 pool is retained as a secondary localization rather than overriding the principal mitochondrial deacylase role. The target-specific support in PMID:23806337 still requires detailed assessment of the experimental results. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic SIRT5 pools are compatible with its extramitochondrial substrates. Reason: Cytoplasmic SIRT5 pools are compatible with its extramitochondrial substrates. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Direct human localization studies identify mitochondrial SIRT5. Reason: Direct human localization studies identify mitochondrial SIRT5. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Direct human localization studies identify mitochondrial SIRT5. Reason: Direct human localization studies identify mitochondrial SIRT5. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Direct human localization studies identify mitochondrial SIRT5. Reason: Direct human localization studies identify mitochondrial SIRT5. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005739 mitochondrion | IDA GO_REF:0000054 | ACCEPT | Summary: Direct human localization studies identify mitochondrial SIRT5. Reason: Direct human localization studies identify mitochondrial SIRT5. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005739 mitochondrion | IDA PMID:16079181 Evolutionarily conserved and nonconserved cellular localizat... | ACCEPT | Summary: Direct human localization studies identify mitochondrial SIRT5. Reason: Direct human localization studies identify mitochondrial SIRT5. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005739 mitochondrion | IDA PMID:23806337 SIRT5-mediated lysine desuccinylation impacts diverse metabo... | UNDECIDED | Summary: Direct human localization studies identify mitochondrial SIRT5. The target-specific support in PMID:23806337 still requires detailed assessment of the experimental results. Reason: Direct human localization studies identify mitochondrial SIRT5. The target-specific support in PMID:23806337 still requires detailed assessment of the experimental results. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Direct human localization studies identify mitochondrial SIRT5. Reason: Direct human localization studies identify mitochondrial SIRT5. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific inner-membrane assignment needs evidence beyond mitochondrial localization and association with mitochondrial substrates. Reason: The specific inner-membrane assignment needs evidence beyond mitochondrial localization and association with mitochondrial substrates. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:18680753 Substrates and regulation mechanisms for the human mitochond... | UNDECIDED | Summary: The intermembrane-space assignment must be distinguished from mitochondrial matrix localization through the original fractionation or imaging evidence. Reason: The intermembrane-space assignment must be distinguished from mitochondrial matrix localization through the original fractionation or imaging evidence. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000044 | UNDECIDED | Summary: The intermembrane-space assignment must be distinguished from mitochondrial matrix localization through the original fractionation or imaging evidence. Reason: The intermembrane-space assignment must be distinguished from mitochondrial matrix localization through the original fractionation or imaging evidence. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005759 mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Reason: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005759 mitochondrial matrix | IDA PMID:18680753 Substrates and regulation mechanisms for the human mitochond... | ACCEPT | Summary: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Reason: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Reason: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-5688294 | ACCEPT | Summary: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Reason: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9955504 | ACCEPT | Summary: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Reason: SIRT5 acts on mitochondrial matrix metabolic substrates, including CPS1 and SHMT2. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosolic SIRT5 activity is compatible with direct regulation of extramitochondrial substrates such as SOD1. Reason: Cytosolic SIRT5 activity is compatible with direct regulation of extramitochondrial substrates such as SOD1. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005829 cytosol | IDA PMID:23806337 SIRT5-mediated lysine desuccinylation impacts diverse metabo... | UNDECIDED | Summary: Cytosolic SIRT5 activity is compatible with direct regulation of extramitochondrial substrates such as SOD1. The target-specific support in PMID:23806337 still requires detailed assessment of the experimental results. Reason: Cytosolic SIRT5 activity is compatible with direct regulation of extramitochondrial substrates such as SOD1. The target-specific support in PMID:23806337 still requires detailed assessment of the experimental results. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Cytosolic SIRT5 activity is compatible with direct regulation of extramitochondrial substrates such as SOD1. Reason: Cytosolic SIRT5 activity is compatible with direct regulation of extramitochondrial substrates such as SOD1. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also CC present extramitochondrially, with a fraction present in the cytosol CC and very small amounts also detected in the nucleus. |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000108 | UNDECIDED | Summary: Chromatin remodeling cannot be established by a broad historical histone-deacetylase label when SIRT5 preferentially removes acidic acyl groups. Reason: Chromatin remodeling cannot be established by a broad historical histone-deacetylase label when SIRT5 preferentially removes acidic acyl groups. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0006476 protein deacetylation | IDA PMID:18680753 Substrates and regulation mechanisms for the human mitochond... | KEEP AS NON CORE | Summary: Weak protein deacetylation is measurable in vitro, but efficient acidic deacylation better defines SIRT5 physiology. The distinction between assay activity and in-vivo function is essential. Reason: Weak protein deacetylation is measurable in vitro, but efficient acidic deacylation better defines SIRT5 physiology. The distinction between assay activity and in-vivo function is essential. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0006476 protein deacetylation | IDA NOT PMID:22076378 Sirt5 is a NAD-dependent protein lysine demalonylase and des... | UNDECIDED | Summary: The annotation is NOT protein deacetylation. The cited study measures weak in-vitro deacetylation while supporting acidic deacylation as the major activity; that distinction does not by itself establish complete absence of the biological process. Reason: The annotation is NOT protein deacetylation. The cited study measures weak in-vitro deacetylation while supporting acidic deacylation as the major activity; that distinction does not by itself establish complete absence of the biological process. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0007005 mitochondrion organization | TAS Reactome:R-HSA-1592230 | ACCEPT | Summary: Regulation of mitochondrial substrates and metabolism connects SIRT5 deacylation to mitochondrial organization and maintenance. Reason: Regulation of mitochondrial substrates and metabolism connects SIRT5 deacylation to mitochondrial organization and maintenance. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0008270 zinc ion binding | IDA PMID:22076378 Sirt5 is a NAD-dependent protein lysine demalonylase and des... | ACCEPT | Summary: The structurally characterized human sirtuin has a conserved zinc-binding subdomain; this judgment is about the intact human reference. Reason: The structurally characterized human sirtuin has a conserved zinc-binding subdomain; this judgment is about the intact human reference. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000104 | ACCEPT | Summary: The structurally characterized human sirtuin has a conserved zinc-binding subdomain; this judgment is about the intact human reference. Reason: The structurally characterized human sirtuin has a conserved zinc-binding subdomain; this judgment is about the intact human reference. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0010566 regulation of ketone biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ketone synthesis is a substrate- and physiological-context role downstream of metabolic enzyme deacylation. Reason: Ketone synthesis is a substrate- and physiological-context role downstream of metabolic enzyme deacylation. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0010566 regulation of ketone biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ketone synthesis is a substrate- and physiological-context role downstream of metabolic enzyme deacylation. Reason: Ketone synthesis is a substrate- and physiological-context role downstream of metabolic enzyme deacylation. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0010667 negative regulation of cardiac muscle cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiomyocyte survival is a tissue-specific consequence of metabolic/stress regulation, not the primary enzyme reaction. Reason: Cardiomyocyte survival is a tissue-specific consequence of metabolic/stress regulation, not the primary enzyme reaction. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000117 | UNDECIDED | Summary: Sirtuin chemistry couples deacylation to ADP-ribose transfer, but this broad acyltransferase term needs a precise reaction interpretation rather than a family-name inference. Reason: Sirtuin chemistry couples deacylation to ADP-ribose transfer, but this broad acyltransferase term needs a precise reaction interpretation rather than a family-name inference. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0017136 histone deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | MODIFY | Summary: The robust characterized activities are demalonylation and desuccinylation; a generic NAD-dependent histone deacetylase label is not the best core function. Reason: The robust characterized activities are demalonylation and desuccinylation; a generic NAD-dependent histone deacetylase label is not the best core function. Proposed replacements: protein-succinyllysine desuccinylase activity Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | ACCEPT | Summary: NAD-linked deacylation of metabolic enzymes connects SIRT5 activity to nutrient availability. Reason: NAD-linked deacylation of metabolic enzymes connects SIRT5 activity to nutrient availability. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Purified human SIRT5 has weak NAD-dependent deacetylation, substantially less efficient than its acidic deacylation activities. Reason: Purified human SIRT5 has weak NAD-dependent deacetylation, substantially less efficient than its acidic deacylation activities. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | TAS Reactome:R-HSA-5688294 | KEEP AS NON CORE | Summary: Purified human SIRT5 has weak NAD-dependent deacetylation, substantially less efficient than its acidic deacylation activities. Reason: Purified human SIRT5 has weak NAD-dependent deacetylation, substantially less efficient than its acidic deacylation activities. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036046 protein demalonylation | IDA PMID:24703693 Lysine glutarylation is a protein posttranslational modifica... | ACCEPT | Summary: Demalonylation is directly established with biochemical assays of human SIRT5. Reason: Demalonylation is directly established with biochemical assays of human SIRT5. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036047 peptidyl-lysine demalonylation | IDA PMID:21908771 The first identification of lysine malonylation substrates a... | ACCEPT | Summary: The enzyme removes malonyl groups from modified lysine residues. Reason: The enzyme removes malonyl groups from modified lysine residues. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036047 peptidyl-lysine demalonylation | IDA PMID:22076378 Sirt5 is a NAD-dependent protein lysine demalonylase and des... | ACCEPT | Summary: The enzyme removes malonyl groups from modified lysine residues. Reason: The enzyme removes malonyl groups from modified lysine residues. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036048 protein desuccinylation | IDA PMID:24140062 SIRT5 desuccinylates and activates SOD1 to eliminate ROS. | ACCEPT | Summary: SIRT5 directly desuccinylates proteins, including substrate-focused SOD1 and SHMT2 examples. Reason: SIRT5 directly desuccinylates proteins, including substrate-focused SOD1 and SHMT2 examples. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036048 protein desuccinylation | IDA PMID:24703693 Lysine glutarylation is a protein posttranslational modifica... | ACCEPT | Summary: SIRT5 directly desuccinylates proteins, including substrate-focused SOD1 and SHMT2 examples. Reason: SIRT5 directly desuccinylates proteins, including substrate-focused SOD1 and SHMT2 examples. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036048 protein desuccinylation | IDA PMID:29180469 SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferat... | ACCEPT | Summary: SIRT5 directly desuccinylates proteins, including substrate-focused SOD1 and SHMT2 examples. Reason: SIRT5 directly desuccinylates proteins, including substrate-focused SOD1 and SHMT2 examples. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036049 peptidyl-lysine desuccinylation | IDA PMID:21908771 The first identification of lysine malonylation substrates a... | ACCEPT | Summary: Removal of succinyl groups from lysine residues is a robust characterized SIRT5 activity. Reason: Removal of succinyl groups from lysine residues is a robust characterized SIRT5 activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036049 peptidyl-lysine desuccinylation | IDA PMID:22076378 Sirt5 is a NAD-dependent protein lysine demalonylase and des... | ACCEPT | Summary: Removal of succinyl groups from lysine residues is a robust characterized SIRT5 activity. Reason: Removal of succinyl groups from lysine residues is a robust characterized SIRT5 activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036054 protein-malonyllysine demalonylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Reason: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036054 protein-malonyllysine demalonylase activity | IDA PMID:21908771 The first identification of lysine malonylation substrates a... | ACCEPT | Summary: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Reason: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036054 protein-malonyllysine demalonylase activity | IDA PMID:22076378 Sirt5 is a NAD-dependent protein lysine demalonylase and des... | ACCEPT | Summary: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Reason: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036054 protein-malonyllysine demalonylase activity | IDA PMID:24703693 Lysine glutarylation is a protein posttranslational modifica... | ACCEPT | Summary: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Reason: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036054 protein-malonyllysine demalonylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Reason: The structural and biochemical study establishes protein-malonyllysine demalonylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036055 protein-succinyllysine desuccinylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Reason: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036055 protein-succinyllysine desuccinylase activity | IDA PMID:21908771 The first identification of lysine malonylation substrates a... | ACCEPT | Summary: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Reason: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036055 protein-succinyllysine desuccinylase activity | IDA PMID:22076378 Sirt5 is a NAD-dependent protein lysine demalonylase and des... | ACCEPT | Summary: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Reason: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036055 protein-succinyllysine desuccinylase activity | IDA PMID:24140062 SIRT5 desuccinylates and activates SOD1 to eliminate ROS. | ACCEPT | Summary: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Reason: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036055 protein-succinyllysine desuccinylase activity | IDA PMID:24703693 Lysine glutarylation is a protein posttranslational modifica... | ACCEPT | Summary: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Reason: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036055 protein-succinyllysine desuccinylase activity | IDA PMID:29180469 SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferat... | ACCEPT | Summary: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Reason: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0036055 protein-succinyllysine desuccinylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Reason: The structural and biochemical study establishes protein-succinyllysine desuccinylase activity. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0061697 protein-glutaryllysine deglutarylase activity | EXP PMID:24703693 Lysine glutarylation is a protein posttranslational modifica... | ACCEPT | Summary: Human SIRT5 is characterized as an NAD-dependent deglutarylase in the substrate-specific biochemical literature. Reason: Human SIRT5 is characterized as an NAD-dependent deglutarylase in the substrate-specific biochemical literature. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0061697 protein-glutaryllysine deglutarylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Human SIRT5 is characterized as an NAD-dependent deglutarylase in the substrate-specific biochemical literature. Reason: Human SIRT5 is characterized as an NAD-dependent deglutarylase in the substrate-specific biochemical literature. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0061697 protein-glutaryllysine deglutarylase activity | IDA PMID:24703693 Lysine glutarylation is a protein posttranslational modifica... | ACCEPT | Summary: Human SIRT5 is characterized as an NAD-dependent deglutarylase in the substrate-specific biochemical literature. Reason: Human SIRT5 is characterized as an NAD-dependent deglutarylase in the substrate-specific biochemical literature. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0061697 protein-glutaryllysine deglutarylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Human SIRT5 is characterized as an NAD-dependent deglutarylase in the substrate-specific biochemical literature. Reason: Human SIRT5 is characterized as an NAD-dependent deglutarylase in the substrate-specific biochemical literature. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0061698 protein deglutarylation | IDA PMID:24703693 Lysine glutarylation is a protein posttranslational modifica... | ACCEPT | Summary: Removal of protein glutaryl groups is a characterized acidic deacylation process. Reason: Removal of protein glutaryl groups is a characterized acidic deacylation process. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0070403 NAD+ binding | IDA PMID:21908771 The first identification of lysine malonylation substrates a... | ACCEPT | Summary: NAD is the cosubstrate in the structurally characterized human sirtuin reaction. Reason: NAD is the cosubstrate in the structurally characterized human sirtuin reaction. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0070403 NAD+ binding | IDA PMID:22076378 Sirt5 is a NAD-dependent protein lysine demalonylase and des... | ACCEPT | Summary: NAD is the cosubstrate in the structurally characterized human sirtuin reaction. Reason: NAD is the cosubstrate in the structurally characterized human sirtuin reaction. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:0070403 NAD+ binding | IEA GO_REF:0000120 | ACCEPT | Summary: NAD is the cosubstrate in the structurally characterized human sirtuin reaction. Reason: NAD is the cosubstrate in the structurally characterized human sirtuin reaction. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | TAS NOT PMID:17456799 Sirtuin functions in health and disease. | UNDECIDED | Summary: The family-level reference alone does not isolate the experimental basis for the target-specific NOT mono-ADP-ribosyltransferase annotation. Reason: The family-level reference alone does not isolate the experimental basis for the target-specific NOT mono-ADP-ribosyltransferase annotation. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
| GO:2000378 negative regulation of reactive oxygen species metabolic process | IDA PMID:24140062 SIRT5 desuccinylates and activates SOD1 to eliminate ROS. | KEEP AS NON CORE | Summary: SIRT5-dependent SOD1 activation reduces ROS in the reported cellular system; this is a substrate-specific downstream consequence. Reason: SIRT5-dependent SOD1 activation reduces ROS in the reported cellular system; this is a substrate-specific downstream consequence. Supporting Evidence: file:human/SIRT5/SIRT5-uniprot.txt CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. |
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Download this section (compressed HTML)The human reference supplies mechanistic evidence for the corresponding selected horse protein; the human conclusion alone is not validation of the horse sequence. The exact horse comparison is in genes/HORSE/SIRT5/SIRT5-bioinformatics/RESULTS.md. Research reports are source leads; annotation decisions cite the underlying publication or experimentally supported UniProt passages. Unresolved source-specific results retain UNDECIDED.
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