SIRT5 of horse (Equus caballus) is a 310-residue NAD+-dependent protein lysine deacylase of the class III sirtuin subfamily (PANTHER PTHR11085:SF10), encoded by Ensembl gene ENSECAG00000026898 and 88% identical to human SIRT5 over its full length. Like its characterised human and mouse orthologs it is predicted to remove negatively charged acyl groups (succinyl, malonyl and glutaryl) from protein lysine residues, transferring the acyl group to ADP-ribose and releasing nicotinamide; Tyr102 and Arg105 of the acyl-binding pocket, the catalytic His158, the four zinc-binding cysteines and the NAD+ binding motifs are all conserved. Deacetylase activity is weak in the orthologs. It has an N-terminal mitochondrial presequence and is expected to act mainly in the mitochondrial matrix, with a cytosolic pool and a minor nuclear pool. In mammals SIRT5 regulates mitochondrial and cytosolic metabolic enzymes such as CPS1 (urea cycle), HMGCS2 (ketogenesis) and SOD1. None of these properties has been tested experimentally in horse; all derive from orthologs within the same PANTHER subfamily and PAINT node.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Minor nuclear pool inherited as an ancestral sirtuin location; not where SIRT5 chiefly acts. Reason: Human SIRT5 is mainly mitochondrial, with a minor nuclear pool detectable by fractionation. The IBA derives from the deep sirtuin node PTN008492176, seeded by the nuclear sirtuins; the PAINT curator placed mitochondrion and cytosol, not nucleus, on the SIRT5-subfamily node PTN000119399, so nucleus is an ancestral location that survives in SIRT5 only as a small secondary pool. The IEA row restates the HAMAP subcellular-location note, which itself says only very small amounts are nuclear. Kept as a minor, non-core location. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN008492176 SUPPORTS SOURCE BUT NOT TARGET Deep sirtuin node seeded by nuclear sirtuins; SIRT5 orthologs show only a minor nuclear pool, so the transfer holds weakly and is non-core. Supporting Evidence: PMID:23806337 A very small amount of SIRT5 was also detected in the nuclear fraction, which was particularly evident in the liver samples file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt Note=Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Minor nuclear pool inherited as an ancestral sirtuin location; not where SIRT5 chiefly acts. Reason: Human SIRT5 is mainly mitochondrial, with a minor nuclear pool detectable by fractionation. The IBA derives from the deep sirtuin node PTN008492176, seeded by the nuclear sirtuins; the PAINT curator placed mitochondrion and cytosol, not nucleus, on the SIRT5-subfamily node PTN000119399, so nucleus is an ancestral location that survives in SIRT5 only as a small secondary pool. The IEA row restates the HAMAP subcellular-location note, which itself says only very small amounts are nuclear. Kept as a minor, non-core location. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Supporting Evidence: PMID:23806337 A very small amount of SIRT5 was also detected in the nuclear fraction, which was particularly evident in the liver samples file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt Note=Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | MODIFY | Summary: Mitochondrion is correct but general; refine to mitochondrial matrix. Reason: The horse product carries the full mitochondrial targeting presequence (the first 50 residues are 40/50 identical to human, and residues 1-30 form the transit-peptide region of human SIRT5), and human SIRT5 is experimentally mitochondrial. The more precise supported location is mitochondrial matrix, which the gene already carries from the eumetazoan PAINT node PTN000872307 and where the characterised substrates (CPS1, HMGCS2, SHMT2) reside. The term is correct but general, so it is refined rather than removed. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000119399 SUPPORTS TRANSFER SIRT5-subfamily node (PTHR11085:SF10 clade) carrying the IBD; horse A0A9L0T9B1 is a full-length descendant with all acyl-pocket, catalytic, zinc and NAD+ residues conserved. UniProtKB:Q9NXA8 SUPPORTS TRANSFER Human SIRT5, experimental seed (IDA/EXP) of the node. MGI:MGI:1915596 SUPPORTS TRANSFER Mouse Sirt5, experimental seed of the node. Proposed replacements: mitochondrial matrix Supporting Evidence: PMID:16079181 SIRT3, SIRT4, and SIRT5 are localized in mitochondria PMID:18680753 Sirt5 can indeed be translocated into the mitochondrial intermembrane space, but also into the matrix file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS-rereview.md A0A9L0T9B1: 310 residues; 273/310 paired residues identical (88.1%); Ensembl transcript ENSECAT00000146678 of gene ENSECAG00000026898, 9 exons. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | MODIFY | Summary: Mitochondrion is correct but general; refine to mitochondrial matrix. Reason: The horse product carries the full mitochondrial targeting presequence (the first 50 residues are 40/50 identical to human, and residues 1-30 form the transit-peptide region of human SIRT5), and human SIRT5 is experimentally mitochondrial. The more precise supported location is mitochondrial matrix, which the gene already carries from the eumetazoan PAINT node PTN000872307 and where the characterised substrates (CPS1, HMGCS2, SHMT2) reside. The term is correct but general, so it is refined rather than removed. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Proposed replacements: mitochondrial matrix Supporting Evidence: PMID:16079181 SIRT3, SIRT4, and SIRT5 are localized in mitochondria PMID:18680753 Sirt5 can indeed be translocated into the mitochondrial intermembrane space, but also into the matrix file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS-rereview.md A0A9L0T9B1: 310 residues; 273/310 paired residues identical (88.1%); Ensembl transcript ENSECAT00000146678 of gene ENSECAG00000026898, 9 exons. |
| GO:0005759 mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial matrix is the principal site of SIRT5 acidic-acyl deacylase activity; IBA from eumetazoan node PTN000872307. Reason: Human SIRT5 is imported into the mitochondrial matrix as well as the intermembrane space, and its best-characterised substrates (CPS1, HMGCS2, SHMT2, PDC, SDH) are matrix enzymes. PAINT placed this location on node PTN000872307 (Eumetazoa) seeded by human SIRT5, and horse A0A9L0T9B1 descends from it, with a conserved N-terminal presequence (88% overall identity to human). No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000872307 SUPPORTS TRANSFER Eumetazoan SIRT5 node carrying the matrix IBD, seeded by human SIRT5; horse retains the presequence. Supporting Evidence: PMID:18680753 Sirt5 can indeed be translocated into the mitochondrial intermembrane space, but also into the matrix file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS-rereview.md A0A9L0T9B1: 310 residues; 273/310 paired residues identical (88.1%); Ensembl transcript ENSECAT00000146678 of gene ENSECAG00000026898, 9 exons. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: A substantial cytosolic SIRT5 pool is documented in human and mouse cells; IBA from SIRT5-subfamily node PTN000119399. Reason: Fractionation shows a significant fraction of endogenous SIRT5 in the cytosol of human cells and mouse liver, and cytosolic substrates such as SOD1 and glycolytic enzymes are desuccinylated by SIRT5. PAINT placed cytosol on the SIRT5-subfamily node PTN000119399, which the horse full-length product inherits. The IEA row (HAMAP subcellular-location mapping) agrees. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000119399 SUPPORTS TRANSFER SIRT5-subfamily node (PTHR11085:SF10 clade) carrying the IBD; horse A0A9L0T9B1 is a full-length descendant with all acyl-pocket, catalytic, zinc and NAD+ residues conserved. UniProtKB:Q9NXA8 SUPPORTS TRANSFER Human SIRT5, experimental seed (IDA/EXP) of the node. MGI:MGI:1915596 SUPPORTS TRANSFER Mouse Sirt5, experimental seed of the node. Supporting Evidence: PMID:23806337 Subcellular fractionation revealed that a significant fraction of endogenous SIRT5 was present cytosolically both in human cells PMID:24140062 SIRT5 binds to, desuccinylates and activates SOD1. file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt Note=Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: A substantial cytosolic SIRT5 pool is documented in human and mouse cells; IBA from SIRT5-subfamily node PTN000119399. Reason: Fractionation shows a significant fraction of endogenous SIRT5 in the cytosol of human cells and mouse liver, and cytosolic substrates such as SOD1 and glycolytic enzymes are desuccinylated by SIRT5. PAINT placed cytosol on the SIRT5-subfamily node PTN000119399, which the horse full-length product inherits. The IEA row (HAMAP subcellular-location mapping) agrees. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Supporting Evidence: PMID:23806337 Subcellular fractionation revealed that a significant fraction of endogenous SIRT5 was present cytosolically both in human cells PMID:24140062 SIRT5 binds to, desuccinylates and activates SOD1. file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt Note=Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus. |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000108 | REMOVE | Summary: Logical inference from the histone deacetylase IBA; no evidence that SIRT5 participates in chromatin remodeling. Reason: This row is derived by inter-ontology inference from GO:0017136 (histone deacetylase activity, NAD-dependent), which is itself a deep-node IBA refined away from SIRT5 in this review. SIRT5 deacetylase activity is about 500-fold weaker than that of SIRT1, and SIRT5 loss does not change global lysine acetylation. No study in any species shows SIRT5 doing work within chromatin remodeling; the electronic chain has no SIRT5-specific grounding. Supporting Evidence: PMID:22076378 The catalytic efficiency (kcat/Km) of Sirt5 was about 500-fold lower than that of Sirt1. PMID:23806337 SIRT5 deficiency does not significantly impact global Lys acetylation |
| GO:0008270 zinc ion binding | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Structural zinc bound by the conserved sirtuin Cys4 motif (Cys166, Cys169, Cys207, Cys212 all present in this horse model). Reason: Sirtuins bind one structural zinc ion in the small domain via four cysteines. In A0A9L0T9B1 all four human zinc-ligand cysteines are conserved (unlike the truncated F6S899 model, which has Trp at two of them). Zinc binding is a true, structural property but not the functional activity of the protein. Supporting Evidence: file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt Note=Binds 1 zinc ion per subunit. file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS-rereview.md | BINDING | 207-207 | Zn(2+) | C | W | C | C | |
| GO:0017136 histone deacetylase activity, NAD-dependent | IBA GO_REF:0000033 | MODIFY | Summary: Deep-node sirtuin IBA; SIRT5 is an acidic-acyl deacylase and the SIRT5-subfamily node carries the deacylase terms instead. Reason: The IBD for histone deacetylase activity sits on deep sirtuin node PTN008718612, seeded by robust deacetylases (SIRT1-3, SIRT6, yeast Sir2/Hst proteins), with no SIRT5 seeds. On the SIRT5-subfamily node PTN000119399 the PAINT curator placed desuccinylase, demalonylase and deglutarylase activities, not deacetylase, which we treat as a deliberate decision. SIRT5 diverges: Tyr102/Arg105 bind carboxylate acyl groups, deacetylation is about 500-fold weaker than SIRT1 and 29 to >1000-fold weaker than its own desuccinylation, and no physiological histone deacetylation is established. Both residues are conserved in the horse product. Refined to the three acidic deacylase activities (matching the human SIRT5 review). Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN008718612 SUPPORTS SOURCE BUT NOT TARGET Deep sirtuin deacetylase node seeded by SIRT1-3, SIRT6 and yeast Sir2/Hst proteins, with no SIRT5 seed; SIRT5 acyl-pocket specialisation (Tyr102/Arg105) shifts it to acidic deacylation, and the SIRT5-subfamily node instead carries the deacylase terms. Proposed replacements: protein-succinyllysine desuccinylase activity protein-malonyllysine demalonylase activity protein-glutaryllysine deglutarylase activity Supporting Evidence: PMID:22076378 With all three peptide sequences, the catalytic efficiencies for demalonylation and desuccinylation were much (29 to >1000 fold) higher than that for deacetylation PMID:22076378 Thus, Tyr102 and Arg105 were important for binding succinyl and malonyl groups. PMID:22076378 The catalytic efficiency (kcat/Km) of Sirt5 was about 500-fold lower than that of Sirt1. |
| GO:0034979 NAD-dependent protein lysine deacetylase activity | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Weak, real in vitro NAD-dependent deacetylase activity of SIRT5 orthologs; not the core activity. Reason: Purified human SIRT5 deacetylates some acetyl peptides and cytochrome c in vitro, but far less efficiently than it removes succinyl, malonyl or glutaryl groups, and SIRT5 loss does not alter global acetylation. The UniRule-derived term is an accurate description of a minor activity and is kept as non-core. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Supporting Evidence: file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. PMID:22076378 With all three peptide sequences, the catalytic efficiencies for demalonylation and desuccinylation were much (29 to >1000 fold) higher than that for deacetylation PMID:23806337 SIRT5 deficiency does not significantly impact global Lys acetylation |
| GO:0036054 protein-malonyllysine demalonylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core NAD-dependent lysine demalonylase activity, inherited from SIRT5-subfamily node PTN000119399. Reason: Demalonylation by SIRT5 is established in vitro and in vivo for human and mouse SIRT5, and PAINT placed this activity on the SIRT5-subfamily node PTN000119399 (seeded by human and mouse SIRT5), from which horse A0A9L0T9B1 (PANTHER PTHR11085:SF10) descends. The substrate-pocket residues Tyr102 and Arg105, the catalytic His158 and the zinc and NAD+ binding residues are all conserved. The IEA (HAMAP MF_03160 / InterPro IPR027546) agrees. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000119399 SUPPORTS TRANSFER SIRT5-subfamily node (PTHR11085:SF10 clade) carrying the IBD; horse A0A9L0T9B1 is a full-length descendant with all acyl-pocket, catalytic, zinc and NAD+ residues conserved. UniProtKB:Q9NXA8 SUPPORTS TRANSFER Human SIRT5, experimental seed (IDA/EXP) of the node. MGI:MGI:1915596 SUPPORTS TRANSFER Mouse Sirt5, experimental seed of the node. Supporting Evidence: PMID:21908771 we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation reactions both in vitro and in vivo PMID:22076378 With all three peptide sequences, the catalytic efficiencies for demalonylation and desuccinylation were much (29 to >1000 fold) higher than that for deacetylation file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS-rereview.md | ACT_SITE | 158-158 | | H | H | H | H | |
| GO:0036054 protein-malonyllysine demalonylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core NAD-dependent lysine demalonylase activity, inherited from SIRT5-subfamily node PTN000119399. Reason: Demalonylation by SIRT5 is established in vitro and in vivo for human and mouse SIRT5, and PAINT placed this activity on the SIRT5-subfamily node PTN000119399 (seeded by human and mouse SIRT5), from which horse A0A9L0T9B1 (PANTHER PTHR11085:SF10) descends. The substrate-pocket residues Tyr102 and Arg105, the catalytic His158 and the zinc and NAD+ binding residues are all conserved. The IEA (HAMAP MF_03160 / InterPro IPR027546) agrees. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Supporting Evidence: PMID:21908771 we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation reactions both in vitro and in vivo PMID:22076378 With all three peptide sequences, the catalytic efficiencies for demalonylation and desuccinylation were much (29 to >1000 fold) higher than that for deacetylation file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS-rereview.md | ACT_SITE | 158-158 | | H | H | H | H | |
| GO:0036055 protein-succinyllysine desuccinylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core NAD-dependent lysine desuccinylase activity, the most efficient SIRT5 reaction; inherited from node PTN000119399. Reason: SIRT5 is the main mitochondrial desuccinylase in human and mouse: Sirt5 loss raises global lysine succinylation and the purified enzyme desuccinylates far more efficiently than it deacetylates. PAINT placed the term on SIRT5-subfamily node PTN000119399, and the horse product conserves Tyr102/Arg105 and all catalytic, zinc and NAD+ binding residues. The IEA (HAMAP/InterPro) agrees. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000119399 SUPPORTS TRANSFER SIRT5-subfamily node (PTHR11085:SF10 clade) carrying the IBD; horse A0A9L0T9B1 is a full-length descendant with all acyl-pocket, catalytic, zinc and NAD+ residues conserved. UniProtKB:Q9NXA8 SUPPORTS TRANSFER Human SIRT5, experimental seed (IDA/EXP) of the node. MGI:MGI:1915596 SUPPORTS TRANSFER Mouse Sirt5, experimental seed of the node. Supporting Evidence: PMID:23806337 SIRT5 is a central regulator of Lys succinylation in mammalian cells PMID:22076378 With all three peptide sequences, the catalytic efficiencies for demalonylation and desuccinylation were much (29 to >1000 fold) higher than that for deacetylation PMID:22076378 Thus, Tyr102 and Arg105 were important for binding succinyl and malonyl groups. file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. |
| GO:0036055 protein-succinyllysine desuccinylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core NAD-dependent lysine desuccinylase activity, the most efficient SIRT5 reaction; inherited from node PTN000119399. Reason: SIRT5 is the main mitochondrial desuccinylase in human and mouse: Sirt5 loss raises global lysine succinylation and the purified enzyme desuccinylates far more efficiently than it deacetylates. PAINT placed the term on SIRT5-subfamily node PTN000119399, and the horse product conserves Tyr102/Arg105 and all catalytic, zinc and NAD+ binding residues. The IEA (HAMAP/InterPro) agrees. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Supporting Evidence: PMID:23806337 SIRT5 is a central regulator of Lys succinylation in mammalian cells PMID:22076378 With all three peptide sequences, the catalytic efficiencies for demalonylation and desuccinylation were much (29 to >1000 fold) higher than that for deacetylation PMID:22076378 Thus, Tyr102 and Arg105 were important for binding succinyl and malonyl groups. file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. |
| GO:0061697 protein-glutaryllysine deglutarylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core NAD-dependent lysine deglutarylase activity, inherited from node PTN000119399. Reason: SIRT5 is the only HDAC with significant lysine deglutarylase activity in vitro (human) and regulates CPS1 glutarylation in mouse. PAINT placed the term on the SIRT5-subfamily node PTN000119399, which the horse full-length product inherits with an intact acyl pocket. No experimental study of SIRT5 in horse exists; this is an inference from the human and mouse orthologs. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000119399 SUPPORTS TRANSFER SIRT5-subfamily node (PTHR11085:SF10 clade) carrying the IBD; horse A0A9L0T9B1 is a full-length descendant with all acyl-pocket, catalytic, zinc and NAD+ residues conserved. UniProtKB:Q9NXA8 SUPPORTS TRANSFER Human SIRT5, experimental seed (IDA/EXP) of the node. MGI:MGI:1915596 SUPPORTS TRANSFER Mouse Sirt5, experimental seed of the node. Supporting Evidence: PMID:24703693 Using this assay, we found SIRT5 is the only HDAC exhibiting significant lysine deglutarylase activity in vitro file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. |
| GO:0070403 NAD+ binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: NAD+ is the co-substrate of the sirtuin deacylation reaction; the Rossmann-fold NAD+ binding motifs are conserved. Reason: SIRT5 deacylation strictly requires NAD+, which is cleaved to nicotinamide and acyl-ADP-ribose. NAD+ binding is a true property implied by the catalytic activity rather than a separate function; it is kept as non-core. The horse product conserves the NAD+ binding segments (GAGISAESGVPTFRGAGGYW, QNID, GTS). Supporting Evidence: PMID:24703693 NAD+ is required for SIRT5-dependent desuccinylation and demalonylation reactions file:HORSE/SIRT5__A0A9L0T9B1/SIRT5__A0A9L0T9B1-uniprot.txt Belongs to the sirtuin family. Class III subfamily. |
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Download this section (compressed HTML)Q: Is the 310-residue A0A9L0T9B1 product (ENSECAT00000146678) the main SIRT5 isoform expressed in horse tissues, given that the Ensembl canonical transcript encodes A0A9L0T6A9 with a divergent C-terminus lacking two NAD+-contacting segments?
Q: Does horse SIRT5 show the same preference for succinyl, malonyl and glutaryl over acetyl lysine as human SIRT5?
Experiment: Express recombinant horse SIRT5 (A0A9L0T9B1 mature form) and measure NAD+-dependent desuccinylation, demalonylation, deglutarylation and deacetylation of acyl-lysine peptides, with a Y102F/R105M mutant as control.
Type: in vitro enzyme assay
Experiment: Map transcript usage of ENSECAG00000026898 by long-read RNA-seq in horse liver and skeletal muscle to determine which C-terminal variant predominates.
Type: transcriptomics
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