AC MF_03160; DC Protein; auto c? TR HAMAP; MF_01121; -; 1; level=0 XX Names: Sirtuin_ClassIII_euk XX ID SIR5 case DE RecName: Full=NAD-dependent protein deacylase sirtuin-5, mitochondrial; DE EC=2.3.1.-; DE AltName: Full=Regulatory protein SIR2 homolog 5; DE AltName: Full=SIR2-like protein 5; DE Flags: Precursor; GN Name=SIRT5; else DE RecName: Full=NAD-dependent protein deacylase; DE EC=2.3.1.-; DE AltName: Full=Regulatory protein SIR2 homolog 5; end case XX case and CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins. Activates CPS1 and contributes to the CC regulation of blood ammonia levels during prolonged fasting: acts by CC mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting. Activates SOD1 by mediating its desuccinylation, leading to CC reduced reactive oxygen species (By similarity). Modulates ketogenesis CC through the desuccinylation and activation of HMGCS2 (By similarity). CC Has weak NAD-dependent protein deacetylase activity; however this CC activity may not be physiologically relevant in vivo. Can deacetylate CC cytochrome c (CYCS) and a number of other proteins in vitro such as CC Uox. CC -!- SUBUNIT: Monomer. Homodimer. Interacts with CPS1. else case and not CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins. Has weak NAD-dependent protein deacetylase CC activity; however this activity may not be physiologically relevant in CC vivo. else CC -!- FUNCTION: NAD-dependent protein deacylase. Catalyzes the NAD-dependent CC hydrolysis of acyl groups from lysine residues. Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. end case case CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-malonyl-L-lysyl-[protein] + NAD(+) = 2''-O-malonyl- CC ADP-D-ribose + L-lysyl-[protein] + nicotinamide; CC Xref=Rhea:RHEA:47672, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11878, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:87831, ChEBI:CHEBI:87833; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-succinyl-L-lysyl-[protein] + NAD(+) = 2''-O- CC succinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; CC Xref=Rhea:RHEA:47668, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11877, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:87830, ChEBI:CHEBI:87832; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-glutaryl-L-lysyl-[protein] + NAD(+) = 2''-O- CC glutaryl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; CC Xref=Rhea:RHEA:47664, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11875, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:87828, ChEBI:CHEBI:87829; end case case CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Note=Binds 1 zinc ion per subunit.; end case case CC -!- SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm, cytosol. Nucleus. CC Note=Mainly mitochondrial. Also present extramitochondrially, with a CC fraction present in the cytosol and very small amounts also detected in CC the nucleus. else CC -!- SUBCELLULAR LOCATION: Mitochondrion. end case case CC -!- DOMAIN: In contrast to class I sirtuins, class III sirtuins have only CC weak deacetylase activity. Difference in substrate specificity is CC probably due to a larger hydrophobic pocket with 2 residues (#{Tyr-102} CC and #{Arg-105}) that bind to malonylated and succinylated substrates CC and define the specificity. end case case not and not CC -!- MISCELLANEOUS: This protein may be expected to contain an N-terminal CC transit peptide but none has been predicted. end case CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily. XX DR PROSITE; PS50305; SIRTUIN; 1; trigger=yes DR Pfam; PF02146; SIR2; 1; trigger=no case not DR General; TransitM; -; 0-1; trigger=yes end case XX KW Transferase KW Mitochondrion KW NAD case KW Metal-binding KW Zinc end case case KW Cytoplasm KW Nucleus KW Transit peptide end case XX GO GO:0005739; C:mitochondrion GO GO:0034979; F:NAD-dependent protein deacetylase activity GO GO:0070403; F:NAD+ binding GO GO:0036054; F:protein-malonyllysine demalonylase activity GO GO:0036055; F:protein-succinyllysine desuccinylase activity GO GO:0006476; P:protein deacetylation case GO GO:0008270; F:zinc ion binding end case XX FT From: SIR5_HUMAN (Q9NXA8) case FT TRANSIT Nter..36 FT /note="Mitochondrion" FT CHAIN 37..Cter FT /note="" end case FT BINDING 58..77 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT Condition: G-A-G-x-S-[AK]-x-S-G-[ILV]-x-T-x(7,8)-W FT BINDING 140..143 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT Condition: Q-N-[IV]-[DE] FT BINDING 249..251 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT Condition: G-[TS]-S FT BINDING 275..277 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT Optional; Condition: N-x(2) FT ACT_SITE 158 FT /note="Proton acceptor" FT Condition: H FT BINDING 166 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT Optional; Group: 1; Condition: C FT BINDING 169 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT Optional; Group: 2; Condition: C FT BINDING 207 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT Optional; Group: 1; Condition: C FT BINDING 212 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT Optional; Group: 2; Condition: C FT BINDING 102 FT /ligand="substrate" FT Optional; Group: 3; Condition: Y FT BINDING 105 FT /ligand="substrate" FT Optional; Group: 3; Condition: R FT BINDING 293 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" XX Size: 273-323; Related: None; Template: Q9NXA8; O28597; Q8IE47; Q8K2C6; Scope: Eukaryota Fusion: Nter: None Cter: None Duplicate: in XENLA Plasmid: None Comments: None XX # Revision 1.13 2022/11/19 //