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HAMAP rule MF_03160

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General rule information [?]

Accession MF_03160
Dates 2-APR-2012 (Created)
25-APR-2024 (Last updated, Version 14)
Name Sirtuin_ClassIII_euk
Scope(s) Eukaryota
Template(s) Q9NXA8 (SIR5_HUMAN); O28597 (NPD1_ARCFU); Q8IE47 (SIR2A_PLAF7); Q8K2C6 (SIR5_MOUSE); [ Recover all ]
Triggered by
case c? <OC:Eukaryota>
HAMAP; MF_01121 (Get profile general information and statistics)
end case

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier SIR5
case <OC:Vertebrata>
Protein name RecName: Full=NAD-dependent protein deacylase sirtuin-5, mitochondrial;
                 EC=2.3.1.-;
AltName: Full=Regulatory protein SIR2 homolog 5;
AltName: Full=SIR2-like protein 5;
                 Flags: Precursor;
Gene name Name=SIRT5;
else
Protein name RecName: Full=NAD-dependent protein deacylase;
                 EC=2.3.1.-;
AltName: Full=Regulatory protein SIR2 homolog 5;
end case

Comments [?]

case <FTGroup:3> and <OC:Mammalia>
FUNCTIONNAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (By similarity). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as Uox.
SUBUNITMonomer. Homodimer. Interacts with CPS1.
else case <FTGroup:3> and not <OC:Mammalia>
FUNCTIONNAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo.
else
FUNCTIONNAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of acyl groups from lysine residues. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo.
end case
case <FTGroup:3>
CATALYTIC ACTIVITY Reaction=H2O + N(6)-malonyl-L-lysyl-[protein] + NAD(+) = 2''-O-malonyl- ADP-D-ribose + L-lysyl-[protein] + nicotinamide; Xref=Rhea:RHEA:47672, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11878, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:87831, ChEBI:CHEBI:87833;
CATALYTIC ACTIVITY Reaction=H2O + N(6)-succinyl-L-lysyl-[protein] + NAD(+) = 2''-O- succinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; Xref=Rhea:RHEA:47668, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11877, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:87830, ChEBI:CHEBI:87832;
CATALYTIC ACTIVITY Reaction=H2O + N(6)-glutaryl-L-lysyl-[protein] + NAD(+) = 2''-O- glutaryl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; Xref=Rhea:RHEA:47664, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11875, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:87828, ChEBI:CHEBI:87829;
end case
case <FTGroup:1>
COFACTOR Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
end case
case <OC:Vertebrata>
SUBCELLULAR LOCATIONMitochondrion. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus.
else
SUBCELLULAR LOCATIONMitochondrion.
end case
case <FTGroup:3>
DOMAINIn contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (#{Tyr-102} and #{Arg-105}) that bind to malonylated and succinylated substrates and define the specificity.
end case
case not <OC:Vertebrata> and not <AnyFeature:TransitM>
MISCELLANEOUSThis protein may be expected to contain an N-terminal transit peptide but none has been predicted.
end case
SIMILARITYBelongs to the sirtuin family. Class III subfamily.

Keywords [?]

Transferase
Mitochondrion
NAD
case <FTGroup:1>
Metal-binding
Zinc
end case
case <OC:Vertebrata>
Cytoplasm
Nucleus
Transit peptide
end case

Gene Ontology [?]

GO:0005739; Cellular component:mitochondrion
GO:0034979; Molecular function:NAD-dependent protein lysine deacetylase activity
GO:0070403; Molecular function:NAD+ binding
GO:0036054; Molecular function:protein-malonyllysine demalonylase activity
GO:0036055; Molecular function:protein-succinyllysine desuccinylase activity
GO:0006476; Biological process:protein deacetylation
case <FTGroup:1>
GO:0008270; Molecular function:zinc ion binding
end case

Cross-references [?]

PROSITE PS50305; SIRTUIN; 1;
Pfam PF02146; SIR2; 1;
General TransitM; -; 0-1;

Features [?]

From: SIR5_HUMAN (Q9NXA8)
Key From To Description Tag Condition FTGroup
case <OC:Vertebrata>
TRANSIT Nter 36 /note="Mitochondrion"
CHAIN 37 Cter /note=""
end case
BINDING 58 77 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"		 G-A-G-x-S-[AK]-x-S-G-[ILV]-x-T-x(7,8)-W
BINDING 140 143 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"		 Q-N-[IV]-[DE]
BINDING 249 251 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"		 G-[TS]-S
BINDING 275 277 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"		 N-x(2)
ACT_SITE 158 158 /note="Proton acceptor" H
BINDING 166 166 /ligand="Zn(2+)"
/ligand_id="ChEBI:CHEBI:29105"		 C 1
BINDING 169 169 /ligand="Zn(2+)"
/ligand_id="ChEBI:CHEBI:29105"		 C 2
BINDING 207 207 /ligand="Zn(2+)"
/ligand_id="ChEBI:CHEBI:29105"		 C 1
BINDING 212 212 /ligand="Zn(2+)"
/ligand_id="ChEBI:CHEBI:29105"		 C 2
BINDING 102 102 /ligand="substrate" Y 3
BINDING 105 105 /ligand="substrate" R 3
BINDING 293 293 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"

Additional information [?]

Size range 273-323 amino acids
Related rules None
Fusion Nter: None Cter: None



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