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HAMAP rule MF_01121

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General rule information [?]

Accession MF_01121
Dates 28-OCT-2003 (Created)
3-SEP-2024 (Last updated, Version 39)
Name Sirtuin_ClassIII
Scope(s) Bacteria
Archaea
Template(s) O28597 (NPD1_ARCFU); Q9NXA8 (SIR5_HUMAN); [ Recover all ]
Triggered by
case c? <OC:Bacteria> or <OC:Archaea>
HAMAP; MF_01121 (Get profile general information and statistics)
end case

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier NPD
Protein name RecName: Full=NAD-dependent protein deacylase;
                 EC=2.3.1.286;
AltName: Full=Regulatory protein SIR2 homolog;
Gene name Name=cobB;

Comments [?]

case <OC:Enterobacterales> and <FTGroup:3>
FUNCTIONNAD-dependent lysine deacetylase that specifically removes acetyl groups on target proteins. Also acts as a protein-lysine deacylase by mediating protein desuccinylation and de-2- hydroxyisobutyrylation. Modulates the activities of several proteins which are inactive in their acylated form.
else case <OC:Bacteria> and <FTGroup:3> and not <OC:Enterobacterales>
FUNCTIONNAD-dependent lysine deacetylase and desuccinylase that specifically removes acetyl and succinyl groups on target proteins. Modulates the activities of several proteins which are inactive in their acylated form.
else case <OC:Archaea> and <FTGroup:3>
FUNCTIONNAD-dependent lysine deacetylase and desuccinylase that specifically removes acetyl and succinyl groups on target proteins. Modulates the activities of several proteins which are inactive in their acylated form. Deacetylates the N-terminal lysine residue of Alba, the major archaeal chromatin protein and that, in turn, increases Alba's DNA binding affinity, thereby repressing transcription.
else case <OC:Bacteria> and not <FTGroup:3>
FUNCTIONNAD-dependent protein deacetylase which modulates the activities of several proteins which are inactive in their acetylated form.
else case <OC:Archaea> and not <FTGroup:3>
FUNCTIONNAD-dependent protein deacetylase which modulates the activities of several proteins which are inactive in their acetylated form. Deacetylates the N-terminal lysine residue of Alba, the major archaeal chromatin protein and that, in turn, increases Alba's DNA binding affinity, thereby repressing transcription.
end case
CATALYTIC ACTIVITY Reaction=N(6)-acetyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-acetyl- ADP-D-ribose + nicotinamide + L-lysyl-[protein]; Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767; EC=2.3.1.286;
case <FTGroup:3>
CATALYTIC ACTIVITY Reaction=N(6)-succinyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O- succinyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]; 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;
end case
case <OC:Enterobacterales> and <FTGroup:3>
CATALYTIC ACTIVITY Reaction=N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-(2-hydroxyisobutanoyl)-ADP-D-ribose + nicotinamide + L-lysyl- [protein]; Xref=Rhea:RHEA:24364, Rhea:RHEA-COMP:9752, Rhea:RHEA- COMP:15921, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:144968, ChEBI:CHEBI:144969;
end case
case <FTGroup:1>
COFACTOR Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
end case
SUBCELLULAR LOCATIONCytoplasm.
case <FTGroup:3>
DOMAIN2 residues (#{Tyr-64} and #{Arg-67}) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity.
end case
SIMILARITYBelongs to the sirtuin family. Class III subfamily.

Keywords [?]

Cytoplasm
NAD
case <FTGroup:1>
Metal-binding
Zinc
end case
case <OC:Archaea>
Transcription
Transcription regulation
Transferase
end case

Gene Ontology [?]

GO:0005737; Cellular component:cytoplasm
GO:0034979; Molecular function:NAD-dependent protein lysine deacetylase activity
GO:0070403; Molecular function:NAD+ binding
GO:0006476; Biological process:protein deacetylation
case <FTGroup:3>
GO:0036055; Molecular function:protein-succinyllysine desuccinylase activity
GO:0036048; Biological process:protein desuccinylation
end case
case <FTGroup:1>
GO:0008270; Molecular function:zinc ion binding
end case

Cross-references [?]

PROSITE PS50305; SIRTUIN; 1;
Pfam PF02146; SIR2; 1;

Features [?]

From: NPD1_ARCFU (O28597)
Key From To Description Tag Condition FTGroup
BINDING 20 39 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"
G-A-G-x-S-[AK]-x-S-G-[ILV]-x-T-x(7,8)-W
BINDING 98 101 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"
Q-N-[IV]-[DE]
BINDING 185 187 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"
G-[TS]-S
BINDING 211 213 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"
N-x(2)
ACT_SITE 116 116 /note="Proton acceptor" H
BINDING 124 124 /ligand="Zn(2+)"
/ligand_id="ChEBI:CHEBI:29105"
C 1
BINDING 127 127 /ligand="Zn(2+)"
/ligand_id="ChEBI:CHEBI:29105"
C 2
BINDING 145 145 /ligand="Zn(2+)"
/ligand_id="ChEBI:CHEBI:29105"
C 1
BINDING 148 148 /ligand="Zn(2+)"
/ligand_id="ChEBI:CHEBI:29105"
C 2
BINDING 64 64 /ligand="substrate" Y 3
BINDING 67 67 /ligand="substrate" R 3
BINDING 229 229 /ligand="NAD(+)"
/ligand_id="ChEBI:CHEBI:57540"

Additional information [?]

Size range 208-262 amino acids
Related rules MF_01967
MF_01968
Fusion Nter: None Cter: None
Comments The gene name sir2 is used in a few prokaryotes. The gene is subject to alternative promoter usage in Salty, giving rise to 2 proteins with different N-termini. The longer protein is used in the seed alignment. Other Enterobacteriaceae probably do that too, maybe other bacteria as well.



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