AC   MF_03161;
DC   Protein; auto
c?   <OC:Eukaryota>
TR   HAMAP; MF_01967; -; 1; level=0
XX
Names: Sirtuin_ClassII_euk
XX
ID   SIR4
case <OC:Mammalia>
DE   RecName: Full=NAD-dependent protein lipoamidase sirtuin-4, mitochondrial;
DE            EC=2.3.1.-;
DE   AltName: Full=NAD-dependent ADP-ribosyltransferase sirtuin-4;
DE            EC=2.4.2.-;
DE   AltName: Full=NAD-dependent protein biotinylase sirtuin-4;
DE            EC=2.3.1.-;
DE   AltName: Full=NAD-dependent protein deacetylase sirtuin-4;
DE            EC=2.3.1.286;
DE   AltName: Full=Regulatory protein SIR2 homolog 4;
DE   AltName: Full=SIR2-like protein 4;
DE   Flags: Precursor;
GN   Name=SIRT4;
else
DE   RecName: Full=NAD-dependent protein deacylase;
DE            EC=2.3.1.-;
DE   AltName: Full=Regulatory protein SIR2 homolog;
end case
XX
case <OC:Mammalia>
CC   -!- FUNCTION: Acts as NAD-dependent protein lipoamidase, biotinylase,
CC       deacetylase and ADP-ribosyl transferase. Catalyzes more efficiently
CC       removal of lipoyl- and biotinyl- than acetyl-lysine modifications.
CC       Inhibits the pyruvate dehydrogenase complex (PDH) activity via the
CC       enzymatic hydrolysis of the lipoamide cofactor from the E2 component,
CC       DLAT, in a phosphorylation-independent manner. Catalyzes the transfer
CC       of ADP-ribosyl groups onto target proteins, including mitochondrial
CC       GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator
CC       of mitochondrial glutamine metabolism by mediating mono ADP-
CC       ribosylation of GLUD1: expressed in response to DNA damage and
CC       negatively regulates anaplerosis by inhibiting GLUD1, leading to block
CC       metabolism of glutamine into tricarboxylic acid cycle and promoting
CC       cell cycle arrest. In response to mTORC1 signal, SIRT4 expression is
CC       repressed, promoting anaplerosis and cell proliferation. Acts as a
CC       tumor suppressor. Also acts as a NAD-dependent protein deacetylase:
CC       mediates deacetylation of 'Lys-471' of MLYCD, inhibiting its activity,
CC       thereby acting as a regulator of lipid homeostasis. Does not seem to
CC       deacetylate PC. Controls fatty acid oxidation by inhibiting PPARA
CC       transcriptional activation. Impairs SIRT1-PPARA interaction probably
CC       through the regulation of NAD(+) levels. Down-regulates insulin
CC       secretion.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-cysteinyl-[protein] + NAD(+) = H(+) + nicotinamide + S-(ADP-
CC         D-ribosyl)-L-cysteinyl-[protein]; Xref=Rhea:RHEA:56612, Rhea:RHEA-
CC         COMP:10131, Rhea:RHEA-COMP:14624, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17154, ChEBI:CHEBI:29950, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:140607;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N(6)-[(R)-lipoyl]-L-lysyl-[protein] + NAD(+) = 2''-O-
CC         lipoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC         Xref=Rhea:RHEA:63640, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10474,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:83099, ChEBI:CHEBI:189572;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N(6)-biotinyl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC         biotinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC         Xref=Rhea:RHEA:70479, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10505,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:83144, ChEBI:CHEBI:189573;
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70480;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
CC         ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC         Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
CC         EC=2.3.1.286;
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43637;
CC   -!- SUBUNIT: Interacts with GLUD1, IDE and SLC25A5. Interacts with DLAT and
CC       PDHX.
CC   -!- MISCELLANEOUS: According to some authors, ADP-ribosyltransferase
CC       activity of sirtuins may be an inefficient side reaction of the
CC       deacetylase activity and may not be physiologically relevant.
else
CC   -!- FUNCTION: NAD-dependent protein deacylase. Catalyzes the NAD-dependent
CC       hydrolysis of acyl groups from lysine residues.
end case
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
CC         ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC         Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
CC         EC=2.3.1.286;
case <FTGroup:1>
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 1 zinc ion per subunit.;
end case
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
case not <OC:Mammalia> and not <AnyFeature:TransitM>
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 II subfamily.
XX
DR   PROSITE; PS50305; SIRTUIN; 1; trigger=yes
DR   Pfam; PF02146; SIR2; 1; trigger=no
case not <OC:Mammalia>
DR   General; TransitM; -; 0-1; trigger=yes
end case
XX
case <OC:Mammalia>
KW   Transit peptide
end case
KW   Metal-binding
KW   Mitochondrion
KW   NAD
case <FTGroup:1>
KW   Metal-binding
KW   Zinc
end case
KW   Transferase
XX
GO   GO:0005759; C:mitochondrial matrix
GO   GO:0034979; F:NAD-dependent protein deacetylase activity
case <OC:Mammalia>
GO   GO:0003950; F:NAD+ ADP-ribosyltransferase activity
end case
GO   GO:0070403; F:NAD+ binding
GO   GO:0006476; P:protein deacetylation
case <FTGroup:1>
GO   GO:0008270; F:zinc ion binding
end case
XX
FT   From: SIR4_HUMAN (Q9Y6E7)
case <OC:Mammalia>
FT   TRANSIT         Nter..28
FT                   /note="Mitochondrion"
FT   CHAIN           29..Cter
FT                   /note="<name>"
end case
FT   BINDING         62..82
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT   Condition: G-A-G-x-S-T-x-x-G-[IV]-P-D-Y-R-x(7)
FT   BINDING         143..146
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT   Condition: Q-N-V-D
FT   BINDING         260..262
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT   Condition: G-[ST]-S
FT   BINDING         286..288
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT   Condition: N-x-G
FT   ACT_SITE        161
FT                   /note="Proton acceptor"
FT   Condition: H
FT   BINDING         169
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   Group: 1; Condition: C
FT   BINDING         172
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   Group: 1; Condition: C
FT   BINDING         220
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   Group: 1; Condition: C
FT   BINDING         223
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   Group: 1; Condition: C
FT   BINDING         304
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
XX
Size: 273-373;
Related: None;
Template: Q9Y6E7;
Scope:
 Eukaryota
Fusion:
 Nter: None
 Cter: None
Duplicate: in CAEEL
Plasmid: None
Comments: None
XX
# Revision 1.18 2023/09/14
//