SIR5_BOVIN
ID SIR5_BOVIN Reviewed; 310 AA.
AC Q3ZBQ0; C6K7D6;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=NAD-dependent protein deacylase sirtuin-5, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03160};
DE EC=2.3.1.- {ECO:0000255|HAMAP-Rule:MF_03160};
DE AltName: Full=Regulatory protein SIR2 homolog 5 {ECO:0000255|HAMAP-Rule:MF_03160};
DE AltName: Full=SIR2-like protein 5 {ECO:0000255|HAMAP-Rule:MF_03160};
DE Flags: Precursor;
GN Name=SIRT5 {ECO:0000255|HAMAP-Rule:MF_03160};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RA Ghinis Y., Gonzalez-Davalos L., Antaramian A., Varela-Echavarria A.,
RA Shimada A., Gonzalez-Gallardo A., Hernandez-Sanabria E., Ramirez P.,
RA Mora O.;
RT "Study of the expression of bovine sirtuins in different tissues.";
RL Submitted (APR-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
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. Activates SHMT2 by mediating its
CC desuccinylation. Modulates ketogenesis through the desuccinylation and
CC activation of HMGCS2. Has weak NAD-dependent protein deacetylase
CC activity; however this activity may not be physiologically relevant in
CC vivo. Can deacetylate cytochrome c (CYCS) and a number of other
CC proteins in vitro such as UOX. {ECO:0000255|HAMAP-Rule:MF_03160}.
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 Evidence={ECO:0000255|HAMAP-Rule:MF_03160};
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 Evidence={ECO:0000255|HAMAP-Rule:MF_03160};
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;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03160};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03160};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03160};
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with CPS1. Interacts with PCCA
CC (By similarity). {ECO:0000250|UniProtKB:Q9NXA8, ECO:0000255|HAMAP-
CC Rule:MF_03160}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03160}.
CC Cytoplasm, cytosol {ECO:0000255|HAMAP-Rule:MF_03160}. Nucleus
CC {ECO:0000255|HAMAP-Rule:MF_03160}. Note=Mainly mitochondrial. Also
CC present extramitochondrially, with a fraction present in the cytosol
CC and very small amounts also detected in the nucleus.
CC {ECO:0000255|HAMAP-Rule:MF_03160}.
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 and
CC define the specificity. {ECO:0000255|HAMAP-Rule:MF_03160}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03160}.
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DR EMBL; GQ166651; ACS66701.1; -; mRNA.
DR EMBL; BC103176; AAI03177.1; -; mRNA.
DR RefSeq; NP_001029467.1; NM_001034295.2.
DR RefSeq; XP_005223802.1; XM_005223745.3.
DR RefSeq; XP_015315433.1; XM_015459947.1.
DR RefSeq; XP_015315434.1; XM_015459948.1.
DR RefSeq; XP_015315435.1; XM_015459949.1.
DR AlphaFoldDB; Q3ZBQ0; -.
DR SMR; Q3ZBQ0; -.
DR STRING; 9913.ENSBTAP00000019842; -.
DR PaxDb; Q3ZBQ0; -.
DR PeptideAtlas; Q3ZBQ0; -.
DR PRIDE; Q3ZBQ0; -.
DR Ensembl; ENSBTAT00000019842; ENSBTAP00000019842; ENSBTAG00000014904.
DR Ensembl; ENSBTAT00000072328; ENSBTAP00000069132; ENSBTAG00000014904.
DR Ensembl; ENSBTAT00000072664; ENSBTAP00000074135; ENSBTAG00000014904.
DR GeneID; 507347; -.
DR KEGG; bta:507347; -.
DR CTD; 23408; -.
DR VEuPathDB; HostDB:ENSBTAG00000014904; -.
DR VGNC; VGNC:34634; SIRT5.
DR eggNOG; KOG2684; Eukaryota.
DR GeneTree; ENSGT00940000156080; -.
DR HOGENOM; CLU_023643_3_1_1; -.
DR InParanoid; Q3ZBQ0; -.
DR OMA; SMQVYPA; -.
DR OrthoDB; 1459156at2759; -.
DR TreeFam; TF106183; -.
DR Reactome; R-BTA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Proteomes; UP000009136; Chromosome 23.
DR Bgee; ENSBTAG00000014904; Expressed in temporal cortex and 103 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0070403; F:NAD+ binding; ISS:UniProtKB.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0061697; F:protein-glutaryllysine deglutarylase activity; IBA:GO_Central.
DR GO; GO:0036054; F:protein-malonyllysine demalonylase activity; ISS:UniProtKB.
DR GO; GO:0036055; F:protein-succinyllysine desuccinylase activity; ISS:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0036047; P:peptidyl-lysine demalonylation; ISS:UniProtKB.
DR GO; GO:0036049; P:peptidyl-lysine desuccinylation; ISS:UniProtKB.
DR GO; GO:0006476; P:protein deacetylation; ISS:UniProtKB.
DR GO; GO:0061698; P:protein deglutarylation; IBA:GO_Central.
DR GO; GO:0036046; P:protein demalonylation; ISS:UniProtKB.
DR GO; GO:0036048; P:protein desuccinylation; ISS:UniProtKB.
DR GO; GO:0010566; P:regulation of ketone biosynthetic process; ISS:UniProtKB.
DR CDD; cd01412; SIRT5_Af1_CobB; 1.
DR Gene3D; 3.30.1600.10; -; 1.
DR HAMAP; MF_01121; Sirtuin_ClassIII; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR027546; Sirtuin_class_III.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Metal-binding; Mitochondrion; NAD; Nucleus; Reference proteome;
KW Transferase; Transit peptide; Zinc.
FT TRANSIT 1..36
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT CHAIN 37..310
FT /note="NAD-dependent protein deacylase sirtuin-5,
FT mitochondrial"
FT /id="PRO_0000260444"
FT DOMAIN 41..309
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 58..77
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 102
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 140..143
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 212
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 249..251
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 275..277
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 293
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT CONFLICT 14
FT /note="Q -> K (in Ref. 1; ACS66701)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 310 AA; 33988 MW; 96D614BFB5DA5325 CRC64;
MPPLWIIRNR LFSQLYCGLK SPVSTQTKIC LTMARPSSNM ADFRKCFAKA KHIVVISGAG
ISAESGVPTF RGAGGYWRKW KAQDLATPQA FARNPSQVWE FYHYRREVVQ STEPNAGHLA
IAECQARLHR QGRQVVVITQ NIDELHRKAG TKNLLEIHGS LFKTRCTSCG VVAENYKSPI
CPALSGKGAP DPQTQDAGIP VEKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDKELA
LCDLCLVVGT SSVVYPAAMF APQVSARGVP VAEFNMETTP ATERFRFHFQ GPCGTTLPEA
LAPHETETVS
