ID A0A2R9AH39_PANPA Unreviewed; 310 AA.
AC A0A2R9AH39;
DT 20-JUN-2018, integrated into UniProtKB/TrEMBL.
DT 20-JUN-2018, sequence version 1.
DT 27-MAR-2024, entry version 25.
DE RecName: Full=NAD-dependent protein deacylase sirtuin-5, mitochondrial {ECO:0000256|HAMAP-Rule:MF_03160};
DE EC=2.3.1.- {ECO:0000256|HAMAP-Rule:MF_03160};
DE AltName: Full=Regulatory protein SIR2 homolog 5 {ECO:0000256|HAMAP-Rule:MF_03160};
DE AltName: Full=SIR2-like protein 5 {ECO:0000256|HAMAP-Rule:MF_03160};
GN Name=SIRT5 {ECO:0000256|HAMAP-Rule:MF_03160,
GN ECO:0000313|Ensembl:ENSPPAP00000014863.1};
OS Pan paniscus (Pygmy chimpanzee) (Bonobo).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9597 {ECO:0000313|Ensembl:ENSPPAP00000014863.1, ECO:0000313|Proteomes:UP000240080};
RN [1] {ECO:0000313|Ensembl:ENSPPAP00000014863.1, ECO:0000313|Proteomes:UP000240080}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=22722832; DOI=10.1038/nature11128;
RA Prufer K., Munch K., Hellmann I., Akagi K., Miller J.R., Walenz B.,
RA Koren S., Sutton G., Kodira C., Winer R., Knight J.R., Mullikin J.C.,
RA Meader S.J., Ponting C.P., Lunter G., Higashino S., Hobolth A., Dutheil J.,
RA Karakoc E., Alkan C., Sajjadian S., Catacchio C.R., Ventura M.,
RA Marques-Bonet T., Eichler E.E., Andre C., Atencia R., Mugisha L.,
RA Junhold J., Patterson N., Siebauer M., Good J.M., Fischer A., Ptak S.E.,
RA Lachmann M., Symer D.E., Mailund T., Schierup M.H., Andres A.M., Kelso J.,
RA Paabo S.;
RT "The bonobo genome compared with the chimpanzee and human genomes.";
RL Nature 486:527-531(2012).
RN [2] {ECO:0000313|Ensembl:ENSPPAP00000014863.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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. Modulates ketogenesis through the
CC desuccinylation and activation of HMGCS2. Has weak NAD-dependent
CC protein deacetylase activity; however this activity may not be
CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS)
CC and a number of other proteins in vitro such as Uox.
CC {ECO:0000256|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:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_03160};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_03160};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000256|HAMAP-Rule:MF_03160};
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with CPS1. {ECO:0000256|HAMAP-
CC Rule:MF_03160}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000256|HAMAP-Rule:MF_03160}.
CC Cytoplasm, cytosol {ECO:0000256|HAMAP-Rule:MF_03160}. Nucleus
CC {ECO:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_03160}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000256|HAMAP-Rule:MF_03160}.
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DR EMBL; AJFE02080843; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AJFE02080844; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_003823210.1; XM_003823162.2.
DR RefSeq; XP_008975005.1; XM_008976757.1.
DR RefSeq; XP_008975006.1; XM_008976758.2.
DR RefSeq; XP_008975007.1; XM_008976759.1.
DR RefSeq; XP_008975008.1; XM_008976760.2.
DR AlphaFoldDB; A0A2R9AH39; -.
DR STRING; 9597.ENSPPAP00000014863; -.
DR Ensembl; ENSPPAT00000037551.1; ENSPPAP00000014863.1; ENSPPAG00000030597.1.
DR GeneID; 100985261; -.
DR KEGG; pps:100985261; -.
DR CTD; 23408; -.
DR GeneTree; ENSGT00940000156080; -.
DR OMA; LIHMHGE; -.
DR OrthoDB; 167219at2759; -.
DR Proteomes; UP000240080; Chromosome 6.
DR Bgee; ENSPPAG00000030597; Expressed in heart and 6 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:Ensembl.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0070403; F:NAD+ binding; IEA:UniProtKB-UniRule.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0061697; F:protein-glutaryllysine deglutarylase activity; IEA:Ensembl.
DR GO; GO:0036054; F:protein-malonyllysine demalonylase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0036055; F:protein-succinyllysine desuccinylase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR CDD; cd01412; SIRT5_Af1_CobB; 1.
DR Gene3D; 3.30.1600.10; SIR2/SIRT2 'Small Domain; 1.
DR Gene3D; 3.40.50.1220; TPP-binding domain; 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 PANTHER; PTHR11085:SF12; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL; 1.
DR PANTHER; PTHR11085; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL-RELATED; 1.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 3: Inferred from homology;
KW Cytoplasm {ECO:0000256|HAMAP-Rule:MF_03160};
KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_03160, ECO:0000256|PROSITE-
KW ProRule:PRU00236}; Mitochondrion {ECO:0000256|HAMAP-Rule:MF_03160};
KW NAD {ECO:0000256|ARBA:ARBA00023027, ECO:0000256|HAMAP-Rule:MF_03160};
KW Nucleus {ECO:0000256|HAMAP-Rule:MF_03160};
KW Reference proteome {ECO:0000313|Proteomes:UP000240080};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|HAMAP-
KW Rule:MF_03160}; Transit peptide {ECO:0000256|HAMAP-Rule:MF_03160};
KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|HAMAP-Rule:MF_03160}.
FT DOMAIN 33..307
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000259|PROSITE:PS50305"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160,
FT ECO:0000256|PROSITE-ProRule:PRU00236"
FT BINDING 58..77
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 102
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 140..143
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160,
FT ECO:0000256|PROSITE-ProRule:PRU00236"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160,
FT ECO:0000256|PROSITE-ProRule:PRU00236"
FT BINDING 207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160,
FT ECO:0000256|PROSITE-ProRule:PRU00236"
FT BINDING 212
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160,
FT ECO:0000256|PROSITE-ProRule:PRU00236"
FT BINDING 249..251
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 275..277
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 293
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
SQ SEQUENCE 310 AA; 33883 MW; 3FE31B374C9298FF CRC64;
MRPLQIVPGR LISQLYCGLK PPASTRNQIC PKMARPSSSM ADFRKFFAKA KHIVIISGAG
VSAESGVPTF RGAGGYWRKW QAQDLATPLA FAHNPSRVWE FYHYRREVMG SKEPNAGHRA
IAECETRLGK QGRRVVVITQ NIDELHRKAG TKNLLEIHGS LFKTRCTSCG VVAENYKSPI
CPALSGKGAP EPGTQDASIP IEKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDRELA
HCDLCLVVGT SSVVYPAAMF APQVAARGVP VAEFNTETTP ATNRFRFHFQ GPCGTTLPEA
LAHHENETVS
//
