ID G3RTP8_GORGO Unreviewed; 280 AA.
AC G3RTP8;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 28-FEB-2018, sequence version 2.
DT 27-MAR-2024, entry version 65.
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};
OS Gorilla gorilla gorilla (Western lowland gorilla).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Gorilla.
OX NCBI_TaxID=9595 {ECO:0000313|Ensembl:ENSGGOP00000019174.2, ECO:0000313|Proteomes:UP000001519};
RN [1] {ECO:0000313|Ensembl:ENSGGOP00000019174.2, ECO:0000313|Proteomes:UP000001519}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Scally A.;
RT "Insights into the evolution of the great apes provided by the gorilla
RT genome.";
RL Submitted (MAY-2011) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSGGOP00000019174.2, ECO:0000313|Proteomes:UP000001519}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=22398555; DOI=10.1038/nature10842;
RA Scally A., Dutheil J.Y., Hillier L.W., Jordan G.E., Goodhead I.,
RA Herrero J., Hobolth A., Lappalainen T., Mailund T., Marques-Bonet T.,
RA McCarthy S., Montgomery S.H., Schwalie P.C., Tang Y.A., Ward M.C., Xue Y.,
RA Yngvadottir B., Alkan C., Andersen L.N., Ayub Q., Ball E.V., Beal K.,
RA Bradley B.J., Chen Y., Clee C.M., Fitzgerald S., Graves T.A., Gu Y.,
RA Heath P., Heger A., Karakoc E., Kolb-Kokocinski A., Laird G.K., Lunter G.,
RA Meader S., Mort M., Mullikin J.C., Munch K., O'Connor T.D., Phillips A.D.,
RA Prado-Martinez J., Rogers A.S., Sajjadian S., Schmidt D., Shaw K.,
RA Simpson J.T., Stenson P.D., Turner D.J., Vigilant L., Vilella A.J.,
RA Whitener W., Zhu B., Cooper D.N., de Jong P., Dermitzakis E.T.,
RA Eichler E.E., Flicek P., Goldman N., Mundy N.I., Ning Z., Odom D.T.,
RA Ponting C.P., Quail M.A., Ryder O.A., Searle S.M., Warren W.C.,
RA Wilson R.K., Schierup M.H., Rogers J., Tyler-Smith C., Durbin R.;
RT "Insights into hominid evolution from the gorilla genome sequence.";
RL Nature 483:169-175(2012).
RN [3] {ECO:0000313|Ensembl:ENSGGOP00000019174.2}
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 -!- 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}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_03160,
CC ECO:0000256|PROSITE-ProRule:PRU00236}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CABD030043369; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABD030043370; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; G3RTP8; -.
DR STRING; 9593.ENSGGOP00000019174; -.
DR Ensembl; ENSGGOT00000022945.2; ENSGGOP00000019174.2; ENSGGOG00000025115.2.
DR GeneTree; ENSGT00940000156080; -.
DR HOGENOM; CLU_023643_3_1_1; -.
DR InParanoid; G3RTP8; -.
DR OMA; LIHMHGE; -.
DR Proteomes; UP000001519; Chromosome 6.
DR Bgee; ENSGGOG00000025115; 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; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0036054; F:protein-malonyllysine demalonylase activity; IBA:GO_Central.
DR GO; GO:0036055; F:protein-succinyllysine desuccinylase activity; IBA:GO_Central.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
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 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:UP000001519};
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}.
FT DOMAIN 33..277
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 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 219..221
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 245..247
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 263
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
SQ SEQUENCE 280 AA; 30792 MW; 47ACC7E34BF4C3BD CRC64;
MRPLQIVPSR LISQLYCGLK PPASTRNQIC LKMARPSSSM ADFRKFFAKA KHIVIISGAG
VSAESGVPTF RGAGGYWRKW QAQDLATPLA FAHNPSRVWE FYHYRREVMG SKEPNAGHRA
IAECETRLGK QGRRVVVITQ NIDELHRKAG TKNLLEIHAP EPGTQDASIP IEKLPRCEEA
GCGGLLRPHV VWFGENLDPA ILEEVDRELA HCDLCLVVGT SSVVYPAAMF APQVAARGVP
VAEFNTETTP ATNRFRFHFQ GPCGTTLPEA LAGHENETVS
//
