ID A0A3P8UTB6_CYNSE Unreviewed; 305 AA.
AC A0A3P8UTB6;
DT 13-FEB-2019, integrated into UniProtKB/TrEMBL.
DT 13-FEB-2019, sequence version 1.
DT 27-MAR-2024, entry version 22.
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 Cynoglossus semilaevis (Tongue sole).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Carangaria; Pleuronectiformes; Pleuronectoidei; Cynoglossidae;
OC Cynoglossinae; Cynoglossus.
OX NCBI_TaxID=244447 {ECO:0000313|Ensembl:ENSCSEP00000003490.1, ECO:0000313|Proteomes:UP000265120};
RN [1] {ECO:0000313|Ensembl:ENSCSEP00000003490.1, ECO:0000313|Proteomes:UP000265120}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=24487278;
RA Chen S., Zhang G., Shao C., Huang Q., Liu G., Zhang P., Song W., An N.,
RA Chalopin D., Volff J.N., Hong Y., Li Q., Sha Z., Zhou H., Xie M., Yu Q.,
RA Liu Y., Xiang H., Wang N., Wu K., Yang C., Zhou Q., Liao X., Yang L.,
RA Hu Q., Zhang J., Meng L., Jin L., Tian Y., Lian J., Yang J., Miao G.,
RA Liu S., Liang Z., Yan F., Li Y., Sun B., Zhang H., Zhang J., Zhu Y., Du M.,
RA Zhao Y., Schartl M., Tang Q., Wang J.;
RT "Whole-genome sequence of a flatfish provides insights into ZW sex
RT chromosome evolution and adaptation to a benthic lifestyle.";
RL Nat. Genet. 46:253-260(2014).
RN [2] {ECO:0000313|Ensembl:ENSCSEP00000003490.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-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. Has weak NAD-dependent protein deacetylase
CC activity; however this activity may not be physiologically relevant in
CC vivo. {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 -!- 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-98 and
CC Arg-101) 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 ---------------------------------------------------------------------------
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 AlphaFoldDB; A0A3P8UTB6; -.
DR Ensembl; ENSCSET00000003535.1; ENSCSEP00000003490.1; ENSCSEG00000002284.1.
DR GeneTree; ENSGT00940000156080; -.
DR OMA; LIHMHGE; -.
DR Proteomes; UP000265120; Chromosome 2.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
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:RHEA.
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 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:UP000265120};
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|HAMAP-Rule:MF_03160, ECO:0000256|PROSITE-
KW ProRule:PRU00236}.
FT DOMAIN 29..305
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000259|PROSITE:PS50305"
FT ACT_SITE 154
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160,
FT ECO:0000256|PROSITE-ProRule:PRU00236"
FT BINDING 54..73
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 136..139
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 162
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 165
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 203
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 208
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 245..247
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 271..273
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 289
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
SQ SEQUENCE 305 AA; 33396 MW; AE4E0E2BFF60ED12 CRC64;
MVPDTGRHFA LYFDTSSAVC GEPVVELQSS NSALNLAAFR EIFSKAKNVA ILTGAGVSAE
SGVPTFRGAG GFWRKWQAQE LATPEAFSRN PSRVWEFYHY RREVMLTKNP NPAHLAIAEC
EERLRQQGRE VTVVTQNIDE LHRRAGSKNI LEIHGSLFKT RCMTCGHEAA NYNSPICAAL
AGKGAPDPDT HDAQIPVEQL PRCEQAGCHG LLRPAVVWFG ETLDADVLTH AERVLDRCDL
CLVVGTSSVV YPAAMFAPQV AARGVPVAEF NMEDTPATMS FRFHFHGPCG TTLPPALVRH
DTEPL
//
