ID A0A3B5RA54_XIPMA Unreviewed; 304 AA.
AC A0A3B5RA54;
DT 05-DEC-2018, integrated into UniProtKB/TrEMBL.
DT 05-DEC-2018, sequence version 1.
DT 27-MAR-2024, entry version 24.
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 Xiphophorus maculatus (Southern platyfish) (Platypoecilus maculatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Ovalentaria; Atherinomorphae; Cyprinodontiformes; Poeciliidae; Poeciliinae;
OC Xiphophorus.
OX NCBI_TaxID=8083 {ECO:0000313|Ensembl:ENSXMAP00000040532.1, ECO:0000313|Proteomes:UP000002852};
RN [1] {ECO:0000313|Proteomes:UP000002852}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=JP 163 A {ECO:0000313|Proteomes:UP000002852};
RA Walter R., Schartl M., Warren W.;
RL Submitted (JAN-2012) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Proteomes:UP000002852}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=JP 163 A {ECO:0000313|Proteomes:UP000002852};
RX PubMed=23542700; DOI=10.1038/ng.2604;
RA Schartl M., Walter R.B., Shen Y., Garcia T., Catchen J., Amores A.,
RA Braasch I., Chalopin D., Volff J.N., Lesch K.P., Bisazza A., Minx P.,
RA Hillier L., Wilson R.K., Fuerstenberg S., Boore J., Searle S.,
RA Postlethwait J.H., Warren W.C.;
RT "The genome of the platyfish, Xiphophorus maculatus, provides insights into
RT evolutionary adaptation and several complex traits.";
RL Nat. Genet. 45:567-572(2013).
RN [3] {ECO:0000313|Ensembl:ENSXMAP00000040532.1}
RP IDENTIFICATION.
RC STRAIN=JP 163 A {ECO:0000313|Ensembl:ENSXMAP00000040532.1};
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. 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-97 and
CC Arg-100) 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 RefSeq; XP_014325465.1; XM_014469979.1.
DR AlphaFoldDB; A0A3B5RA54; -.
DR STRING; 8083.ENSXMAP00000040532; -.
DR Ensembl; ENSXMAT00000034934.1; ENSXMAP00000040532.1; ENSXMAG00000029946.1.
DR GeneID; 102226825; -.
DR KEGG; xma:102226825; -.
DR CTD; 23408; -.
DR GeneTree; ENSGT00940000156080; -.
DR InParanoid; A0A3B5RA54; -.
DR OMA; LIHMHGE; -.
DR OrthoDB; 167219at2759; -.
DR Proteomes; UP000002852; Unassembled WGS sequence.
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:0000035; F:acyl binding; IEA:Ensembl.
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:UP000002852};
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 28..302
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000259|PROSITE:PS50305"
FT ACT_SITE 153
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160,
FT ECO:0000256|PROSITE-ProRule:PRU00236"
FT BINDING 53..72
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 100
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 135..138
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 161
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 164
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 202
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 244..246
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 270..272
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
FT BINDING 288
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03160"
SQ SEQUENCE 304 AA; 33596 MW; 2F32CF514FD4C28A CRC64;
MIVHRFTCGV INTHLYAQLR KTWGIQAMAR PSSDLAAFRE IFSKSNNIAI ITGAGVSAES
GVPTFRGAGG YWRKWQAQEL ATPTAFAHNP SRVWEFYHYR REVMLTKNPN PAHQAIAECE
ERLGKQGRKV TIITQNIDEL HRRAGTKNLL EIHGSLFKTR CMMCGHEEAN YKSPICSALE
GRGAPDPDAN DAQIPVEELP RCEHRGCNGL LRPAVVWFGE TLDADILSDA EKVLDNCDLC
LIVGTSSVVY PAAMFAPQVA ARGVPVAEFN LENTPATERF KFHFHGSCGS TLPPALARHE
NEAN
//
