SIR5_RAT
ID SIR5_RAT Reviewed; 310 AA.
AC Q68FX9;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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:Q8K2C6,
CC ECO:0000250|UniProtKB:Q9NXA8, ECO:0000255|HAMAP-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; BC078958; AAH78958.1; -; mRNA.
DR RefSeq; NP_001004256.1; NM_001004256.1.
DR RefSeq; XP_006253863.1; XM_006253801.1.
DR RefSeq; XP_006253864.1; XM_006253802.2.
DR RefSeq; XP_006253865.1; XM_006253803.3.
DR RefSeq; XP_006253866.1; XM_006253804.3.
DR RefSeq; XP_017456010.1; XM_017600521.1.
DR AlphaFoldDB; Q68FX9; -.
DR SMR; Q68FX9; -.
DR STRING; 10116.ENSRNOP00000024067; -.
DR iPTMnet; Q68FX9; -.
DR PhosphoSitePlus; Q68FX9; -.
DR jPOST; Q68FX9; -.
DR PaxDb; Q68FX9; -.
DR PRIDE; Q68FX9; -.
DR Ensembl; ENSRNOT00000024066; ENSRNOP00000024067; ENSRNOG00000017866.
DR GeneID; 306840; -.
DR KEGG; rno:306840; -.
DR CTD; 23408; -.
DR RGD; 1303285; Sirt5.
DR eggNOG; KOG2684; Eukaryota.
DR GeneTree; ENSGT00940000156080; -.
DR HOGENOM; CLU_023643_3_1_1; -.
DR InParanoid; Q68FX9; -.
DR OMA; SMQVYPA; -.
DR OrthoDB; 1459156at2759; -.
DR PhylomeDB; Q68FX9; -.
DR TreeFam; TF106183; -.
DR BRENDA; 2.3.1.B43; 5301.
DR Reactome; R-RNO-2151201; Transcriptional activation of mitochondrial biogenesis.
DR PRO; PR:Q68FX9; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000017866; Expressed in heart and 20 other tissues.
DR Genevisible; Q68FX9; RN.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:RGD.
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; ISO:RGD.
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:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:RGD.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISO:RGD.
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; ISO:RGD.
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 GO; GO:1904229; P:regulation of succinate dehydrogenase activity; ISO:RGD.
DR GO; GO:0002931; P:response to ischemia; ISO:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
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_0000260445"
FT DOMAIN 41..310
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"
SQ SEQUENCE 310 AA; 34098 MW; 3AF68B4A66441D4D CRC64;
MRPLPVAPGR LFSQLCCGPK PSASPQSKIC LTMARPSSNM ADFRKCFANA KHIVIISGAG
VSAESGVPTF RGTGGYWRKW QAQHLATPLA FAHNPSQVWE FYHYRREVMR NKEPNPGHLA
IAQCEARLRD QGRRVVVITQ NIDELHRKAG TKNLLEIHGT LFKTRCTSCG NVAENYKSPI
CPALLGKGAP EPDTQESRIP VHKLPRCEEA GCGGLLRPHV VWFGENLDPA ILKEVDRELA
RCDLCLVVGT SSVVYPAAMF APQVASRGVP VAEFNMETTP ATNRFRFHFP GPCGVTLPEA
LAPHETERIS
