SIR5_DANRE
ID SIR5_DANRE Reviewed; 305 AA.
AC Q6DHI5;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 124.
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 Flags: Precursor;
GN Name=sirt5; ORFNames=si:ch211-121a2.1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
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: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 -!- 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-98 and
CC Arg-101) 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; BX511260; CAP09604.1; -; Genomic_DNA.
DR EMBL; BC075987; AAH75987.1; -; mRNA.
DR RefSeq; NP_001002605.1; NM_001002605.1.
DR PDB; 4UTN; X-ray; 3.00 A; A/B=30-298.
DR PDB; 4UTR; X-ray; 2.90 A; A/B=30-298.
DR PDB; 4UTV; X-ray; 2.40 A; A/B=30-298.
DR PDB; 4UTX; X-ray; 3.10 A; A/B=30-298.
DR PDB; 4UTZ; X-ray; 3.30 A; A/B=30-298.
DR PDB; 4UU7; X-ray; 3.00 A; A/B=30-298.
DR PDB; 4UU8; X-ray; 2.90 A; A/B=30-298.
DR PDB; 4UUA; X-ray; 2.80 A; A/B=30-298.
DR PDB; 4UUB; X-ray; 2.90 A; A/B=30-298.
DR PDB; 5OJO; X-ray; 3.10 A; A/B=30-298.
DR PDB; 6ENX; X-ray; 1.95 A; A=28-298.
DR PDB; 6EO0; X-ray; 2.40 A; A/B/C/D=28-298.
DR PDB; 6FKY; X-ray; 2.98 A; A/B=28-305.
DR PDB; 6FKZ; X-ray; 3.30 A; A/B=28-305.
DR PDB; 6FLG; X-ray; 2.50 A; A/B=28-305.
DR PDBsum; 4UTN; -.
DR PDBsum; 4UTR; -.
DR PDBsum; 4UTV; -.
DR PDBsum; 4UTX; -.
DR PDBsum; 4UTZ; -.
DR PDBsum; 4UU7; -.
DR PDBsum; 4UU8; -.
DR PDBsum; 4UUA; -.
DR PDBsum; 4UUB; -.
DR PDBsum; 5OJO; -.
DR PDBsum; 6ENX; -.
DR PDBsum; 6EO0; -.
DR PDBsum; 6FKY; -.
DR PDBsum; 6FKZ; -.
DR PDBsum; 6FLG; -.
DR AlphaFoldDB; Q6DHI5; -.
DR SMR; Q6DHI5; -.
DR STRING; 7955.ENSDARP00000104727; -.
DR PaxDb; Q6DHI5; -.
DR Ensembl; ENSDART00000040793; ENSDARP00000040792; ENSDARG00000039684.
DR GeneID; 436878; -.
DR KEGG; dre:436878; -.
DR CTD; 23408; -.
DR ZFIN; ZDB-GENE-040718-349; sirt5.
DR eggNOG; KOG2684; Eukaryota.
DR GeneTree; ENSGT00940000156080; -.
DR HOGENOM; CLU_023643_3_1_1; -.
DR InParanoid; Q6DHI5; -.
DR OMA; SMQVYPA; -.
DR OrthoDB; 1459156at2759; -.
DR PhylomeDB; Q6DHI5; -.
DR TreeFam; TF106183; -.
DR BRENDA; 2.3.1.B43; 928.
DR Reactome; R-DRE-2151201; Transcriptional activation of mitochondrial biogenesis.
DR PRO; PR:Q6DHI5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 20.
DR Bgee; ENSDARG00000039684; Expressed in muscle tissue and 21 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000035; F:acyl binding; IDA:ZFIN.
DR GO; GO:1901363; F:heterocyclic compound binding; IDA:ZFIN.
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; IBA:GO_Central.
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:0036047; P:peptidyl-lysine demalonylation; ISS:UniProtKB.
DR GO; GO:0036049; P:peptidyl-lysine desuccinylation; ISS:UniProtKB.
DR GO; GO:0061698; P:protein deglutarylation; IBA:GO_Central.
DR GO; GO:0036048; P:protein desuccinylation; ISS:UniProtKB.
DR GO; GO:0010566; P:regulation of ketone biosynthetic process; ISS:UniProtKB.
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 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Metal-binding; Mitochondrion; NAD; Nucleus;
KW Reference proteome; Transferase; Transit peptide; Zinc.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT CHAIN 33..305
FT /note="NAD-dependent protein deacylase sirtuin-5,
FT mitochondrial"
FT /id="PRO_0000415573"
FT DOMAIN 37..305
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT ACT_SITE 154
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 54..73
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 136..139
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 162
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 208
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 245..247
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 271..273
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 289
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT HELIX 36..45
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 47..53
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:6EO0"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 84..89
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 91..105
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 112..126
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 130..135
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 155..162
FT /evidence="ECO:0007829|PDB:6ENX"
FT TURN 163..165
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:6ENX"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 225..237
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 239..245
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:6FLG"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 256..261
FT /evidence="ECO:0007829|PDB:6ENX"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 267..273
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:6ENX"
FT STRAND 281..287
FT /evidence="ECO:0007829|PDB:6ENX"
FT HELIX 289..296
FT /evidence="ECO:0007829|PDB:6ENX"
SQ SEQUENCE 305 AA; 33929 MW; DF76E09F9396B8F4 CRC64;
MIVRQLWCSR GSTSHLCAAV RLNWRSPKMT RPSSDLTAFR EHFAKAKHIA IITGAGVSAE
SGVPTFRGPG GFWRKWQAQD LATPEAFSRD PSLVWEFYHY RREVMRSKMP NPAHLAIAEC
EARLGQQGRS VVIITQNIDE LHHRAGSKHV YEIHGSLFKT RCMSCGEVKA NHKSPICPAL
DGKGAPDPNT KEARIPVELL PRCERKSCNG LLRPHVVWFG ETLDSDILTA VERELEKCDL
CLVVGTSSIV YPAAMFAPQV ASRGVPVAEF NMECTPATQR FKYHFEGPCG STLPPALERH
ESEAV
