SIR5_CHICK
ID SIR5_CHICK Reviewed; 309 AA.
AC E1BRE2;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 70.
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 {ECO:0000255|HAMAP-Rule:MF_03160};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
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-101
CC and Arg-104) 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; AADN02027504; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001263293.1; NM_001276364.1.
DR RefSeq; XP_015131358.1; XM_015275872.1.
DR RefSeq; XP_015131359.1; XM_015275873.1.
DR AlphaFoldDB; E1BRE2; -.
DR SMR; E1BRE2; -.
DR STRING; 9031.ENSGALP00000020691; -.
DR PaxDb; E1BRE2; -.
DR Ensembl; ENSGALT00000020720; ENSGALP00000020691; ENSGALG00000012692.
DR GeneID; 420834; -.
DR KEGG; gga:420834; -.
DR CTD; 23408; -.
DR VEuPathDB; HostDB:geneid_420834; -.
DR eggNOG; KOG2684; Eukaryota.
DR GeneTree; ENSGT00940000156080; -.
DR HOGENOM; CLU_023643_3_1_1; -.
DR InParanoid; E1BRE2; -.
DR OMA; SMQVYPA; -.
DR OrthoDB; 1459156at2759; -.
DR PhylomeDB; E1BRE2; -.
DR TreeFam; TF106183; -.
DR PRO; PR:E1BRE2; -.
DR Proteomes; UP000000539; Chromosome 2.
DR Bgee; ENSGALG00000012692; Expressed in heart and 13 other tissues.
DR ExpressionAtlas; E1BRE2; baseline and differential.
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: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 3: Inferred from homology;
KW Cytoplasm; Metal-binding; Mitochondrion; NAD; Nucleus; Reference proteome;
KW Transferase; Transit peptide; Zinc.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT CHAIN 36..309
FT /note="NAD-dependent protein deacylase sirtuin-5,
FT mitochondrial"
FT /id="PRO_0000415572"
FT DOMAIN 40..308
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT ACT_SITE 157
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 57..76
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 104
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 139..142
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
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 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 206
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 248..250
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 274..276
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 292
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
SQ SEQUENCE 309 AA; 33956 MW; C05067AD756E33E9 CRC64;
MCLAQCAARR LLAQVHGALK PAPKKPNWCW EMARPSSNMA DFREVFAKAK HIAIITGAGV
SAESGVPTFR GAGGFWRKWQ AQELATPGAF ARNPSRVWEF YHYRREVMLS KHPNAAHIAI
AECEKRLRKQ GRSVVVITQN IDELHRKAGT KHLLEIHGSL FKTRCTNCGN VTANYKSPIC
PALAGKGAPD PEIEDAAIPV EELPQCEEDG CHGLLRPHVV WFGETLDPDV LTEVEKELDL
CDLCLVVGTS SVVYPAAMFA PQVSARGVPV AEFNMEATPA TDRFRFHFEG PCGTTLPPAL
ARHESEIIA
