SIR3_MOUSE
ID SIR3_MOUSE Reviewed; 334 AA.
AC Q8R104; B9W0A9; C6ZII7; Q9EPA8;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-3;
DE EC=2.3.1.286 {ECO:0000269|PubMed:21858060, ECO:0000269|PubMed:26620563, ECO:0000305|PubMed:17923681, ECO:0000305|PubMed:18794531, ECO:0000305|PubMed:21172655, ECO:0000305|PubMed:23835326};
DE AltName: Full=Regulatory protein SIR2 homolog 3;
DE AltName: Full=SIR2-like protein 3;
DE Short=mSIR2L3;
DE Flags: Precursor;
GN Name=Sirt3; Synonyms=Sir2l3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM S), SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC STRAIN=129/Ola;
RX PubMed=11056054; DOI=10.1006/geno.2000.6360;
RA Yang Y.H., Chen Y.H., Zhang C.Y., Nimmakayalu M.A., Ward D.C., Weissman S.;
RT "Cloning and characterization of two mouse genes with homology to the yeast
RT sir2 gene.";
RL Genomics 69:355-369(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM L), SUBCELLULAR LOCATION, AND
RP ALTERNATIVE SPLICING.
RC STRAIN=NIH Swiss;
RX PubMed=19333382; DOI=10.1371/journal.pone.0004986;
RA Cooper H.M., Huang J.Y., Verdin E., Spelbrink J.N.;
RT "A new splice variant of the mouse SIRT3 gene encodes the mitochondrial
RT precursor protein.";
RL PLoS ONE 4:E4986-E4986(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM L), SUBCELLULAR LOCATION, AND
RP ALTERNATIVE SPLICING.
RC STRAIN=ICR; TISSUE=Liver;
RX PubMed=19241369; DOI=10.1002/pro.50;
RA Jin L., Galonek H., Israelian K., Choy W., Morrison M., Xia Y., Wang X.,
RA Xu Y., Yang Y., Smith J.J., Hoffmann E., Carney D.P., Perni R.B.,
RA Jirousek M.R., Bemis J.E., Milne J.C., Sinclair D.A., Westphal C.H.;
RT "Biochemical characterization, localization, and tissue distribution of the
RT longer form of mouse SIRT3.";
RL Protein Sci. 18:514-525(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM S).
RC STRAIN=C57BL/6J; TISSUE=Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM S).
RC TISSUE=Mammary tumor;
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).
RN [6]
RP FUNCTION.
RX PubMed=16790548; DOI=10.1073/pnas.0604392103;
RA Hallows W.C., Lee S., Denu J.M.;
RT "Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10230-10235(2006).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17923681; DOI=10.1128/mcb.01636-07;
RA Lombard D.B., Alt F.W., Cheng H.L., Bunkenborg J., Streeper R.S.,
RA Mostoslavsky R., Kim J., Yancopoulos G., Valenzuela D., Murphy A., Yang Y.,
RA Chen Y., Hirschey M.D., Bronson R.T., Haigis M., Guarente L.P.,
RA Farese R.V. Jr., Weissman S., Verdin E., Schwer B.;
RT "Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine
RT acetylation.";
RL Mol. Cell. Biol. 27:8807-8814(2007).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=18794531; DOI=10.1073/pnas.0803790105;
RA Ahn B.-H., Kim H.-S., Song S., Lee I.H., Liu J., Vassilopoulos A.,
RA Deng C.-X., Finkel T.;
RT "A role for the mitochondrial deacetylase Sirt3 in regulating energy
RT homeostasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:14447-14452(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=21172655; DOI=10.1016/j.molcel.2010.12.013;
RA Tao R., Coleman M.C., Pennington J.D., Ozden O., Park S.H., Jiang H.,
RA Kim H.S., Flynn C.R., Hill S., Hayes McDonald W., Olivier A.K., Spitz D.R.,
RA Gius D.;
RT "Sirt3-mediated deacetylation of evolutionarily conserved lysine 122
RT regulates MnSOD activity in response to stress.";
RL Mol. Cell 40:893-904(2010).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21858060; DOI=10.1371/journal.pone.0023295;
RA Finley L.W., Haas W., Desquiret-Dumas V., Wallace D.C., Procaccio V.,
RA Gygi S.P., Haigis M.C.;
RT "Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase
RT activity.";
RL PLoS ONE 6:E23295-E23295(2011).
RN [12]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH FOXO3 AND POLRMT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23283301; DOI=10.1007/s00018-012-1244-6;
RA Peserico A., Chiacchiera F., Grossi V., Matrone A., Latorre D.,
RA Simonatto M., Fusella A., Ryall J.G., Finley L.W., Haigis M.C., Villani G.,
RA Puri P.L., Sartorelli V., Simone C.;
RT "A novel AMPK-dependent FoxO3A-SIRT3 intramitochondrial complex sensing
RT glucose levels.";
RL Cell. Mol. Life Sci. 70:2015-2029(2013).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND INDUCTION BY FASTING.
RX PubMed=23835326; DOI=10.2337/db12-1650;
RA Jing E., O'Neill B.T., Rardin M.J., Kleinridders A., Ilkeyeva O.R.,
RA Ussar S., Bain J.R., Lee K.Y., Verdin E.M., Newgard C.B., Gibson B.W.,
RA Kahn C.R.;
RT "Sirt3 regulates metabolic flexibility of skeletal muscle through
RT reversible enzymatic deacetylation.";
RL Diabetes 62:3404-3417(2013).
RN [14]
RP INTERACTION WITH PCCA.
RX PubMed=23438705; DOI=10.1016/j.mito.2013.02.002;
RA Wirth M., Karaca S., Wenzel D., Ho L., Tishkoff D., Lombard D.B.,
RA Verdin E., Urlaub H., Jedrusik-Bode M., Fischle W.;
RT "Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals
RT interact with pyruvate carboxylase and other acetylated biotin-dependent
RT carboxylases.";
RL Mitochondrion 13:705-720(2013).
RN [15]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-57, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24252090; DOI=10.1089/ars.2013.5420;
RA Vassilopoulos A., Pennington D.J., Andresson T., Rees D., Fearnley I.,
RA Ham A., Yan Y., Flynn C.R., Jones K., Kim H.S., Deng C., Walker J.,
RA Gius D.;
RT "SIRT3 deacetylates ATP synthase F1 complex proteins in response to
RT nutrient and exercise-induced stress.";
RL Antioxid. Redox Signal. 21:551-564(2014).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26620563; DOI=10.1074/jbc.m115.668228;
RA Novgorodov S.A., Riley C.L., Keffler J.A., Yu J., Kindy M.S., Macklin W.B.,
RA Lombard D.B., Gudz T.I.;
RT "SIRT3 deacetylates ceramide synthases: Implications for mitochondrial
RT dysfunction and brain injury.";
RL J. Biol. Chem. 291:1957-1973(2016).
CC -!- FUNCTION: NAD-dependent protein deacetylase (PubMed:23835326,
CC PubMed:17923681, PubMed:18794531, PubMed:21172655, PubMed:26620563).
CC Activates or deactivates mitochondrial target proteins by deacetylating
CC key lysine residues (PubMed:23835326, PubMed:17923681, PubMed:18794531,
CC PubMed:21172655). Known targets include ACSS1, IDH, GDH, PDHA1, SOD2,
CC LCAD, SDHA and the ATP synthase subunit ATP5PO (PubMed:16790548,
CC PubMed:18794531, PubMed:21172655). Contributes to the regulation of the
CC cellular energy metabolism (PubMed:23835326). Important for regulating
CC tissue-specific ATP levels (PubMed:18794531, PubMed:24252090). In
CC response to metabolic stress, deacetylates transcription factor FOXO3
CC and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to
CC promote mtDNA transcription (PubMed:23283301). Acts as a regulator of
CC ceramide metabolism by mediating deacetylation of ceramide synthases
CC CERS1, CERS2 and CERS6, thereby increasing their activity and promoting
CC mitochondrial ceramide accumulation (PubMed:26620563).
CC {ECO:0000269|PubMed:16790548, ECO:0000269|PubMed:17923681,
CC ECO:0000269|PubMed:18794531, ECO:0000269|PubMed:21172655,
CC ECO:0000269|PubMed:21858060, ECO:0000269|PubMed:23283301,
CC ECO:0000269|PubMed:23835326, ECO:0000269|PubMed:24252090,
CC ECO:0000269|PubMed:26620563}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
CC ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
CC EC=2.3.1.286; Evidence={ECO:0000255|PROSITE-ProRule:PRU00236,
CC ECO:0000269|PubMed:21858060, ECO:0000269|PubMed:26620563,
CC ECO:0000305|PubMed:17923681, ECO:0000305|PubMed:18794531,
CC ECO:0000305|PubMed:21172655, ECO:0000305|PubMed:23835326};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9NTG7};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9NTG7};
CC -!- SUBUNIT: Upon metabolic stress, forms a complex composed of FOXO3,
CC SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited
CC to mtDNA in a SIRT3-dependent manner (PubMed:23283301). Also forms a
CC complex composed of FOXO3, SIRT3, TFAM and POLRMT (By similarity).
CC Interacts with NDUFA9, ACSS1, IDH2 and GDH (By similarity). Interacts
CC with PCCA (PubMed:23438705). {ECO:0000250|UniProtKB:Q9NTG7,
CC ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:23438705}.
CC -!- INTERACTION:
CC Q8R104; P47738: Aldh2; NbExp=2; IntAct=EBI-6999888, EBI-2308120;
CC -!- SUBCELLULAR LOCATION: [Isoform L]: Mitochondrion matrix
CC {ECO:0000269|PubMed:19241369, ECO:0000269|PubMed:19333382,
CC ECO:0000269|PubMed:23283301}.
CC -!- SUBCELLULAR LOCATION: [Isoform S]: Cytoplasm
CC {ECO:0000269|PubMed:11056054}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=L; Synonyms=M1;
CC IsoId=Q8R104-1; Sequence=Displayed;
CC Name=S; Synonyms=M3;
CC IsoId=Q8R104-2; Sequence=VSP_053760;
CC -!- TISSUE SPECIFICITY: Strongly expressed in liver and kidney
CC (PubMed:11056054). Expressed in skeletal muscles (at protein level)
CC (PubMed:23283301, PubMed:23835326). Weakly expressed in lung
CC (PubMed:11056054). {ECO:0000269|PubMed:11056054,
CC ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:23835326}.
CC -!- INDUCTION: Sirt3 expression decreases by 50% in skeletal muscle upon
CC fasting. {ECO:0000269|PubMed:23835326}.
CC -!- DISRUPTION PHENOTYPE: Decreased muscle endurance under energetically
CC demanding conditions (PubMed:24252090). Decreased Mn-SOD activity in
CC liver, increased mitochondrial superoxide levels and genomic
CC instability upon exposure to ionizing radiations (PubMed:21172655). In
CC vivo ATP levels are reduced by 50 % in organs that normally express
CC high levels of this protein (PubMed:18794531). ATP levels are unchanged
CC in organs that normally express low levels of this protein
CC (PubMed:18794531). Leads to increased mitochondrial protein acetylation
CC (PubMed:18794531). Decreased ceramide accumulation in brain
CC mitochondria (PubMed:26620563). {ECO:0000269|PubMed:18794531,
CC ECO:0000269|PubMed:21172655, ECO:0000269|PubMed:24252090,
CC ECO:0000269|PubMed:26620563}.
CC -!- MISCELLANEOUS: Has some ability to deacetylate histones in vitro, but
CC seeing its subcellular location, this is unlikely in vivo.
CC {ECO:0000250|UniProtKB:Q9NTG7}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; AF299339; AAG39258.1; -; mRNA.
DR EMBL; FJ621493; ACM68947.1; -; mRNA.
DR EMBL; EU886466; ACJ70655.1; -; mRNA.
DR EMBL; AF302278; AAG33227.1; -; Genomic_DNA.
DR EMBL; AF302274; AAG33227.1; JOINED; Genomic_DNA.
DR EMBL; AF302275; AAG33227.1; JOINED; Genomic_DNA.
DR EMBL; AF302276; AAG33227.1; JOINED; Genomic_DNA.
DR EMBL; AF302277; AAG33227.1; JOINED; Genomic_DNA.
DR EMBL; AF299338; AAG39257.1; -; mRNA.
DR EMBL; AK075861; BAC36012.1; -; mRNA.
DR EMBL; BC025878; AAH25878.1; -; mRNA.
DR CCDS; CCDS21989.1; -. [Q8R104-2]
DR RefSeq; NP_001120823.1; NM_001127351.1. [Q8R104-2]
DR RefSeq; NP_001171275.1; NM_001177804.1. [Q8R104-1]
DR RefSeq; NP_071878.2; NM_022433.2. [Q8R104-2]
DR AlphaFoldDB; Q8R104; -.
DR SMR; Q8R104; -.
DR BioGRID; 211071; 15.
DR IntAct; Q8R104; 3.
DR MINT; Q8R104; -.
DR STRING; 10090.ENSMUSP00000026559; -.
DR iPTMnet; Q8R104; -.
DR PhosphoSitePlus; Q8R104; -.
DR SwissPalm; Q8R104; -.
DR EPD; Q8R104; -.
DR MaxQB; Q8R104; -.
DR PaxDb; Q8R104; -.
DR PeptideAtlas; Q8R104; -.
DR PRIDE; Q8R104; -.
DR ProteomicsDB; 257018; -. [Q8R104-1]
DR ProteomicsDB; 257019; -. [Q8R104-2]
DR Antibodypedia; 9472; 781 antibodies from 47 providers.
DR DNASU; 64384; -.
DR Ensembl; ENSMUST00000026559; ENSMUSP00000026559; ENSMUSG00000025486. [Q8R104-2]
DR Ensembl; ENSMUST00000106048; ENSMUSP00000101663; ENSMUSG00000025486. [Q8R104-2]
DR GeneID; 64384; -.
DR KEGG; mmu:64384; -.
DR UCSC; uc009kik.2; mouse. [Q8R104-1]
DR CTD; 23410; -.
DR MGI; MGI:1927665; Sirt3.
DR VEuPathDB; HostDB:ENSMUSG00000025486; -.
DR eggNOG; KOG2682; Eukaryota.
DR GeneTree; ENSGT00940000159464; -.
DR InParanoid; Q8R104; -.
DR OMA; PCSRLPR; -.
DR OrthoDB; 973532at2759; -.
DR TreeFam; TF106181; -.
DR BRENDA; 2.3.1.286; 3474.
DR Reactome; R-MMU-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-MMU-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR BioGRID-ORCS; 64384; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Sirt3; mouse.
DR PRO; PR:Q8R104; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8R104; protein.
DR Bgee; ENSMUSG00000025486; Expressed in proximal tubule and 264 other tissues.
DR ExpressionAtlas; Q8R104; baseline and differential.
DR Genevisible; Q8R104; MM.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:CACAO.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IBA:GO_Central.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0009060; P:aerobic respiration; ISS:UniProtKB.
DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; IDA:MGI.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:UniProtKB.
DR GO; GO:1902553; P:positive regulation of catalase activity; ISO:MGI.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:1903109; P:positive regulation of mitochondrial transcription; IMP:UniProtKB.
DR GO; GO:1901671; P:positive regulation of superoxide dismutase activity; ISO:MGI.
DR GO; GO:0006476; P:protein deacetylation; IMP:MGI.
DR Gene3D; 3.30.1600.10; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR017328; Sirtuin_class_I.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR PIRSF; PIRSF037938; SIR2_euk; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Metal-binding; Mitochondrion; NAD;
KW Reference proteome; Transferase; Transit peptide; Zinc.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT CHAIN ?..334
FT /note="NAD-dependent protein deacetylase sirtuin-3"
FT /id="PRO_0000110263"
FT DOMAIN 78..334
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT ACT_SITE 183
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 80..100
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9NTG7"
FT BINDING 163..166
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9NTG7"
FT BINDING 191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 215
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 218
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 254..256
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9NTG7"
FT BINDING 279..281
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9NTG7"
FT MOD_RES 57
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT VAR_SEQ 1..77
FT /note="Missing (in isoform S)"
FT /evidence="ECO:0000303|PubMed:11056054,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072"
FT /id="VSP_053760"
FT CONFLICT 216
FT /note="P -> A (in Ref. 1; AAG39258/AAG33227/AAG39257 and 3;
FT ACJ70655)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 334 AA; 36615 MW; D8C936A83C4A8AF7 CRC64;
MALDPLGAVV LQSIMALSGR LALAALRLWG PGGGRRPISL CVGASGGFGG GGSSEKKFSL
QDVAELLRTR ACSRVVVMVG AGISTPSGIP DFRSPGSGLY SNLQQYDIPY PEAIFELGFF
FHNPKPFFML AKELYPGHYR PNVTHYFLRL LHDKELLLRL YTQNIDGLER ASGIPASKLV
EAHGTFVTAT CTVCRRSFPG EDIWADVMAD RVPRCPVCTG VVKPDIVFFG EQLPARFLLH
MADFALADLL LILGTSLEVE PFASLSEAVQ KSVPRLLINR DLVGPFVLSP RRKDVVQLGD
VVHGVERLVD LLGWTQELLD LMQRERGKLD GQDR
