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 27-MAR-2024, entry version 171. DE RecName: Full=NAD-dependent protein deacetylase sirtuin-3; DE EC=2.3.1.286 {ECO:0000255|PROSITE-ProRule:PRU00236, 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). RN [18] RP TISSUE SPECIFICITY. RX PubMed=35959657; DOI=10.1161/circulationaha.122.060454; RA Perez-Hernandez M., van Opbergen C.J.M., Bagwan N., Vissing C.R., RA Marron-Linares G.M., Zhang M., Torres Vega E., Sorrentino A., Drici L., RA Sulek K., Zhai R., Hansen F.B., Christensen A.H., Boesgaard S., RA Gustafsson F., Rossing K., Small E.M., Davies M.J., Rothenberg E., RA Sato P.Y., Cerrone M., Jensen T.H.L., Qvortrup K., Bundgaard H., Delmar M., RA Lundby A.; RT "Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause RT DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of RT ARVC."; RL Circulation 146:851-867(2022). RN [19] RP FUNCTION. RX PubMed=36804859; DOI=10.1097/hep.0000000000000314; RA Cheng L., Deepak R.N.V.K., Wang G., Meng Z., Tao L., Xie M., Chi W., RA Zhang Y., Yang M., Liao Y., Chen R., Liang Y., Zhang J., Huang Y., Wang W., RA Guo Z., Wang Y., Lin J.D., Fan H., Chen L.; RT "Hepatic mitochondrial NAD + transporter SLC25A47 activates AMPKalpha RT mediating lipid metabolism and tumorigenesis."; RL Hepatology 0:0-0(2023). 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, PubMed:36804859). CC Important for regulating tissue-specific ATP levels (PubMed:18794531, CC PubMed:24252090). In response to metabolic stress, deacetylates CC transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA CC polymerase POLRMT to mtDNA to promote mtDNA transcription CC (PubMed:23283301). Acts as a regulator of ceramide metabolism by CC mediating deacetylation of ceramide synthases CERS1, CERS2 and CERS6, CC thereby increasing their activity and promoting mitochondrial ceramide CC accumulation (PubMed:26620563). Regulates hepatic lipogenesis. Uses CC NAD(+) substrate imported by SLC25A47, triggering downstream activation CC of PRKAA1/AMPK-alpha signaling cascade that ultimately downregulates CC sterol regulatory element-binding protein (SREBP) transcriptional CC activities and ATP-consuming lipogenesis to restore cellular energy CC balance. {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, ECO:0000269|PubMed:36804859}. 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: Expressed in cardiomyocytes (at protein level) CC (PubMed:11056054, PubMed:35959657). Expressed in the brain, liver, CC kidney and testes (PubMed:11056054). Expressed in skeletal muscles (at CC protein level) (PubMed:23283301, PubMed:23835326). CC {ECO:0000269|PubMed:11056054, ECO:0000269|PubMed:23283301, CC ECO:0000269|PubMed:23835326, ECO:0000269|PubMed:35959657}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 ChEMBL; CHEMBL5169177; -. DR iPTMnet; Q8R104; -. DR PhosphoSitePlus; Q8R104; -. DR SwissPalm; Q8R104; -. DR EPD; Q8R104; -. DR MaxQB; Q8R104; -. DR PaxDb; 10090-ENSMUSP00000026559; -. DR PeptideAtlas; Q8R104; -. DR ProteomicsDB; 257018; -. [Q8R104-1] DR ProteomicsDB; 257019; -. [Q8R104-2] DR Antibodypedia; 9472; 875 antibodies from 47 providers. DR DNASU; 64384; -. DR Ensembl; ENSMUST00000026559.14; ENSMUSP00000026559.8; ENSMUSG00000025486.18. [Q8R104-2] DR Ensembl; ENSMUST00000106048.10; ENSMUSP00000101663.4; ENSMUSG00000025486.18. [Q8R104-2] DR GeneID; 64384; -. DR KEGG; mmu:64384; -. DR UCSC; uc009kik.2; mouse. [Q8R104-1] DR AGR; MGI:1927665; -. DR CTD; 23410; -. DR MGI; MGI:1927665; Sirt3. DR VEuPathDB; HostDB:ENSMUSG00000025486; -. DR eggNOG; KOG2682; Eukaryota. DR GeneTree; ENSGT00940000159464; -. DR InParanoid; Q8R104; -. DR OMA; PYCQVPD; -. DR OrthoDB; 10545at2759; -. 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 80 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 267 other cell types or tissues. DR ExpressionAtlas; Q8R104; baseline and differential. 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:0019899; F:enzyme binding; ISO:MGI. 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:0033558; F:protein lysine deacetylase activity; IDA:MGI. 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:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISO:MGI. DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; IDA:MGI. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISO:MGI. DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:UniProtKB. DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; IDA:UniProtKB. DR GO; GO:0032024; P:positive regulation of insulin secretion; ISO:MGI. DR GO; GO:1903109; P:positive regulation of mitochondrial transcription; IMP:UniProtKB. DR GO; GO:0006476; P:protein deacetylation; ISS:UniProtKB. DR CDD; cd01408; SIRT1; 1. DR Gene3D; 3.30.1600.10; SIR2/SIRT2 'Small Domain; 1. DR Gene3D; 3.40.50.1220; TPP-binding domain; 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 PANTHER; PTHR11085:SF15; NAD-DEPENDENT PROTEIN DEACETYLASE SIRTUIN-3, MITOCHONDRIAL; 1. DR PANTHER; PTHR11085; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL-RELATED; 1. DR Pfam; PF02146; SIR2; 1. DR PIRSF; PIRSF037938; SIR2_euk; 1. DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 1. DR PROSITE; PS50305; SIRTUIN; 1. DR Genevisible; Q8R104; MM. 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 53..315 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 //