SIR3_HUMAN
ID SIR3_HUMAN Reviewed; 399 AA.
AC Q9NTG7; B7Z5U6; Q9Y6E8;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-3, mitochondrial;
DE Short=hSIRT3;
DE EC=2.3.1.286 {ECO:0000269|PubMed:12186850, ECO:0000269|PubMed:12374852, ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18680753, ECO:0000269|PubMed:18794531, ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:24121500};
DE AltName: Full=Regulatory protein SIR2 homolog 3;
DE AltName: Full=SIR2-like protein 3;
DE Flags: Precursor;
GN Name=SIRT3; Synonyms=SIR2L3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=10381378; DOI=10.1006/bbrc.1999.0897;
RA Frye R.A.;
RT "Characterization of five human cDNAs with homology to the yeast SIR2 gene:
RT Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-
RT ribosyltransferase activity.";
RL Biochem. Biophys. Res. Commun. 260:273-279(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 282-399 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING
RP BY MPP, MUTAGENESIS OF ARG-7; ARG-13; ARG-17; ARG-21; 99-ARG-ARG-100;
RP ASN-229 AND HIS-248, AND ACTIVE SITE.
RX PubMed=12186850; DOI=10.1083/jcb.200205057;
RA Schwer B., North B.J., Frye R.A., Ott M., Verdin E.;
RT "The human silent information regulator (Sir)2 homologue hSIRT3 is a
RT mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase.";
RL J. Cell Biol. 158:647-657(2002).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12374852; DOI=10.1073/pnas.222538099;
RA Onyango P., Celic I., McCaffery J.M., Boeke J.D., Feinberg A.P.;
RT "SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized
RT to mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13653-13658(2002).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=16079181; DOI=10.1091/mbc.e05-01-0033;
RA Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.;
RT "Evolutionarily conserved and nonconserved cellular localizations and
RT functions of human SIRT proteins.";
RL Mol. Biol. Cell 16:4623-4635(2005).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-248, INTERACTION WITH
RP ACSS1, AND ACTIVE SITE.
RX PubMed=16788062; DOI=10.1073/pnas.0603968103;
RA Schwer B., Bunkenborg J., Verdin R.O., Andersen J.S., Verdin E.;
RT "Reversible lysine acetylation controls the activity of the mitochondrial
RT enzyme acetyl-CoA synthetase 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10224-10229(2006).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=18215119; DOI=10.1042/bj20071624;
RA Cooper H.M., Spelbrink J.N.;
RT "The human SIRT3 protein deacetylase is exclusively mitochondrial.";
RL Biochem. J. 411:279-285(2008).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18680753; DOI=10.1016/j.jmb.2008.07.048;
RA Schlicker C., Gertz M., Papatheodorou P., Kachholz B., Becker C.F.W.,
RA Steegborn C.;
RT "Substrates and regulation mechanisms for the human mitochondrial sirtuins
RT Sirt3 and Sirt5.";
RL J. Mol. Biol. 382:790-801(2008).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH NDUFA9, MUTAGENESIS OF
RP HIS-248, AND ACTIVE SITE.
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [15]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN A COMPLEX WITH FOXO3 AND
RP POLRMT, AND 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 [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24121500; DOI=10.1074/jbc.m113.510354;
RA Bharathi S.S., Zhang Y., Mohsen A.W., Uppala R., Balasubramani M.,
RA Schreiber E., Uechi G., Beck M.E., Rardin M.J., Vockley J., Verdin E.,
RA Gibson B.W., Hirschey M.D., Goetzman E.S.;
RT "SIRT3 regulates long-chain acyl-coA dehydrogenase by deacetylating
RT conserved lysines near the active site.";
RL J. Biol. Chem. 288:33837-33847(2013).
RN [17]
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 [18]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
RP IDENTIFICATION IN A COMPLEX WITH FOXO3; TFAM AND POLRMT, AND SUBCELLULAR
RP LOCATION.
RX PubMed=29445193; DOI=10.1038/s41419-018-0336-0;
RA Celestini V., Tezil T., Russo L., Fasano C., Sanese P., Forte G.,
RA Peserico A., Lepore Signorile M., Longo G., De Rasmo D., Signorile A.,
RA Gadaleta R.M., Scialpi N., Terao M., Garattini E., Cocco T., Villani G.,
RA Moschetta A., Grossi V., Simone C.;
RT "Uncoupling FoxO3A mitochondrial and nuclear functions in cancer cells
RT undergoing metabolic stress and chemotherapy.";
RL Cell Death Dis. 9:231-231(2018).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 118-399 IN COMPLEX WITH ZINC IONS
RP AND ACSS1, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP NAD-BINDING.
RX PubMed=19535340; DOI=10.1074/jbc.m109.014928;
RA Jin L., Wei W., Jiang Y., Peng H., Cai J., Mao C., Dai H., Choy W.,
RA Bemis J.E., Jirousek M.R., Milne J.C., Westphal C.H., Perni R.B.;
RT "Crystal structures of human SIRT3 displaying substrate-induced
RT conformational changes.";
RL J. Biol. Chem. 284:24394-24405(2009).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 116-399 IN COMPLEX WITH INHIBITOR,
RP NAD-BINDING SITES, AND ZINC-BINDING SITES.
RX PubMed=23897466; DOI=10.1107/s0907444913015448;
RA Nguyen G.T., Schaefer S., Gertz M., Weyand M., Steegborn C.;
RT "Structures of human sirtuin 3 complexes with ADP-ribose and with carba-
RT NAD+ and SRT1720: binding details and inhibition mechanism.";
RL Acta Crystallogr. D 69:1423-1432(2013).
CC -!- FUNCTION: NAD-dependent protein deacetylase (PubMed:12186850,
CC PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531,
CC PubMed:23283301, PubMed:24121500, PubMed:24252090, PubMed:19535340).
CC Activates or deactivates mitochondrial target proteins by deacetylating
CC key lysine residues (PubMed:12186850, PubMed:12374852, PubMed:16788062,
CC PubMed:18680753, PubMed:18794531, PubMed:23283301, PubMed:24121500,
CC PubMed:24252090). Known targets include ACSS1, IDH, GDH, SOD2, PDHA1,
CC LCAD, SDHA and the ATP synthase subunit ATP5PO (PubMed:16788062,
CC PubMed:18680753, PubMed:24121500, PubMed:24252090, PubMed:19535340).
CC Contributes to the regulation of the cellular energy metabolism
CC (PubMed:24252090). Important for regulating tissue-specific ATP levels
CC (PubMed:18794531). 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 (By similarity). {ECO:0000250|UniProtKB:Q8R104,
CC ECO:0000269|PubMed:12186850, ECO:0000269|PubMed:12374852,
CC ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18680753,
CC ECO:0000269|PubMed:18794531, ECO:0000269|PubMed:19535340,
CC ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:24121500,
CC ECO:0000269|PubMed:24252090}.
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:12186850, ECO:0000269|PubMed:12374852,
CC ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18680753,
CC ECO:0000269|PubMed:18794531, ECO:0000269|PubMed:19535340,
CC ECO:0000269|PubMed:24121500, ECO:0000305|PubMed:23283301};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23897466};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:19535340,
CC ECO:0000269|PubMed:23897466};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=600 uM for NAD {ECO:0000269|PubMed:19535340};
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 (PubMed:29445193).
CC Interacts with NDUFA9, ACSS1, IDH2 and GDH (PubMed:16788062,
CC PubMed:18794531, PubMed:19535340, PubMed:18680753). Interacts with PCCA
CC (PubMed:23438705). {ECO:0000269|PubMed:16788062,
CC ECO:0000269|PubMed:18680753, ECO:0000269|PubMed:18794531,
CC ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23283301,
CC ECO:0000269|PubMed:23438705, ECO:0000269|PubMed:29445193}.
CC -!- INTERACTION:
CC Q9NTG7; P25705: ATP5F1A; NbExp=2; IntAct=EBI-724621, EBI-351437;
CC Q9NTG7; P28799-2: GRN; NbExp=3; IntAct=EBI-724621, EBI-25860013;
CC Q9NTG7; O60313: OPA1; NbExp=3; IntAct=EBI-724621, EBI-1054131;
CC Q9NTG7; Q13309: SKP2; NbExp=5; IntAct=EBI-724621, EBI-456291;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:12186850, ECO:0000269|PubMed:12374852,
CC ECO:0000269|PubMed:16079181, ECO:0000269|PubMed:18215119,
CC ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:29445193}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NTG7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NTG7-2; Sequence=VSP_043792;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10381378,
CC ECO:0000269|PubMed:12374852}.
CC -!- PTM: Processed by mitochondrial processing peptidase (MPP) to give a 28
CC kDa product. Such processing is probably essential for its enzymatic
CC activity. {ECO:0000269|PubMed:12186850}.
CC -!- MISCELLANEOUS: Has some ability to deacetylate histones in vitro, but
CC seeing its subcellular location, this is unlikely in vivo.
CC {ECO:0000269|PubMed:12374852}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; AF083108; AAD40851.1; -; mRNA.
DR EMBL; AK299438; BAH13032.1; -; mRNA.
DR EMBL; AC136475; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001042; AAH01042.1; -; mRNA.
DR EMBL; AL137276; CAB70674.1; -; mRNA.
DR CCDS; CCDS53590.1; -. [Q9NTG7-2]
DR CCDS; CCDS7691.1; -. [Q9NTG7-1]
DR PIR; T46348; T46348.
DR RefSeq; NP_001017524.1; NM_001017524.2. [Q9NTG7-2]
DR RefSeq; NP_036371.1; NM_012239.5. [Q9NTG7-1]
DR RefSeq; XP_016872919.1; XM_017017430.1.
DR PDB; 3GLR; X-ray; 1.80 A; A=118-399.
DR PDB; 3GLS; X-ray; 2.70 A; A/B/C/D/E/F=118-399.
DR PDB; 3GLT; X-ray; 2.10 A; A=118-399.
DR PDB; 3GLU; X-ray; 2.50 A; A=118-399.
DR PDB; 4BN4; X-ray; 1.30 A; A=116-399.
DR PDB; 4BN5; X-ray; 3.25 A; A/B/C/D/E/F/G/H/I/J/K/L=119-399.
DR PDB; 4BV3; X-ray; 2.00 A; A=116-399.
DR PDB; 4BVB; X-ray; 2.00 A; A=116-399.
DR PDB; 4BVE; X-ray; 2.05 A; A=116-399.
DR PDB; 4BVF; X-ray; 2.70 A; A=116-399.
DR PDB; 4BVG; X-ray; 2.50 A; A=116-399.
DR PDB; 4BVH; X-ray; 1.90 A; A/B/C=116-399.
DR PDB; 4C78; X-ray; 2.00 A; A=116-399.
DR PDB; 4C7B; X-ray; 2.10 A; A=117-399.
DR PDB; 4FVT; X-ray; 2.47 A; A=122-395.
DR PDB; 4FZ3; X-ray; 2.10 A; A=118-399.
DR PDB; 4HD8; X-ray; 2.30 A; A=116-399.
DR PDB; 4JSR; X-ray; 1.70 A; A=118-399.
DR PDB; 4JT8; X-ray; 2.26 A; A=118-399.
DR PDB; 4JT9; X-ray; 2.24 A; A=118-399.
DR PDB; 4O8Z; X-ray; 2.00 A; A=116-399.
DR PDB; 5BWN; X-ray; 1.94 A; A=118-399.
DR PDB; 5BWO; X-ray; 2.38 A; A=118-399.
DR PDB; 5D7N; X-ray; 1.83 A; A/B/C/D/E/F=118-395.
DR PDB; 5H4D; X-ray; 3.21 A; A/H=121-391.
DR PDB; 5Y4H; X-ray; 2.60 A; A=118-399.
DR PDB; 5YTK; X-ray; 2.70 A; A/B/C/D/E/F=121-394.
DR PDB; 5Z93; X-ray; 1.95 A; A=117-399.
DR PDB; 5Z94; X-ray; 1.90 A; A/B=117-399.
DR PDB; 5ZGC; X-ray; 2.90 A; A/B/C/D/E/F=121-394.
DR PDB; 6ISO; X-ray; 2.95 A; A/B/E/G/I/K=121-394.
DR PDBsum; 3GLR; -.
DR PDBsum; 3GLS; -.
DR PDBsum; 3GLT; -.
DR PDBsum; 3GLU; -.
DR PDBsum; 4BN4; -.
DR PDBsum; 4BN5; -.
DR PDBsum; 4BV3; -.
DR PDBsum; 4BVB; -.
DR PDBsum; 4BVE; -.
DR PDBsum; 4BVF; -.
DR PDBsum; 4BVG; -.
DR PDBsum; 4BVH; -.
DR PDBsum; 4C78; -.
DR PDBsum; 4C7B; -.
DR PDBsum; 4FVT; -.
DR PDBsum; 4FZ3; -.
DR PDBsum; 4HD8; -.
DR PDBsum; 4JSR; -.
DR PDBsum; 4JT8; -.
DR PDBsum; 4JT9; -.
DR PDBsum; 4O8Z; -.
DR PDBsum; 5BWN; -.
DR PDBsum; 5BWO; -.
DR PDBsum; 5D7N; -.
DR PDBsum; 5H4D; -.
DR PDBsum; 5Y4H; -.
DR PDBsum; 5YTK; -.
DR PDBsum; 5Z93; -.
DR PDBsum; 5Z94; -.
DR PDBsum; 5ZGC; -.
DR PDBsum; 6ISO; -.
DR AlphaFoldDB; Q9NTG7; -.
DR SMR; Q9NTG7; -.
DR BioGRID; 116982; 87.
DR DIP; DIP-46861N; -.
DR IntAct; Q9NTG7; 56.
DR MINT; Q9NTG7; -.
DR STRING; 9606.ENSP00000372191; -.
DR BindingDB; Q9NTG7; -.
DR ChEMBL; CHEMBL4461; -.
DR DrugBank; DB02059; Adenosine-5-Diphosphoribose.
DR DrugCentral; Q9NTG7; -.
DR GuidetoPHARMACOLOGY; 2709; -.
DR iPTMnet; Q9NTG7; -.
DR PhosphoSitePlus; Q9NTG7; -.
DR BioMuta; SIRT3; -.
DR DMDM; 38258651; -.
DR EPD; Q9NTG7; -.
DR jPOST; Q9NTG7; -.
DR MassIVE; Q9NTG7; -.
DR MaxQB; Q9NTG7; -.
DR PaxDb; Q9NTG7; -.
DR PeptideAtlas; Q9NTG7; -.
DR PRIDE; Q9NTG7; -.
DR ProteomicsDB; 82606; -. [Q9NTG7-1]
DR ProteomicsDB; 82607; -. [Q9NTG7-2]
DR Antibodypedia; 9472; 781 antibodies from 47 providers.
DR DNASU; 23410; -.
DR Ensembl; ENST00000382743.9; ENSP00000372191.4; ENSG00000142082.15. [Q9NTG7-1]
DR Ensembl; ENST00000529382.5; ENSP00000437216.1; ENSG00000142082.15. [Q9NTG7-2]
DR GeneID; 23410; -.
DR KEGG; hsa:23410; -.
DR MANE-Select; ENST00000382743.9; ENSP00000372191.4; NM_012239.6; NP_036371.1.
DR UCSC; uc001lok.5; human. [Q9NTG7-1]
DR CTD; 23410; -.
DR DisGeNET; 23410; -.
DR GeneCards; SIRT3; -.
DR HGNC; HGNC:14931; SIRT3.
DR HPA; ENSG00000142082; Low tissue specificity.
DR MIM; 604481; gene.
DR neXtProt; NX_Q9NTG7; -.
DR OpenTargets; ENSG00000142082; -.
DR PharmGKB; PA37936; -.
DR VEuPathDB; HostDB:ENSG00000142082; -.
DR eggNOG; KOG2682; Eukaryota.
DR GeneTree; ENSGT00940000159464; -.
DR HOGENOM; CLU_023643_7_0_1; -.
DR InParanoid; Q9NTG7; -.
DR OMA; PCSRLPR; -.
DR OrthoDB; 973532at2759; -.
DR PhylomeDB; Q9NTG7; -.
DR TreeFam; TF106181; -.
DR BRENDA; 2.3.1.24; 2681.
DR BRENDA; 2.3.1.286; 2681.
DR PathwayCommons; Q9NTG7; -.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR Reactome; R-HSA-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR SABIO-RK; Q9NTG7; -.
DR SignaLink; Q9NTG7; -.
DR SIGNOR; Q9NTG7; -.
DR BioGRID-ORCS; 23410; 12 hits in 1094 CRISPR screens.
DR ChiTaRS; SIRT3; human.
DR EvolutionaryTrace; Q9NTG7; -.
DR GeneWiki; SIRT3; -.
DR GenomeRNAi; 23410; -.
DR Pharos; Q9NTG7; Tchem.
DR PRO; PR:Q9NTG7; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9NTG7; protein.
DR Bgee; ENSG00000142082; Expressed in right frontal lobe and 190 other tissues.
DR ExpressionAtlas; Q9NTG7; baseline and differential.
DR Genevisible; Q9NTG7; HS.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; TAS:ProtInc.
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; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0009060; P:aerobic respiration; IMP:UniProtKB.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IMP:UniProtKB.
DR GO; GO:1902553; P:positive regulation of catalase activity; IDA:CACAO.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:1901671; P:positive regulation of superoxide dismutase activity; IDA:CACAO.
DR GO; GO:0006471; P:protein ADP-ribosylation; ISS:GO_Central.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
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; 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; Alternative splicing; Metal-binding; Mitochondrion; NAD;
KW Reference proteome; Transferase; Transit peptide; Zinc.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..399
FT /note="NAD-dependent protein deacetylase sirtuin-3,
FT mitochondrial"
FT /id="PRO_0000032612"
FT DOMAIN 126..382
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 49..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 248
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:12186850,
FT ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18794531"
FT BINDING 145..165
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23897466"
FT BINDING 228..231
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23897466"
FT BINDING 256
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19535340,
FT ECO:0000269|PubMed:23897466"
FT BINDING 259
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19535340,
FT ECO:0000269|PubMed:23897466"
FT BINDING 280
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19535340,
FT ECO:0000269|PubMed:23897466"
FT BINDING 283
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19535340,
FT ECO:0000269|PubMed:23897466"
FT BINDING 319..321
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23897466"
FT BINDING 344..346
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23897466"
FT MOD_RES 122
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8R104"
FT VAR_SEQ 1..142
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043792"
FT VARIANT 80
FT /note="R -> W (in dbSNP:rs28365927)"
FT /id="VAR_051977"
FT VARIANT 208
FT /note="V -> I (in dbSNP:rs11246020)"
FT /id="VAR_051978"
FT VARIANT 369
FT /note="G -> S (in dbSNP:rs3020901)"
FT /id="VAR_051979"
FT MUTAGEN 7
FT /note="R->G,Q: Suppresses targeting to mitochondrion; when
FT associated with G-13 or Q-13."
FT /evidence="ECO:0000269|PubMed:12186850"
FT MUTAGEN 13
FT /note="R->G,Q: Suppresses targeting to mitochondrion; when
FT associated with G-7 or Q-7."
FT /evidence="ECO:0000269|PubMed:12186850"
FT MUTAGEN 17
FT /note="R->G,Q: Reduces targeting to mitochondrion; when
FT associated with G-21 or Q-21."
FT /evidence="ECO:0000269|PubMed:12186850"
FT MUTAGEN 21
FT /note="R->G,Q: Reduces targeting to mitochondrion; when
FT associated with G-17 or Q-17."
FT /evidence="ECO:0000269|PubMed:12186850"
FT MUTAGEN 99..100
FT /note="RR->GG: Abolishes processing by MPP (in vitro)."
FT /evidence="ECO:0000269|PubMed:12186850"
FT MUTAGEN 229
FT /note="N->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:12186850"
FT MUTAGEN 248
FT /note="H->Y: Loss of function."
FT /evidence="ECO:0000269|PubMed:12186850,
FT ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18794531"
FT HELIX 125..133
FT /evidence="ECO:0007829|PDB:4BN4"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:4C7B"
FT STRAND 140..144
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 146..152
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:4BN4"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 164..168
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 176..180
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 182..187
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 190..199
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:4BV3"
FT HELIX 208..218
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 233..236
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 249..256
FT /evidence="ECO:0007829|PDB:4BN4"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 265..273
FT /evidence="ECO:0007829|PDB:4BN4"
FT TURN 281..283
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 286..291
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 300..304
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 305..311
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 313..319
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 327..330
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 331..333
FT /evidence="ECO:0007829|PDB:4C7B"
FT STRAND 340..346
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 349..353
FT /evidence="ECO:0007829|PDB:4BN4"
FT STRAND 359..364
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 366..377
FT /evidence="ECO:0007829|PDB:4BN4"
FT HELIX 380..391
FT /evidence="ECO:0007829|PDB:4BN4"
SQ SEQUENCE 399 AA; 43573 MW; 4BA8BD3AC5FC7901 CRC64;
MAFWGWRAAA ALRLWGRVVE RVEAGGGVGP FQACGCRLVL GGRDDVSAGL RGSHGARGEP
LDPARPLQRP PRPEVPRAFR RQPRAAAPSF FFSSIKGGRR SISFSVGASS VVGSGGSSDK
GKLSLQDVAE LIRARACQRV VVMVGAGIST PSGIPDFRSP GSGLYSNLQQ YDLPYPEAIF
ELPFFFHNPK PFFTLAKELY PGNYKPNVTH YFLRLLHDKG LLLRLYTQNI DGLERVSGIP
ASKLVEAHGT FASATCTVCQ RPFPGEDIRA DVMADRVPRC PVCTGVVKPD IVFFGEPLPQ
RFLLHVVDFP MADLLLILGT SLEVEPFASL TEAVRSSVPR LLINRDLVGP LAWHPRSRDV
AQLGDVVHGV ESLVELLGWT EEMRDLVQRE TGKLDGPDK
