ID SIR5_HUMAN Reviewed; 310 AA. AC Q9NXA8; B4DFM4; B4DYJ5; F5H5Z9; Q5T294; Q5T295; Q9Y6E6; DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2003, sequence version 2. DT 02-SEP-2026, entry version 197. 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, ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:24703693, ECO:0000269|PubMed:29180469}; DE AltName: Full=Regulatory protein SIR2 homolog 5 {ECO:0000255|HAMAP-Rule:MF_03160}; DE AltName: Full=SIR2-like protein 5 {ECO:0000255|HAMAP-Rule:MF_03160}; DE Flags: Precursor; GN Name=SIRT5 {ECO:0000255|HAMAP-Rule:MF_03160}; Synonyms=SIR2L5; 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] (ISOFORMS 2; 3 AND 4). RC TISSUE=Amygdala, Hepatoblastoma, and Testis; 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 MRNA]. 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Eye; 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 [7] 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 [8] RP FUNCTION, AND SUBCELLULAR LOCATION. 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 [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), AND SUBCELLULAR LOCATION (ISOFORMS RP 1 AND 2). RX PubMed=21143562; DOI=10.1111/j.1365-2443.2010.01475.x; RA Matsushita N., Yonashiro R., Ogata Y., Sugiura A., Nagashima S., Fukuda T., RA Inatome R., Yanagi S.; RT "Distinct regulation of mitochondrial localization and stability of two RT human Sirt5 isoforms."; RL Genes Cells 16:190-202(2011). RN [11] RP FUNCTION, NAD-BINDING, AND MUTAGENESIS OF HIS-158. RX PubMed=21908771; DOI=10.1074/mcp.m111.012658; RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., RA Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J., RA Verdin E., Ye Y., Zhao Y.; RT "The first identification of lysine malonylation substrates and its RT regulatory enzyme."; RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011). RN [12] RP ACTIVITY REGULATION, AND MUTAGENESIS OF THR-69 AND ARG-105. RX PubMed=23028781; DOI=10.1371/journal.pone.0045098; RA Fischer F., Gertz M., Suenkel B., Lakshminarasimhan M., Schutkowski M., RA Steegborn C.; RT "Sirt5 deacylation activities show differential sensitivities to RT nicotinamide inhibition."; RL PLoS ONE 7:E45098-E45098(2012). RN [13] RP FUNCTION. RX PubMed=24140062; DOI=10.1016/j.bbrc.2013.10.033; RA Lin Z.F., Xu H.B., Wang J.Y., Lin Q., Ruan Z., Liu F.B., Jin W., RA Huang H.H., Chen X.; RT "SIRT5 desuccinylates and activates SOD1 to eliminate ROS."; RL Biochem. Biophys. Res. Commun. 441:191-195(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 SUBCELLULAR LOCATION. 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, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-158. RX PubMed=24703693; DOI=10.1016/j.cmet.2014.03.014; RA Tan M., Peng C., Anderson K.A., Chhoy P., Xie Z., Dai L., Park J., Chen Y., RA Huang H., Zhang Y., Ro J., Wagner G.R., Green M.F., Madsen A.S., RA Schmiesing J., Peterson B.S., Xu G., Ilkayeva O.R., Muehlbauer M.J., RA Braulke T., Muehlhausen C., Backos D.S., Olsen C.A., McGuire P.J., RA Pletcher S.D., Lombard D.B., Hirschey M.D., Zhao Y.; RT "Lysine glutarylation is a protein posttranslational modification regulated RT by SIRT5."; RL Cell Metab. 19:605-617(2014). RN [17] 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 [18] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-158. RX PubMed=29180469; DOI=10.1158/0008-5472.can-17-1912; RA Yang X., Wang Z., Li X., Liu B., Liu M., Liu L., Chen S., Ren M., Wang Y., RA Yu M., Wang B., Zou J., Zhu W.G., Yin Y., Gu W., Luo J.; RT "SHMT2 desuccinylation by SIRT5 drives cancer cell proliferation."; RL Cancer Res. 78:372-386(2018). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD AND RP ZINC IONS. RG Structural genomics consortium (SGC); RT "Crystal structure of human sirtuin homolog 5 in complex with NAD."; RL Submitted (FEB-2006) to the PDB data bank. RN [20] RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 34-302 IN COMPLEXES WITH ZINC RP IONS; SURAMIN AND ADP-RIBOSE, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND RP SUBUNIT. RX PubMed=17355872; DOI=10.1016/j.str.2007.02.002; RA Schuetz A., Min J., Antoshenko T., Wang C.-L., Allali-Hassani A., Dong A., RA Loppnau P., Vedadi M., Bochkarev A., Sternglanz R., Plotnikov A.N.; RT "Structural basis of inhibition of the human NAD+-dependent deacetylase RT SIRT5 by suramin."; RL Structure 15:377-389(2007). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD; ZINC RP IONS AND SUCCINYLATED PEPTIDE, COFACTOR, ACTIVE SITE, BIOPHYSICOCHEMICAL RP PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-102; RP ARG-105 AND HIS-158. RX PubMed=22076378; DOI=10.1126/science.1207861; RA Du J., Zhou Y., Su X., Yu J.J., Khan S., Jiang H., Kim J., Woo J., RA Kim J.H., Choi B.H., He B., Chen W., Zhang S., Cerione R.A., Auwerx J., RA Hao Q., Lin H.; RT "Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase."; RL Science 334:806-809(2011). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD; ZINC RP IONS AND SUCCINYLATED PEPTIDE, AND REACTION MECHANISM. RX PubMed=22767592; DOI=10.1074/jbc.m112.384511; RA Zhou Y., Zhang H., He B., Du J., Lin H., Cerione R.A., Hao Q.; RT "The bicyclic intermediate structure provides insights into the RT desuccinylation mechanism of human sirtuin 5 (SIRT5)."; RL J. Biol. Chem. 287:28307-28314(2012). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 36-302 IN COMPLEX WITH CARBA-NAD RP AND ZINC IONS. RX PubMed=22849721; DOI=10.1021/jo301067e; RA Szczepankiewicz B.G., Dai H., Koppetsch K.J., Qian D., Jiang F., Mao C., RA Perni R.B.; RT "Synthesis of carba-NAD and the structures of its ternary complexes with RT SIRT3 and SIRT5."; RL J. Org. Chem. 77:7319-7329(2012). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-302 IN COMPLEX WITH PROTEIN RP PEPTIDE; ZINC IONS AND RESVERATROL, AND ACTIVITY REGULATION. RX PubMed=23185430; DOI=10.1371/journal.pone.0049761; RA Gertz M., Nguyen G.T., Fischer F., Suenkel B., Schlicker C., Franzel B., RA Tomaschewski J., Aladini F., Becker C., Wolters D., Steegborn C.; RT "A molecular mechanism for direct sirtuin activation by resveratrol."; RL PLoS ONE 7:E49761-E49761(2012). CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-malonyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-malonyl- CC ADP-D-ribose + nicotinamide + L-lysyl-[protein]; 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 ECO:0000269|PubMed:22076378}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-succinyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O- CC succinyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]; 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 ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:29180469}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-glutaryl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O- CC glutaryl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]; 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 ECO:0000269|PubMed:24703693}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|HAMAP- CC Rule:MF_03160, ECO:0000269|PubMed:22076378}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03160, CC ECO:0000269|PubMed:22076378}; CC -!- ACTIVITY REGULATION: Inhibited by suramin. NAD-dependent lysine CC desuccinylase activity is inhibited by physiological nicotinamide CC concentrations, while deacetylase activity is not. In contrast, CC resveratrol activates deacetylase activity, while inhibiting CC desuccinylase activity. {ECO:0000269|PubMed:17355872, CC ECO:0000269|PubMed:23028781, ECO:0000269|PubMed:23185430}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=6.1 uM for a synthetic histone H3K9 malonyllysine peptide CC {ECO:0000269|PubMed:22076378}; CC KM=5.8 uM for a synthetic histone H3K9 succinyllysine peptide CC {ECO:0000269|PubMed:22076378}; CC KM=8.7 uM for a synthetic GLUD1 peptide malonylated at 'Lys-503' CC {ECO:0000269|PubMed:22076378}; CC KM=14 uM for a synthetic GLUD1 peptide succinylated at 'Lys-503' CC {ECO:0000269|PubMed:22076378}; CC KM=150 uM for a synthetic ACSS1 peptide malonylated at 'Lys-628' CC {ECO:0000269|PubMed:22076378}; CC KM=450 uM for a synthetic ACSS1 peptide succinylated at 'Lys-628' CC {ECO:0000269|PubMed:22076378}; CC -!- SUBUNIT: Interacts with CPS1 (By similarity). Interacts with PCCA CC (PubMed:23438705). Monomer (PubMed:17355872). Homodimer CC (PubMed:17355872). Forms homodimers upon suramin binding CC (PubMed:17355872). {ECO:0000250|UniProtKB:Q8K2C6, CC ECO:0000269|PubMed:17355872, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:22767592, ECO:0000269|PubMed:22849721, CC ECO:0000269|PubMed:23185430, ECO:0000269|PubMed:23438705, CC ECO:0000269|Ref.19}. CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane CC space. Cytoplasm, cytosol. Nucleus. 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 -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm CC {ECO:0000269|PubMed:21143562}. Mitochondrion {ECO:0000255|HAMAP- CC Rule:MF_03160, ECO:0000269|PubMed:21143562}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion {ECO:0000255|HAMAP- CC Rule:MF_03160, ECO:0000269|PubMed:21143562}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q9NXA8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NXA8-2; Sequence=VSP_008730, VSP_008731; CC Name=3; CC IsoId=Q9NXA8-3; Sequence=VSP_042292; CC Name=4; CC IsoId=Q9NXA8-4; Sequence=VSP_042291; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10381378}. 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-102 CC and Arg-105) that bind to malonylated and succinylated substrates and CC define the specificity (PubMed:22076378). CC {ECO:0000269|PubMed:22076378}. CC -!- MISCELLANEOUS: The mechanism of demalonylation and desuccinylation CC involves the presence of a 1',2'-cyclic intermediate, suggesting that CC sirtuins use the ADP-ribose-peptidylamidate mechanism to remove acyl CC groups from substrate lysine residues. {ECO:0000305|PubMed:22767592}. CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily. CC {ECO:0000255|HAMAP-Rule:MF_03160}. 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; AF083110; AAD40853.1; -; mRNA. DR EMBL; AK000355; BAA91107.1; -; mRNA. DR EMBL; AK294162; BAG57485.1; -; mRNA. DR EMBL; AK302467; BAG63757.1; -; mRNA. DR EMBL; AM393414; CAL38292.1; -; mRNA. DR EMBL; AL441883; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471087; EAW55332.1; -; Genomic_DNA. DR EMBL; BC000126; AAH00126.1; -; mRNA. DR CCDS; CCDS4526.1; -. [Q9NXA8-1] DR CCDS; CCDS4527.1; -. [Q9NXA8-2] DR CCDS; CCDS54966.1; -. [Q9NXA8-3] DR RefSeq; NP_001180196.1; NM_001193267.2. [Q9NXA8-3] DR RefSeq; NP_001229756.1; NM_001242827.1. [Q9NXA8-4] DR RefSeq; NP_001363727.1; NM_001376798.1. [Q9NXA8-1] DR RefSeq; NP_001363728.1; NM_001376799.1. [Q9NXA8-1] DR RefSeq; NP_001363729.1; NM_001376800.1. [Q9NXA8-1] DR RefSeq; NP_001363730.1; NM_001376801.1. [Q9NXA8-1] DR RefSeq; NP_001363731.1; NM_001376802.1. [Q9NXA8-1] DR RefSeq; NP_001363732.1; NM_001376803.1. [Q9NXA8-1] DR RefSeq; NP_001363733.1; NM_001376804.1. [Q9NXA8-1] DR RefSeq; NP_001363734.1; NM_001376805.1. [Q9NXA8-1] DR RefSeq; NP_001363735.1; NM_001376806.1. [Q9NXA8-1] DR RefSeq; NP_001363736.1; NM_001376807.1. [Q9NXA8-1] DR RefSeq; NP_001363737.1; NM_001376808.1. [Q9NXA8-2] DR RefSeq; NP_001363741.1; NM_001376812.1. [Q9NXA8-4] DR RefSeq; NP_036373.1; NM_012241.5. [Q9NXA8-1] DR RefSeq; NP_112534.1; NM_031244.3. [Q9NXA8-2] DR RefSeq; XP_047274470.1; XM_047418514.1. [Q9NXA8-1] DR RefSeq; XP_047274471.1; XM_047418515.1. [Q9NXA8-1] DR RefSeq; XP_047274472.1; XM_047418516.1. [Q9NXA8-1] DR RefSeq; XP_047274473.1; XM_047418517.1. [Q9NXA8-2] DR RefSeq; XP_047274474.1; XM_047418518.1. [Q9NXA8-2] DR RefSeq; XP_047274475.1; XM_047418519.1. [Q9NXA8-2] DR RefSeq; XP_047274476.1; XM_047418520.1. [Q9NXA8-2] DR RefSeq; XP_054210899.1; XM_054354924.1. [Q9NXA8-1] DR RefSeq; XP_054210900.1; XM_054354925.1. [Q9NXA8-1] DR RefSeq; XP_054210901.1; XM_054354926.1. [Q9NXA8-1] DR RefSeq; XP_054210902.1; XM_054354927.1. [Q9NXA8-2] DR RefSeq; XP_054210903.1; XM_054354928.1. [Q9NXA8-2] DR RefSeq; XP_054210904.1; XM_054354929.1. [Q9NXA8-2] DR RefSeq; XP_054210905.1; XM_054354930.1. [Q9NXA8-2] DR PDB; 2B4Y; X-ray; 1.90 A; A/B/C/D=34-302. DR PDB; 2NYR; X-ray; 2.06 A; A/B=34-302. DR PDB; 3RIG; X-ray; 2.00 A; A/B=34-302. DR PDB; 3RIY; X-ray; 1.55 A; A/B=34-302. DR PDB; 4F4U; X-ray; 2.00 A; A/B=34-302. DR PDB; 4F56; X-ray; 1.70 A; A/B=34-302. DR PDB; 4G1C; X-ray; 1.94 A; A/B=36-302. DR PDB; 4HDA; X-ray; 2.60 A; A/B=34-302. DR PDB; 5BWL; X-ray; 1.55 A; A=33-302. DR PDB; 5XHS; X-ray; 2.19 A; A=34-302. DR PDB; 6ACE; X-ray; 1.98 A; A=36-302. DR PDB; 6ACL; X-ray; 1.92 A; A=36-302. DR PDB; 6ACO; X-ray; 1.71 A; A=34-302. DR PDB; 6ACP; X-ray; 2.30 A; A=36-302. DR PDB; 6EQS; X-ray; 1.32 A; A/B/C/D=34-302. DR PDB; 6LJK; X-ray; 1.39 A; A=34-302. DR PDB; 6LJM; X-ray; 1.78 A; A=34-302. DR PDB; 6LJN; X-ray; 1.80 A; A=34-302. DR PDB; 7X3P; X-ray; 1.56 A; A=34-310. DR PDB; 8GBL; X-ray; 2.24 A; A/B=32-302. DR PDB; 8GBN; X-ray; 2.70 A; A/B=32-302. DR PDB; 8Z54; X-ray; 1.45 A; A=36-302. DR PDB; 8Z55; X-ray; 1.83 A; A=36-302. DR PDB; 8Z56; X-ray; 1.81 A; A=36-302. DR PDB; 8Z57; X-ray; 1.96 A; A=36-302. DR PDB; 8Z58; X-ray; 2.40 A; A=36-302. DR AlphaFoldDB; Q9NXA8; -. DR SMR; Q9NXA8; -. DR BioGRID; 116980; 71. DR FunCoup; Q9NXA8; 1237. DR IntAct; Q9NXA8; 49. DR MINT; Q9NXA8; -. DR NDEx; IQUERY-CP-SIRT5; 4 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000476228; -. DR BindingDB; Q9NXA8; -. DR ChEMBL; CHEMBL2163183; -. DR DrugBank; DB03478; 2'-O-Acetyl Adenosine-5-Diphosphoribose. DR DrugBank; DB02059; Adenosine-5-Diphosphoribose. DR DrugBank; DB15493; Cambinol. DR DrugBank; DB02701; Nicotinamide. DR DrugBank; DB04786; Suramin. DR DrugCentral; Q9NXA8; -. DR GuidetoPHARMACOLOGY; 2711; -. DR GlyGen; Q9NXA8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NXA8; -. DR PhosphoSitePlus; Q9NXA8; -. DR SwissPalm; Q9NXA8; -. DR BioMuta; SIRT5; -. DR DMDM; 38258652; -. DR jPOST; Q9NXA8; -. DR MassIVE; Q9NXA8; -. DR PaxDb; 9606-ENSP00000476228; -. DR PeptideAtlas; Q9NXA8; -. DR ProteomicsDB; 83064; -. [Q9NXA8-1] DR ProteomicsDB; 83065; -. [Q9NXA8-2] DR ProteomicsDB; 83066; -. [Q9NXA8-3] DR ProteomicsDB; 83067; -. [Q9NXA8-4] DR Pumba; Q9NXA8; -. DR ABCD; Q9NXA8; 5 sequenced antibodies. DR Antibodypedia; 10177; 681 antibodies from 46 providers. DR DNASU; 23408; -. DR Ensembl; ENST00000359782.8; ENSP00000352830.3; ENSG00000124523.18. [Q9NXA8-3] DR Ensembl; ENST00000379262.8; ENSP00000368564.4; ENSG00000124523.18. [Q9NXA8-2] DR Ensembl; ENST00000397350.7; ENSP00000380509.3; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000606117.2; ENSP00000476228.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000680151.1; ENSP00000505086.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000680432.1; ENSP00000505496.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000680707.1; ENSP00000505469.1; ENSG00000124523.18. [Q9NXA8-2] DR Ensembl; ENST00000888571.1; ENSP00000558630.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888572.1; ENSP00000558631.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888574.1; ENSP00000558633.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888575.1; ENSP00000558634.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888576.1; ENSP00000558635.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888577.1; ENSP00000558636.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888579.1; ENSP00000558638.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888580.1; ENSP00000558639.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888581.1; ENSP00000558640.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888582.1; ENSP00000558641.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888583.1; ENSP00000558642.1; ENSG00000124523.18. [Q9NXA8-3] DR Ensembl; ENST00000888584.1; ENSP00000558643.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888585.1; ENSP00000558644.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888586.1; ENSP00000558645.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888587.1; ENSP00000558646.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888588.1; ENSP00000558647.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888589.1; ENSP00000558648.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000888590.1; ENSP00000558649.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000915669.1; ENSP00000585728.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000915670.1; ENSP00000585729.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000915672.1; ENSP00000585731.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000915674.1; ENSP00000585733.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949353.1; ENSP00000619412.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949354.1; ENSP00000619413.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949357.1; ENSP00000619416.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949360.1; ENSP00000619419.1; ENSG00000124523.18. [Q9NXA8-3] DR Ensembl; ENST00000949361.1; ENSP00000619420.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949362.1; ENSP00000619421.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949363.1; ENSP00000619422.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949365.1; ENSP00000619424.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949366.1; ENSP00000619425.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949368.1; ENSP00000619427.1; ENSG00000124523.18. [Q9NXA8-3] DR Ensembl; ENST00000949370.1; ENSP00000619429.1; ENSG00000124523.18. [Q9NXA8-1] DR Ensembl; ENST00000949371.1; ENSP00000619430.1; ENSG00000124523.18. [Q9NXA8-3] DR Ensembl; ENST00000949373.1; ENSP00000619432.1; ENSG00000124523.18. [Q9NXA8-1] DR GeneID; 23408; -. DR KEGG; hsa:23408; -. DR MANE-Select; ENST00000606117.2; ENSP00000476228.1; NM_012241.5; NP_036373.1. DR UCSC; uc003naw.4; human. [Q9NXA8-1] DR AGR; HGNC:14933; -. DR ClinPGx; PA37938; -. DR CTD; 23408; -. DR DisGeNET; 23408; -. DR GeneCards; SIRT5; -. DR HGNC; HGNC:14933; SIRT5. DR HPA; ENSG00000124523; Low tissue specificity. DR MIM; 604483; gene. DR OpenTargets; ENSG00000124523; -. DR VEuPathDB; HostDB:ENSG00000124523; -. DR eggNOG; KOG2684; Eukaryota. DR GeneTree; ENSGT00940000156080; -. DR HOGENOM; CLU_023643_3_1_1; -. DR InParanoid; Q9NXA8; -. DR OMA; LIHMHGE; -. DR OrthoDB; 424302at2759; -. DR PAN-GO; Q9NXA8; 8 GO annotations based on evolutionary models. DR PhylomeDB; Q9NXA8; -. DR BRENDA; 2.3.1.B43; 2681. DR PathwayCommons; Q9NXA8; -. DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis. DR Reactome; R-HSA-70635; Urea cycle. DR SABIO-RK; Q9NXA8; -. DR SignaLink; Q9NXA8; -. DR SIGNOR; Q9NXA8; -. DR Agora; ENSG00000124523; -. DR BioGRID-ORCS; 23408; 14 hits in 1194 CRISPR screens. DR ChiTaRS; SIRT5; human. DR EvolutionaryTrace; Q9NXA8; -. DR GeneWiki; SIRT5; -. DR GenomeRNAi; 23408; -. DR Pharos; Q9NXA8; Tchem. DR PRO; PR:Q9NXA8; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q9NXA8; protein. DR Bgee; ENSG00000124523; Expressed in diaphragm and 203 other cell types or tissues. DR ExpressionAtlas; Q9NXA8; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; TAS:UniProtKB. DR GO; GO:0017136; F:histone deacetylase activity, NAD-dependent; IBA:GO_Central. DR GO; GO:0070403; F:NAD+ binding; IDA:UniProtKB. DR GO; GO:0034979; F:NAD-dependent protein lysine deacetylase activity; TAS:Reactome. DR GO; GO:0061697; F:protein-glutaryllysine deglutarylase activity; IDA:UniProtKB. DR GO; GO:0036054; F:protein-malonyllysine demalonylase activity; IDA:UniProtKB. DR GO; GO:0036055; F:protein-succinyllysine desuccinylase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0007005; P:mitochondrion organization; TAS:Reactome. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IDA:UniProtKB. DR GO; GO:0036047; P:peptidyl-lysine demalonylation; IDA:UniProtKB. DR GO; GO:0036049; P:peptidyl-lysine desuccinylation; IDA:UniProtKB. DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB. DR GO; GO:0061698; P:protein deglutarylation; IDA:UniProtKB. DR GO; GO:0036046; P:protein demalonylation; IDA:UniProtKB. DR GO; GO:0036048; P:protein desuccinylation; IDA:UniProtKB. DR GO; GO:0010566; P:regulation of ketone biosynthetic process; ISS:UniProtKB. DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl. DR GO; GO:0000050; P:urea cycle; TAS:Reactome. DR CDD; cd01412; SIRT5_Af1_CobB; 1. DR FunFam; 3.30.1600.10:FF:000005; NAD-dependent protein deacylase sirtuin-5, mitochondrial; 1. DR Gene3D; 3.30.1600.10; SIR2/SIRT2 'Small Domain; 1. DR Gene3D; 3.40.50.1220; TPP-binding domain; 1. DR HAMAP; MF_01121; Sirtuin_ClassIII; 1. DR IDEAL; IID00502; -. DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom. DR InterPro; IPR050134; NAD-dep_sirtuin_deacylases. 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 PANTHER; PTHR11085; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL-RELATED; 1. DR PANTHER; PTHR11085:SF10; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL-RELATED; 1. DR Pfam; PF02146; SIR2; 1. DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 1. DR PROSITE; PS50305; SIRTUIN; 1. DR PDBsum; 2B4Y; -. DR PDBsum; 2NYR; -. DR PDBsum; 3RIG; -. DR PDBsum; 3RIY; -. DR PDBsum; 4F4U; -. DR PDBsum; 4F56; -. DR PDBsum; 4G1C; -. DR PDBsum; 4HDA; -. DR PDBsum; 5BWL; -. DR PDBsum; 5XHS; -. DR PDBsum; 6ACE; -. DR PDBsum; 6ACL; -. DR PDBsum; 6ACO; -. DR PDBsum; 6ACP; -. DR PDBsum; 6EQS; -. DR PDBsum; 6LJK; -. DR PDBsum; 6LJM; -. DR PDBsum; 6LJN; -. DR PDBsum; 7X3P; -. DR PDBsum; 8GBL; -. DR PDBsum; 8GBN; -. DR PDBsum; 8Z54; -. DR PDBsum; 8Z55; -. DR PDBsum; 8Z56; -. DR PDBsum; 8Z57; -. DR PDBsum; 8Z58; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Metal-binding; KW Mitochondrion; NAD; Nucleus; Proteomics identification; Reference proteome; KW Transferase; Transit peptide; Zinc. FT TRANSIT 1..36 FT /note="Mitochondrion" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160" FT CHAIN 37..310 FT /note="NAD-dependent protein deacylase sirtuin-5, FT mitochondrial" FT /id="PRO_0000110266" FT DOMAIN 37..307 FT /note="Deacetylase sirtuin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236" FT ACT_SITE 158 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236, FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:29180469" FT BINDING 58..77 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160, FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592, FT ECO:0000269|Ref.19" FT BINDING 102 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160" FT BINDING 105 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160" FT BINDING 140..143 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160, FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592, FT ECO:0000269|Ref.19" FT BINDING 166 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160" FT BINDING 169 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160" FT BINDING 207 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160" FT BINDING 212 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160" FT BINDING 249..251 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160, FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592, FT ECO:0000269|Ref.19" FT BINDING 275..277 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160, FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592, FT ECO:0000269|Ref.19" FT BINDING 293 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160, FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592, FT ECO:0000269|Ref.19" FT VAR_SEQ 1..108 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042291" FT VAR_SEQ 189..206 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042292" FT VAR_SEQ 286..299 FT /note="RFHFQGPCGTTLPE -> SHLISISSLIIIKN (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_008730" FT VAR_SEQ 300..310 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_008731" FT VARIANT 285 FT /note="F -> L (in dbSNP:rs9464003)" FT /id="VAR_029042" FT VARIANT 305 FT /note="E -> G (in dbSNP:rs34162626)" FT /id="VAR_051980" FT MUTAGEN 69 FT /note="T->A: Abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:23028781" FT MUTAGEN 102 FT /note="Y->F: Increases the KM for desuccinylation." FT /evidence="ECO:0000269|PubMed:22076378" FT MUTAGEN 105 FT /note="R->M: Increases the KM for desuccinylation. Does not FT affect deacetylase activity." FT /evidence="ECO:0000269|PubMed:22076378, FT ECO:0000269|PubMed:23028781" FT MUTAGEN 158 FT /note="H->A: Abolishes desuccinylation and deglutarylation FT activity." FT /evidence="ECO:0000269|PubMed:21908771, FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:24703693, FT ECO:0000269|PubMed:29180469" FT CONFLICT 53 FT /note="I -> M (in Ref. 2; BAG63757)" FT /evidence="ECO:0000305" FT HELIX 40..49 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 51..57 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 60..63 FT /evidence="ECO:0007829|PDB:6EQS" FT TURN 64..66 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 67..69 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 72..75 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 82..85 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 88..93 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 95..109 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 112..114 FT /evidence="ECO:0007829|PDB:3RIG" FT HELIX 116..130 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 134..139 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 145..148 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 152..156 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 159..166 FT /evidence="ECO:0007829|PDB:6EQS" FT TURN 167..169 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 172..174 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 178..181 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 182..184 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 190..193 FT /evidence="ECO:0007829|PDB:4HDA" FT HELIX 194..196 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:6EQS" FT TURN 210..212 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 215..220 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 229..241 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 243..249 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 252..254 FT /evidence="ECO:0007829|PDB:5BWL" FT HELIX 257..259 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 260..266 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 271..277 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 282..284 FT /evidence="ECO:0007829|PDB:6EQS" FT STRAND 285..291 FT /evidence="ECO:0007829|PDB:6EQS" FT HELIX 293..300 FT /evidence="ECO:0007829|PDB:6EQS" SQ SEQUENCE 310 AA; 33881 MW; 022DA32CDB43AC3A CRC64; MRPLQIVPSR LISQLYCGLK PPASTRNQIC LKMARPSSSM ADFRKFFAKA KHIVIISGAG VSAESGVPTF RGAGGYWRKW QAQDLATPLA FAHNPSRVWE FYHYRREVMG SKEPNAGHRA IAECETRLGK QGRRVVVITQ NIDELHRKAG TKNLLEIHGS LFKTRCTSCG VVAENYKSPI CPALSGKGAP EPGTQDASIP VEKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDRELA HCDLCLVVGT SSVVYPAAMF APQVAARGVP VAEFNTETTP ATNRFRFHFQ GPCGTTLPEA LACHENETVS //