Full text data of SIRT5
SIRT5
(SIR2L5)
[Confidence: low (only semi-automatic identification from reviews)]
NAD-dependent protein deacylase sirtuin-5, mitochondrial; 3.5.1.- (Regulatory protein SIR2 homolog 5; SIR2-like protein 5; Flags: Precursor)
NAD-dependent protein deacylase sirtuin-5, mitochondrial; 3.5.1.- (Regulatory protein SIR2 homolog 5; SIR2-like protein 5; Flags: Precursor)
UniProt
Q9NXA8
ID SIR5_HUMAN Reviewed; 310 AA.
AC Q9NXA8; B4DFM4; B4DYJ5; F5H5Z9; Q5T294; Q5T295; Q9Y6E6;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 31-OCT-2003, sequence version 2.
DT 22-JAN-2014, entry version 116.
DE RecName: Full=NAD-dependent protein deacylase sirtuin-5, mitochondrial;
DE EC=3.5.1.-;
DE AltName: Full=Regulatory protein SIR2 homolog 5;
DE AltName: Full=SIR2-like protein 5;
DE Flags: Precursor;
GN Name=SIRT5; Synonyms=SIR2L5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT gene: Sir2-like proteins (sirtuins) metabolize NAD and may have
RT protein ADP-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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT sirtuins 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.,
RA Buerckstuemmer T., 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
RP (ISOFORMS 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.,
RA Fukuda T., Inatome R., Yanagi S.;
RT "Distinct regulation of mitochondrial localization and stability of
RT two 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.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., 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 ENZYME 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.,
RA Schutkowski M., 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. 0:0-0(2013).
RN [14]
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.,
RA Zhang Y., 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 [15]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD
RP AND 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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 34-302 IN COMPLEXES WITH
RP ZINC IONS; SURAMIN AND ADP-RIBOSE, CATALYTIC ACTIVITY, ENZYME
RP REGULATION, AND 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.,
RA Dong A., Loppnau P., Vedadi M., Bochkarev A., Sternglanz R.,
RA Plotnikov A.N.;
RT "Structural basis of inhibition of the human NAD+-dependent
RT deacetylase SIRT5 by suramin.";
RL Structure 15:377-389(2007).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD;
RP ZINC IONS AND SUCCINYLATED PEPTIDE, COFACTOR, ACTIVE SITE,
RP BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF TYR-102; 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.,
RA Auwerx J., Hao Q., Lin H.;
RT "Sirt5 is a NAD-dependent protein lysine demalonylase and
RT desuccinylase.";
RL Science 334:806-809(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD;
RP ZINC 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 [19]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 36-302 IN COMPLEX WITH
RP CARBA-NAD AND ZINC IONS.
RX PubMed=22849721; DOI=10.1021/jo301067e;
RA Szczepankiewicz B.G., Dai H., Koppetsch K.J., Qian D., Jiang F.,
RA Mao C., Perni R.B.;
RT "Synthesis of carba-NAD and the structures of its ternary complexes
RT with SIRT3 and SIRT5.";
RL J. Org. Chem. 77:7319-7329(2012).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-302 IN COMPLEX WITH
RP PROTEIN PEPTIDE; ZINC IONS AND RESVERATROL, AND ENZYME REGULATION.
RX PubMed=23185430; DOI=10.1371/journal.pone.0049761;
RA Gertz M., Nguyen G.T., Fischer F., Suenkel B., Schlicker C.,
RA Franzel B., Tomaschewski J., Aladini F., Becker C., Wolters D.,
RA 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 and desuccinylase that
CC specifically removes malonyl and succinyl groups on target
CC proteins. Activates CPS1 and contributes to the regulation of
CC blood ammonia levels during prolonged fasting: acts by mediating
CC desuccinylation of CPS1, thereby increasing CPS1 activity in
CC response to elevated NAD levels during fasting. Activates SOD1 by
CC mediating its desuccinylation, leading to reduced reactive oxygen
CC species. Has weak NAD-dependent protein deacetylase activity;
CC however this activity may not be physiologically relevant in vivo.
CC Can deacetylate cytochrome c (CYCS) and a number of other proteins
CC in vitro.
CC -!- CATALYTIC ACTIVITY: NAD(+) + a malonylprotein = nicotinamide + O-
CC malonyl-ADP-ribose + a protein.
CC -!- CATALYTIC ACTIVITY: NAD(+) + a succinylprotein = nicotinamide + O-
CC succinyl-ADP-ribose + a protein.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- ENZYME 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.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.1 uM for a synthetic histone H3K9 malonyllysine peptide;
CC KM=5.8 uM for a synthetic histone H3K9 succinyllysine peptide;
CC KM=8.7 uM for a synthetic GLUD1 peptide malonylated at 'Lys-
CC 503';
CC KM=14 uM for a synthetic GLUD1 peptide succinylated at 'Lys-
CC 503';
CC KM=150 uM for a synthetic ACSS1 peptide malonylated at 'Lys-
CC 628';
CC KM=450 uM for a synthetic ACSS1 peptide succinylated at 'Lys-
CC 628';
CC -!- SUBUNIT: Interacts with CPS1 (By similarity). Monomer. Homodimer.
CC Forms homodimers upon suramin binding.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion
CC intermembrane space. Cytoplasm, cytosol. Nucleus. Note=Mainly
CC mitochondrial. Also present extramitochondrially: a fraction is
CC present in the cytosol and very small amounts are also detected in
CC the nucleus.
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Mitochondrion.
CC -!- SUBCELLULAR LOCATION: Isoform 2: Mitochondrion.
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 Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9NXA8-3; Sequence=VSP_042292;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9NXA8-4; Sequence=VSP_042291;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: In contrast to class I sirtuins, class III sirtuins have
CC only weak deacetylase activity. Difference in substrate
CC specificity is probably due to a larger hydrophobic pocket with 2
CC residues (Tyr-102 and Arg-105) that bind to malonylated and
CC succinylated substrates and define the specificity
CC (PubMed:22076378).
CC -!- MISCELLANEOUS: The mechanism of demalonylation and desuccinylation
CC involves the presence of a 1',2'-cyclic intermediate, suggesting
CC that sirtuins use the ADP-ribose-peptidylamidate mechanism to
CC remove acyl groups from substrate lysine residues
CC (PubMed:22767592).
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC -!- SIMILARITY: Contains 1 deacetylase sirtuin-type domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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; CAI19837.1; -; Genomic_DNA.
DR EMBL; AL441883; CAI19838.1; -; Genomic_DNA.
DR EMBL; CH471087; EAW55332.1; -; Genomic_DNA.
DR EMBL; BC000126; AAH00126.1; -; mRNA.
DR RefSeq; NP_001180196.1; NM_001193267.2.
DR RefSeq; NP_001229756.1; NM_001242827.1.
DR RefSeq; NP_036373.1; NM_012241.4.
DR RefSeq; NP_112534.1; NM_031244.3.
DR RefSeq; XP_005249024.1; XM_005248967.1.
DR RefSeq; XP_005249025.1; XM_005248968.1.
DR UniGene; Hs.567431; -.
DR UniGene; Hs.594133; -.
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 PDBsum; 2B4Y; -.
DR PDBsum; 2NYR; -.
DR PDBsum; 3RIG; -.
DR PDBsum; 3RIY; -.
DR PDBsum; 4F4U; -.
DR PDBsum; 4F56; -.
DR PDBsum; 4G1C; -.
DR PDBsum; 4HDA; -.
DR ProteinModelPortal; Q9NXA8; -.
DR SMR; Q9NXA8; 34-302.
DR IntAct; Q9NXA8; 1.
DR STRING; 9606.ENSP00000368552; -.
DR ChEMBL; CHEMBL2163183; -.
DR DrugBank; DB04786; Suramin.
DR PhosphoSite; Q9NXA8; -.
DR DMDM; 38258652; -.
DR PaxDb; Q9NXA8; -.
DR PRIDE; Q9NXA8; -.
DR DNASU; 23408; -.
DR Ensembl; ENST00000359782; ENSP00000352830; ENSG00000124523.
DR Ensembl; ENST00000379262; ENSP00000368564; ENSG00000124523.
DR Ensembl; ENST00000397350; ENSP00000380509; ENSG00000124523.
DR Ensembl; ENST00000606117; ENSP00000476228; ENSG00000124523.
DR GeneID; 23408; -.
DR KEGG; hsa:23408; -.
DR UCSC; uc003nax.3; human.
DR CTD; 23408; -.
DR GeneCards; GC06P013574; -.
DR HGNC; HGNC:14933; SIRT5.
DR HPA; HPA021798; -.
DR HPA; HPA022002; -.
DR HPA; HPA022992; -.
DR MIM; 604483; gene.
DR neXtProt; NX_Q9NXA8; -.
DR PharmGKB; PA37938; -.
DR eggNOG; COG0846; -.
DR HOGENOM; HOG000085950; -.
DR HOVERGEN; HBG056009; -.
DR InParanoid; Q9NXA8; -.
DR KO; K11415; -.
DR OMA; VLHMHGE; -.
DR OrthoDB; EOG77Q4XG; -.
DR PhylomeDB; Q9NXA8; -.
DR EvolutionaryTrace; Q9NXA8; -.
DR GeneWiki; SIRT5; -.
DR GenomeRNAi; 23408; -.
DR NextBio; 45587; -.
DR PRO; PR:Q9NXA8; -.
DR Bgee; Q9NXA8; -.
DR CleanEx; HS_SIRT5; -.
DR Genevestigator; Q9NXA8; -.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; TAS:ProtInc.
DR GO; GO:0070403; F:NAD+ binding; 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:0006342; P:chromatin silencing; TAS:ProtInc.
DR GO; GO:0006471; P:protein ADP-ribosylation; TAS:ProtInc.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR Gene3D; 3.30.1600.10; -; 2.
DR HAMAP; MF_01121; Sirtuin_ClassIII; 1; -.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom.
DR InterPro; IPR027546; Sirtuin_class_III.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR PANTHER; PTHR11085; PTHR11085; 1.
DR Pfam; PF02146; SIR2; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Hydrolase; Metal-binding; Mitochondrion; NAD; Nucleus; Polymorphism;
KW Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1 36 Mitochondrion (By similarity).
FT CHAIN 37 310 NAD-dependent protein deacylase sirtuin-
FT 5, mitochondrial.
FT /FTId=PRO_0000110266.
FT DOMAIN 41 309 Deacetylase sirtuin-type.
FT NP_BIND 58 77 NAD.
FT NP_BIND 140 143 NAD.
FT NP_BIND 249 251 NAD.
FT NP_BIND 275 277 NAD.
FT ACT_SITE 158 158 Proton acceptor.
FT METAL 166 166 Zinc.
FT METAL 169 169 Zinc.
FT METAL 207 207 Zinc.
FT METAL 212 212 Zinc.
FT BINDING 102 102 Substrate.
FT BINDING 105 105 Substrate.
FT BINDING 293 293 NAD; via amide nitrogen.
FT VAR_SEQ 1 108 Missing (in isoform 4).
FT /FTId=VSP_042291.
FT VAR_SEQ 189 206 Missing (in isoform 3).
FT /FTId=VSP_042292.
FT VAR_SEQ 286 299 RFHFQGPCGTTLPE -> SHLISISSLIIIKN (in
FT isoform 2).
FT /FTId=VSP_008730.
FT VAR_SEQ 300 310 Missing (in isoform 2).
FT /FTId=VSP_008731.
FT VARIANT 285 285 F -> L (in dbSNP:rs9464003).
FT /FTId=VAR_029042.
FT VARIANT 305 305 E -> G (in dbSNP:rs34162626).
FT /FTId=VAR_051980.
FT MUTAGEN 69 69 T->A: Abolishes enzyme activity.
FT MUTAGEN 102 102 Y->F: Increases the KM for
FT desuccinylation.
FT MUTAGEN 105 105 R->M: Increases the KM for
FT desuccinylation. Does not affect
FT deacetylase activity.
FT MUTAGEN 158 158 H->A: Abolishes desuccinylation activity.
FT CONFLICT 53 53 I -> M (in Ref. 2; BAG63757).
FT HELIX 40 49
FT STRAND 51 57
FT HELIX 59 61
FT HELIX 63 65
FT STRAND 70 72
FT HELIX 73 75
FT HELIX 82 85
FT HELIX 88 93
FT HELIX 95 109
FT HELIX 116 129
FT TURN 130 132
FT STRAND 134 140
FT HELIX 145 149
FT STRAND 153 156
FT STRAND 159 166
FT TURN 167 169
FT STRAND 172 174
FT STRAND 178 181
FT HELIX 182 184
FT STRAND 190 193
FT HELIX 201 203
FT HELIX 209 211
FT STRAND 215 220
FT HELIX 229 241
FT STRAND 243 249
FT STRAND 252 255
FT HELIX 257 259
FT HELIX 260 266
FT STRAND 271 277
FT HELIX 282 284
FT STRAND 285 291
FT HELIX 293 301
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
//
ID SIR5_HUMAN Reviewed; 310 AA.
AC Q9NXA8; B4DFM4; B4DYJ5; F5H5Z9; Q5T294; Q5T295; Q9Y6E6;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 31-OCT-2003, sequence version 2.
DT 22-JAN-2014, entry version 116.
DE RecName: Full=NAD-dependent protein deacylase sirtuin-5, mitochondrial;
DE EC=3.5.1.-;
DE AltName: Full=Regulatory protein SIR2 homolog 5;
DE AltName: Full=SIR2-like protein 5;
DE Flags: Precursor;
GN Name=SIRT5; Synonyms=SIR2L5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT gene: Sir2-like proteins (sirtuins) metabolize NAD and may have
RT protein ADP-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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT sirtuins 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.,
RA Buerckstuemmer T., 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
RP (ISOFORMS 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.,
RA Fukuda T., Inatome R., Yanagi S.;
RT "Distinct regulation of mitochondrial localization and stability of
RT two 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.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., 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 ENZYME 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.,
RA Schutkowski M., 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. 0:0-0(2013).
RN [14]
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.,
RA Zhang Y., 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 [15]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD
RP AND 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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 34-302 IN COMPLEXES WITH
RP ZINC IONS; SURAMIN AND ADP-RIBOSE, CATALYTIC ACTIVITY, ENZYME
RP REGULATION, AND 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.,
RA Dong A., Loppnau P., Vedadi M., Bochkarev A., Sternglanz R.,
RA Plotnikov A.N.;
RT "Structural basis of inhibition of the human NAD+-dependent
RT deacetylase SIRT5 by suramin.";
RL Structure 15:377-389(2007).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD;
RP ZINC IONS AND SUCCINYLATED PEPTIDE, COFACTOR, ACTIVE SITE,
RP BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF TYR-102; 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.,
RA Auwerx J., Hao Q., Lin H.;
RT "Sirt5 is a NAD-dependent protein lysine demalonylase and
RT desuccinylase.";
RL Science 334:806-809(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD;
RP ZINC 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 [19]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 36-302 IN COMPLEX WITH
RP CARBA-NAD AND ZINC IONS.
RX PubMed=22849721; DOI=10.1021/jo301067e;
RA Szczepankiewicz B.G., Dai H., Koppetsch K.J., Qian D., Jiang F.,
RA Mao C., Perni R.B.;
RT "Synthesis of carba-NAD and the structures of its ternary complexes
RT with SIRT3 and SIRT5.";
RL J. Org. Chem. 77:7319-7329(2012).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-302 IN COMPLEX WITH
RP PROTEIN PEPTIDE; ZINC IONS AND RESVERATROL, AND ENZYME REGULATION.
RX PubMed=23185430; DOI=10.1371/journal.pone.0049761;
RA Gertz M., Nguyen G.T., Fischer F., Suenkel B., Schlicker C.,
RA Franzel B., Tomaschewski J., Aladini F., Becker C., Wolters D.,
RA 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 and desuccinylase that
CC specifically removes malonyl and succinyl groups on target
CC proteins. Activates CPS1 and contributes to the regulation of
CC blood ammonia levels during prolonged fasting: acts by mediating
CC desuccinylation of CPS1, thereby increasing CPS1 activity in
CC response to elevated NAD levels during fasting. Activates SOD1 by
CC mediating its desuccinylation, leading to reduced reactive oxygen
CC species. Has weak NAD-dependent protein deacetylase activity;
CC however this activity may not be physiologically relevant in vivo.
CC Can deacetylate cytochrome c (CYCS) and a number of other proteins
CC in vitro.
CC -!- CATALYTIC ACTIVITY: NAD(+) + a malonylprotein = nicotinamide + O-
CC malonyl-ADP-ribose + a protein.
CC -!- CATALYTIC ACTIVITY: NAD(+) + a succinylprotein = nicotinamide + O-
CC succinyl-ADP-ribose + a protein.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- ENZYME 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.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.1 uM for a synthetic histone H3K9 malonyllysine peptide;
CC KM=5.8 uM for a synthetic histone H3K9 succinyllysine peptide;
CC KM=8.7 uM for a synthetic GLUD1 peptide malonylated at 'Lys-
CC 503';
CC KM=14 uM for a synthetic GLUD1 peptide succinylated at 'Lys-
CC 503';
CC KM=150 uM for a synthetic ACSS1 peptide malonylated at 'Lys-
CC 628';
CC KM=450 uM for a synthetic ACSS1 peptide succinylated at 'Lys-
CC 628';
CC -!- SUBUNIT: Interacts with CPS1 (By similarity). Monomer. Homodimer.
CC Forms homodimers upon suramin binding.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion
CC intermembrane space. Cytoplasm, cytosol. Nucleus. Note=Mainly
CC mitochondrial. Also present extramitochondrially: a fraction is
CC present in the cytosol and very small amounts are also detected in
CC the nucleus.
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Mitochondrion.
CC -!- SUBCELLULAR LOCATION: Isoform 2: Mitochondrion.
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 Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9NXA8-3; Sequence=VSP_042292;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9NXA8-4; Sequence=VSP_042291;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: In contrast to class I sirtuins, class III sirtuins have
CC only weak deacetylase activity. Difference in substrate
CC specificity is probably due to a larger hydrophobic pocket with 2
CC residues (Tyr-102 and Arg-105) that bind to malonylated and
CC succinylated substrates and define the specificity
CC (PubMed:22076378).
CC -!- MISCELLANEOUS: The mechanism of demalonylation and desuccinylation
CC involves the presence of a 1',2'-cyclic intermediate, suggesting
CC that sirtuins use the ADP-ribose-peptidylamidate mechanism to
CC remove acyl groups from substrate lysine residues
CC (PubMed:22767592).
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC -!- SIMILARITY: Contains 1 deacetylase sirtuin-type domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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; CAI19837.1; -; Genomic_DNA.
DR EMBL; AL441883; CAI19838.1; -; Genomic_DNA.
DR EMBL; CH471087; EAW55332.1; -; Genomic_DNA.
DR EMBL; BC000126; AAH00126.1; -; mRNA.
DR RefSeq; NP_001180196.1; NM_001193267.2.
DR RefSeq; NP_001229756.1; NM_001242827.1.
DR RefSeq; NP_036373.1; NM_012241.4.
DR RefSeq; NP_112534.1; NM_031244.3.
DR RefSeq; XP_005249024.1; XM_005248967.1.
DR RefSeq; XP_005249025.1; XM_005248968.1.
DR UniGene; Hs.567431; -.
DR UniGene; Hs.594133; -.
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 PDBsum; 2B4Y; -.
DR PDBsum; 2NYR; -.
DR PDBsum; 3RIG; -.
DR PDBsum; 3RIY; -.
DR PDBsum; 4F4U; -.
DR PDBsum; 4F56; -.
DR PDBsum; 4G1C; -.
DR PDBsum; 4HDA; -.
DR ProteinModelPortal; Q9NXA8; -.
DR SMR; Q9NXA8; 34-302.
DR IntAct; Q9NXA8; 1.
DR STRING; 9606.ENSP00000368552; -.
DR ChEMBL; CHEMBL2163183; -.
DR DrugBank; DB04786; Suramin.
DR PhosphoSite; Q9NXA8; -.
DR DMDM; 38258652; -.
DR PaxDb; Q9NXA8; -.
DR PRIDE; Q9NXA8; -.
DR DNASU; 23408; -.
DR Ensembl; ENST00000359782; ENSP00000352830; ENSG00000124523.
DR Ensembl; ENST00000379262; ENSP00000368564; ENSG00000124523.
DR Ensembl; ENST00000397350; ENSP00000380509; ENSG00000124523.
DR Ensembl; ENST00000606117; ENSP00000476228; ENSG00000124523.
DR GeneID; 23408; -.
DR KEGG; hsa:23408; -.
DR UCSC; uc003nax.3; human.
DR CTD; 23408; -.
DR GeneCards; GC06P013574; -.
DR HGNC; HGNC:14933; SIRT5.
DR HPA; HPA021798; -.
DR HPA; HPA022002; -.
DR HPA; HPA022992; -.
DR MIM; 604483; gene.
DR neXtProt; NX_Q9NXA8; -.
DR PharmGKB; PA37938; -.
DR eggNOG; COG0846; -.
DR HOGENOM; HOG000085950; -.
DR HOVERGEN; HBG056009; -.
DR InParanoid; Q9NXA8; -.
DR KO; K11415; -.
DR OMA; VLHMHGE; -.
DR OrthoDB; EOG77Q4XG; -.
DR PhylomeDB; Q9NXA8; -.
DR EvolutionaryTrace; Q9NXA8; -.
DR GeneWiki; SIRT5; -.
DR GenomeRNAi; 23408; -.
DR NextBio; 45587; -.
DR PRO; PR:Q9NXA8; -.
DR Bgee; Q9NXA8; -.
DR CleanEx; HS_SIRT5; -.
DR Genevestigator; Q9NXA8; -.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; TAS:ProtInc.
DR GO; GO:0070403; F:NAD+ binding; 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:0006342; P:chromatin silencing; TAS:ProtInc.
DR GO; GO:0006471; P:protein ADP-ribosylation; TAS:ProtInc.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR Gene3D; 3.30.1600.10; -; 2.
DR HAMAP; MF_01121; Sirtuin_ClassIII; 1; -.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom.
DR InterPro; IPR027546; Sirtuin_class_III.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR PANTHER; PTHR11085; PTHR11085; 1.
DR Pfam; PF02146; SIR2; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Hydrolase; Metal-binding; Mitochondrion; NAD; Nucleus; Polymorphism;
KW Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1 36 Mitochondrion (By similarity).
FT CHAIN 37 310 NAD-dependent protein deacylase sirtuin-
FT 5, mitochondrial.
FT /FTId=PRO_0000110266.
FT DOMAIN 41 309 Deacetylase sirtuin-type.
FT NP_BIND 58 77 NAD.
FT NP_BIND 140 143 NAD.
FT NP_BIND 249 251 NAD.
FT NP_BIND 275 277 NAD.
FT ACT_SITE 158 158 Proton acceptor.
FT METAL 166 166 Zinc.
FT METAL 169 169 Zinc.
FT METAL 207 207 Zinc.
FT METAL 212 212 Zinc.
FT BINDING 102 102 Substrate.
FT BINDING 105 105 Substrate.
FT BINDING 293 293 NAD; via amide nitrogen.
FT VAR_SEQ 1 108 Missing (in isoform 4).
FT /FTId=VSP_042291.
FT VAR_SEQ 189 206 Missing (in isoform 3).
FT /FTId=VSP_042292.
FT VAR_SEQ 286 299 RFHFQGPCGTTLPE -> SHLISISSLIIIKN (in
FT isoform 2).
FT /FTId=VSP_008730.
FT VAR_SEQ 300 310 Missing (in isoform 2).
FT /FTId=VSP_008731.
FT VARIANT 285 285 F -> L (in dbSNP:rs9464003).
FT /FTId=VAR_029042.
FT VARIANT 305 305 E -> G (in dbSNP:rs34162626).
FT /FTId=VAR_051980.
FT MUTAGEN 69 69 T->A: Abolishes enzyme activity.
FT MUTAGEN 102 102 Y->F: Increases the KM for
FT desuccinylation.
FT MUTAGEN 105 105 R->M: Increases the KM for
FT desuccinylation. Does not affect
FT deacetylase activity.
FT MUTAGEN 158 158 H->A: Abolishes desuccinylation activity.
FT CONFLICT 53 53 I -> M (in Ref. 2; BAG63757).
FT HELIX 40 49
FT STRAND 51 57
FT HELIX 59 61
FT HELIX 63 65
FT STRAND 70 72
FT HELIX 73 75
FT HELIX 82 85
FT HELIX 88 93
FT HELIX 95 109
FT HELIX 116 129
FT TURN 130 132
FT STRAND 134 140
FT HELIX 145 149
FT STRAND 153 156
FT STRAND 159 166
FT TURN 167 169
FT STRAND 172 174
FT STRAND 178 181
FT HELIX 182 184
FT STRAND 190 193
FT HELIX 201 203
FT HELIX 209 211
FT STRAND 215 220
FT HELIX 229 241
FT STRAND 243 249
FT STRAND 252 255
FT HELIX 257 259
FT HELIX 260 266
FT STRAND 271 277
FT HELIX 282 284
FT STRAND 285 291
FT HELIX 293 301
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
//
MIM
604483
*RECORD*
*FIELD* NO
604483
*FIELD* TI
*604483 SIRTUIN 5; SIRT5
;;SIR2, S. CEREVISIAE, HOMOLOG-LIKE 5; SIR2L5
*FIELD* TX
read moreDESCRIPTION
SIRT5 belongs to the sirtuin family of NAD(+)-dependent deacetylases and
mono-ADP-ribosyltransferases. Sirtuins control a variety of cellular
processes, such as aging, metabolism, and gene silencing (summary by
Lombard et al., 2007).
CLONING
The yeast Sir2 (silent information regulator 2) protein (Shore et al.,
1984) regulates epigenetic gene silencing and, as a possible antiaging
effect, suppresses recombination of rDNA. Studies involving cobB, a
bacterial Sir2-like gene, have suggested that Sir2 may encode a pyridine
nucleotide transferase. By in silico and PCR-cloning techniques, Frye
(1999) obtained cDNA sequences encoding 5 human Sir2-like genes, which
they called sirtuin-1 to -5 (SIRT1 to SIRT5). The SIRT1 (604479)
sequence has the closest homology to the S. cerevisiae Sir2 protein,
while SIRT4 (604482) and SIRT5 more closely resemble prokaryotic sirtuin
sequences. PCR analysis showed that the 5 human sirtuins are widely
expressed in fetal and adult tissues.
Lombard et al. (2007) showed that mouse Sirt5 localized to mitochondria.
GENE FUNCTION
Frye (1999) showed that recombinant human SIRT2 (604480) was able to
cause radioactivity to be transferred from (32P)NAD to bovine serum
albumin (BSA). When a conserved histidine within SIRT2 was converted to
tyrosine, the mutant recombinant protein was unable to transfer
radioactivity from (32P)NAD to BSA. These results suggested that the
sirtuins may function via mono-ADP-ribosylation of proteins.
Tanny et al. (1999) showed that the yeast Sir2 protein can transfer
labeled phosphate from nicotinamide adenine dinucleotide to itself and
histones in vitro. A modified form of Sir2, which results from its
automodification activity, was specifically recognized by
anti-mono-ADP-ribose antibodies, suggesting that Sir2 is an
ADP-ribosyltransferase. Mutation of a phylogenetically invariant
histidine (his364 to tyr) in Sir2 abolished both its enzymatic activity
in vitro and its silencing functions in vivo. However, the mutant
protein was associated with chromatin and other silencing factors in a
manner similar to wildtype Sir2. These findings suggested that Sir2
contains an ADP-ribosyltransferase activity that is essential for its
silencing function.
Du et al. (2011) demonstrated that Sirt5 is an efficient protein lysine
desuccinylase and demalonylase in vitro. The preference for succinyl and
malonyl groups was explained by the presence of an arginine residue
(arg105) and tyrosine residue (tyr102) in the acyl pocket of Sirt5.
Several mammalian proteins were identified with mass spectrometry to
have succinyl or malonyl lysine modifications. Deletion of Sirt5 in mice
appeared to increase the level of succinylation on carbamoyl phosphate
synthase-1 (CPS1; 608307), a target of Sirt5. Thus, Du et al. (2011)
concluded that protein lysine succinylation may represent a
posttranslational modification that can be reversed by Sirt5 in vivo.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SIRT5
gene to chromosome 6 (TMAP WI-14994).
ANIMAL MODEL
Lombard et al. (2007) found that Sirt5 -/- mice were born at the
expected mendelian ratio. They appeared healthy and showed normal
fertility.
*FIELD* RF
1. Du, J.; Zhou, Y.; Su, X.; Yu, J. J.; Khan, S.; Jiang, H.; Kim,
J.; Woo, J.; Kim, J. H.; Choi, B. H.; He, B.; Chen, W.; Zhang, S.;
Cerione, R. A.; Auwerx, J.; Hao, Q.; Lin, H.: Sirt5 is a NAD-dependent
protein lysine demalonylase and desuccinylase. Science 334: 806-809,
2011.
2. Frye, R. A.: Characterization of five human cDNAs with homology
to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD
and may have protein ADP-ribosyltransferase activity. Biochem. Biophys.
Res. Commun. 260: 273-279, 1999.
3. Lombard, D. B.; Alt, F. W.; Cheng, H.-L.; Bunkenborg, J.; Streeper,
R. S.; Mostoslavsky, R.; Kim, J.; Yancopoulos, G.; Valenzuela, D.;
Murphy, A.; Yang, Y.; Chen, Y.; Hirschey, M. D.; Bronson, R. T.; Haigis,
M.; Guarente, L. P.; Farese, R. V., Jr.; Weissman, S.; Verdin, E.;
Schwer, B.: Mammalian Sir2 homolog SIRT3 regulates global mitochondrial
lysine acetylation. Molec. Cell. Biol. 27: 8807-8814, 2007.
4. Shore, D.; Squire, M.; Nasmyth, K. A.: Characterization of two
genes required for the position-effect control of yeast mating-type
genes. EMBO J. 3: 2817-2823, 1984.
5. Tanny, J. C.; Dowd, G. J.; Huang, J.; Hilz, H.; Moazed, D.: An
enzymatic activity in the yeast Sir2 protein that is essential for
gene silencing. Cell 99: 735-745, 1999.
*FIELD* CN
Ada Hamosh - updated: 11/29/2011
Patricia A. Hartz - updated: 8/2/2010
Joanna S. Amberger - updated: 3/22/2001
*FIELD* CD
Stylianos E. Antonarakis: 1/31/2000
*FIELD* ED
alopez: 12/01/2011
terry: 11/29/2011
mgross: 8/16/2010
terry: 8/2/2010
joanna: 9/10/2009
cwells: 11/19/2002
terry: 11/15/2002
carol: 3/23/2001
joanna: 3/22/2001
mgross: 1/31/2000
*RECORD*
*FIELD* NO
604483
*FIELD* TI
*604483 SIRTUIN 5; SIRT5
;;SIR2, S. CEREVISIAE, HOMOLOG-LIKE 5; SIR2L5
*FIELD* TX
read moreDESCRIPTION
SIRT5 belongs to the sirtuin family of NAD(+)-dependent deacetylases and
mono-ADP-ribosyltransferases. Sirtuins control a variety of cellular
processes, such as aging, metabolism, and gene silencing (summary by
Lombard et al., 2007).
CLONING
The yeast Sir2 (silent information regulator 2) protein (Shore et al.,
1984) regulates epigenetic gene silencing and, as a possible antiaging
effect, suppresses recombination of rDNA. Studies involving cobB, a
bacterial Sir2-like gene, have suggested that Sir2 may encode a pyridine
nucleotide transferase. By in silico and PCR-cloning techniques, Frye
(1999) obtained cDNA sequences encoding 5 human Sir2-like genes, which
they called sirtuin-1 to -5 (SIRT1 to SIRT5). The SIRT1 (604479)
sequence has the closest homology to the S. cerevisiae Sir2 protein,
while SIRT4 (604482) and SIRT5 more closely resemble prokaryotic sirtuin
sequences. PCR analysis showed that the 5 human sirtuins are widely
expressed in fetal and adult tissues.
Lombard et al. (2007) showed that mouse Sirt5 localized to mitochondria.
GENE FUNCTION
Frye (1999) showed that recombinant human SIRT2 (604480) was able to
cause radioactivity to be transferred from (32P)NAD to bovine serum
albumin (BSA). When a conserved histidine within SIRT2 was converted to
tyrosine, the mutant recombinant protein was unable to transfer
radioactivity from (32P)NAD to BSA. These results suggested that the
sirtuins may function via mono-ADP-ribosylation of proteins.
Tanny et al. (1999) showed that the yeast Sir2 protein can transfer
labeled phosphate from nicotinamide adenine dinucleotide to itself and
histones in vitro. A modified form of Sir2, which results from its
automodification activity, was specifically recognized by
anti-mono-ADP-ribose antibodies, suggesting that Sir2 is an
ADP-ribosyltransferase. Mutation of a phylogenetically invariant
histidine (his364 to tyr) in Sir2 abolished both its enzymatic activity
in vitro and its silencing functions in vivo. However, the mutant
protein was associated with chromatin and other silencing factors in a
manner similar to wildtype Sir2. These findings suggested that Sir2
contains an ADP-ribosyltransferase activity that is essential for its
silencing function.
Du et al. (2011) demonstrated that Sirt5 is an efficient protein lysine
desuccinylase and demalonylase in vitro. The preference for succinyl and
malonyl groups was explained by the presence of an arginine residue
(arg105) and tyrosine residue (tyr102) in the acyl pocket of Sirt5.
Several mammalian proteins were identified with mass spectrometry to
have succinyl or malonyl lysine modifications. Deletion of Sirt5 in mice
appeared to increase the level of succinylation on carbamoyl phosphate
synthase-1 (CPS1; 608307), a target of Sirt5. Thus, Du et al. (2011)
concluded that protein lysine succinylation may represent a
posttranslational modification that can be reversed by Sirt5 in vivo.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SIRT5
gene to chromosome 6 (TMAP WI-14994).
ANIMAL MODEL
Lombard et al. (2007) found that Sirt5 -/- mice were born at the
expected mendelian ratio. They appeared healthy and showed normal
fertility.
*FIELD* RF
1. Du, J.; Zhou, Y.; Su, X.; Yu, J. J.; Khan, S.; Jiang, H.; Kim,
J.; Woo, J.; Kim, J. H.; Choi, B. H.; He, B.; Chen, W.; Zhang, S.;
Cerione, R. A.; Auwerx, J.; Hao, Q.; Lin, H.: Sirt5 is a NAD-dependent
protein lysine demalonylase and desuccinylase. Science 334: 806-809,
2011.
2. Frye, R. A.: Characterization of five human cDNAs with homology
to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD
and may have protein ADP-ribosyltransferase activity. Biochem. Biophys.
Res. Commun. 260: 273-279, 1999.
3. Lombard, D. B.; Alt, F. W.; Cheng, H.-L.; Bunkenborg, J.; Streeper,
R. S.; Mostoslavsky, R.; Kim, J.; Yancopoulos, G.; Valenzuela, D.;
Murphy, A.; Yang, Y.; Chen, Y.; Hirschey, M. D.; Bronson, R. T.; Haigis,
M.; Guarente, L. P.; Farese, R. V., Jr.; Weissman, S.; Verdin, E.;
Schwer, B.: Mammalian Sir2 homolog SIRT3 regulates global mitochondrial
lysine acetylation. Molec. Cell. Biol. 27: 8807-8814, 2007.
4. Shore, D.; Squire, M.; Nasmyth, K. A.: Characterization of two
genes required for the position-effect control of yeast mating-type
genes. EMBO J. 3: 2817-2823, 1984.
5. Tanny, J. C.; Dowd, G. J.; Huang, J.; Hilz, H.; Moazed, D.: An
enzymatic activity in the yeast Sir2 protein that is essential for
gene silencing. Cell 99: 735-745, 1999.
*FIELD* CN
Ada Hamosh - updated: 11/29/2011
Patricia A. Hartz - updated: 8/2/2010
Joanna S. Amberger - updated: 3/22/2001
*FIELD* CD
Stylianos E. Antonarakis: 1/31/2000
*FIELD* ED
alopez: 12/01/2011
terry: 11/29/2011
mgross: 8/16/2010
terry: 8/2/2010
joanna: 9/10/2009
cwells: 11/19/2002
terry: 11/15/2002
carol: 3/23/2001
joanna: 3/22/2001
mgross: 1/31/2000