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Identification
HMDB Protein ID HMDBP08881
Secondary Accession Numbers
  • 14608
Name NAD-dependent protein deacetylase sirtuin-3, mitochondrial
Synonyms
  1. SIR2-like protein 3
  2. hSIRT3
  3. Regulatory protein SIR2 homolog 3
Gene Name SIRT3
Protein Type Unknown
Biological Properties
General Function Involved in zinc ion binding
Specific Function NAD-dependent protein deacetylase. Activates mitochondrial target proteins, including ACSS1, IDH2 and GDH by deacetylating key lysine residues. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.
Pathways Not Available
Reactions
NAD + an acetylprotein → Niacinamide + O-acetyl-ADP-ribose + a protein details
GO Classification
Biological Process
protein ADP-ribosylation
aerobic respiration
peptidyl-lysine deacetylation
Cellular Component
mitochondrial matrix
mitochondrion
membrane
Function
ion binding
cation binding
metal ion binding
binding
nucleotide binding
catalytic activity
hydrolase activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
transition metal ion binding
zinc ion binding
nad or nadh binding
nad binding
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
Molecular Function
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
metal ion binding
NAD+ ADP-ribosyltransferase activity
zinc ion binding
NAD+ binding
Process
metabolic process
macromolecule metabolic process
protein amino acid deacetylation
gene silencing
chromatin silencing
cellular process
biological regulation
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
regulation of gene expression
regulation of transcription
post-translational protein modification
macromolecule modification
protein modification process
Cellular Location
  1. Mitochondrion matrix
Gene Properties
Chromosome Location 11
Locus 11p15.5
SNPs SIRT3
Gene Sequence
>1200 bp
ATGGCGTTCTGGGGTTGGCGCGCCGCGGCAGCCCTCCGGCTGTGGGGCCGGGTAGTTGAA
CGGGTCGAGGCCGGGGGAGGCGTGGGGCCGTTTCAGGCCTGCGGCTGTCGGCTGGTGCTT
GGCGGCAGGGACGATGTGAGTGCGGGGCTGAGAGGCAGCCATGGGGCCCGCGGTGAGCCC
TTGGACCCGGCGCGCCCCTTGCAGAGGCCTCCCAGACCCGAGGTGCCCAGGGCATTCCGG
AGGCAGCCGAGGGCAGCAGCTCCCAGTTTCTTCTTTTCGAGTATTAAAGGTGGAAGAAGG
TCCATATCTTTTTCTGTGGGTGCTTCAAGTGTTGTTGGAAGTGGAGGCAGCAGTGACAAG
GGGAAGCTTTCCCTGCAGGATGTAGCTGAGCTGATTCGGGCCAGAGCCTGCCAGAGGGTG
GTGGTCATGGTGGGGGCCGGCATCAGCACACCCAGTGGCATTCCAGACTTCAGATCGCCG
GGGAGTGGCCTGTACAGCAACCTCCAGCAGTACGATCTCCCGTACCCCGAGGCCATTTTT
GAACTCCCATTCTTCTTTCACAACCCCAAGCCCTTTTTCACTTTGGCCAAGGAGCTGTAC
CCTGGAAACTACAAGCCCAACGTCACTCACTACTTTCTCCGGCTGCTTCATGACAAGGGG
CTGCTTCTGCGGCTCTACACGCAGAACATCGATGGGCTTGAGAGAGTGTCGGGCATCCCT
GCCTCAAAGCTGGTTGAAGCTCATGGAACCTTTGCCTCTGCCACCTGCACAGTCTGCCAA
AGACCCTTCCCAGGGGAGGACATTCGGGCTGACGTGATGGCAGACAGGGTTCCCCGCTGC
CCGGTCTGCACCGGCGTTGTGAAGCCCGACATTGTGTTCTTTGGGGAGCCGCTGCCCCAG
AGGTTCTTGCTGCATGTGGTTGATTTCCCCATGGCAGATCTGCTGCTCATCCTTGGGACC
TCCCTGGAGGTGGAGCCTTTTGCCAGCTTGACCGAGGCCGTGCGGAGCTCAGTTCCCCGA
CTGCTCATCAACCGGGACTTGGTGGGGCCCTTGGCTTGGCATCCTCGCAGCAGGGACGTG
GCCCAGCTGGGGGACGTGGTTCACGGCGTGGAAAGCCTAGTGGAGCTTCTGGGCTGGACA
GAAGAGATGCGGGACCTTGTGCAGCGGGAAACTGGGAAGCTTGATGGACCAGACAAATAG
Protein Properties
Number of Residues 399
Molecular Weight 28566.64
Theoretical pI 5.802
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>NAD-dependent deacetylase sirtuin-3, mitochondrial
MAFWGWRAAAALRLWGRVVERVEAGGGVGPFQACGCRLVLGGRDDVSAGLRGSHGARGEP
LDPARPLQRPPRPEVPRAFRRQPRAAAPSFFFSSIKGGRRSISFSVGASSVVGSGGSSDK
GKLSLQDVAELIRARACQRVVVMVGAGISTPSGIPDFRSPGSGLYSNLQQYDLPYPEAIF
ELPFFFHNPKPFFTLAKELYPGNYKPNVTHYFLRLLHDKGLLLRLYTQNIDGLERVSGIP
ASKLVEAHGTFASATCTVCQRPFPGEDIRADVMADRVPRCPVCTGVVKPDIVFFGEPLPQ
RFLLHVVDFPMADLLLILGTSLEVEPFASLTEAVRSSVPRLLINRDLVGPLAWHPRSRDV
AQLGDVVHGVESLVELLGWTEEMRDLVQRETGKLDGPDK
GenBank ID Protein 5225322
UniProtKB/Swiss-Prot ID Q9NTG7
UniProtKB/Swiss-Prot Entry Name SIRT3_HUMAN
PDB IDs
GenBank Gene ID AF083108
GeneCard ID SIRT3
GenAtlas ID SIRT3
HGNC ID HGNC:14931
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E: Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10224-9. Epub 2006 Jun 20. [PubMed:16788062 ]
  3. Jin L, Wei W, Jiang Y, Peng H, Cai J, Mao C, Dai H, Choy W, Bemis JE, Jirousek MR, Milne JC, Westphal CH, Perni RB: Crystal structures of human SIRT3 displaying substrate-induced conformational changes. J Biol Chem. 2009 Sep 4;284(36):24394-405. doi: 10.1074/jbc.M109.014928. Epub 2009 Jun 16. [PubMed:19535340 ]
  4. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  5. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I: Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005 Oct;16(10):4623-35. Epub 2005 Aug 3. [PubMed:16079181 ]
  6. Frye RA: 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. 1999 Jun 24;260(1):273-9. [PubMed:10381378 ]
  7. Schwer B, North BJ, Frye RA, Ott M, Verdin E: The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase. J Cell Biol. 2002 Aug 19;158(4):647-57. Epub 2002 Aug 19. [PubMed:12186850 ]
  8. Onyango P, Celic I, McCaffery JM, Boeke JD, Feinberg AP: SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13653-8. Epub 2002 Oct 8. [PubMed:12374852 ]
  9. Cooper HM, Spelbrink JN: The human SIRT3 protein deacetylase is exclusively mitochondrial. Biochem J. 2008 Apr 15;411(2):279-85. doi: 10.1042/BJ20071624. [PubMed:18215119 ]
  10. Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, Steegborn C: Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol. 2008 Oct 10;382(3):790-801. doi: 10.1016/j.jmb.2008.07.048. Epub 2008 Jul 25. [PubMed:18680753 ]
  11. Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T: A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14447-52. doi: 10.1073/pnas.0803790105. Epub 2008 Sep 15. [PubMed:18794531 ]