Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

NAD-dependent protein deacetylase sirtuin-3

Gene

Sirt3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

NAD-dependent protein deacetylase. Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues. Known targets include ACSS1, IDH, GDH, PDHA1, SOD2, LCAD, SDHA and the ATP synthase subunit ATP5O. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.7 Publications

Catalytic activityi

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.PROSITE-ProRule annotation

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei183 – 1831Proton acceptorPROSITE-ProRule annotation
Metal bindingi191 – 1911ZincPROSITE-ProRule annotation
Metal bindingi194 – 1941ZincPROSITE-ProRule annotation
Metal bindingi215 – 2151ZincPROSITE-ProRule annotation
Metal bindingi218 – 2181ZincPROSITE-ProRule annotation
Binding sitei301 – 3011NAD; via amide nitrogenBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi80 – 10021NADBy similarityAdd
BLAST
Nucleotide bindingi163 – 1664NADBy similarity
Nucleotide bindingi254 – 2563NADBy similarity
Nucleotide bindingi279 – 2813NADBy similarity

GO - Molecular functioni

GO - Biological processi

  • aerobic respiration Source: UniProtKB
  • aging Source: Ensembl
  • histone H3 deacetylation Source: GOC
  • negative regulation of peptidyl-lysine acetylation Source: MGI
  • peptidyl-lysine deacetylation Source: UniProtKB
  • protein deacetylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, NAD, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-3 (EC:3.5.1.-)
Alternative name(s):
Regulatory protein SIR2 homolog 3
SIR2-like protein 3
Short name:
mSIR2L3
Gene namesi
Name:Sirt3
Synonyms:Sir2l3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1927665. Sirt3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • membrane Source: MGI
  • mitochondrial inner membrane Source: CACAO
  • mitochondrial matrix Source: MGI
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Disruption phenotypei

Decreased muscle endurance under energetically demanding conditions. Decreased Mn-SOD activity in liver, increased mitochondrial superoxide levels and genomic instability upon exposure to ionizing radiations. In vivo ATP levels are reduced by 50 % in organs that normally express high levels of this protein. ATP levels are unchanged in organs that normally express low levels of this protein. Leads to increased mitochondrial protein acetylation.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 334NAD-dependent protein deacetylase sirtuin-3PRO_0000110263
Transit peptidei1 – ?Mitochondrion

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei57 – 571N6-succinyllysine1 Publication

Proteomic databases

MaxQBiQ8R104.
PaxDbiQ8R104.
PRIDEiQ8R104.

Expressioni

Tissue specificityi

Strongly expressed in liver and kidney. Weakly expressed in lung.1 Publication

Inductioni

Sirt3 expression decreases by 50% in skeletal muscle upon fasting.1 Publication

Gene expression databases

BgeeiQ8R104.
ExpressionAtlasiQ8R104. baseline and differential.
GenevisibleiQ8R104. MM.

Interactioni

Subunit structurei

Interacts with NDUFA9, ACSS1, IDH2 and GDH.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Aldh2P477382EBI-6999888,EBI-2308120

Protein-protein interaction databases

BioGridi211071. 2 interactions.
IntActiQ8R104. 1 interaction.
STRINGi10090.ENSMUSP00000026559.

Structurei

3D structure databases

ProteinModelPortaliQ8R104.
SMRiQ8R104. Positions 57-325.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini78 – 334257Deacetylase sirtuin-typePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the sirtuin family. Class I subfamily.Curated
Contains 1 deacetylase sirtuin-type domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0846.
GeneTreeiENSGT00740000115546.
HOGENOMiHOG000085952.
HOVERGENiHBG057095.
InParanoidiQ8R104.
KOiK11413.
OMAiWETHMEC.
OrthoDBiEOG7WX09C.
TreeFamiTF106181.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR017328. Sirtuin_class_I.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 1 hit.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
PIRSFiPIRSF037938. SIR2_euk. 1 hit.
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform L (identifier: Q8R104-1) [UniParc]FASTAAdd to basket

Also known as: M1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALDPLGAVV LQSIMALSGR LALAALRLWG PGGGRRPISL CVGASGGFGG
60 70 80 90 100
GGSSEKKFSL QDVAELLRTR ACSRVVVMVG AGISTPSGIP DFRSPGSGLY
110 120 130 140 150
SNLQQYDIPY PEAIFELGFF FHNPKPFFML AKELYPGHYR PNVTHYFLRL
160 170 180 190 200
LHDKELLLRL YTQNIDGLER ASGIPASKLV EAHGTFVTAT CTVCRRSFPG
210 220 230 240 250
EDIWADVMAD RVPRCPVCTG VVKPDIVFFG EQLPARFLLH MADFALADLL
260 270 280 290 300
LILGTSLEVE PFASLSEAVQ KSVPRLLINR DLVGPFVLSP RRKDVVQLGD
310 320 330
VVHGVERLVD LLGWTQELLD LMQRERGKLD GQDR
Length:334
Mass (Da):36,615
Last modified:March 19, 2014 - v2
Checksum:iD8C936A83C4A8AF7
GO
Isoform S (identifier: Q8R104-2) [UniParc]FASTAAdd to basket

Also known as: M3

The sequence of this isoform differs from the canonical sequence as follows:
     1-77: Missing.

Show »
Length:257
Mass (Da):28,822
Checksum:iF756041FBC9B985E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti216 – 2161P → A in AAG39258 (PubMed:11056054).Curated
Sequence conflicti216 – 2161P → A in AAG33227 (PubMed:11056054).Curated
Sequence conflicti216 – 2161P → A in AAG39257 (PubMed:11056054).Curated
Sequence conflicti216 – 2161P → A in ACJ70655 (PubMed:19241369).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7777Missing in isoform S. 3 PublicationsVSP_053760Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF299339 mRNA. Translation: AAG39258.1.
FJ621493 mRNA. Translation: ACM68947.1.
EU886466 mRNA. Translation: ACJ70655.1.
AF302278
, AF302274, AF302275, AF302276, AF302277 Genomic DNA. Translation: AAG33227.1.
AF299338 mRNA. Translation: AAG39257.1.
AK075861 mRNA. Translation: BAC36012.1.
BC025878 mRNA. Translation: AAH25878.1.
CCDSiCCDS21989.1. [Q8R104-2]
RefSeqiNP_001120823.1. NM_001127351.1. [Q8R104-2]
NP_001171275.1. NM_001177804.1. [Q8R104-1]
NP_071878.2. NM_022433.2. [Q8R104-2]
UniGeneiMm.244216.

Genome annotation databases

EnsembliENSMUST00000026559; ENSMUSP00000026559; ENSMUSG00000025486. [Q8R104-2]
ENSMUST00000106048; ENSMUSP00000101663; ENSMUSG00000025486. [Q8R104-2]
GeneIDi64384.
KEGGimmu:64384.
UCSCiuc009kik.2. mouse. [Q8R104-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF299339 mRNA. Translation: AAG39258.1.
FJ621493 mRNA. Translation: ACM68947.1.
EU886466 mRNA. Translation: ACJ70655.1.
AF302278
, AF302274, AF302275, AF302276, AF302277 Genomic DNA. Translation: AAG33227.1.
AF299338 mRNA. Translation: AAG39257.1.
AK075861 mRNA. Translation: BAC36012.1.
BC025878 mRNA. Translation: AAH25878.1.
CCDSiCCDS21989.1. [Q8R104-2]
RefSeqiNP_001120823.1. NM_001127351.1. [Q8R104-2]
NP_001171275.1. NM_001177804.1. [Q8R104-1]
NP_071878.2. NM_022433.2. [Q8R104-2]
UniGeneiMm.244216.

3D structure databases

ProteinModelPortaliQ8R104.
SMRiQ8R104. Positions 57-325.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi211071. 2 interactions.
IntActiQ8R104. 1 interaction.
STRINGi10090.ENSMUSP00000026559.

Proteomic databases

MaxQBiQ8R104.
PaxDbiQ8R104.
PRIDEiQ8R104.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026559; ENSMUSP00000026559; ENSMUSG00000025486. [Q8R104-2]
ENSMUST00000106048; ENSMUSP00000101663; ENSMUSG00000025486. [Q8R104-2]
GeneIDi64384.
KEGGimmu:64384.
UCSCiuc009kik.2. mouse. [Q8R104-1]

Organism-specific databases

CTDi23410.
MGIiMGI:1927665. Sirt3.

Phylogenomic databases

eggNOGiCOG0846.
GeneTreeiENSGT00740000115546.
HOGENOMiHOG000085952.
HOVERGENiHBG057095.
InParanoidiQ8R104.
KOiK11413.
OMAiWETHMEC.
OrthoDBiEOG7WX09C.
TreeFamiTF106181.

Miscellaneous databases

ChiTaRSiSirt3. mouse.
NextBioi320063.
PROiQ8R104.
SOURCEiSearch...

Gene expression databases

BgeeiQ8R104.
ExpressionAtlasiQ8R104. baseline and differential.
GenevisibleiQ8R104. MM.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR017328. Sirtuin_class_I.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 1 hit.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
PIRSFiPIRSF037938. SIR2_euk. 1 hit.
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of two mouse genes with homology to the yeast sir2 gene."
    Yang Y.H., Chen Y.H., Zhang C.Y., Nimmakayalu M.A., Ward D.C., Weissman S.
    Genomics 69:355-369(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM S), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Strain: 129/Ola.
  2. "A new splice variant of the mouse SIRT3 gene encodes the mitochondrial precursor protein."
    Cooper H.M., Huang J.Y., Verdin E., Spelbrink J.N.
    PLoS ONE 4:E4986-E4986(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM L), SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
    Strain: NIH Swiss.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM L), SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
    Strain: ICR.
    Tissue: Liver.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM S).
    Strain: C57BL/6J.
    Tissue: Tongue.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM S).
    Tissue: Mammary tumor.
  6. "Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases."
    Hallows W.C., Lee S., Denu J.M.
    Proc. Natl. Acad. Sci. U.S.A. 103:10230-10235(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. Cited for: FUNCTION.
  8. "A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis."
    Ahn B.-H., Kim H.-S., Song S., Lee I.H., Liu J., Vassilopoulos A., Deng C.-X., Finkel T.
    Proc. Natl. Acad. Sci. U.S.A. 105:14447-14452(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  9. "Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress."
    Tao R., Coleman M.C., Pennington J.D., Ozden O., Park S.H., Jiang H., Kim H.S., Flynn C.R., Hill S., Hayes McDonald W., Olivier A.K., Spitz D.R., Gius D.
    Mol. Cell 40:893-904(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  10. "Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity."
    Finley L.W., Haas W., Desquiret-Dumas V., Wallace D.C., Procaccio V., Gygi S.P., Haigis M.C.
    PLoS ONE 6:E23295-E23295(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-57, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  12. "SIRT3 deacetylates ATP synthase F1 complex proteins in response to nutrient and exercise-induced stress."
    Vassilopoulos A., Pennington D.J., Andresson T., Rees D., Fearnley I., Ham A., Yan Y., Flynn C.R., Jones K., Kim H.S., Deng C., Walker J., Gius D.
    Antioxid. Redox Signal. 21:551-564(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  13. "Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation."
    Jing E., O'Neill B.T., Rardin M.J., Kleinridders A., Ilkeyeva O.R., Ussar S., Bain J.R., Lee K.Y., Verdin E.M., Newgard C.B., Gibson B.W., Kahn C.R.
    Diabetes 62:3404-3417(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION BY FASTING.

Entry informationi

Entry nameiSIR3_MOUSE
AccessioniPrimary (citable) accession number: Q8R104
Secondary accession number(s): B9W0A9, C6ZII7, Q9EPA8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: March 19, 2014
Last modified: June 24, 2015
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Has some ability to deacetylate histones in vitro, but seeing its subcellular location, this is unlikely in vivo.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.