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Q8R104 (SIR3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Sirt3
Synonyms:Sir2l3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length334 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Catalytic activity

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

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

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

Subcellular location

Isoform L: Mitochondrion matrix Ref.1 Ref.2 Ref.3.

Isoform S: Cytoplasm Ref.1 Ref.2 Ref.3.

Tissue specificity

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

Induction

Sirt3 expression decreases by 50% in skeletal muscle upon fasting. Ref.12

Disruption phenotype

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. Ref.8 Ref.9 Ref.11

Miscellaneous

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

Sequence similarities

Belongs to the sirtuin family. Class I subfamily.

Contains 1 deacetylase sirtuin-type domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Aldh2P477382EBI-6999888,EBI-2308120

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform L (identifier: Q8R104-1)

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.
Isoform S (identifier: Q8R104-2)

Also known as: M3;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion
Chain? – 334NAD-dependent protein deacetylase sirtuin-3PRO_0000110263

Regions

Domain78 – 334257Deacetylase sirtuin-type
Nucleotide binding80 – 10021NAD By similarity
Nucleotide binding163 – 1664NAD By similarity
Nucleotide binding254 – 2563NAD By similarity
Nucleotide binding279 – 2813NAD By similarity

Sites

Active site1831Proton acceptor By similarity
Metal binding1911Zinc By similarity
Metal binding1941Zinc By similarity
Metal binding2151Zinc By similarity
Metal binding2181Zinc By similarity
Binding site3011NAD; via amide nitrogen By similarity

Natural variations

Alternative sequence1 – 7777Missing in isoform S.
VSP_053760

Experimental info

Sequence conflict2161P → A in AAG39258. Ref.1
Sequence conflict2161P → A in AAG33227. Ref.1
Sequence conflict2161P → A in AAG39257. Ref.1
Sequence conflict2161P → A in ACJ70655. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform L (M1) [UniParc].

Last modified March 19, 2014. Version 2.
Checksum: D8C936A83C4A8AF7

FASTA33436,615
        10         20         30         40         50         60 
MALDPLGAVV LQSIMALSGR LALAALRLWG PGGGRRPISL CVGASGGFGG GGSSEKKFSL 

        70         80         90        100        110        120 
QDVAELLRTR ACSRVVVMVG AGISTPSGIP DFRSPGSGLY SNLQQYDIPY PEAIFELGFF 

       130        140        150        160        170        180 
FHNPKPFFML AKELYPGHYR PNVTHYFLRL LHDKELLLRL YTQNIDGLER ASGIPASKLV 

       190        200        210        220        230        240 
EAHGTFVTAT CTVCRRSFPG EDIWADVMAD RVPRCPVCTG VVKPDIVFFG EQLPARFLLH 

       250        260        270        280        290        300 
MADFALADLL LILGTSLEVE PFASLSEAVQ KSVPRLLINR DLVGPFVLSP RRKDVVQLGD 

       310        320        330 
VVHGVERLVD LLGWTQELLD LMQRERGKLD GQDR 

« Hide

Isoform S (M3) [UniParc].

Checksum: F756041FBC9B985E
Show »

FASTA25728,822

References

« Hide 'large scale' references
[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]"Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3."
Jin L., Galonek H., Israelian K., Choy W., Morrison M., Xia Y., Wang X., Xu Y., Yang Y., Smith J.J., Hoffmann E., Carney D.P., Perni R.B., Jirousek M.R., Bemis J.E., Milne J.C., Sinclair D.A., Westphal C.H.
Protein Sci. 18:514-525(2009) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation."
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.
Mol. Cell. Biol. 27:8807-8814(2007) [PubMed] [Europe PMC] [Abstract]
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]"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. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[12]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF299339 mRNA. Translation: AAG39258.1.
FJ621493 mRNA. Translation: ACM68947.1.
EU886466 mRNA. Translation: ACJ70655.1.
AF302278 expand/collapse EMBL AC list , AF302274, AF302275, AF302276, AF302277 Genomic DNA. Translation: AAG33227.1.
AF299338 mRNA. Translation: AAG39257.1.
AK075861 mRNA. Translation: BAC36012.1.
BC025878 mRNA. Translation: AAH25878.1.
RefSeqNP_001120823.1. NM_001127351.1.
NP_001171275.1. NM_001177804.1.
NP_071878.2. NM_022433.2.
UniGeneMm.244216.

3D structure databases

ProteinModelPortalQ8R104.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid211071. 2 interactions.
IntActQ8R104. 1 interaction.

Proteomic databases

PaxDbQ8R104.
PRIDEQ8R104.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026559; ENSMUSP00000026559; ENSMUSG00000025486. [Q8R104-2]
ENSMUST00000106048; ENSMUSP00000101663; ENSMUSG00000025486. [Q8R104-2]
GeneID64384.
KEGGmmu:64384.
UCSCuc009kik.2. mouse. [Q8R104-1]

Organism-specific databases

CTD23410.
MGIMGI:1927665. Sirt3.

Phylogenomic databases

eggNOGCOG0846.
GeneTreeENSGT00740000115546.
HOVERGENHBG057095.
InParanoidQ8R104.
KOK11413.
OMARVAGIPP.
OrthoDBEOG7WX09C.
TreeFamTF106181.

Gene expression databases

ArrayExpressQ8R104.
BgeeQ8R104.
GenevestigatorQ8R104.

Family and domain databases

Gene3D3.30.1600.10. 2 hits.
InterProIPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR017328. Sirtuin_class_I.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERPTHR11085. PTHR11085. 1 hit.
PfamPF02146. SIR2. 1 hit.
[Graphical view]
PIRSFPIRSF037938. SIR2_euk. 1 hit.
PROSITEPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSIRT3. mouse.
NextBio320063.
PROQ8R104.
SOURCESearch...

Entry information

Entry nameSIR3_MOUSE
AccessionPrimary (citable) accession number: Q8R104
Secondary accession number(s): B9W0A9, C6ZII7, Q9EPA8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: March 19, 2014
Last modified: April 16, 2014
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot