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Q8R104

- SIR3_MOUSE

UniProt

Q8R104 - SIR3_MOUSE

Protein

NAD-dependent protein deacetylase sirtuin-3

Gene

Sirt3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 2 (19 Mar 2014)
      Previous versions | rss
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    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

    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

    1. NAD+ binding Source: InterPro
    2. NAD-dependent histone deacetylase activity (H3-K14 specific) Source: MGI
    3. protein binding Source: IntAct
    4. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. aerobic respiration Source: UniProtKB
    2. histone H3 deacetylation Source: GOC
    3. peptidyl-lysine deacetylation Source: UniProtKB
    4. protein deacetylation Source: UniProtKB

    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: Chromosome 7

    Organism-specific databases

    MGIiMGI:1927665. Sirt3.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. membrane Source: MGI
    3. mitochondrial matrix Source: UniProtKB-SubCell
    4. mitochondrion Source: UniProtKB

    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

    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

    ArrayExpressiQ8R104.
    BgeeiQ8R104.
    GenevestigatoriQ8R104.

    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.

    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.
    HOVERGENiHBG057095.
    InParanoidiQ8R104.
    KOiK11413.
    OMAiVGPFAWQ.
    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. Align

    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

    MALDPLGAVV LQSIMALSGR LALAALRLWG PGGGRRPISL CVGASGGFGG    50
    GGSSEKKFSL QDVAELLRTR ACSRVVVMVG AGISTPSGIP DFRSPGSGLY 100
    SNLQQYDIPY PEAIFELGFF FHNPKPFFML AKELYPGHYR PNVTHYFLRL 150
    LHDKELLLRL YTQNIDGLER ASGIPASKLV EAHGTFVTAT CTVCRRSFPG 200
    EDIWADVMAD RVPRCPVCTG VVKPDIVFFG EQLPARFLLH MADFALADLL 250
    LILGTSLEVE PFASLSEAVQ KSVPRLLINR DLVGPFVLSP RRKDVVQLGD 300
    VVHGVERLVD LLGWTQELLD LMQRERGKLD GQDR 334
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS21989.1. [Q8R104-2 ]
    RefSeqi NP_001120823.1. NM_001127351.1. [Q8R104-2 ]
    NP_001171275.1. NM_001177804.1. [Q8R104-1 ]
    NP_071878.2. NM_022433.2. [Q8R104-2 ]
    UniGenei Mm.244216.

    3D structure databases

    ProteinModelPortali Q8R104.
    SMRi Q8R104. Positions 57-325.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 211071. 2 interactions.
    IntActi Q8R104. 1 interaction.

    Proteomic databases

    MaxQBi Q8R104.
    PaxDbi Q8R104.
    PRIDEi Q8R104.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000026559 ; ENSMUSP00000026559 ; ENSMUSG00000025486 . [Q8R104-2 ]
    ENSMUST00000106048 ; ENSMUSP00000101663 ; ENSMUSG00000025486 . [Q8R104-2 ]
    GeneIDi 64384.
    KEGGi mmu:64384.
    UCSCi uc009kik.2. mouse. [Q8R104-1 ]

    Organism-specific databases

    CTDi 23410.
    MGIi MGI:1927665. Sirt3.

    Phylogenomic databases

    eggNOGi COG0846.
    GeneTreei ENSGT00740000115546.
    HOVERGENi HBG057095.
    InParanoidi Q8R104.
    KOi K11413.
    OMAi VGPFAWQ.
    OrthoDBi EOG7WX09C.
    TreeFami TF106181.

    Miscellaneous databases

    ChiTaRSi SIRT3. mouse.
    NextBioi 320063.
    PROi Q8R104.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8R104.
    Bgeei Q8R104.
    Genevestigatori Q8R104.

    Family and domain databases

    Gene3Di 3.30.1600.10. 2 hits.
    3.40.50.1220. 3 hits.
    InterProi IPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR003000. Sirtuin.
    IPR026591. Sirtuin_cat_small_dom.
    IPR017328. Sirtuin_class_I.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view ]
    PANTHERi PTHR11085. PTHR11085. 1 hit.
    Pfami PF02146. SIR2. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF037938. SIR2_euk. 1 hit.
    SUPFAMi SSF52467. SSF52467. 1 hit.
    PROSITEi PS50305. SIRTUIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. "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.

    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: October 1, 2014
    This is version 110 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