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Protein

NAD-dependent protein deacetylase sirtuin-3, mitochondrial

Gene

SIRT3

Organism
Homo sapiens (Human)
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, SOD2, PDHA1, LCAD, SDHA and the ATP synthase subunit ATP5O. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.6 Publications

Catalytic activityi

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.PROSITE-ProRule annotation3 Publications

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Kineticsi

  1. KM=600 µM for NAD1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei248Proton acceptor1
    Metal bindingi256Zinc1
    Metal bindingi259Zinc1
    Metal bindingi280Zinc1
    Metal bindingi283Zinc1
    Binding sitei366NAD; via amide nitrogenBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi145 – 165NADAdd BLAST21
    Nucleotide bindingi228 – 231NAD4
    Nucleotide bindingi319 – 321NAD3
    Nucleotide bindingi344 – 346NAD3

    GO - Molecular functioni

    • NAD+ ADP-ribosyltransferase activity Source: ProtInc
    • NAD+ binding Source: InterPro
    • NAD-dependent histone deacetylase activity (H3-K14 specific) Source: Ensembl
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    • aerobic respiration Source: UniProtKB
    • aging Source: Ensembl
    • mitochondrion organization Source: Reactome
    • negative regulation of ERK1 and ERK2 cascade Source: Ensembl
    • negative regulation of peptidyl-lysine acetylation Source: Ensembl
    • negative regulation of reactive oxygen species metabolic process Source: Ensembl
    • peptidyl-lysine deacetylation Source: UniProtKB
    • positive regulation of insulin secretion Source: Ensembl
    • protein ADP-ribosylation Source: ProtInc
    • protein deacetylation Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    Metal-binding, NAD, Zinc

    Enzyme and pathway databases

    ReactomeiR-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
    SIGNORiQ9NTG7.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NAD-dependent protein deacetylase sirtuin-3, mitochondrial (EC:3.5.1.-)
    Short name:
    hSIRT3
    Alternative name(s):
    Regulatory protein SIR2 homolog 3
    SIR2-like protein 3
    Gene namesi
    Name:SIRT3
    Synonyms:SIR2L3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:14931. SIRT3.

    Subcellular locationi

    GO - Cellular componenti

    • mitochondrial inner membrane Source: Ensembl
    • mitochondrial matrix Source: Reactome
    • mitochondrion Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi7R → G or Q: Suppresses targeting to mitochondrion; when associated with G-13 or Q-13. 1 Publication1
    Mutagenesisi13R → G or Q: Suppresses targeting to mitochondrion; when associated with G-7 or Q-7. 1 Publication1
    Mutagenesisi17R → G or Q: Reduces targeting to mitochondrion; when associated with G-21 or Q-21. 1 Publication1
    Mutagenesisi21R → G or Q: Reduces targeting to mitochondrion; when associated with G-17 or Q-17. 1 Publication1
    Mutagenesisi99 – 100RR → GG: Abolishes processing by MPP (in vitro). 1 Publication2
    Mutagenesisi229N → A: Loss of function. 1 Publication1
    Mutagenesisi248H → Y: Loss of function. 3 Publications1

    Organism-specific databases

    DisGeNETi23410.
    OpenTargetsiENSG00000142082.
    PharmGKBiPA37936.

    Chemistry databases

    ChEMBLiCHEMBL4461.
    GuidetoPHARMACOLOGYi2709.

    Polymorphism and mutation databases

    BioMutaiSIRT3.
    DMDMi38258651.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_0000032612? – 399NAD-dependent protein deacetylase sirtuin-3, mitochondrial
    Transit peptidei1 – ?MitochondrionSequence analysis

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei122N6-succinyllysineBy similarity1

    Post-translational modificationi

    Processed by mitochondrial processing peptidase (MPP) to give a 28 kDa product. Such processing is probably essential for its enzymatic activity.1 Publication

    Proteomic databases

    EPDiQ9NTG7.
    MaxQBiQ9NTG7.
    PaxDbiQ9NTG7.
    PeptideAtlasiQ9NTG7.
    PRIDEiQ9NTG7.

    PTM databases

    iPTMnetiQ9NTG7.
    PhosphoSitePlusiQ9NTG7.

    Expressioni

    Tissue specificityi

    Widely expressed.2 Publications

    Gene expression databases

    BgeeiENSG00000142082.
    CleanExiHS_SIRT3.
    ExpressionAtlasiQ9NTG7. baseline and differential.
    GenevisibleiQ9NTG7. HS.

    Organism-specific databases

    HPAiCAB037142.
    HPA026809.

    Interactioni

    Subunit structurei

    Interacts with NDUFA9, ACSS1, IDH2 and GDH.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ATP5A1P257052EBI-724621,EBI-351437
    OPA1O603133EBI-724621,EBI-1054131
    SKP2Q133095EBI-724621,EBI-456291

    Protein-protein interaction databases

    BioGridi116982. 47 interactors.
    DIPiDIP-46861N.
    IntActiQ9NTG7. 29 interactors.
    MINTiMINT-4540133.
    STRINGi9606.ENSP00000372191.

    Chemistry databases

    BindingDBiQ9NTG7.

    Structurei

    Secondary structure

    1399
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi125 – 133Combined sources9
    Turni134 – 136Combined sources3
    Beta strandi140 – 144Combined sources5
    Helixi146 – 152Combined sources7
    Beta strandi157 – 159Combined sources3
    Turni160 – 162Combined sources3
    Helixi164 – 168Combined sources5
    Beta strandi171 – 175Combined sources5
    Helixi176 – 180Combined sources5
    Helixi182 – 187Combined sources6
    Helixi190 – 199Combined sources10
    Beta strandi201 – 203Combined sources3
    Helixi208 – 218Combined sources11
    Beta strandi222 – 227Combined sources6
    Helixi233 – 236Combined sources4
    Helixi241 – 243Combined sources3
    Beta strandi244 – 246Combined sources3
    Beta strandi249 – 256Combined sources8
    Turni257 – 259Combined sources3
    Beta strandi262 – 264Combined sources3
    Helixi265 – 273Combined sources9
    Turni281 – 283Combined sources3
    Beta strandi286 – 291Combined sources6
    Helixi300 – 304Combined sources5
    Helixi305 – 311Combined sources7
    Beta strandi313 – 319Combined sources7
    Helixi327 – 330Combined sources4
    Helixi331 – 333Combined sources3
    Beta strandi340 – 346Combined sources7
    Helixi349 – 353Combined sources5
    Beta strandi359 – 364Combined sources6
    Helixi366 – 377Combined sources12
    Helixi380 – 391Combined sources12

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3GLRX-ray1.80A118-399[»]
    3GLSX-ray2.70A/B/C/D/E/F118-399[»]
    3GLTX-ray2.10A118-399[»]
    3GLUX-ray2.50A118-399[»]
    4BN4X-ray1.30A116-399[»]
    4BN5X-ray3.25A/B/C/D/E/F/G/H/I/J/K/L119-399[»]
    4BV3X-ray2.00A116-399[»]
    4BVBX-ray2.00A116-399[»]
    4BVEX-ray2.05A116-399[»]
    4BVFX-ray2.70A116-399[»]
    4BVGX-ray2.50A116-399[»]
    4BVHX-ray1.90A/B/C116-399[»]
    4C78X-ray2.00A116-399[»]
    4C7BX-ray2.10A117-399[»]
    4FVTX-ray2.47A122-395[»]
    4FZ3X-ray2.10A118-399[»]
    4HD8X-ray2.30A116-399[»]
    4JSRX-ray1.70A118-399[»]
    4JT8X-ray2.26A118-399[»]
    4JT9X-ray2.24A118-399[»]
    4O8ZX-ray2.00A116-399[»]
    4V1CX-ray2.95A/B/E/G/I/K121-394[»]
    5BWNX-ray1.94A118-399[»]
    5BWOX-ray2.38A118-399[»]
    5D7NX-ray1.83A/B/C/D/E/F118-395[»]
    ProteinModelPortaliQ9NTG7.
    SMRiQ9NTG7.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9NTG7.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini126 – 382Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST257

    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

    eggNOGiKOG2682. Eukaryota.
    COG0846. LUCA.
    GeneTreeiENSGT00850000132288.
    HOVERGENiHBG057095.
    InParanoidiQ9NTG7.
    KOiK11413.
    OMAiCTGIVKP.
    OrthoDBiEOG091G07CT.
    PhylomeDBiQ9NTG7.
    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.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view]
    PANTHERiPTHR11085. PTHR11085. 1 hit.
    PfamiPF02146. SIR2. 1 hit.
    [Graphical view]
    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 1 (identifier: Q9NTG7-1) [UniParc]FASTAAdd to basket

    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
    MAFWGWRAAA ALRLWGRVVE RVEAGGGVGP FQACGCRLVL GGRDDVSAGL
    60 70 80 90 100
    RGSHGARGEP LDPARPLQRP PRPEVPRAFR RQPRAAAPSF FFSSIKGGRR
    110 120 130 140 150
    SISFSVGASS VVGSGGSSDK GKLSLQDVAE LIRARACQRV VVMVGAGIST
    160 170 180 190 200
    PSGIPDFRSP GSGLYSNLQQ YDLPYPEAIF ELPFFFHNPK PFFTLAKELY
    210 220 230 240 250
    PGNYKPNVTH YFLRLLHDKG LLLRLYTQNI DGLERVSGIP ASKLVEAHGT
    260 270 280 290 300
    FASATCTVCQ RPFPGEDIRA DVMADRVPRC PVCTGVVKPD IVFFGEPLPQ
    310 320 330 340 350
    RFLLHVVDFP MADLLLILGT SLEVEPFASL TEAVRSSVPR LLINRDLVGP
    360 370 380 390
    LAWHPRSRDV AQLGDVVHGV ESLVELLGWT EEMRDLVQRE TGKLDGPDK
    Length:399
    Mass (Da):43,573
    Last modified:October 31, 2003 - v2
    Checksum:i4BA8BD3AC5FC7901
    GO
    Isoform 2 (identifier: Q9NTG7-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-142: Missing.

    Show »
    Length:257
    Mass (Da):28,567
    Checksum:i33043FAB6B3F0307
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_05197780R → W.Corresponds to variant rs28365927dbSNPEnsembl.1
    Natural variantiVAR_051978208V → I.Corresponds to variant rs11246020dbSNPEnsembl.1
    Natural variantiVAR_051979369G → S.Corresponds to variant rs3020901dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0437921 – 142Missing in isoform 2. 1 PublicationAdd BLAST142

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF083108 mRNA. Translation: AAD40851.1.
    AK299438 mRNA. Translation: BAH13032.1.
    AC136475 Genomic DNA. No translation available.
    BC001042 mRNA. Translation: AAH01042.1.
    AL137276 mRNA. Translation: CAB70674.1.
    CCDSiCCDS53590.1. [Q9NTG7-2]
    CCDS7691.1. [Q9NTG7-1]
    PIRiT46348.
    RefSeqiNP_001017524.1. NM_001017524.2. [Q9NTG7-2]
    NP_036371.1. NM_012239.5. [Q9NTG7-1]
    XP_016872919.1. XM_017017430.1. [Q9NTG7-2]
    UniGeneiHs.716456.

    Genome annotation databases

    EnsembliENST00000382743; ENSP00000372191; ENSG00000142082. [Q9NTG7-1]
    ENST00000529382; ENSP00000437216; ENSG00000142082. [Q9NTG7-2]
    GeneIDi23410.
    KEGGihsa:23410.
    UCSCiuc001lok.5. human. [Q9NTG7-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF083108 mRNA. Translation: AAD40851.1.
    AK299438 mRNA. Translation: BAH13032.1.
    AC136475 Genomic DNA. No translation available.
    BC001042 mRNA. Translation: AAH01042.1.
    AL137276 mRNA. Translation: CAB70674.1.
    CCDSiCCDS53590.1. [Q9NTG7-2]
    CCDS7691.1. [Q9NTG7-1]
    PIRiT46348.
    RefSeqiNP_001017524.1. NM_001017524.2. [Q9NTG7-2]
    NP_036371.1. NM_012239.5. [Q9NTG7-1]
    XP_016872919.1. XM_017017430.1. [Q9NTG7-2]
    UniGeneiHs.716456.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3GLRX-ray1.80A118-399[»]
    3GLSX-ray2.70A/B/C/D/E/F118-399[»]
    3GLTX-ray2.10A118-399[»]
    3GLUX-ray2.50A118-399[»]
    4BN4X-ray1.30A116-399[»]
    4BN5X-ray3.25A/B/C/D/E/F/G/H/I/J/K/L119-399[»]
    4BV3X-ray2.00A116-399[»]
    4BVBX-ray2.00A116-399[»]
    4BVEX-ray2.05A116-399[»]
    4BVFX-ray2.70A116-399[»]
    4BVGX-ray2.50A116-399[»]
    4BVHX-ray1.90A/B/C116-399[»]
    4C78X-ray2.00A116-399[»]
    4C7BX-ray2.10A117-399[»]
    4FVTX-ray2.47A122-395[»]
    4FZ3X-ray2.10A118-399[»]
    4HD8X-ray2.30A116-399[»]
    4JSRX-ray1.70A118-399[»]
    4JT8X-ray2.26A118-399[»]
    4JT9X-ray2.24A118-399[»]
    4O8ZX-ray2.00A116-399[»]
    4V1CX-ray2.95A/B/E/G/I/K121-394[»]
    5BWNX-ray1.94A118-399[»]
    5BWOX-ray2.38A118-399[»]
    5D7NX-ray1.83A/B/C/D/E/F118-395[»]
    ProteinModelPortaliQ9NTG7.
    SMRiQ9NTG7.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116982. 47 interactors.
    DIPiDIP-46861N.
    IntActiQ9NTG7. 29 interactors.
    MINTiMINT-4540133.
    STRINGi9606.ENSP00000372191.

    Chemistry databases

    BindingDBiQ9NTG7.
    ChEMBLiCHEMBL4461.
    GuidetoPHARMACOLOGYi2709.

    PTM databases

    iPTMnetiQ9NTG7.
    PhosphoSitePlusiQ9NTG7.

    Polymorphism and mutation databases

    BioMutaiSIRT3.
    DMDMi38258651.

    Proteomic databases

    EPDiQ9NTG7.
    MaxQBiQ9NTG7.
    PaxDbiQ9NTG7.
    PeptideAtlasiQ9NTG7.
    PRIDEiQ9NTG7.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000382743; ENSP00000372191; ENSG00000142082. [Q9NTG7-1]
    ENST00000529382; ENSP00000437216; ENSG00000142082. [Q9NTG7-2]
    GeneIDi23410.
    KEGGihsa:23410.
    UCSCiuc001lok.5. human. [Q9NTG7-1]

    Organism-specific databases

    CTDi23410.
    DisGeNETi23410.
    GeneCardsiSIRT3.
    HGNCiHGNC:14931. SIRT3.
    HPAiCAB037142.
    HPA026809.
    MIMi604481. gene.
    neXtProtiNX_Q9NTG7.
    OpenTargetsiENSG00000142082.
    PharmGKBiPA37936.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2682. Eukaryota.
    COG0846. LUCA.
    GeneTreeiENSGT00850000132288.
    HOVERGENiHBG057095.
    InParanoidiQ9NTG7.
    KOiK11413.
    OMAiCTGIVKP.
    OrthoDBiEOG091G07CT.
    PhylomeDBiQ9NTG7.
    TreeFamiTF106181.

    Enzyme and pathway databases

    ReactomeiR-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
    SIGNORiQ9NTG7.

    Miscellaneous databases

    ChiTaRSiSIRT3. human.
    EvolutionaryTraceiQ9NTG7.
    GeneWikiiSIRT3.
    GenomeRNAii23410.
    PROiQ9NTG7.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000142082.
    CleanExiHS_SIRT3.
    ExpressionAtlasiQ9NTG7. baseline and differential.
    GenevisibleiQ9NTG7. HS.

    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.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view]
    PANTHERiPTHR11085. PTHR11085. 1 hit.
    PfamiPF02146. SIR2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52467. SSF52467. 1 hit.
    PROSITEiPS50305. SIRTUIN. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSIR3_HUMAN
    AccessioniPrimary (citable) accession number: Q9NTG7
    Secondary accession number(s): B7Z5U6, Q9Y6E8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 31, 2003
    Last sequence update: October 31, 2003
    Last modified: November 2, 2016
    This is version 141 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    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 one 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.