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Protein

NAD-dependent protein deacylase sirtuin-5, mitochondrial

Gene

SIRT5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693). Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (PubMed:24140062). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as UOX.By similarity5 Publications

Catalytic activityi

NAD+ + a malonylprotein = nicotinamide + O-malonyl-ADP-ribose + a protein.UniRule annotation
NAD+ + a succinylprotein = nicotinamide + O-succinyl-ADP-ribose + a protein.UniRule annotation
NAD+ + a glutarylprotein = nicotinamide + O-glutaryl-ADP-ribose + a protein.UniRule annotation1 Publication

Cofactori

Zn2+UniRule annotation1 PublicationNote: Binds 1 zinc ion per subunit.UniRule annotation1 Publication

Enzyme regulationi

Inhibited by suramin. NAD-dependent lysine desuccinylase activity is inhibited by physiological nicotinamide concentrations, while deacetylase activity is not. In contrast, resveratrol activates deacetylase activity, while inhibiting desuccinylase activity.3 Publications

Kineticsi

  1. KM=6.1 µM for a synthetic histone H3K9 malonyllysine peptide1 Publication
  2. KM=5.8 µM for a synthetic histone H3K9 succinyllysine peptide1 Publication
  3. KM=8.7 µM for a synthetic GLUD1 peptide malonylated at 'Lys-503'1 Publication
  4. KM=14 µM for a synthetic GLUD1 peptide succinylated at 'Lys-503'1 Publication
  5. KM=150 µM for a synthetic ACSS1 peptide malonylated at 'Lys-628'1 Publication
  6. KM=450 µM for a synthetic ACSS1 peptide succinylated at 'Lys-628'1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei102 – 1021SubstrateUniRule annotation
    Binding sitei105 – 1051SubstrateUniRule annotation
    Active sitei158 – 1581Proton acceptorUniRule annotation1 Publication
    Metal bindingi166 – 1661ZincUniRule annotation
    Metal bindingi169 – 1691ZincUniRule annotation
    Metal bindingi207 – 2071ZincUniRule annotation
    Metal bindingi212 – 2121ZincUniRule annotation
    Binding sitei293 – 2931NAD; via amide nitrogenUniRule annotation3 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi58 – 7720NADUniRule annotation3 PublicationsAdd
    BLAST
    Nucleotide bindingi140 – 1434NADUniRule annotation3 Publications
    Nucleotide bindingi249 – 2513NADUniRule annotation3 Publications
    Nucleotide bindingi275 – 2773NADUniRule annotation3 Publications

    GO - Molecular functioni

    • NAD+ ADP-ribosyltransferase activity Source: ProtInc
    • NAD+ binding Source: UniProtKB
    • protein-glutaryllysine deglutarylase activity Source: UniProtKB
    • protein-malonyllysine demalonylase activity Source: UniProtKB
    • protein-succinyllysine desuccinylase activity Source: UniProtKB
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    • chromatin silencing Source: ProtInc
    • negative regulation of cardiac muscle cell apoptotic process Source: Ensembl
    • negative regulation of reactive oxygen species metabolic process Source: UniProtKB
    • peptidyl-lysine deglutarylation Source: GOC
    • peptidyl-lysine demalonylation Source: UniProtKB
    • peptidyl-lysine desuccinylation Source: UniProtKB
    • protein ADP-ribosylation Source: ProtInc
    • protein deacetylation Source: UniProtKB
    • protein deglutarylation Source: UniProtKB
    • protein demalonylation Source: UniProtKB
    • protein desuccinylation Source: UniProtKB
    • regulation of ketone biosynthetic process Source: UniProtKB
    • response to nutrient levels Source: Ensembl
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    Metal-binding, NAD, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NAD-dependent protein deacylase sirtuin-5, mitochondrialUniRule annotation (EC:3.5.1.-UniRule annotation1 Publication)
    Alternative name(s):
    Regulatory protein SIR2 homolog 5UniRule annotation
    SIR2-like protein 5UniRule annotation
    Gene namesi
    Name:SIRT5UniRule annotation
    Synonyms:SIR2L5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:14933. SIRT5.

    Subcellular locationi

    Isoform 1 :
    Isoform 2 :

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    • mitochondrial inner membrane Source: Ensembl
    • mitochondrial intermembrane space Source: UniProtKB
    • mitochondrial matrix Source: UniProtKB
    • mitochondrion Source: UniProtKB
    • nucleus Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi69 – 691T → A: Abolishes enzyme activity. 1 Publication
    Mutagenesisi102 – 1021Y → F: Increases the KM for desuccinylation. 1 Publication
    Mutagenesisi105 – 1051R → M: Increases the KM for desuccinylation. Does not affect deacetylase activity. 2 Publications
    Mutagenesisi158 – 1581H → A: Abolishes desuccinylation and deglutarylation activity. 3 Publications

    Organism-specific databases

    PharmGKBiPA37938.

    Chemistry

    DrugBankiDB04786. Suramin.

    Polymorphism and mutation databases

    BioMutaiSIRT5.
    DMDMi38258652.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 3636MitochondrionUniRule annotationAdd
    BLAST
    Chaini37 – 310274NAD-dependent protein deacylase sirtuin-5, mitochondrialPRO_0000110266Add
    BLAST

    Proteomic databases

    MaxQBiQ9NXA8.
    PaxDbiQ9NXA8.
    PRIDEiQ9NXA8.

    PTM databases

    PhosphoSiteiQ9NXA8.

    Expressioni

    Tissue specificityi

    Widely expressed.1 Publication

    Gene expression databases

    BgeeiQ9NXA8.
    CleanExiHS_SIRT5.
    ExpressionAtlasiQ9NXA8. baseline and differential.
    GenevisibleiQ9NXA8. HS.

    Organism-specific databases

    HPAiHPA021798.
    HPA022002.
    HPA022992.

    Interactioni

    Subunit structurei

    Interacts with CPS1 (By similarity). Monomer. Homodimer. Forms homodimers upon suramin binding.By similarity6 Publications

    Protein-protein interaction databases

    BioGridi116980. 14 interactions.
    IntActiQ9NXA8. 1 interaction.
    STRINGi9606.ENSP00000368552.

    Structurei

    Secondary structure

    1
    310
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi40 – 4910Combined sources
    Beta strandi51 – 577Combined sources
    Helixi59 – 613Combined sources
    Helixi63 – 653Combined sources
    Beta strandi70 – 723Combined sources
    Helixi73 – 753Combined sources
    Helixi82 – 854Combined sources
    Helixi88 – 936Combined sources
    Helixi95 – 10915Combined sources
    Helixi116 – 12914Combined sources
    Turni130 – 1323Combined sources
    Beta strandi134 – 1407Combined sources
    Helixi145 – 1495Combined sources
    Beta strandi153 – 1564Combined sources
    Beta strandi159 – 1668Combined sources
    Turni167 – 1693Combined sources
    Beta strandi172 – 1743Combined sources
    Beta strandi178 – 1814Combined sources
    Helixi182 – 1843Combined sources
    Beta strandi190 – 1934Combined sources
    Helixi201 – 2033Combined sources
    Helixi209 – 2113Combined sources
    Beta strandi215 – 2206Combined sources
    Helixi229 – 24113Combined sources
    Beta strandi243 – 2497Combined sources
    Beta strandi252 – 2554Combined sources
    Helixi257 – 2593Combined sources
    Helixi260 – 2667Combined sources
    Beta strandi271 – 2777Combined sources
    Helixi282 – 2843Combined sources
    Beta strandi285 – 2917Combined sources
    Helixi293 – 3019Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2B4YX-ray1.90A/B/C/D34-302[»]
    2NYRX-ray2.06A/B34-302[»]
    3RIGX-ray2.00A/B34-302[»]
    3RIYX-ray1.55A/B34-302[»]
    4F4UX-ray2.00A/B34-302[»]
    4F56X-ray1.70A/B34-302[»]
    4G1CX-ray1.94A/B36-302[»]
    4HDAX-ray2.60A/B34-302[»]
    ProteinModelPortaliQ9NXA8.
    SMRiQ9NXA8. Positions 34-302.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9NXA8.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini41 – 309269Deacetylase sirtuin-typeUniRule annotationAdd
    BLAST

    Domaini

    In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity (PubMed:22076378).1 Publication

    Sequence similaritiesi

    Belongs to the sirtuin family. Class III subfamily.UniRule annotation
    Contains 1 deacetylase sirtuin-type domain.UniRule annotation

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0846.
    GeneTreeiENSGT00740000115330.
    HOGENOMiHOG000085950.
    HOVERGENiHBG056009.
    InParanoidiQ9NXA8.
    KOiK11415.
    OMAiLIHMHGE.
    OrthoDBiEOG77Q4XG.
    PhylomeDBiQ9NXA8.
    TreeFamiTF106183.

    Family and domain databases

    Gene3Di3.30.1600.10. 2 hits.
    3.40.50.1220. 3 hits.
    HAMAPiMF_01121. Sirtuin_ClassIII.
    InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR003000. Sirtuin.
    IPR026591. Sirtuin_cat_small_dom.
    IPR027546. Sirtuin_class_III.
    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 (4)i

    Sequence statusi: Complete.

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

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9NXA8-1) [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
    MRPLQIVPSR LISQLYCGLK PPASTRNQIC LKMARPSSSM ADFRKFFAKA
    60 70 80 90 100
    KHIVIISGAG VSAESGVPTF RGAGGYWRKW QAQDLATPLA FAHNPSRVWE
    110 120 130 140 150
    FYHYRREVMG SKEPNAGHRA IAECETRLGK QGRRVVVITQ NIDELHRKAG
    160 170 180 190 200
    TKNLLEIHGS LFKTRCTSCG VVAENYKSPI CPALSGKGAP EPGTQDASIP
    210 220 230 240 250
    VEKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDRELA HCDLCLVVGT
    260 270 280 290 300
    SSVVYPAAMF APQVAARGVP VAEFNTETTP ATNRFRFHFQ GPCGTTLPEA
    310
    LACHENETVS
    Length:310
    Mass (Da):33,881
    Last modified:October 31, 2003 - v2
    Checksum:i022DA32CDB43AC3A
    GO
    Isoform 2 (identifier: Q9NXA8-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         286-299: RFHFQGPCGTTLPE → SHLISISSLIIIKN
         300-310: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:299
    Mass (Da):32,674
    Checksum:i2EE7C311AAA34CBA
    GO
    Isoform 3 (identifier: Q9NXA8-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         189-206: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:292
    Mass (Da):31,994
    Checksum:iD89A65C251224735
    GO
    Isoform 4 (identifier: Q9NXA8-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-108: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:202
    Mass (Da):21,689
    Checksum:i051C7D4BE508D66B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti53 – 531I → M in BAG63757 (PubMed:14702039).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti285 – 2851F → L.
    Corresponds to variant rs9464003 [ dbSNP | Ensembl ].
    VAR_029042
    Natural varianti305 – 3051E → G.
    Corresponds to variant rs34162626 [ dbSNP | Ensembl ].
    VAR_051980

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 108108Missing in isoform 4. 1 PublicationVSP_042291Add
    BLAST
    Alternative sequencei189 – 20618Missing in isoform 3. 1 PublicationVSP_042292Add
    BLAST
    Alternative sequencei286 – 29914RFHFQ…TTLPE → SHLISISSLIIIKN in isoform 2. 1 PublicationVSP_008730Add
    BLAST
    Alternative sequencei300 – 31011Missing in isoform 2. 1 PublicationVSP_008731Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF083110 mRNA. Translation: AAD40853.1.
    AK000355 mRNA. Translation: BAA91107.1.
    AK294162 mRNA. Translation: BAG57485.1.
    AK302467 mRNA. Translation: BAG63757.1.
    AM393414 mRNA. Translation: CAL38292.1.
    AL441883 Genomic DNA. Translation: CAI19837.1.
    AL441883 Genomic DNA. Translation: CAI19838.1.
    CH471087 Genomic DNA. Translation: EAW55332.1.
    BC000126 mRNA. Translation: AAH00126.1.
    CCDSiCCDS4526.1. [Q9NXA8-1]
    CCDS4527.1. [Q9NXA8-2]
    CCDS54966.1. [Q9NXA8-3]
    CCDS56398.1. [Q9NXA8-4]
    RefSeqiNP_001180196.1. NM_001193267.2. [Q9NXA8-3]
    NP_001229756.1. NM_001242827.1. [Q9NXA8-4]
    NP_036373.1. NM_012241.4. [Q9NXA8-1]
    NP_112534.1. NM_031244.3. [Q9NXA8-2]
    XP_005249024.1. XM_005248967.3. [Q9NXA8-1]
    XP_005249025.1. XM_005248968.3. [Q9NXA8-1]
    UniGeneiHs.567431.
    Hs.594133.

    Genome annotation databases

    EnsembliENST00000359782; ENSP00000352830; ENSG00000124523. [Q9NXA8-3]
    ENST00000379262; ENSP00000368564; ENSG00000124523. [Q9NXA8-2]
    ENST00000397350; ENSP00000380509; ENSG00000124523. [Q9NXA8-4]
    ENST00000606117; ENSP00000476228; ENSG00000124523.
    GeneIDi23408.
    KEGGihsa:23408.
    UCSCiuc003naw.3. human. [Q9NXA8-2]
    uc003nax.3. human. [Q9NXA8-1]
    uc011dit.2. human. [Q9NXA8-3]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF083110 mRNA. Translation: AAD40853.1.
    AK000355 mRNA. Translation: BAA91107.1.
    AK294162 mRNA. Translation: BAG57485.1.
    AK302467 mRNA. Translation: BAG63757.1.
    AM393414 mRNA. Translation: CAL38292.1.
    AL441883 Genomic DNA. Translation: CAI19837.1.
    AL441883 Genomic DNA. Translation: CAI19838.1.
    CH471087 Genomic DNA. Translation: EAW55332.1.
    BC000126 mRNA. Translation: AAH00126.1.
    CCDSiCCDS4526.1. [Q9NXA8-1]
    CCDS4527.1. [Q9NXA8-2]
    CCDS54966.1. [Q9NXA8-3]
    CCDS56398.1. [Q9NXA8-4]
    RefSeqiNP_001180196.1. NM_001193267.2. [Q9NXA8-3]
    NP_001229756.1. NM_001242827.1. [Q9NXA8-4]
    NP_036373.1. NM_012241.4. [Q9NXA8-1]
    NP_112534.1. NM_031244.3. [Q9NXA8-2]
    XP_005249024.1. XM_005248967.3. [Q9NXA8-1]
    XP_005249025.1. XM_005248968.3. [Q9NXA8-1]
    UniGeneiHs.567431.
    Hs.594133.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2B4YX-ray1.90A/B/C/D34-302[»]
    2NYRX-ray2.06A/B34-302[»]
    3RIGX-ray2.00A/B34-302[»]
    3RIYX-ray1.55A/B34-302[»]
    4F4UX-ray2.00A/B34-302[»]
    4F56X-ray1.70A/B34-302[»]
    4G1CX-ray1.94A/B36-302[»]
    4HDAX-ray2.60A/B34-302[»]
    ProteinModelPortaliQ9NXA8.
    SMRiQ9NXA8. Positions 34-302.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116980. 14 interactions.
    IntActiQ9NXA8. 1 interaction.
    STRINGi9606.ENSP00000368552.

    Chemistry

    BindingDBiQ9NXA8.
    ChEMBLiCHEMBL2163183.
    DrugBankiDB04786. Suramin.

    PTM databases

    PhosphoSiteiQ9NXA8.

    Polymorphism and mutation databases

    BioMutaiSIRT5.
    DMDMi38258652.

    Proteomic databases

    MaxQBiQ9NXA8.
    PaxDbiQ9NXA8.
    PRIDEiQ9NXA8.

    Protocols and materials databases

    DNASUi23408.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000359782; ENSP00000352830; ENSG00000124523. [Q9NXA8-3]
    ENST00000379262; ENSP00000368564; ENSG00000124523. [Q9NXA8-2]
    ENST00000397350; ENSP00000380509; ENSG00000124523. [Q9NXA8-4]
    ENST00000606117; ENSP00000476228; ENSG00000124523.
    GeneIDi23408.
    KEGGihsa:23408.
    UCSCiuc003naw.3. human. [Q9NXA8-2]
    uc003nax.3. human. [Q9NXA8-1]
    uc011dit.2. human. [Q9NXA8-3]

    Organism-specific databases

    CTDi23408.
    GeneCardsiGC06P013574.
    HGNCiHGNC:14933. SIRT5.
    HPAiHPA021798.
    HPA022002.
    HPA022992.
    MIMi604483. gene.
    neXtProtiNX_Q9NXA8.
    PharmGKBiPA37938.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0846.
    GeneTreeiENSGT00740000115330.
    HOGENOMiHOG000085950.
    HOVERGENiHBG056009.
    InParanoidiQ9NXA8.
    KOiK11415.
    OMAiLIHMHGE.
    OrthoDBiEOG77Q4XG.
    PhylomeDBiQ9NXA8.
    TreeFamiTF106183.

    Miscellaneous databases

    EvolutionaryTraceiQ9NXA8.
    GeneWikiiSIRT5.
    GenomeRNAii23408.
    NextBioi45587.
    PROiQ9NXA8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9NXA8.
    CleanExiHS_SIRT5.
    ExpressionAtlasiQ9NXA8. baseline and differential.
    GenevisibleiQ9NXA8. HS.

    Family and domain databases

    Gene3Di3.30.1600.10. 2 hits.
    3.40.50.1220. 3 hits.
    HAMAPiMF_01121. Sirtuin_ClassIII.
    InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR003000. Sirtuin.
    IPR026591. Sirtuin_cat_small_dom.
    IPR027546. Sirtuin_class_III.
    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...

    Publicationsi

    « Hide 'large scale' publications
    1. "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."
      Frye R.A.
      Biochem. Biophys. Res. Commun. 260:273-279(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
      Tissue: Testis.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
      Tissue: Amygdala, Hepatoblastoma and Testis.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    4. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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 1).
      Tissue: Eye.
    7. "Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins."
      Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.
      Mol. Biol. Cell 16:4623-4635(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    8. "Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5."
      Schlicker C., Gertz M., Papatheodorou P., Kachholz B., Becker C.F.W., Steegborn C.
      J. Mol. Biol. 382:790-801(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms."
      Matsushita N., Yonashiro R., Ogata Y., Sugiura A., Nagashima S., Fukuda T., Inatome R., Yanagi S.
      Genes Cells 16:190-202(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION (ISOFORMS 1 AND 2).
    11. Cited for: FUNCTION, NAD-BINDING, MUTAGENESIS OF HIS-158.
    12. "Sirt5 deacylation activities show differential sensitivities to nicotinamide inhibition."
      Fischer F., Gertz M., Suenkel B., Lakshminarasimhan M., Schutkowski M., Steegborn C.
      PLoS ONE 7:E45098-E45098(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, MUTAGENESIS OF THR-69 AND ARG-105.
    13. Cited for: FUNCTION.
    14. "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: SUBCELLULAR LOCATION.
    15. Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-158.
    16. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    17. "Crystal structure of human sirtuin homolog 5 in complex with NAD."
      Structural genomics consortium (SGC)
      Submitted (FEB-2006) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD AND ZINC IONS.
    18. "Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin."
      Schuetz A., Min J., Antoshenko T., Wang C.-L., Allali-Hassani A., Dong A., Loppnau P., Vedadi M., Bochkarev A., Sternglanz R., Plotnikov A.N.
      Structure 15:377-389(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 34-302 IN COMPLEXES WITH ZINC IONS; SURAMIN AND ADP-RIBOSE, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBUNIT.
    19. "Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase."
      Du J., Zhou Y., Su X., Yu J.J., Khan S., Jiang H., Kim J., Woo J., Kim J.H., Choi B.H., He B., Chen W., Zhang S., Cerione R.A., Auwerx J., Hao Q., Lin H.
      Science 334:806-809(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD; ZINC IONS AND SUCCINYLATED PEPTIDE, COFACTOR, ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF TYR-102; ARG-105 AND HIS-158.
    20. "The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5)."
      Zhou Y., Zhang H., He B., Du J., Lin H., Cerione R.A., Hao Q.
      J. Biol. Chem. 287:28307-28314(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD; ZINC IONS AND SUCCINYLATED PEPTIDE, REACTION MECHANISM.
    21. "Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5."
      Szczepankiewicz B.G., Dai H., Koppetsch K.J., Qian D., Jiang F., Mao C., Perni R.B.
      J. Org. Chem. 77:7319-7329(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 36-302 IN COMPLEX WITH CARBA-NAD AND ZINC IONS.
    22. Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-302 IN COMPLEX WITH PROTEIN PEPTIDE; ZINC IONS AND RESVERATROL, ENZYME REGULATION.

    Entry informationi

    Entry nameiSIR5_HUMAN
    AccessioniPrimary (citable) accession number: Q9NXA8
    Secondary accession number(s): B4DFM4
    , B4DYJ5, F5H5Z9, Q5T294, Q5T295, Q9Y6E6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 31, 2003
    Last sequence update: October 31, 2003
    Last modified: July 22, 2015
    This is version 130 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

    The mechanism of demalonylation and desuccinylation involves the presence of a 1',2'-cyclic intermediate, suggesting that sirtuins use the ADP-ribose-peptidylamidate mechanism to remove acyl groups from substrate lysine residues.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 6
      Human chromosome 6: 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

    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.