Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q9Y6E7

- SIR4_HUMAN

UniProt

Q9Y6E7 - SIR4_HUMAN

Protein

NAD-dependent protein deacetylase sirtuin-4

Gene

SIRT4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Acts both as NAD-dependent protein ADP-ribosyl transferase and NAD-dependent protein deacetylase. Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest. In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. Acts as a tumor suppressor. Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of 'Lys-471' of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis. Down-regulates insulin secretion.4 PublicationsUniRule annotation

    Catalytic activityi

    NAD+ + a protein = nicotinamide + an N-(ADP-D-ribosyl)-protein.UniRule annotation
    NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.UniRule annotation

    Cofactori

    Binds 1 zinc ion per subunit.UniRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei161 – 1611Proton acceptorUniRule annotation
    Metal bindingi169 – 1691ZincUniRule annotation
    Metal bindingi172 – 1721ZincUniRule annotation
    Metal bindingi220 – 2201ZincUniRule annotation
    Metal bindingi223 – 2231ZincUniRule annotation
    Binding sitei304 – 3041NAD; via amide nitrogenUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi62 – 8221NADUniRule annotationAdd
    BLAST
    Nucleotide bindingi143 – 1464NADUniRule annotation
    Nucleotide bindingi260 – 2623NADUniRule annotation
    Nucleotide bindingi286 – 2883NADUniRule annotation

    GO - Molecular functioni

    1. hydrolase activity Source: UniProtKB-HAMAP
    2. NAD+ ADP-ribosyltransferase activity Source: UniProtKB
    3. NAD+ binding Source: UniProtKB-HAMAP
    4. protein binding Source: UniProtKB
    5. zinc ion binding Source: UniProtKB-HAMAP

    GO - Biological processi

    1. cellular response to DNA damage stimulus Source: UniProtKB
    2. chromatin silencing Source: ProtInc
    3. glutamine metabolic process Source: UniProtKB
    4. negative regulation of fatty acid oxidation Source: UniProtKB
    5. negative regulation of insulin secretion Source: UniProtKB
    6. peptidyl-lysine deacetylation Source: UniProtKB
    7. positive regulation of lipid biosynthetic process Source: UniProtKB
    8. protein ADP-ribosylation Source: UniProtKB
    9. tricarboxylic acid metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Transferase

    Keywords - Biological processi

    DNA damage

    Keywords - Ligandi

    Metal-binding, NAD, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NAD-dependent protein deacetylase sirtuin-4UniRule annotation (EC:3.5.1.-UniRule annotation)
    Alternative name(s):
    NAD-dependent ADP-ribosyltransferase sirtuin-4UniRule annotation (EC:2.4.2.-UniRule annotation)
    Regulatory protein SIR2 homolog 4UniRule annotation
    SIR2-like protein 4UniRule annotation
    Gene namesi
    Name:SIRT4UniRule annotation
    Synonyms:SIR2L4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:14932. SIRT4.

    Subcellular locationi

    Mitochondrion matrix 3 PublicationsUniRule annotation

    GO - Cellular componenti

    1. mitochondrial matrix Source: UniProtKB
    2. mitochondrion Source: UniProtKB

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    PharmGKBiPA37937.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 2828Mitochondrion2 PublicationsUniRule annotationAdd
    BLAST
    Chaini29 – 314286NAD-dependent protein deacetylase sirtuin-4PRO_0000110264Add
    BLAST

    Proteomic databases

    PaxDbiQ9Y6E7.
    PRIDEiQ9Y6E7.

    PTM databases

    PhosphoSiteiQ9Y6E7.

    Expressioni

    Tissue specificityi

    Detected in vascular smooth muscle and striated muscle. Detected in insulin-producing beta-cells in pancreas islets of Langerhans (at protein level). Widely expressed. Weakly expressed in leukocytes and fetal thymus.1 Publication

    Gene expression databases

    ArrayExpressiQ9Y6E7.
    BgeeiQ9Y6E7.
    CleanExiHS_SIRT4.
    GenevestigatoriQ9Y6E7.

    Organism-specific databases

    HPAiHPA029691.
    HPA029692.

    Interactioni

    Subunit structurei

    Interacts with GLUD1, IDE and SLC25A5.2 PublicationsUniRule annotation

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SLC25A5P051412EBI-2606540,EBI-355133

    Protein-protein interaction databases

    BioGridi116981. 8 interactions.
    IntActiQ9Y6E7. 5 interactions.
    STRINGi9606.ENSP00000202967.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Y6E7.
    SMRiQ9Y6E7. Positions 42-311.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini45 – 314270Deacetylase sirtuin-typeUniRule annotationAdd
    BLAST

    Sequence similaritiesi

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

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0846.
    HOGENOMiHOG000085953.
    HOVERGENiHBG059577.
    InParanoidiQ9Y6E7.
    KOiK11414.
    OMAiLCLNCGE.
    PhylomeDBiQ9Y6E7.
    TreeFamiTF106182.

    Family and domain databases

    Gene3Di3.30.1600.10. 2 hits.
    3.40.50.1220. 3 hits.
    HAMAPiMF_01967. Sirtuin_ClassII.
    InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR003000. Sirtuin.
    IPR026591. Sirtuin_cat_small_dom.
    IPR026587. Sirtuin_class_II.
    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]

    Sequencei

    Sequence statusi: Complete.

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

    Q9Y6E7-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKMSFALTFR SAKGRWIANP SQPCSKASIG LFVPASPPLD PEKVKELQRF    50
    ITLSKRLLVM TGAGISTESG IPDYRSEKVG LYARTDRRPI QHGDFVRSAP 100
    IRQRYWARNF VGWPQFSSHQ PNPAHWALST WEKLGKLYWL VTQNVDALHT 150
    KAGSRRLTEL HGCMDRVLCL DCGEQTPRGV LQERFQVLNP TWSAEAHGLA 200
    PDGDVFLSEE QVRSFQVPTC VQCGGHLKPD VVFFGDTVNP DKVDFVHKRV 250
    KEADSLLVVG SSLQVYSGYR FILTAWEKKL PIAILNIGPT RSDDLACLKL 300
    NSRCGELLPL IDPC 314
    Length:314
    Mass (Da):35,188
    Last modified:November 1, 1999 - v1
    Checksum:i2B76963AD2C3B354
    GO

    Sequence cautioni

    The sequence AAB95634.1 differs from that shown. Reason: Erroneous gene model prediction.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF083109 mRNA. Translation: AAD40852.1.
    AC003982 Genomic DNA. Translation: AAB95634.1. Sequence problems.
    BC109319 mRNA. Translation: AAI09320.1.
    BC109320 mRNA. Translation: AAI09321.1.
    CCDSiCCDS9194.1.
    RefSeqiNP_036372.1. NM_012240.2.
    XP_006719371.1. XM_006719308.1.
    XP_006719372.1. XM_006719309.1.
    XP_006719373.1. XM_006719310.1.
    XP_006719374.1. XM_006719311.1.
    UniGeneiHs.50861.

    Genome annotation databases

    EnsembliENST00000202967; ENSP00000202967; ENSG00000089163.
    GeneIDi23409.
    KEGGihsa:23409.
    UCSCiuc001tyc.3. human.

    Polymorphism databases

    DMDMi38258657.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF083109 mRNA. Translation: AAD40852.1 .
    AC003982 Genomic DNA. Translation: AAB95634.1 . Sequence problems.
    BC109319 mRNA. Translation: AAI09320.1 .
    BC109320 mRNA. Translation: AAI09321.1 .
    CCDSi CCDS9194.1.
    RefSeqi NP_036372.1. NM_012240.2.
    XP_006719371.1. XM_006719308.1.
    XP_006719372.1. XM_006719309.1.
    XP_006719373.1. XM_006719310.1.
    XP_006719374.1. XM_006719311.1.
    UniGenei Hs.50861.

    3D structure databases

    ProteinModelPortali Q9Y6E7.
    SMRi Q9Y6E7. Positions 42-311.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116981. 8 interactions.
    IntActi Q9Y6E7. 5 interactions.
    STRINGi 9606.ENSP00000202967.

    Chemistry

    ChEMBLi CHEMBL2163185.

    PTM databases

    PhosphoSitei Q9Y6E7.

    Polymorphism databases

    DMDMi 38258657.

    Proteomic databases

    PaxDbi Q9Y6E7.
    PRIDEi Q9Y6E7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000202967 ; ENSP00000202967 ; ENSG00000089163 .
    GeneIDi 23409.
    KEGGi hsa:23409.
    UCSCi uc001tyc.3. human.

    Organism-specific databases

    CTDi 23409.
    GeneCardsi GC12P120740.
    HGNCi HGNC:14932. SIRT4.
    HPAi HPA029691.
    HPA029692.
    MIMi 604482. gene.
    neXtProti NX_Q9Y6E7.
    PharmGKBi PA37937.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0846.
    HOGENOMi HOG000085953.
    HOVERGENi HBG059577.
    InParanoidi Q9Y6E7.
    KOi K11414.
    OMAi LCLNCGE.
    PhylomeDBi Q9Y6E7.
    TreeFami TF106182.

    Miscellaneous databases

    GeneWikii SIRT4.
    GenomeRNAii 23409.
    NextBioi 45593.
    PROi Q9Y6E7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y6E7.
    Bgeei Q9Y6E7.
    CleanExi HS_SIRT4.
    Genevestigatori Q9Y6E7.

    Family and domain databases

    Gene3Di 3.30.1600.10. 2 hits.
    3.40.50.1220. 3 hits.
    HAMAPi MF_01967. Sirtuin_ClassII.
    InterProi IPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR003000. Sirtuin.
    IPR026591. Sirtuin_cat_small_dom.
    IPR026587. Sirtuin_class_II.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view ]
    PANTHERi PTHR11085. PTHR11085. 1 hit.
    Pfami PF02146. SIR2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52467. SSF52467. 1 hit.
    PROSITEi PS50305. SIRTUIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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], TISSUE SPECIFICITY.
      Tissue: Testis.
    2. "The finished DNA sequence of human chromosome 12."
      Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
      , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
      Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "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].
    4. "SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells."
      Haigis M.C., Mostoslavsky R., Haigis K.M., Fahie K., Christodoulou D.C., Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Karow M., Blander G., Wolberger C., Prolla T.A., Weindruch R., Alt F.W., Guarente L.
      Cell 126:941-954(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, INTERACTION WITH GLUD1, SUBCELLULAR LOCATION.
    5. "Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase."
      Ahuja N., Schwer B., Carobbio S., Waltregny D., North B.J., Castronovo V., Maechler P., Verdin E.
      J. Biol. Chem. 282:33583-33592(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH IDE AND SLC25A5.
    6. "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.
    7. "SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism."
      Jeong S.M., Xiao C., Finley L.W., Lahusen T., Souza A.L., Pierce K., Li Y.H., Wang X., Laurent G., German N.J., Xu X., Li C., Wang R.H., Lee J., Csibi A., Cerione R., Blenis J., Clish C.B.
      , Kimmelman A., Deng C.X., Haigis M.C.
      Cancer Cell 23:450-463(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS A TUMOR SUPPRESSOR.
    8. Cited for: FUNCTION AS A TUMOR SUPPRESSOR.

    Entry informationi

    Entry nameiSIR4_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y6E7
    Secondary accession number(s): O43346, Q32M33
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 31, 2003
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 115 of the entry and version 1 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

    Expression is down-regulated in a number of cancers, while overexpression reduces cell proliferation, transformation, and tumor development (PubMed:23562301, PubMed:23663782).2 Publications
    According to some authors, ADP-ribosyltransferase activity of sirtuins may be an inefficient side reaction of the deacetylase activity and may not be physiologically relevant.UniRule annotation

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3