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O35613

- DAXX_MOUSE

UniProt

O35613 - DAXX_MOUSE

Protein

Death domain-associated protein 6

Gene

Daxx

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activatiopn of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Acts as histone chaperone that facilitates deposition of histone H3.3. Acts as targeting component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Does not affect the ATPase activity of ATRX but alleviates its transcription repression activity. Upopn neuronal activation asociates with regulatory elements of selected immediate early genes where it promotes deposition of histone H3.3 which may be linked to transcriptional induction of these genes. Required for the recruitment of histone H3.3:H4 dimers to PML-nuclear bodies (PML-NBs); the process is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested to function as regulatory sites for the incorporation of newly synthesized histone H3.3 into chromatin. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX.3 Publications

    GO - Molecular functioni

    1. androgen receptor binding Source: UniProtKB
    2. histone binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. protein homodimerization activity Source: UniProtKB
    5. transcription coactivator activity Source: UniProtKB
    6. transcription corepressor activity Source: UniProtKB
    7. transcription factor binding Source: UniProtKB

    GO - Biological processi

    1. androgen receptor signaling pathway Source: UniProtKB
    2. apoptotic signaling pathway Source: MGI
    3. chromatin modification Source: UniProtKB-KW
    4. mitotic cytokinesis Source: MGI
    5. negative regulation of transcription, DNA-templated Source: UniProtKB
    6. nucleosome assembly Source: UniProtKB
    7. positive regulation of apoptotic signaling pathway Source: MGI
    8. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    9. regulation of protein ubiquitination Source: UniProtKB
    10. regulation of transcription, DNA-templated Source: MGI
    11. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Chaperone, Chromatin regulator, Repressor

    Keywords - Biological processi

    Apoptosis, Transcription, Transcription regulation

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Death domain-associated protein 6
    Alternative name(s):
    Daxx
    Gene namesi
    Name:Daxx
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:1197015. Daxx.

    Subcellular locationi

    Cytoplasm. Nucleusnucleoplasm. NucleusPML body. Nucleusnucleolus By similarity
    Note: Dispersed throughout the nucleoplasm, in PML/POD/ND10 nuclear bodies, and in nucleoli. Colocalizes with histone H3.3, ATRX, HIRA and ASF1A at PML-nuclear bodies. Colocalizes with a subset of interphase centromeres, but is absent from mitotic centromeres. Detected in cytoplasmic punctate structures. Translocates from the nucleus to the cytoplasm upon glucose deprivation or oxidative stress. Colocalizes with RASSF1 in the nucleus. Colocalizes with USP7 in nucleoplasma with accumulation in speckled structures. Colocalizes with histone H3.3, ATRX, HIRA and ASF1A at PML-nuclear bodies By similarity.By similarity

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. heterochromatin Source: MGI
    3. nucleolus Source: UniProtKB-SubCell
    4. nucleus Source: UniProtKB
    5. PML body Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi502 – 5021S → A: No effect on phosphorylation by HIPK1. 1 Publication
    Mutagenesisi669 – 6691S → A: Diminishes phosphorylation by HIPK1. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 739739Death domain-associated protein 6PRO_0000151259Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei219 – 2191Phosphoserine1 Publication
    Modified residuei472 – 4721Phosphothreonine1 Publication
    Modified residuei502 – 5021Phosphoserine1 Publication
    Modified residuei515 – 5151Phosphoserine1 Publication
    Modified residuei523 – 5231Phosphothreonine1 Publication
    Modified residuei626 – 6261Phosphoserine1 Publication
    Cross-linki630 – 630Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
    Modified residuei669 – 6691Phosphoserine; by HIPK11 Publication
    Modified residuei687 – 6871PhosphoserineBy similarity
    Modified residuei701 – 7011PhosphoserineBy similarity
    Modified residuei736 – 7361PhosphoserineBy similarity
    Modified residuei738 – 7381PhosphoserineBy similarity

    Post-translational modificationi

    Sumoylated with SUMO1 on multiple lysine residues.By similarity
    Repressor activity is down-regulated upon Ser-669 phosphorylation. Upon neuronal activation dephosphorylated by calcineurin in a Ca2+ dependent manner at Ser-669; dephosphorylation positively affects histone H3.3 loading and transcriptional activation.1 Publication
    Polyubiquitinated; which is promoted by CUL3 and SPOP and results in proteasomal degradation. Ubiquitinated by MDM2; inducing its degradation. Deubiquitinated by USP7; leading to stabilize it By similarity.By similarity

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiO35613.
    PaxDbiO35613.
    PRIDEiO35613.

    PTM databases

    PhosphoSiteiO35613.

    Expressioni

    Developmental stagei

    Expressed as early as embryonic day 12.5 (E12. 5) in the neuroepithelium (ventricular zone). At E17.5, expression becomes more pronounced in postmitotic cells of the cortical plate (CP). Early postnatally (postnatal day 2 [P2]) and in the adult brain (P30) expressed both in the cortex and in the hippocampus.1 Publication

    Gene expression databases

    CleanExiMM_DAXX.
    GenevestigatoriO35613.

    Interactioni

    Subunit structurei

    Homomultimer. Interacts (via C-terminus) with TNFRSF6 (via death domain). Interacts with PAX5, SLC2A4/GLUT4, MAP3K5, TGFBR2, phosphorylated dimeric HSPB1/HSP27, CENPC, ETS1, sumoylated PML, UBE2I, MCRS1 and TP53. Interacts (via N-terminus) with HIPK2 and HIPK3. Interacts with HIPK1, which induces translocation from PML/POD/ND10 nuclear bodies to chromatin and enhances association with HDAC1. Interacts (non-phosphorylated) with PAX3, PAX7, DEK, HDAC1, HDAC2, HDAC3, acetylated histone H4 and histones H2A, H2B, H3, H3.3 and H4. Interacts with SPOP; mediating CUL3-dependent proteosomal degradation. Interacts with CBP; the interaction is dependent the sumoylation of CBP and suppresses CBP transcriptional activity via recruitment of HDAC2 directly in the complex with TP53 and HIPK2. Interacts with AXIN1; the interaction stimulates the interaction of DAXX with TP53, stimulates 'Ser-46' phosphorylation of TP53 on and induces cell death on UV irradiation. Interacts with MDM2; the interaction is direct. Interacts with USP7; the interaction is direct and independent of MDM2 and TP53. Part of a complex with DAXX, MDM2 and USP7 under non-stress conditions. Interacts (via N-terminus) with RASSF1 (via C-terminus); the interaction is independent of MDM2 and TP53; RASSF1 isoform A disrupts interactions among MDM2, DAXX and USP7, thus contributing to the efficient activation of TP53 by promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in response to DNA damage. Interacts with ATRX to form the chromatin remodeling complex ATRX:DAXX.6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Dapk3O547842EBI-77304,EBI-77359
    FasP254462EBI-77304,EBI-296206
    Hipk1O889043EBI-77304,EBI-692945

    Protein-protein interaction databases

    BioGridi199054. 12 interactions.
    IntActiO35613. 14 interactions.
    MINTiMINT-1172660.

    Structurei

    3D structure databases

    DisProtiDP00708.
    ProteinModelPortaliO35613.
    SMRiO35613. Positions 62-150, 188-392.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 166166Necessary for interaction with USP7 and ATRXBy similarityAdd
    BLAST
    Regioni189 – 423235Interaction with histone H3.3By similarityAdd
    BLAST
    Regioni353 – 576224Necessary for interaction with USP7By similarityAdd
    BLAST
    Regioni626 – 739114Interaction with SPOPBy similarityAdd
    BLAST
    Regioni732 – 7398Sumo interaction motif (SIM)By similarity

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili185 – 22339Sequence AnalysisAdd
    BLAST
    Coiled coili364 – 40340Sequence AnalysisAdd
    BLAST
    Coiled coili445 – 48844Sequence AnalysisAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi391 – 3955Nuclear localization signalSequence Analysis
    Motifi622 – 6287Nuclear localization signalSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi11 – 166Poly-Asp
    Compositional biasi442 – 50160Asp/Glu-rich (acidic)Add
    BLAST

    Domaini

    The Sumo interaction motif mediates Sumo binding, and is required both for sumoylation and binding to sumoylated targets.By similarity

    Sequence similaritiesi

    Belongs to the DAXX family.Curated

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    eggNOGiNOG39676.
    HOVERGENiHBG031495.
    InParanoidiO35613.
    KOiK02308.
    PhylomeDBiO35613.

    Family and domain databases

    InterProiIPR005012. Daxx.
    [Graphical view]
    PANTHERiPTHR12766. PTHR12766. 1 hit.
    PfamiPF03344. Daxx. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O35613-1 [UniParc]FASTAAdd to Basket

    « Hide

    MATDDSIIVL DDDDEDEAAA QPGPSNLPPN PASTGPGPGL SQQATGLSEP    50
    RVDGGSSNSG SRKCYKLDNE KLFEEFLELC KTETSDHPEV VPFLHKLQQR 100
    AQSVFLASAE FCNILSRVLA RSRKRPAKIY VYINELCTVL KAHSIKKKLN 150
    LAPAASTTSE ASGPNPPTEP PSDLTNTENT ASEASRTRGS RRQIQRLEQL 200
    LALYVAEIRR LQEKELDLSE LDDPDSSYLQ EARLKRKLIR LFGRLCELKD 250
    CSSLTGRVIE QRIPYRGTRY PEVNRRIERL INKPGLDTFP DYGDVLRAVE 300
    KAATRHSLGL PRQQLQLLAQ DAFRDVGVRL QERRHLDLIY NFGCHLTDDY 350
    RPGVDPALSD PTLARRLREN RTLAMNRLDE VISKYAMMQD KTEEGERQKR 400
    RARLLGTAPQ PSDPPQASSE SGEGPSGMAS QECPTTSKAE TDDDDDDDDD 450
    DDEDNEESEE EEEEEEEEKE ATEDEDEDLE QLQEDQGGDE EEEGGDNEGN 500
    ESPTSPSDFF HRRNSEPAEG LRTPEGQQKR GLTETPASPP GASLDPPSTD 550
    AESSGEQLLE PLLGDESPVS QLAELEMEAL PEERDISSPR KKSEDSLPTI 600
    LENGAAVVTS TSVNGRVSSH TWRDASPPSK RFRKEKKQLG SGLLGNSYIK 650
    EPMAQQDSGQ NTSVQPMPSP PLASVASVAD SSTRVDSPSH ELVTSSLCSP 700
    SPSLLLQTPQ AQSLRQCIYK TSVATQCDPE EIIVLSDSD 739
    Length:739
    Mass (Da):81,489
    Last modified:January 1, 1998 - v1
    Checksum:i8407D5788528AC2D
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti416 – 4161Q → K in AAC97971. 1 PublicationCurated
    Sequence conflicti452 – 4521D → DD in AAC97971. 1 PublicationCurated
    Sequence conflicti589 – 5891P → S in AAC97971. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF006040 mRNA. Translation: AAC53284.1.
    AF110520 Genomic DNA. Translation: AAC97971.1.
    AF100956 Genomic DNA. Translation: AAC69891.1.
    RefSeqiNP_001186662.1. NM_001199733.1.
    NP_031855.3. NM_007829.4.
    XP_006523643.1. XM_006523580.1.
    XP_006523644.1. XM_006523581.1.
    XP_006523645.1. XM_006523582.1.
    XP_006525362.1. XM_006525299.1.
    XP_006525363.1. XM_006525300.1.
    XP_006525364.1. XM_006525301.1.
    UniGeneiMm.271809.

    Genome annotation databases

    GeneIDi13163.
    KEGGimmu:13163.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF006040 mRNA. Translation: AAC53284.1 .
    AF110520 Genomic DNA. Translation: AAC97971.1 .
    AF100956 Genomic DNA. Translation: AAC69891.1 .
    RefSeqi NP_001186662.1. NM_001199733.1.
    NP_031855.3. NM_007829.4.
    XP_006523643.1. XM_006523580.1.
    XP_006523644.1. XM_006523581.1.
    XP_006523645.1. XM_006523582.1.
    XP_006525362.1. XM_006525299.1.
    XP_006525363.1. XM_006525300.1.
    XP_006525364.1. XM_006525301.1.
    UniGenei Mm.271809.

    3D structure databases

    DisProti DP00708.
    ProteinModelPortali O35613.
    SMRi O35613. Positions 62-150, 188-392.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199054. 12 interactions.
    IntActi O35613. 14 interactions.
    MINTi MINT-1172660.

    PTM databases

    PhosphoSitei O35613.

    Proteomic databases

    MaxQBi O35613.
    PaxDbi O35613.
    PRIDEi O35613.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 13163.
    KEGGi mmu:13163.

    Organism-specific databases

    CTDi 1616.
    MGIi MGI:1197015. Daxx.

    Phylogenomic databases

    eggNOGi NOG39676.
    HOVERGENi HBG031495.
    InParanoidi O35613.
    KOi K02308.
    PhylomeDBi O35613.

    Miscellaneous databases

    NextBioi 283238.
    PROi O35613.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_DAXX.
    Genevestigatori O35613.

    Family and domain databases

    InterProi IPR005012. Daxx.
    [Graphical view ]
    PANTHERi PTHR12766. PTHR12766. 1 hit.
    Pfami PF03344. Daxx. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Daxx, a novel Fas-binding protein that activates JNK and apoptosis."
      Yang X., Khosravi-Far R., Chang H.Y., Baltimore D.
      Cell 89:1067-1076(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Thymus.
    2. "Sequence of the mouse major histocompatibility complex class II region."
      Rowen L., Qin S., Madan A., Loretz C., James R., Dors M., Mix L., Hall J., Lasky S., Hood L.
      Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: 129/SvJ.
    3. "Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis."
      Zhong S., Salomoni P., Ronchetti S., Guo A., Ruggero D., Pandolfi P.P.
      J. Exp. Med. 191:631-640(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PML.
    4. "FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits Fas-mediated Jun NH2-terminal kinase activation."
      Rochat-Steiner V., Becker K., Micheau O., Schneider P., Burns K., Tschopp J.
      J. Exp. Med. 192:1165-1174(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIPK3.
    5. "The interaction of Pax5 (BSAP) with Daxx can result in transcriptional activation in B cells."
      Emelyanov A.V., Kovac C.R., Sepulveda M.A., Birshtein B.K.
      J. Biol. Chem. 277:11156-11164(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PAX5.
    6. "Homeodomain-interacting protein kinase 1 modulates Daxx localization, phosphorylation, and transcriptional activity."
      Ecsedy J.A., Michaelson J.S., Leder P.
      Mol. Cell. Biol. 23:950-960(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIPK1, MUTAGENESIS OF SER-502 AND SER-669, PHOSPHORYLATION AT SER-219; THR-472; SER-502; SER-515; THR-523; SER-626 AND SER-669, IDENTIFICATION BY MASS SPECTROMETRY.
    7. "SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx."
      Kuo H.-Y., Chang C.-C., Jeng J.-C., Hu H.-M., Lin D.-Y., Maul G.G., Kwok R.P.S., Shih H.-M.
      Proc. Natl. Acad. Sci. U.S.A. 102:16973-16978(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CBP.
    8. "The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3."
      Drane P., Ouararhni K., Depaux A., Shuaib M., Hamiche A.
      Genes Dev. 24:1253-1265(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HISTONE H3.3.
    9. "Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres."
      Lewis P.W., Elsaesser S.J., Noh K.M., Stadler S.C., Allis C.D.
      Proc. Natl. Acad. Sci. U.S.A. 107:14075-14080(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS HISTONE CHAPERONE.
    10. "Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation."
      Michod D., Bartesaghi S., Khelifi A., Bellodi C., Berliocchi L., Nicotera P., Salomoni P.
      Neuron 74:122-135(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN HISTONE H3.3 DEPOSITION, SUBCELLULAR LOCATION, DEPHOSPHORYLATION AT SER-669 BY CALCINEURIN, DEVELOPMENTAL STAGE.

    Entry informationi

    Entry nameiDAXX_MOUSE
    AccessioniPrimary (citable) accession number: O35613
    Secondary accession number(s): Q9QWT8, Q9QWV3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 2002
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 118 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    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