O35613 · DAXX_MOUSE

  • Protein
    Death domain-associated protein 6
  • Gene
    Daxx
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

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 activation 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 a histone chaperone that facilitates deposition of histone H3.3. Acts as a 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. Upon neuronal activation associates 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. Plays a role as a positive regulator of the heat shock transcription factor HSF1 activity during the stress protein response (By similarity).

GO annotations

AspectTerm
Cellular Componentcell body
Cellular Componentcell cortex
Cellular Componentchromosome, centromeric region
Cellular Componentcytosol
Cellular Componentheterochromatin
Cellular Componentmicrotubule
Cellular Componentnucleolus
Cellular Componentnucleus
Cellular ComponentPML body
Cellular ComponentXY body
Molecular Functionhistone binding
Molecular FunctionJUN kinase binding
Molecular Functionkinesin binding
Molecular Functionnuclear androgen receptor binding
Molecular Functionprotein homodimerization activity
Molecular Functionprotein kinase binding
Molecular FunctionRNA polymerase II-specific DNA-binding transcription factor binding
Molecular Functiontranscription coactivator activity
Molecular Functiontranscription corepressor activity
Biological Processandrogen receptor signaling pathway
Biological Processapoptotic signaling pathway
Biological Processcell population proliferation
Biological Processcellular response to cadmium ion
Biological Processcellular response to copper ion
Biological Processcellular response to diamide
Biological Processcellular response to heat
Biological Processcellular response to sodium arsenite
Biological Processcellular response to type II interferon
Biological Processcellular response to unfolded protein
Biological Processmitotic cytokinesis
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of cellular response to hypoxia
Biological Processnegative regulation of DNA-templated transcription
Biological Processnegative regulation of myotube differentiation
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processnucleosome assembly
Biological ProcessPML body organization
Biological Processpositive regulation of apoptotic process
Biological Processpositive regulation of apoptotic signaling pathway
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processprotein localization to chromatin
Biological Processregulation of apoptotic process
Biological Processregulation of DNA-templated transcription
Biological Processregulation of multicellular organism growth
Biological Processregulation of protein ubiquitination

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Death domain-associated protein 6
  • Alternative names
    • Daxx

Gene names

    • Name
      Daxx

Organism names

  • Taxonomic identifier
  • Strain
    • 129/SvJ
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    O35613
  • Secondary accessions
    • Q9QWT8
    • Q9QWV3

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus, nucleoplasm
Nucleus, PML body
Nucleus, nucleolus
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.

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis502No effect on phosphorylation by HIPK1.
Mutagenesis669Diminishes phosphorylation by HIPK1.

PTM/Processing

Features

Showing features for chain, modified residue, cross-link.

TypeIDPosition(s)Description
ChainPRO_00001512591-739Death domain-associated protein 6
Modified residue25Phosphoserine
Cross-link148Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue219Phosphoserine
Modified residue418Phosphoserine
Modified residue430Phosphoserine
Modified residue472Phosphothreonine
Modified residue502Phosphoserine
Modified residue505Phosphoserine
Modified residue507Phosphoserine
Modified residue515Phosphoserine
Modified residue523Phosphothreonine
Modified residue543Phosphoserine
Modified residue567Phosphoserine
Modified residue626Phosphoserine
Cross-link630Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)
Modified residue669Phosphoserine; by HIPK1
Modified residue687Phosphoserine
Modified residue701Phosphoserine
Modified residue736Phosphoserine
Modified residue738Phosphoserine

Post-translational modification

Sumoylated with SUMO1 on multiple lysine residues.
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.
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).

Keywords

Proteomic databases

PTM databases

Expression

Developmental stage

Expressed as early as 12.5 dpc in the neuroepithelium (ventricular zone). At 17.5 dpc, 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.

Interaction

Subunit

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 proteasomal 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. Interacts with HSF1 (via homotrimeric form preferentially); this interaction relieves homotrimeric HSF1 from repression of its transcriptional activity by HSP90-dependent multichaperone complex upon heat shock (By similarity).

Binary interactions

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias, coiled coil, motif.

TypeIDPosition(s)Description
Region1-60Disordered
Region1-166Necessary for interaction with USP7 and ATRX
Compositional bias36-60Polar residues
Region155-191Disordered
Compositional bias172-188Polar residues
Coiled coil185-223
Region189-423Interaction with histone H3.3
Region353-576Necessary for interaction with USP7
Coiled coil364-403
Motif391-395Nuclear localization signal
Region405-599Disordered
Compositional bias411-436Polar residues
Compositional bias439-498Acidic residues
Coiled coil445-488
Compositional bias577-597Basic and acidic residues
Compositional bias611-625Polar residues
Region611-688Disordered
Motif622-628Nuclear localization signal
Region626-739Interaction with SPOP
Compositional bias651-688Polar residues
Region732-739Sumo interaction motif (SIM)

Domain

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

Sequence similarities

Belongs to the DAXX family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    739
  • Mass (Da)
    81,489
  • Last updated
    1998-01-01 v1
  • Checksum
    8407D5788528AC2D
MATDDSIIVLDDDDEDEAAAQPGPSNLPPNPASTGPGPGLSQQATGLSEPRVDGGSSNSGSRKCYKLDNEKLFEEFLELCKTETSDHPEVVPFLHKLQQRAQSVFLASAEFCNILSRVLARSRKRPAKIYVYINELCTVLKAHSIKKKLNLAPAASTTSEASGPNPPTEPPSDLTNTENTASEASRTRGSRRQIQRLEQLLALYVAEIRRLQEKELDLSELDDPDSSYLQEARLKRKLIRLFGRLCELKDCSSLTGRVIEQRIPYRGTRYPEVNRRIERLINKPGLDTFPDYGDVLRAVEKAATRHSLGLPRQQLQLLAQDAFRDVGVRLQERRHLDLIYNFGCHLTDDYRPGVDPALSDPTLARRLRENRTLAMNRLDEVISKYAMMQDKTEEGERQKRRARLLGTAPQPSDPPQASSESGEGPSGMASQECPTTSKAETDDDDDDDDDDDEDNEESEEEEEEEEEEKEATEDEDEDLEQLQEDQGGDEEEEGGDNEGNESPTSPSDFFHRRNSEPAEGLRTPEGQQKRGLTETPASPPGASLDPPSTDAESSGEQLLEPLLGDESPVSQLAELEMEALPEERDISSPRKKSEDSLPTILENGAAVVTSTSVNGRVSSHTWRDASPPSKRFRKEKKQLGSGLLGNSYIKEPMAQQDSGQNTSVQPMPSPPLASVASVADSSTRVDSPSHELVTSSLCSPSPSLLLQTPQAQSLRQCIYKTSVATQCDPEEIIVLSDSD

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
Q3UKR0Q3UKR0_MOUSEDaxx740
G3UYN8G3UYN8_MOUSEDaxx186
G3UWI4G3UWI4_MOUSEDaxx166
G3UWJ9G3UWJ9_MOUSEDaxx137
G3UX50G3UX50_MOUSEDaxx206

Features

Showing features for compositional bias, sequence conflict.

TypeIDPosition(s)Description
Compositional bias36-60Polar residues
Compositional bias172-188Polar residues
Compositional bias411-436Polar residues
Sequence conflict416in Ref. 2; AAC97971
Compositional bias439-498Acidic residues
Sequence conflict452in Ref. 2; AAC97971
Compositional bias577-597Basic and acidic residues
Sequence conflict589in Ref. 2; AAC97971
Compositional bias611-625Polar residues
Compositional bias651-688Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF006040
EMBL· GenBank· DDBJ
AAC53284.1
EMBL· GenBank· DDBJ
mRNA
AF110520
EMBL· GenBank· DDBJ
AAC97971.1
EMBL· GenBank· DDBJ
Genomic DNA
AF100956
EMBL· GenBank· DDBJ
AAC69891.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

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