O35613 · DAXX_MOUSE
- ProteinDeath domain-associated protein 6
- GeneDaxx
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids739 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDeath domain-associated protein 6
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO35613
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 502 | No effect on phosphorylation by HIPK1. | ||||
Sequence: S → A | ||||||
Mutagenesis | 669 | Diminishes phosphorylation by HIPK1. | ||||
Sequence: S → A |
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000151259 | 1-739 | Death domain-associated protein 6 | |||
Sequence: MATDDSIIVLDDDDEDEAAAQPGPSNLPPNPASTGPGPGLSQQATGLSEPRVDGGSSNSGSRKCYKLDNEKLFEEFLELCKTETSDHPEVVPFLHKLQQRAQSVFLASAEFCNILSRVLARSRKRPAKIYVYINELCTVLKAHSIKKKLNLAPAASTTSEASGPNPPTEPPSDLTNTENTASEASRTRGSRRQIQRLEQLLALYVAEIRRLQEKELDLSELDDPDSSYLQEARLKRKLIRLFGRLCELKDCSSLTGRVIEQRIPYRGTRYPEVNRRIERLINKPGLDTFPDYGDVLRAVEKAATRHSLGLPRQQLQLLAQDAFRDVGVRLQERRHLDLIYNFGCHLTDDYRPGVDPALSDPTLARRLRENRTLAMNRLDEVISKYAMMQDKTEEGERQKRRARLLGTAPQPSDPPQASSESGEGPSGMASQECPTTSKAETDDDDDDDDDDDEDNEESEEEEEEEEEEKEATEDEDEDLEQLQEDQGGDEEEEGGDNEGNESPTSPSDFFHRRNSEPAEGLRTPEGQQKRGLTETPASPPGASLDPPSTDAESSGEQLLEPLLGDESPVSQLAELEMEALPEERDISSPRKKSEDSLPTILENGAAVVTSTSVNGRVSSHTWRDASPPSKRFRKEKKQLGSGLLGNSYIKEPMAQQDSGQNTSVQPMPSPPLASVASVADSSTRVDSPSHELVTSSLCSPSPSLLLQTPQAQSLRQCIYKTSVATQCDPEEIIVLSDSD | ||||||
Modified residue | 25 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 148 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 219 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 418 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 430 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 472 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 502 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 505 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 507 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 515 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 523 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 543 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 567 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 626 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 630 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K | ||||||
Modified residue | 669 | Phosphoserine; by HIPK1 | ||||
Sequence: S | ||||||
Modified residue | 687 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 701 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 736 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 738 | Phosphoserine | ||||
Sequence: S |
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
- PTM
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
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O35613 | Dapk3 O54784 | 2 | EBI-77304, EBI-77359 | |
BINARY | O35613 | Fas P25446 | 2 | EBI-77304, EBI-296206 | |
BINARY | O35613 | Hipk1 O88904 | 3 | EBI-77304, EBI-692945 | |
BINARY | O35613 | Trim28 Q62318 | 2 | EBI-77304, EBI-346909 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, coiled coil, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-60 | Disordered | ||||
Sequence: MATDDSIIVLDDDDEDEAAAQPGPSNLPPNPASTGPGPGLSQQATGLSEPRVDGGSSNSG | ||||||
Region | 1-166 | Necessary for interaction with USP7 and ATRX | ||||
Sequence: MATDDSIIVLDDDDEDEAAAQPGPSNLPPNPASTGPGPGLSQQATGLSEPRVDGGSSNSGSRKCYKLDNEKLFEEFLELCKTETSDHPEVVPFLHKLQQRAQSVFLASAEFCNILSRVLARSRKRPAKIYVYINELCTVLKAHSIKKKLNLAPAASTTSEASGPNP | ||||||
Compositional bias | 36-60 | Polar residues | ||||
Sequence: PGPGLSQQATGLSEPRVDGGSSNSG | ||||||
Region | 155-191 | Disordered | ||||
Sequence: ASTTSEASGPNPPTEPPSDLTNTENTASEASRTRGSR | ||||||
Compositional bias | 172-188 | Polar residues | ||||
Sequence: SDLTNTENTASEASRTR | ||||||
Coiled coil | 185-223 | |||||
Sequence: SRTRGSRRQIQRLEQLLALYVAEIRRLQEKELDLSELDD | ||||||
Region | 189-423 | Interaction with histone H3.3 | ||||
Sequence: GSRRQIQRLEQLLALYVAEIRRLQEKELDLSELDDPDSSYLQEARLKRKLIRLFGRLCELKDCSSLTGRVIEQRIPYRGTRYPEVNRRIERLINKPGLDTFPDYGDVLRAVEKAATRHSLGLPRQQLQLLAQDAFRDVGVRLQERRHLDLIYNFGCHLTDDYRPGVDPALSDPTLARRLRENRTLAMNRLDEVISKYAMMQDKTEEGERQKRRARLLGTAPQPSDPPQASSESGE | ||||||
Region | 353-576 | Necessary for interaction with USP7 | ||||
Sequence: GVDPALSDPTLARRLRENRTLAMNRLDEVISKYAMMQDKTEEGERQKRRARLLGTAPQPSDPPQASSESGEGPSGMASQECPTTSKAETDDDDDDDDDDDEDNEESEEEEEEEEEEKEATEDEDEDLEQLQEDQGGDEEEEGGDNEGNESPTSPSDFFHRRNSEPAEGLRTPEGQQKRGLTETPASPPGASLDPPSTDAESSGEQLLEPLLGDESPVSQLAELE | ||||||
Coiled coil | 364-403 | |||||
Sequence: ARRLRENRTLAMNRLDEVISKYAMMQDKTEEGERQKRRAR | ||||||
Motif | 391-395 | Nuclear localization signal | ||||
Sequence: KTEEG | ||||||
Region | 405-599 | Disordered | ||||
Sequence: LGTAPQPSDPPQASSESGEGPSGMASQECPTTSKAETDDDDDDDDDDDEDNEESEEEEEEEEEEKEATEDEDEDLEQLQEDQGGDEEEEGGDNEGNESPTSPSDFFHRRNSEPAEGLRTPEGQQKRGLTETPASPPGASLDPPSTDAESSGEQLLEPLLGDESPVSQLAELEMEALPEERDISSPRKKSEDSLPT | ||||||
Compositional bias | 411-436 | Polar residues | ||||
Sequence: PSDPPQASSESGEGPSGMASQECPTT | ||||||
Compositional bias | 439-498 | Acidic residues | ||||
Sequence: AETDDDDDDDDDDDEDNEESEEEEEEEEEEKEATEDEDEDLEQLQEDQGGDEEEEGGDNE | ||||||
Coiled coil | 445-488 | |||||
Sequence: DDDDDDDDEDNEESEEEEEEEEEEKEATEDEDEDLEQLQEDQGG | ||||||
Compositional bias | 577-597 | Basic and acidic residues | ||||
Sequence: MEALPEERDISSPRKKSEDSL | ||||||
Compositional bias | 611-625 | Polar residues | ||||
Sequence: TSVNGRVSSHTWRDA | ||||||
Region | 611-688 | Disordered | ||||
Sequence: TSVNGRVSSHTWRDASPPSKRFRKEKKQLGSGLLGNSYIKEPMAQQDSGQNTSVQPMPSPPLASVASVADSSTRVDSP | ||||||
Motif | 622-628 | Nuclear localization signal | ||||
Sequence: WRDASPP | ||||||
Region | 626-739 | Interaction with SPOP | ||||
Sequence: SPPSKRFRKEKKQLGSGLLGNSYIKEPMAQQDSGQNTSVQPMPSPPLASVASVADSSTRVDSPSHELVTSSLCSPSPSLLLQTPQAQSLRQCIYKTSVATQCDPEEIIVLSDSD | ||||||
Compositional bias | 651-688 | Polar residues | ||||
Sequence: EPMAQQDSGQNTSVQPMPSPPLASVASVADSSTRVDSP | ||||||
Region | 732-739 | Sumo interaction motif (SIM) | ||||
Sequence: IIVLSDSD |
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length739
- Mass (Da)81,489
- Last updated1998-01-01 v1
- Checksum8407D5788528AC2D
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 36-60 | Polar residues | ||||
Sequence: PGPGLSQQATGLSEPRVDGGSSNSG | ||||||
Compositional bias | 172-188 | Polar residues | ||||
Sequence: SDLTNTENTASEASRTR | ||||||
Compositional bias | 411-436 | Polar residues | ||||
Sequence: PSDPPQASSESGEGPSGMASQECPTT | ||||||
Sequence conflict | 416 | in Ref. 2; AAC97971 | ||||
Sequence: Q → K | ||||||
Compositional bias | 439-498 | Acidic residues | ||||
Sequence: AETDDDDDDDDDDDEDNEESEEEEEEEEEEKEATEDEDEDLEQLQEDQGGDEEEEGGDNE | ||||||
Sequence conflict | 452 | in Ref. 2; AAC97971 | ||||
Sequence: D → DD | ||||||
Compositional bias | 577-597 | Basic and acidic residues | ||||
Sequence: MEALPEERDISSPRKKSEDSL | ||||||
Sequence conflict | 589 | in Ref. 2; AAC97971 | ||||
Sequence: P → S | ||||||
Compositional bias | 611-625 | Polar residues | ||||
Sequence: TSVNGRVSSHTWRDA | ||||||
Compositional bias | 651-688 | Polar residues | ||||
Sequence: EPMAQQDSGQNTSVQPMPSPPLASVASVADSSTRVDSP |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |