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Protein

Death domain-associated protein 6

Gene

Daxx

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 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 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. 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.3 Publications

GO - Molecular functioni

GO - Biological processi

  • androgen receptor signaling pathway Source: UniProtKB
  • apoptotic signaling pathway Source: MGI
  • chromatin modification Source: UniProtKB-KW
  • chromatin remodeling Source: MGI
  • mitotic cytokinesis Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • nucleosome assembly Source: UniProtKB
  • positive regulation of apoptotic signaling pathway Source: MGI
  • positive regulation of neuron death Source: MGI
  • positive regulation of protein kinase activity Source: MGI
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of multicellular organism growth Source: MGI
  • regulation of protein ubiquitination Source: UniProtKB
  • regulation of transcription, DNA-templated Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

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
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1197015. Daxx.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleusnucleoplasm 1 Publication
  • NucleusPML body 1 Publication
  • Nucleusnucleolus By similarity
  • Chromosomecentromere 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.By similarity

GO - Cellular componenti

  • chromosome, centromeric region Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: UniProtKB
  • heterochromatin Source: MGI
  • nucleolus Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB
  • SWI/SNF superfamily-type complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi502S → A: No effect on phosphorylation by HIPK1. 1 Publication1
Mutagenesisi669S → A: Diminishes phosphorylation by HIPK1. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001512591 – 739Death domain-associated protein 6Add BLAST739

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25PhosphoserineBy similarity1
Modified residuei219Phosphoserine1 Publication1
Modified residuei418PhosphoserineBy similarity1
Modified residuei430PhosphoserineBy similarity1
Modified residuei472Phosphothreonine1 Publication1
Modified residuei502Phosphoserine1 Publication1
Modified residuei505PhosphoserineBy similarity1
Modified residuei507PhosphoserineBy similarity1
Modified residuei515Phosphoserine1 Publication1
Modified residuei523Phosphothreonine1 Publication1
Modified residuei543PhosphoserineBy similarity1
Modified residuei567PhosphoserineBy similarity1
Modified residuei626Phosphoserine1 Publication1
Cross-linki630Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Modified residuei669Phosphoserine; by HIPK11 Publication1
Modified residuei687PhosphoserineCombined sources1
Modified residuei701PhosphoserineBy similarity1
Modified residuei736PhosphoserineCombined sources1
Modified residuei738PhosphoserineCombined sources1

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

EPDiO35613.
MaxQBiO35613.
PaxDbiO35613.
PeptideAtlasiO35613.
PRIDEiO35613.

PTM databases

iPTMnetiO35613.
PhosphoSitePlusiO35613.

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.

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199054. 15 interactors.
DIPiDIP-30972N.
IntActiO35613. 15 interactors.
MINTiMINT-1172660.
STRINGi10090.ENSMUSP00000078390.

Structurei

3D structure databases

DisProtiDP00708.
ProteinModelPortaliO35613.
SMRiO35613.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 166Necessary for interaction with USP7 and ATRXBy similarityAdd BLAST166
Regioni189 – 423Interaction with histone H3.3By similarityAdd BLAST235
Regioni353 – 576Necessary for interaction with USP7By similarityAdd BLAST224
Regioni626 – 739Interaction with SPOPBy similarityAdd BLAST114
Regioni732 – 739Sumo interaction motif (SIM)By similarity8

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili185 – 223Sequence analysisAdd BLAST39
Coiled coili364 – 403Sequence analysisAdd BLAST40
Coiled coili445 – 488Sequence analysisAdd BLAST44

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi391 – 395Nuclear localization signalSequence analysis5
Motifi622 – 628Nuclear localization signalSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi11 – 16Poly-Asp6
Compositional biasi442 – 501Asp/Glu-rich (acidic)Add BLAST60

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

eggNOGiENOG410IGIP. Eukaryota.
ENOG4111K0B. LUCA.
HOVERGENiHBG031495.
InParanoidiO35613.
KOiK02308.
PhylomeDBiO35613.

Family and domain databases

CDDicd13151. DAXX_helical_bundle. 1 hit.
InterProiIPR005012. Daxx.
IPR031333. Daxx_N.
[Graphical view]
PANTHERiPTHR12766. PTHR12766. 1 hit.
PfamiPF03344. Daxx. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O35613-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATDDSIIVL DDDDEDEAAA QPGPSNLPPN PASTGPGPGL SQQATGLSEP
60 70 80 90 100
RVDGGSSNSG SRKCYKLDNE KLFEEFLELC KTETSDHPEV VPFLHKLQQR
110 120 130 140 150
AQSVFLASAE FCNILSRVLA RSRKRPAKIY VYINELCTVL KAHSIKKKLN
160 170 180 190 200
LAPAASTTSE ASGPNPPTEP PSDLTNTENT ASEASRTRGS RRQIQRLEQL
210 220 230 240 250
LALYVAEIRR LQEKELDLSE LDDPDSSYLQ EARLKRKLIR LFGRLCELKD
260 270 280 290 300
CSSLTGRVIE QRIPYRGTRY PEVNRRIERL INKPGLDTFP DYGDVLRAVE
310 320 330 340 350
KAATRHSLGL PRQQLQLLAQ DAFRDVGVRL QERRHLDLIY NFGCHLTDDY
360 370 380 390 400
RPGVDPALSD PTLARRLREN RTLAMNRLDE VISKYAMMQD KTEEGERQKR
410 420 430 440 450
RARLLGTAPQ PSDPPQASSE SGEGPSGMAS QECPTTSKAE TDDDDDDDDD
460 470 480 490 500
DDEDNEESEE EEEEEEEEKE ATEDEDEDLE QLQEDQGGDE EEEGGDNEGN
510 520 530 540 550
ESPTSPSDFF HRRNSEPAEG LRTPEGQQKR GLTETPASPP GASLDPPSTD
560 570 580 590 600
AESSGEQLLE PLLGDESPVS QLAELEMEAL PEERDISSPR KKSEDSLPTI
610 620 630 640 650
LENGAAVVTS TSVNGRVSSH TWRDASPPSK RFRKEKKQLG SGLLGNSYIK
660 670 680 690 700
EPMAQQDSGQ NTSVQPMPSP PLASVASVAD SSTRVDSPSH ELVTSSLCSP
710 720 730
SPSLLLQTPQ AQSLRQCIYK TSVATQCDPE EIIVLSDSD
Length:739
Mass (Da):81,489
Last modified:January 1, 1998 - v1
Checksum:i8407D5788528AC2D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti416Q → K in AAC97971 (Ref. 2) Curated1
Sequence conflicti452D → DD in AAC97971 (Ref. 2) Curated1
Sequence conflicti589P → S in AAC97971 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006523580.2.
XP_006523644.1. XM_006523581.2.
XP_006523645.1. XM_006523582.2.
UniGeneiMm.271809.

Genome annotation databases

GeneIDi13163.
KEGGimmu:13163.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006523580.2.
XP_006523644.1. XM_006523581.2.
XP_006523645.1. XM_006523582.2.
UniGeneiMm.271809.

3D structure databases

DisProtiDP00708.
ProteinModelPortaliO35613.
SMRiO35613.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199054. 15 interactors.
DIPiDIP-30972N.
IntActiO35613. 15 interactors.
MINTiMINT-1172660.
STRINGi10090.ENSMUSP00000078390.

PTM databases

iPTMnetiO35613.
PhosphoSitePlusiO35613.

Proteomic databases

EPDiO35613.
MaxQBiO35613.
PaxDbiO35613.
PeptideAtlasiO35613.
PRIDEiO35613.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi13163.
KEGGimmu:13163.

Organism-specific databases

CTDi1616.
MGIiMGI:1197015. Daxx.

Phylogenomic databases

eggNOGiENOG410IGIP. Eukaryota.
ENOG4111K0B. LUCA.
HOVERGENiHBG031495.
InParanoidiO35613.
KOiK02308.
PhylomeDBiO35613.

Miscellaneous databases

PROiO35613.
SOURCEiSearch...

Gene expression databases

CleanExiMM_DAXX.

Family and domain databases

CDDicd13151. DAXX_helical_bundle. 1 hit.
InterProiIPR005012. Daxx.
IPR031333. Daxx_N.
[Graphical view]
PANTHERiPTHR12766. PTHR12766. 1 hit.
PfamiPF03344. Daxx. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 138 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

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 one 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.