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Protein

Death domain-associated protein 6

Gene

Daxx

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

GO - Molecular functioni

  • androgen receptor binding Source: RGD
  • JUN kinase binding Source: RGD
  • kinesin binding Source: RGD
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: RGD
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cellular response to anoxia Source: RGD
  • cellular response to tumor necrosis factor Source: RGD
  • chromatin modification Source: UniProtKB-KW
  • negative regulation of myotube differentiation Source: RGD
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: RGD
  • PML body organization Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of histone phosphorylation Source: RGD
  • regulation of protein ubiquitination Source: UniProtKB
  • response to metal ion Source: RGD
  • 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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621227. Daxx.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleusnucleoplasm By similarity
  • NucleusPML body By similarity
  • 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

  • cell body Source: RGD
  • cell cortex Source: RGD
  • chromosome, centromeric region Source: UniProtKB-SubCell
  • cytoplasm Source: RGD
  • cytosol Source: UniProtKB
  • microtubule Source: RGD
  • neuron projection Source: RGD
  • nucleolus Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB
  • XY body Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001512601 – 731Death domain-associated protein 6Add BLAST731

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25PhosphoserineBy similarity1
Modified residuei211PhosphoserineBy similarity1
Modified residuei409PhosphoserineBy similarity1
Modified residuei421PhosphoserineBy similarity1
Modified residuei456PhosphothreonineBy similarity1
Modified residuei485PhosphoserineBy similarity1
Modified residuei488PhosphoserineCombined sources1
Modified residuei490PhosphoserineCombined sources1
Modified residuei499PhosphoserineBy similarity1
Modified residuei503N6-acetyllysineBy similarity1
Modified residuei527PhosphoserineCombined sources1
Modified residuei551PhosphoserineCombined sources1
Modified residuei571PhosphoserineCombined sources1
Modified residuei617PhosphoserineBy similarity1
Cross-linki621Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Modified residuei661PhosphoserineBy similarity1
Modified residuei662PhosphoserineBy similarity1
Modified residuei679PhosphoserineBy similarity1
Modified residuei693PhosphoserineBy similarity1
Modified residuei728PhosphoserineBy similarity1
Modified residuei730PhosphoserineBy similarity1

Post-translational modificationi

Sumoylated with SUMO1 on multiple lysine residues.By similarity
Repressor activity is down-regulated upon Ser-661 phosphorylation. Upon neuronal activation dephosphorylated by calcineurin in a Ca2+ dependent manner at Ser-661; dephosphorylation positively affects histone H3.3 loading and transcriptional activation (By similarity).By similarity
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

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8VIB2.
PRIDEiQ8VIB2.

PTM databases

iPTMnetiQ8VIB2.
PhosphoSitePlusiQ8VIB2.

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 (By similarity).By similarity

GO - Molecular functioni

  • androgen receptor binding Source: RGD
  • JUN kinase binding Source: RGD
  • kinesin binding Source: RGD
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: RGD
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

IntActiQ8VIB2. 4 interactors.
MINTiMINT-4651789.
STRINGi10116.ENSRNOP00000000559.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 158Necessary for interaction with USP7 and ATRXBy similarityAdd BLAST158
Regioni181 – 414Interaction with histone H3.3By similarityAdd BLAST234
Regioni345 – 560Necessary for interaction with USP7By similarityAdd BLAST216
Regioni617 – 731Interaction with SPOPBy similarityAdd BLAST115
Regioni724 – 731Sumo interaction motif (SIM)By similarity8

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili177 – 215Sequence analysisAdd BLAST39
Coiled coili368 – 395Sequence analysisAdd BLAST28
Coiled coili428 – 485Sequence analysisAdd BLAST58

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 biasi431 – 581Asp/Glu-rich (acidic)Add BLAST151

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.
HOGENOMiHOG000112148.
HOVERGENiHBG031495.
InParanoidiQ8VIB2.
PhylomeDBiQ8VIB2.

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.

Q8VIB2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATDDSIIVL DDDDEDEAAA QPGPSNPASN PVSPGPEASG PSESHGDGGS
60 70 80 90 100
SNSGSRKCYK LENEKLFEEF LELCKMQTSD HPEVVPFLHK LQQRAQSAFL
110 120 130 140 150
ASAEFRNILS RVLSRSRNRP AKLYVYINEL CTVLKAHSIK KKLNLAPAAS
160 170 180 190 200
AESSGDNPPT DPPSDLTNTE TTASEASRTR GSRRQIQRLE QLLALYVAEI
210 220 230 240 250
QRLQEKELDL SELDDPDSSY LQEARLKRKL IRLFGRLCDL KDCSSLTGKV
260 270 280 290 300
IEQRIPYRGT RYPEVNRRIE RLINKPGPDT FPDYGDVLRA VEKAATRHSL
310 320 330 340 350
GLPRQQLQLL AQDAFRDVGV RLQERRHLDL IYNFGCHLTD DYRPGVDPAL
360 370 380 390 400
TDPTLARRLR ENRTLAMSRL DEVISKYAMM QDKSEEGERQ KRRARLLATS
410 420 430 440 450
QSSDLPKASS DSGEGPSGVA SQEDPTTPKA ETEDEEDDEE SDDEEEEEEE
460 470 480 490 500
EEEEATEDED EDLEQLQEDQ DDEEEEEGDN EDDKSPASPS PIFRRKEFSN
510 520 530 540 550
PQKGSGPQEE QQERGLTGTP ASPLEASPGL PSTDAESSGE QLQERLLAGE
560 570 580 590 600
SPVSQLSELD MEALPEETIP SPEERGISSS RRKSDSSLPT ILENGAAMVT
610 620 630 640 650
STSFNGRVSS HPCRDASPPS KRFRKEKKQL GPGPLGNSYV KKQTMAQQDS
660 670 680 690 700
GWKISVLSTP SSPLASVGPV ADSSTRVDSP SHELVTSSLC NPSPSLILQT
710 720 730
PQSQSPRPCI YKTSVATQCD PEEIIVLSDS D
Length:731
Mass (Da):80,687
Last modified:March 1, 2002 - v1
Checksum:i17EEBAAB5AA73157
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB064671 mRNA. Translation: BAB83524.1.
UniGeneiRn.870.

Genome annotation databases

UCSCiRGD:621227. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB064671 mRNA. Translation: BAB83524.1.
UniGeneiRn.870.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8VIB2. 4 interactors.
MINTiMINT-4651789.
STRINGi10116.ENSRNOP00000000559.

PTM databases

iPTMnetiQ8VIB2.
PhosphoSitePlusiQ8VIB2.

Proteomic databases

PaxDbiQ8VIB2.
PRIDEiQ8VIB2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:621227. rat.

Organism-specific databases

RGDi621227. Daxx.

Phylogenomic databases

eggNOGiENOG410IGIP. Eukaryota.
ENOG4111K0B. LUCA.
HOGENOMiHOG000112148.
HOVERGENiHBG031495.
InParanoidiQ8VIB2.
PhylomeDBiQ8VIB2.

Miscellaneous databases

PROiQ8VIB2.

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_RAT
AccessioniPrimary (citable) accession number: Q8VIB2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: March 1, 2002
Last modified: November 2, 2016
This is version 102 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. 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.