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O35613

- DAXX_MOUSE

UniProt

O35613 - DAXX_MOUSE

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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

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 homodimerization activity Source: UniProtKB
  4. transcription coactivator activity Source: UniProtKB
  5. transcription corepressor activity Source: UniProtKB
  6. 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
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
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. nucleus Source: UniProtKB
  4. PML body Source: UniProtKB
Complete GO annotation...

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

        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)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:
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_006523580.1.
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:
EMBLi
GenBanki
DDBJi
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

« Hide 'large scale' publications
  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 29, 2014
This is version 119 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