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O35613 (DAXX_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Death domain-associated protein 6
Alternative name(s):
Daxx
Gene names
Name:Daxx
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length739 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. 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. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Down-regulates basal and activated transcription. Seems to act as a transcriptional corepressor and inhibits PAX3 and ETS1 through direct protein-protein interaction. Modulates PAX5 activity. 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 By similarity. Interacts with CBP; the interaction is dependent on the sumoylation of CBP and suppresses CBP transcriptional activity via recruitment of HDAC2. Ref.3

Subunit structure

Homomultimer. Binds to the TNFRSF6 death domain via its C-terminus and to PAX5. Binds to SLC2A4/GLUT4, MAP3K5, TGFBR2, phosphorylated dimeric HSPB1/HSP27, CENPC, ETS1, sumoylated PML, UBE2I and MCRS1. Is part of a complex containing PAX5 and CREBBP. Interacts with HIPK2 and HIPK3 via its N-terminus. Interacts with HIPK1, which induces translocation from PML/POD/ND10 nuclear bodies to chromatin and enhances association with HDAC1. The non-phosphorylated form binds to PAX3, PAX7, DEK, HDAC1, HDAC2, HDAC3, acetylated histone H4 and histones H2A, H2B, H3 and H4. Interacts with SPOP. Part of a complex consisting of DAXX, CUL3 and SPOP. 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. Part of a complex with MDM2, DAXX, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts (via N-terminus) with RASSF1 (via C-terminus); the interaction is independent of MDM2 and TP53. Interacts with MDM2; the interaction is direct. Interacts with USP7; the interaction is direct and independent of MDM2 and TP53. Interacts with TP53 By similarity. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7

Subcellular location

Cytoplasm. Nucleusnucleoplasm By similarity. NucleusPML body. Nucleusnucleolus By similarity. Note: Dispersed throughout the nucleoplasm, in PML/POD/ND10 nuclear bodies, and in nucleoli. 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. Ref.3

Domain

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

Post-translational modification

Sumoylated with SUMO1 on multiple lysine residues By similarity.

Repressor activity is down-regulated upon Ser-669 phosphorylation.

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.

Sequence similarities

Belongs to the DAXX family.

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainCoiled coil
   Molecular functionRepressor
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processandrogen receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic signaling pathway

Inferred from genetic interaction PubMed 12917339. Source: MGI

mitotic cytokinesis

Inferred from mutant phenotype PubMed 15252119. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic signaling pathway

Inferred from direct assay Ref.3. Source: MGI

regulation of protein ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from sequence orthology PubMed 15878163. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from direct assay Ref.3. Source: UniProtKB

cytosol

Inferred from direct assay Ref.3. Source: UniProtKB

heterochromatin

Inferred from direct assay PubMed 15252119. Source: MGI

nucleolus

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionandrogen receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

transcription coactivator activity

Inferred from direct assay Ref.5. Source: UniProtKB

transcription corepressor activity

Traceable author statement Ref.5. Source: UniProtKB

transcription factor binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 739739Death domain-associated protein 6
PRO_0000151259

Regions

Region1 – 166166Necessary for interaction with USP7 By similarity
Region353 – 576224Necessary for interaction with USP7 By similarity
Region626 – 739114Interaction with SPOP By similarity
Region732 – 7398Sumo interaction motif (SIM) By similarity
Coiled coil185 – 22339 Potential
Coiled coil364 – 40340 Potential
Coiled coil445 – 48844 Potential
Motif391 – 3955Nuclear localization signal Potential
Motif622 – 6287Nuclear localization signal Potential
Compositional bias11 – 166Poly-Asp
Compositional bias442 – 50160Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue2191Phosphoserine Ref.6
Modified residue4721Phosphothreonine Ref.6
Modified residue5021Phosphoserine Ref.6
Modified residue5151Phosphoserine Ref.6
Modified residue5231Phosphothreonine Ref.6
Modified residue6261Phosphoserine Ref.6
Modified residue6691Phosphoserine; by HIPK1 Ref.6
Modified residue6871Phosphoserine By similarity
Modified residue7011Phosphoserine By similarity
Modified residue7361Phosphoserine By similarity
Modified residue7381Phosphoserine By similarity
Cross-link630Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) By similarity

Experimental info

Mutagenesis5021S → A: No effect on phosphorylation by HIPK1. Ref.6
Mutagenesis6691S → A: Diminishes phosphorylation by HIPK1. Ref.6
Sequence conflict4161Q → K in AAC97971. Ref.2
Sequence conflict4521D → DD in AAC97971. Ref.2
Sequence conflict5891P → S in AAC97971. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O35613 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 8407D5788528AC2D

FASTA73981,489
        10         20         30         40         50         60 
MATDDSIIVL DDDDEDEAAA QPGPSNLPPN PASTGPGPGL SQQATGLSEP RVDGGSSNSG 

        70         80         90        100        110        120 
SRKCYKLDNE KLFEEFLELC KTETSDHPEV VPFLHKLQQR AQSVFLASAE FCNILSRVLA 

       130        140        150        160        170        180 
RSRKRPAKIY VYINELCTVL KAHSIKKKLN LAPAASTTSE ASGPNPPTEP PSDLTNTENT 

       190        200        210        220        230        240 
ASEASRTRGS RRQIQRLEQL LALYVAEIRR LQEKELDLSE LDDPDSSYLQ EARLKRKLIR 

       250        260        270        280        290        300 
LFGRLCELKD CSSLTGRVIE QRIPYRGTRY PEVNRRIERL INKPGLDTFP DYGDVLRAVE 

       310        320        330        340        350        360 
KAATRHSLGL PRQQLQLLAQ DAFRDVGVRL QERRHLDLIY NFGCHLTDDY RPGVDPALSD 

       370        380        390        400        410        420 
PTLARRLREN RTLAMNRLDE VISKYAMMQD KTEEGERQKR RARLLGTAPQ PSDPPQASSE 

       430        440        450        460        470        480 
SGEGPSGMAS QECPTTSKAE TDDDDDDDDD DDEDNEESEE EEEEEEEEKE ATEDEDEDLE 

       490        500        510        520        530        540 
QLQEDQGGDE EEEGGDNEGN ESPTSPSDFF HRRNSEPAEG LRTPEGQQKR GLTETPASPP 

       550        560        570        580        590        600 
GASLDPPSTD AESSGEQLLE PLLGDESPVS QLAELEMEAL PEERDISSPR KKSEDSLPTI 

       610        620        630        640        650        660 
LENGAAVVTS TSVNGRVSSH TWRDASPPSK RFRKEKKQLG SGLLGNSYIK EPMAQQDSGQ 

       670        680        690        700        710        720 
NTSVQPMPSP PLASVASVAD SSTRVDSPSH ELVTSSLCSP SPSLLLQTPQ AQSLRQCIYK 

       730 
TSVATQCDPE EIIVLSDSD 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF006040 mRNA. Translation: AAC53284.1.
AF110520 Genomic DNA. Translation: AAC97971.1.
AF100956 Genomic DNA. Translation: AAC69891.1.
RefSeqNP_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.
UniGeneMm.271809.

3D structure databases

DisProtDP00708.
ProteinModelPortalO35613.
SMRO35613. Positions 62-150, 188-392.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199054. 12 interactions.
IntActO35613. 14 interactions.
MINTMINT-1172660.

PTM databases

PhosphoSiteO35613.

Proteomic databases

PaxDbO35613.
PRIDEO35613.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID13163.
KEGGmmu:13163.

Organism-specific databases

CTD1616.
MGIMGI:1197015. Daxx.

Phylogenomic databases

eggNOGNOG39676.
HOVERGENHBG031495.
InParanoidO35613.
KOK02308.
PhylomeDBO35613.

Gene expression databases

CleanExMM_DAXX.
GenevestigatorO35613.

Family and domain databases

InterProIPR005012. Daxx.
[Graphical view]
PANTHERPTHR12766. PTHR12766. 1 hit.
PfamPF03344. Daxx. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio283238.
PROO35613.
SOURCESearch...

Entry information

Entry nameDAXX_MOUSE
AccessionPrimary (citable) accession number: O35613
Secondary accession number(s): Q9QWT8, Q9QWV3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot