Death domain-associated protein 6 - Mus musculus (Mouse)

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Reviewed, UniProtKB/Swiss-Prot O35613 (DAXX_MOUSE)

Last modified December 16, 2008. Version 69. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
Death domain-associated protein 6
Alternative name(s):
Daxx

Gene names

Name:

Daxx

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length	739 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	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 co-repressor 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.
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, CENPC1, 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 By similarity.
Subcellular location	NucleusBy similarity. CytoplasmBy similarity. Note= Translocates from the nucleus to the cytoplasm upon glucose deprivation or oxidative stress By similarity.
Post-translational modification	Sumoylated By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR By similarity. Repressor activity is down-regulated upon Ser-669 phosphorylation. Polyubiquitinated; which is promoted by CUL3 and SPOP and results in proteasomal degradation By similarity.
Sequence similarities	Belongs to the DAXX family.

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Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	Coiled coil
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	androgen receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cytokinesis after mitosis Inferred from mutant phenotype. Source: MGI negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	PML body Ref.5 Inferred from direct assay. Source: MGI cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW heterochromatin Inferred from direct assay. Source: MGI
Molecular function	androgen receptor binding Inferred from sequence or structural similarity. Source: UniProtKB protein N-terminus binding Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB transcription coactivator activity Ref.4 Inferred from direct assay. Source: UniProtKB transcription corepressor activity Ref.4 Traceable author statement. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAPK3	O43293	1	EBI-77304,EBI-77293	From a different organism.
Dapk3	O54784	1	EBI-77304,EBI-77359
Fas	P25446	2	EBI-77304,EBI-296206
HIPK1	Q86Z02	1	EBI-77304,EBI-692891	From a different organism.
Hipk1	O88904	2	EBI-77304,EBI-692945
Hipk3	Q9ERH7	1	EBI-77304,EBI-524356
TGFBR2	P37173	1	EBI-77304,EBI-296151	From a different organism.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 739

739

Death domain-associated protein 6

PRO_0000151259

Regions

Region

626 – 739

114

Interaction with SPOP By similarity

Coiled coil

185 – 223

Potential

Coiled coil

364 – 403

Potential

Coiled coil

445 – 488

Potential

Motif

391 – 395

Nuclear localization signal Potential

Motif

622 – 628

Nuclear localization signal Potential

Compositional bias

11 – 16

Poly-Asp

Compositional bias

442 – 501

Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue

219

Phosphoserine Ref.5

Modified residue

472

Phosphothreonine Ref.5

Modified residue

502

Phosphoserine Ref.5

Modified residue

515

Phosphoserine Ref.5

Modified residue

523

Phosphothreonine Ref.5

Modified residue

626

Phosphoserine Ref.5

Modified residue

648

Phosphotyrosine By similarity

Modified residue

669

Phosphoserine; by HIPK1 Ref.5

Modified residue

687

Phosphoserine By similarity

Modified residue

689

Phosphoserine By similarity

Modified residue

701

Phosphoserine By similarity

Modified residue

708

Phosphothreonine By similarity

Modified residue

736

Phosphoserine Ref.7

Modified residue

738

Phosphoserine By similarity

Experimental info

Mutagenesis

502

S → A: No effect on phosphorylation by HIPK1 Ref.5

Mutagenesis

669

S → A: Diminishes phosphorylation by HIPK1 Ref.5

Sequence conflict

416

Q → K in AAC97971. Ref.2

Sequence conflict

452

D → DD in AAC97971. Ref.2

Sequence conflict

589

P → S in AAC97971. Ref.2

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Sequences

Sequence

Length

Mass (Da)

Tools

O35613-1 [UniParc].

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

739

81,489

        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

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References

	« Hide 'large scale' referencesShow '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: 9215629] [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]	"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: 11034606] [Abstract] Cited for: INTERACTION WITH HIPK3.
[4]	"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: 11799127] [Abstract] Cited for: INTERACTION WITH PAX5.
[5]	"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: 12529400] [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, MASS SPECTROMETRY.
[6]	"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: 16287980] [Abstract] Cited for: INTERACTION WITH CBP.
[7]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-736, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	AF006040 mRNA. Translation: AAC53284.1. AF110520 Genomic DNA. Translation: AAC97971.1. AF100956 Genomic DNA. Translation: AAC69891.1.
UniGene	Mm.271809
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O35613. 7 interactions.
PTM databases
PhosphoSite	O35613.
Genome annotation databases
Ensembl	ENSMUSG00000002307. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:1197015. Daxx.
Phylogenomic databases
HOVERGEN	O35613.
Gene expression databases
ArrayExpress	O35613.
CleanEx	MM_DAXX.
GermOnline	ENSMUSG00000002307. Mus musculus.
Family and domain databases
InterPro	IPR005012. Daxx. [Graphical view]
PANTHER	PTHR12766. Daxx. 1 hit.
Pfam	PF03344. Daxx. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

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Entry information

Entry name

DAXX_MOUSE

Accession

Primary (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:	December 16, 2008
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents