Q9UER7 (DAXX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Death domain-associated protein 6

Alternative name(s):
Daxx
Short name=hDaxx
ETS1-associated protein 1
Short name=EAP1
Fas death domain-associated protein

Gene names

Name:	DAXX
Synonyms:	BING2, DAP6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	740 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.20 Ref.25 Ref.29
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 By similarity. 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 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 HCMV tegument phosphoprotein pp71. 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. Ref.3 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.29 Ref.30 Ref.33 Ref.35 Ref.42
Subcellular location	Cytoplasm. Nucleus › nucleoplasm. Nucleus › PML body. Nucleus › nucleolus. Chromosome › centromere. 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. Ref.2 Ref.3 Ref.13 Ref.15 Ref.18 Ref.22 Ref.29 Ref.33
Tissue specificity	Ubiquitous.
Induction	Upon mitogenic stimulation by concanavalin-A.
Post-translational modification	Sumoylated. Ref.17 Ref.18 Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated by HIPK1 upon glucose deprivation. Ref.11 Ref.20 Ref.22 Ref.26 Ref.27 Ref.31 Ref.32 Ref.34 Ref.36 Ref.37 Ref.38 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. Ref.28 Ref.40
Sequence similarities	Belongs to the DAXX family.

Ontologies

Keywords
Biological process	Apoptosis Host-virus interaction Transcription Transcription regulation
Cellular component	Centromere Chromosome Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of JUN kinase activity Traceable author statement. Source: ProtInc androgen receptor signaling pathway Inferred from direct assay. Source: UniProtKB apoptotic process Traceable author statement. Source: UniProtKB induction of apoptosis via death domain receptors Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.5. Source: UniProtKB regulation of protein ubiquitination Inferred from direct assay Ref.33. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	PML body Inferred from direct assay Ref.13Ref.33. Source: UniProtKB chromosome, centromeric region Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from sequence or structural similarity. Source: UniProtKB nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	androgen receptor binding Inferred from physical interaction. Source: UniProtKB heat shock protein binding Traceable author statement. Source: UniProtKB p53 binding Inferred from physical interaction Ref.29. Source: UniProtKB protein N-terminus binding Inferred from physical interaction Ref.33. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.5. Source: UniProtKB receptor signaling protein activity Traceable author statement. Source: ProtInc transcription factor binding Inferred from direct assay Ref.5. Source: UniProtKB ubiquitin protein ligase binding Inferred from physical interaction Ref.29. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P03243	4	EBI-77321,EBI-1561361	From a different organism.
AIRE	O43918	5	EBI-77321,EBI-1753081
AR	P10275	5	EBI-77321,EBI-608057
ATRX	P46100	3	EBI-77321,EBI-396461
CDKN2A	Q8N726	8	EBI-77321,EBI-625922
CREBBP	Q92793	2	EBI-77321,EBI-81215
E1B	P03244	4	EBI-77321,EBI-1561155	From a different organism.
ETS1	P14921-1	3	EBI-287635,EBI-913224
ETS1	P14921-2	2	EBI-287635,EBI-913228
FAS	P25445	2	EBI-77321,EBI-494743
Fas	P25446	4	EBI-77321,EBI-296206	From a different organism.
FTH1	P02794	5	EBI-77321,EBI-713259
HDAC1	Q13547	2	EBI-77321,EBI-301834
HDAC2	Q92769	2	EBI-77321,EBI-301821
Hipk1	O88904	3	EBI-77321,EBI-692945	From a different organism.
HSPB1	P04792	3	EBI-77321,EBI-352682
HSPB1	P15991	3	EBI-77321,EBI-1559114	From a different organism.
MAP3K5	Q99683	6	EBI-77321,EBI-476263
MCRS1	Q96EZ8	7	EBI-77321,EBI-348259
MDM2	Q00987	14	EBI-77321,EBI-389668
PARK7	Q99497	3	EBI-77321,EBI-1164361
Pax5	Q02650	4	EBI-77321,EBI-296260	From a different organism.
PML	P29590	6	EBI-77321,EBI-295890
SLC2A4	P14672	7	EBI-77321,EBI-367146
SPOP	O43791	5	EBI-77321,EBI-743549
STAT3	P40763	4	EBI-77321,EBI-518675
SUMO1	P63165	5	EBI-77321,EBI-80140
TCF7L2	Q9NQB0	5	EBI-77321,EBI-924724
TGFBR2	P37173	2	EBI-77321,EBI-296151
TP53	P04637	11	EBI-77321,EBI-366083
TSG101	Q99816	4	EBI-77321,EBI-346882
USP7	Q93009	10	EBI-77321,EBI-302474

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UER7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9UER7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     696-740: SSLCIPSPARLSQTPHSQPPRPGTCKTSVATQCDPEEIIVLSDSD → PAKNLGRRRSKQDQG

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 740	740	Death domain-associated protein 6		PRO_0000151258
Regions
	Region	1 – 160	160	Necessary for interaction with USP7
	Region	347 – 570	224	Necessary for interaction with USP7
	Region	501 – 625	125	Interaction with MAP3K5
	Region	626 – 740	115	Interaction with SPOP
	Coiled coil	180 – 217	38	Potential
	Coiled coil	358 – 399	42	Potential
	Coiled coil	430 – 489	60	Potential
	Motif	391 – 395	5	Nuclear localization signal Potential
	Motif	628 – 634	7	Nuclear localization signal Potential
	Compositional bias	11 – 16	6	Poly-Asp
	Compositional bias	434 – 572	139	Asp/Glu-rich (acidic)
Amino acid modifications
	Modified residue	178	1	Phosphoserine Ref.34 Ref.36
	Modified residue	213	1	Phosphoserine Ref.36
	Modified residue	459	1	Phosphothreonine By similarity
	Modified residue	495	1	Phosphoserine Ref.36 Ref.37
	Modified residue	512	1	N6-acetyllysine Ref.39
	Modified residue	648	1	Phosphotyrosine Ref.31
	Modified residue	668	1	Phosphoserine Ref.22 Ref.36
	Modified residue	671	1	Phosphoserine Ref.26 Ref.34 Ref.36 Ref.37
	Modified residue	688	1	Phosphoserine Ref.34 Ref.36 Ref.37
	Modified residue	690	1	Phosphoserine Ref.34
	Modified residue	702	1	Phosphoserine Ref.34 Ref.36 Ref.37 Ref.38
	Modified residue	709	1	Phosphothreonine Ref.32
	Modified residue	712	1	Phosphoserine Ref.32
	Modified residue	737	1	Phosphoserine Ref.27 Ref.36 Ref.38
	Modified residue	739	1	Phosphoserine Ref.27 Ref.36 Ref.38
Natural variations
	Alternative sequence	696 – 740	45	SSLCI…LSDSD → PAKNLGRRRSKQDQG in isoform 2.		VSP_001270
Experimental info
	Mutagenesis	630	1	K → A: Abolishes sumoylation. Ref.17
	Mutagenesis	631	1	K → A: Abolishes sumoylation. Ref.17
	Mutagenesis	668	1	S → A: No translocation to the cytosol upon glucose deprivation. Ref.22
	Mutagenesis	671	1	S → A: No effect on cytosol translocation. upon glucose deprivation. Ref.22
	Sequence conflict	177	1	Q → R in AAB66585. Ref.2
	Sequence conflict	263	1	R → H in AAC72843. Ref.5
	Sequence conflict	323	1	R → W in AAB66585. Ref.2
	Sequence conflict	365	1	R → Q in AAB66585. Ref.2
	Sequence conflict	382	1	L → S in AAB66585. Ref.2
	Sequence conflict	647	1	S → R in CAB09986. Ref.8
	Sequence conflict	647	1	S → R in CAB09989. Ref.8
	Sequence conflict	722	1	T → A in CAB09986. Ref.8
	Sequence conflict	722	1	T → A in CAB09989. Ref.8
	Sequence conflict	731 – 732	2	EE → KK in AAC72843. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 2002. Version 2. Checksum: 1B309ADDAA878040	FASTA	740	81,373
	10 20 30 40 50 60 MATANSIIVL DDDDEDEAAA QPGPSHPLPN AASPGAEAPS SSEPHGARGS SSSGGKKCYK 70 80 90 100 110 120 LENEKLFEEF LELCKMQTAD HPEVVPFLYN RQQRAHSLFL ASAEFCNILS RVLSRARSRP 130 140 150 160 170 180 AKLYVYINEL CTVLKAHSAK KKLNLAPAAT TSNEPSGNNP PTHLSLDPTN AENTASQSPR 190 200 210 220 230 240 TRGSRRQIQR LEQLLALYVA EIRRLQEKEL DLSELDDPDS AYLQEARLKR KLIRLFGRLC 250 260 270 280 290 300 ELKDCSSLTG RVIEQRIPYR GTRYPEVNRR IERLINKPGP DTFPDYGDVL RAVEKAAARH 310 320 330 340 350 360 SLGLPRQQLQ LMAQDAFRDV GIRLQERRHL DLIYNFGCHL TDDYRPGVDP ALSDPVLARR 370 380 390 400 410 420 LRENRSLAMS RLDEVISKYA MLQDKSEEGE RKKRRARLQG TSSHSADTPE ASLDSGEGPS 430 440 450 460 470 480 GMASQGCPSA SRAETDDEDD EESDEEEEEE EEEEEEEATD SEEEEDLEQM QEGQEDDEEE 490 500 510 520 530 540 DEEEEAAAGK DGDKSPMSSL QISNEKNLEP GKQISRSSGE QQNKGRIVSP SLLSEEPLAP 550 560 570 580 590 600 SSIDAESNGE QPEELTLEEE SPVSQLFELE IEALPLDTPS SVETDISSSR KQSEEPFTTV 610 620 630 640 650 660 LENGAGMVSS TSFNGGVSPH NWGDSGPPCK KSRKEKKQTG SGPLGNSYVE RQRSVHEKNG 670 680 690 700 710 720 KKICTLPSPP SPLASLAPVA DSSTRVDSPS HGLVTSSLCI PSPARLSQTP HSQPPRPGTC 730 740 KTSVATQCDP EEIIVLSDSD
	Isoform 2 [UniParc]. Checksum: 47E099676EB7315C	FASTA	710	78,333
	10 20 30 40 50 60 MATANSIIVL DDDDEDEAAA QPGPSHPLPN AASPGAEAPS SSEPHGARGS SSSGGKKCYK 70 80 90 100 110 120 LENEKLFEEF LELCKMQTAD HPEVVPFLYN RQQRAHSLFL ASAEFCNILS RVLSRARSRP 130 140 150 160 170 180 AKLYVYINEL CTVLKAHSAK KKLNLAPAAT TSNEPSGNNP PTHLSLDPTN AENTASQSPR 190 200 210 220 230 240 TRGSRRQIQR LEQLLALYVA EIRRLQEKEL DLSELDDPDS AYLQEARLKR KLIRLFGRLC 250 260 270 280 290 300 ELKDCSSLTG RVIEQRIPYR GTRYPEVNRR IERLINKPGP DTFPDYGDVL RAVEKAAARH 310 320 330 340 350 360 SLGLPRQQLQ LMAQDAFRDV GIRLQERRHL DLIYNFGCHL TDDYRPGVDP ALSDPVLARR 370 380 390 400 410 420 LRENRSLAMS RLDEVISKYA MLQDKSEEGE RKKRRARLQG TSSHSADTPE ASLDSGEGPS 430 440 450 460 470 480 GMASQGCPSA SRAETDDEDD EESDEEEEEE EEEEEEEATD SEEEEDLEQM QEGQEDDEEE 490 500 510 520 530 540 DEEEEAAAGK DGDKSPMSSL QISNEKNLEP GKQISRSSGE QQNKGRIVSP SLLSEEPLAP 550 560 570 580 590 600 SSIDAESNGE QPEELTLEEE SPVSQLFELE IEALPLDTPS SVETDISSSR KQSEEPFTTV 610 620 630 640 650 660 LENGAGMVSS TSFNGGVSPH NWGDSGPPCK KSRKEKKQTG SGPLGNSYVE RQRSVHEKNG 670 680 690 700 710 KKICTLPSPP SPLASLAPVA DSSTRVDSPS HGLVTPAKNL GRRRSKQDQG

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] (ISOFORM 1).
[2]	"Cloning and expression of primate Daxx cDNAs and mapping of the human gene to chromosome 6p21.3 in the MHC region." Kiriakidou M., Driscoll D.A., Lopez-Guisa J.M., Strauss J.F. III DNA Cell Biol. 16:1289-1298(1997) [PubMed: 9407001] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION. Tissue: Placenta.
[3]	"Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death." Pluta A.F., Earnshaw W.C., Goldberg I.G. J. Cell Sci. 111:2029-2041(1998) [PubMed: 9645950] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CENPC1, SUBCELLULAR LOCATION. Tissue: Cervix carcinoma.
[4]	"TAPASIN, DAXX, RGL2, HKE2 and four new genes (BING 1, 3 to 5) form a dense cluster at the centromeric end of the MHC." Herberg J.A., Beck S., Trowsdale J. J. Mol. Biol. 277:839-857(1998) [PubMed: 9545376] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[5]	"EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes." Li R., Pei H., Watson D.K., Papas T.S. Oncogene 19:745-753(2000) [PubMed: 10698492] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: T-cell.
[6]	Usui T. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 334-740 (ISOFORM 2). Tissue: Eye.
[11]	"The Pax3-FKHR oncoprotein is unresponsive to the Pax3-associated repressor hDaxx." Hollenbach A.D., Sublett J.E., McPherson C.J., Grosveld G. EMBO J. 18:3702-3711(1999) [PubMed: 10393185] [Abstract] Cited for: INTERACTION WITH PAX3 AND PAX7, PHOSPHORYLATION.
[12]	"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: 10684855] [Abstract] Cited for: INTERACTION WITH PML.
[13]	"Sequestration and inhibition of Daxx-mediated transcriptional repression by PML." Li H., Leo C., Zhu J., Wu X., O'Neil J., Park E.-J., Chen J.D. Mol. Cell. Biol. 20:1784-1796(2000) [PubMed: 10669754] [Abstract] Cited for: INTERACTION WITH SUMOYLATED PML; HDAC1; HDAC2 AND HDAC3, SUBCELLULAR LOCATION.
[14]	"Inhibition of Daxx-mediated apoptosis by heat shock protein 27." Charette S.J., Lavoie J.N., Lambert H., Landry J. Mol. Cell. Biol. 20:7602-7612(2000) [PubMed: 11003656] [Abstract] Cited for: INTERACTION WITH HSPB1.
[15]	"Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm." Ko Y.-G., Kang Y.-S., Park H., Seol W., Kim J., Kim T., Park H.-S., Choi E.-J., Kim S. J. Biol. Chem. 276:39103-39106(2001) [PubMed: 11495919] [Abstract] Cited for: INTERACTION WITH MAP3K5, SUBCELLULAR LOCATION.
[16]	"TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation." Perlman R., Schiemann W.P., Brooks M.W., Lodish H.F., Weinberg R.A. Nat. Cell Biol. 3:708-714(2001) [PubMed: 11483955] [Abstract] Cited for: INTERACTION WITH TGFBR2.
[17]	"Modification of Daxx by small ubiquitin-related modifier-1." Jang M.-S., Ryu S.-W., Kim E. Biochem. Biophys. Res. Commun. 295:495-500(2002) [PubMed: 12150977] [Abstract] Cited for: SUMOYLATION, MUTAGENESIS OF LYS-630 AND LYS-631.
[18]	"The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx. Two proteins with capacity to bind Ubc9 and conjugated to SUMO1." Lalioti V.S., Vergarajauregui S., Pulido D., Sandoval I.V. J. Biol. Chem. 277:19783-19791(2002) [PubMed: 11842083] [Abstract] Cited for: INTERACTION WITH SLC2A4 AND UBE2I, SUMOYLATION, SUBCELLULAR LOCATION.
[19]	"Essential role of the 58-kDa microspherule protein in the modulation of Daxx-dependent transcriptional repression as revealed by nucleolar sequestration." Lin D.-Y., Shih H.-M. J. Biol. Chem. 277:25446-25456(2002) [PubMed: 11948183] [Abstract] Cited for: INTERACTION WITH MCRS1.
[20]	"Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek." Hollenbach A.D., McPherson C.J., Mientjes E.J., Iyengar R., Grosveld G. J. Cell Sci. 115:3319-3330(2002) [PubMed: 12140263] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH HDAC2; HISTONES AND DEK.
[21]	"HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in human hepatoma cells." Hofmann T.G., Stollberg N., Schmitz M.L., Will H. Cancer Res. 63:8271-8277(2003) [PubMed: 14678985] [Abstract] Cited for: INTERACTION WITH HIPK2.
[22]	"Role of the ASK1-SEK1-JNK1-HIPK1 signal in Daxx trafficking and ASK1 oligomerization." Song J.J., Lee Y.J. J. Biol. Chem. 278:47245-47252(2003) [PubMed: 12968034] [Abstract] Cited for: OLIGOMERIZATION, SUBCELLULAR LOCATION, INTERACTION WITH MAP3K5, MUTAGENESIS OF SER-668 AND SER-671, PHOSPHORYLATION AT SER-668.
[23]	"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.
[24]	"Daxx-mediated transcriptional repression of MMP1 gene is reversed by SPOP." La M., Kim K., Park J., Won J., Lee J.-H., Fu Y.M., Meadows G.G., Joe C.O. Biochem. Biophys. Res. Commun. 320:760-765(2004) [PubMed: 15240113] [Abstract] Cited for: INTERACTION WITH SPOP.
[25]	"Negative regulation of p53 functions by Daxx and the involvement of MDM2." Zhao L.Y., Liu J., Sidhu G.S., Niu Y., Liu Y., Wang R., Liao D. J. Biol. Chem. 279:50566-50579(2004) [PubMed: 15364927] [Abstract] Cited for: FUNCTION, INTERACTION WITH MDM2 AND TP53.
[26]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-671, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-737 AND SER-739, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[28]	"BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase." Kwon J.E., La M., Oh K.H., Oh Y.M., Kim G.R., Seol J.H., Baek S.H., Chiba T., Tanaka K., Bang O.S., Joe C.O., Chung C.H. J. Biol. Chem. 281:12664-12672(2006) [PubMed: 16524876] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH CUL3 AND SPOP, UBIQUITINATION.
[29]	"Critical role for Daxx in regulating Mdm2." Tang J., Qu L.K., Zhang J., Wang W., Michaelson J.S., Degenhardt Y.Y., El-Deiry W.S., Yang X. Nat. Cell Biol. 8:855-862(2006) [PubMed: 16845383] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH MDM2 AND USP7, INTERACTION WITH MDM2; TP53 AND USP7, SUBCELLULAR LOCATION.
[30]	"Daxx cooperates with the Axin/HIPK2/p53 complex to induce cell death." Li Q., Wang X., Wu X., Rui Y., Liu W., Wang J., Wang X., Liou Y.C., Ye Z., Lin S.C. Cancer Res. 67:66-74(2007) [PubMed: 17210684] [Abstract] Cited for: INTERACTION WITH AXIN1.
[31]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-648, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[32]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-709 AND SER-712, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[33]	"The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex." Song M.S., Song S.J., Kim S.Y., Oh H.J., Lim D.S. EMBO J. 27:1863-1874(2008) [PubMed: 18566590] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH MDM2; RASSF1 AND USP7, INTERACTION WITH RASSF1; USP7 AND MDM2, SUBCELLULAR LOCATION.
[34]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-178; SER-671; SER-688; SER-690 AND SER-702, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[35]	"Human cytomegalovirus protein pp71 displaces the chromatin-associated factor ATRX from nuclear domain 10 at early stages of infection." Lukashchuk V., McFarlane S., Everett R.D., Preston C.M. J. Virol. 82:12543-12554(2008) [PubMed: 18922870] [Abstract] Cited for: INTERACTION WITH HCMV PP71.
[36]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-178; SER-213; SER-495; SER-668; SER-671; SER-688; SER-702; SER-737 AND SER-739, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[37]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495; SER-671; SER-688 AND SER-702, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[38]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-702; SER-737 AND SER-739, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[39]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-512, MASS SPECTROMETRY.
[40]	"Daxx is reciprocally regulated by Mdm2 and Hausp." Tang J., Qu L., Pang M., Yang X. Biochem. Biophys. Res. Commun. 393:542-545(2010) [PubMed: 20153724] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP7.
[41]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[42]	"Structural characterization of the DAXX N-terminal helical bundle domain and its complex with Rassf1C." Escobar-Cabrera E., Lau D.K., Giovinazzi S., Ishov A.M., McIntosh L.P. Structure 18:1642-1653(2010) [PubMed: 21134643] [Abstract] Cited for: STRUCTURE BY NMR OF 55-144 IN COMPLEX WITH RASSF1, INTERACTION WITH RASSF1.
[43]	"NMR chemical shift assignments of a complex between SUMO-1 and SIM peptide derived from the C-terminus of Daxx." Naik M.T., Chang C.C., Naik N.M., Kung C.C., Shih H.M., Huang T.H. Biomol. NMR. Assign. 5:75-77(2011) [PubMed: 20927612] [Abstract] Cited for: STRUCTURE BY NMR OF 721-740.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF039136 mRNA. Translation: AAB92671.1.
AF006041 mRNA. Translation: AAB63043.1.
AF015956 mRNA. Translation: AAB66585.2.
AF050179 mRNA. Translation: AAC39853.1.
AF097742 mRNA. Translation: AAC72843.1.
AB015051 mRNA. Translation: BAA34295.1.
CR457085 mRNA. Translation: CAG33366.1.
AL662827 Genomic DNA. Translation: CAI17527.1.
AL662820 Genomic DNA. Translation: CAI18124.1.
BX248088 Genomic DNA. Translation: CAI41788.1.
CR759817 Genomic DNA. Translation: CAQ08035.1.
CR759786 Genomic DNA. Translation: CAQ08265.1.
Z97183, Z97184 Genomic DNA. Translation: CAB09986.2.
Z97184, Z97183 Genomic DNA. Translation: CAB09989.2.
CH471081 Genomic DNA. Translation: EAX03722.1.
BC000220 mRNA. Translation: AAH00220.1.
BC109073 mRNA. Translation: AAI09074.1.
BC109074 mRNA. Translation: AAI09075.1.

IPI

IPI00170867.
IPI00220885.

PIR

T03847.

RefSeq

NP_001135441.1. NM_001141969.1.
NP_001341.1. NM_001350.4.

UniGene

Hs.336916.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KQS	NMR	-	B	721-740	[»]
2KZS	NMR	-	A	55-144	[»]
2KZU	NMR	-	A	55-144	[»]

ProteinModelPortal

Q9UER7.

SMR

Q9UER7. Positions 52-144.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27628N.

IntAct

Q9UER7. 56 interactions.

MINT

MINT-122943.

STRING

Q9UER7.

PTM databases

PhosphoSite

Q9UER7.

Polymorphism databases

DMDM

24636785.

Proteomic databases

PeptideAtlas

Q9UER7.

PRIDE

Q9UER7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000266000; ENSP00000266000; ENSG00000204209.
ENST00000374542; ENSP00000363668; ENSG00000204209.
ENST00000383062; ENSP00000372539; ENSG00000206206.
ENST00000383194; ENSP00000372681; ENSG00000206279.
ENST00000399060; ENSP00000382014; ENSG00000206206.
ENST00000399344; ENSP00000382281; ENSG00000206279.
ENST00000433482; ENSP00000404623; ENSG00000231617.
ENST00000436311; ENSP00000404376; ENSG00000227046.
ENST00000445009; ENSP00000394108; ENSG00000231617.
ENST00000455860; ENSP00000410772; ENSG00000227046.

GeneID

1616.

KEGG

hsa:1616.

UCSC

uc003oec.1. human.

Organism-specific databases

CTD

1616.

GeneCards

GC06M033286.

HGNC

HGNC:2681. DAXX.

HPA

CAB002224.
CAB025546.
HPA008736.

MIM

603186. gene.

neXtProt

NX_Q9UER7.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000009448.

HOGENOM

HBG125607.

HOVERGEN

HBG031495.

InParanoid

Q9UER7.

OMA

EQMQEGQ.

OrthoDB

EOG41NTMN.

PhylomeDB

Q9UER7.

Enzyme and pathway databases

Pathway_Interaction_DB

hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
tgfbrpathway. TGF-beta receptor signaling.

Gene expression databases

CleanEx

HS_DAXX.

Genevestigator

Q9UER7.

GermOnline

ENSG00000204209. Homo sapiens.

Family and domain databases

InterPro

IPR011989. ARM-like.
IPR005012. Daxx.
[Graphical view]

Gene3D

G3DSA:1.25.10.10. ARM-like. 2 hits.

KO

K02308.

PANTHER

PTHR12766. Daxx. 1 hit.

Pfam

PF03344. Daxx. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

6638.

SOURCE

Search...

Entry information

Entry name

DAXX_HUMAN

Accession

Primary (citable) accession number: Q9UER7
Secondary accession number(s): O14747 , O15141, O15208, Q5STK9, Q9BWI3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 2002
Last sequence update:	November 1, 2002
Last modified:	January 25, 2012
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.