UniProt Accession

 DAXX_HUMAN; Q9UER7; B4E1I3; F5H082; O14747; O15141; O15208; Q5STK9; Q9BWI3 

Genbank Protein ID

 AF039136; AF006041; AF015956; AF050179; AF097742; AB015051; AK303854; CR457085; AL662827; AL662820; BX248088; CR759793; CR759817; CR759786; Z97183; Z97184; Z97184; Z97183; CH471081; BC000220; BC109073; BC109074 

Genbank Nucleotide ID

 AAB92671.1; AAB63043.1; AAB66585.2; AAC39853.1; AAC72843.1; BAA34295.1; BAG64795.1; CAG33366.1; CAI17527.1; CAI18124.1; CAI41788.1; CAQ08035.1; CAQ08265.1; CAB09986.2; CAB09986.2; CAB09989.2; CAB09989.2; EAX03722.1; AAH00220.1; AAI09074.1; AAI09075.1 

Protein Name

 Death domain-associated protein 6 

Protein Synonyms/Alias

 Daxx; hDaxx; ETS1-associated protein 1; EAP1; Fas death domain-associated protein 

Gene Name

 DAXX 

Gene Synonyms/Alias

 BING2; DAP6 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
60	SGGKKCYKLENEKLF	ubiquitination	[1]
65	CYKLENEKLFEEFLE	ubiquitination	[1]
75	EEFLELCKMQTADHP	ubiquitination	[1]
141	LKAHSAKKKLNLAPA	ubiquitination	[1]
142	KAHSAKKKLNLAPAA	ubiquitination	[1]
208	EIRRLQEKELDLSEL	ubiquitination	[1, 2, 3]
243	FGRLCELKDCSSLTG	ubiquitination	[1, 3, 4, 5]
277	RIERLINKPGPDTFP	ubiquitination	[1, 2, 4]
295	DVLRAVEKAAARHSL	ubiquitination	[4]
378	RLDEVISKYAMLQDK	ubiquitination	[1, 2, 3, 4, 5, 6]
385	KYAMLQDKSEEGERK	ubiquitination	[1, 2, 3, 4, 5]
512	EKNLEPGKQISRSSG	acetylation	[5, 7, 8, 9]
512	EKNLEPGKQISRSSG	ubiquitination	[1, 2]
630	GDSGPPCKKSRKEKK	sumoylation	[10]
631	DSGPPCKKSRKEKKQ	sumoylation	[10]
637	KKSRKEKKQTGSGPL	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [6] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [8] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [10] Modification of Daxx by small ubiquitin-related modifier-1.
 Jang MS, Ryu SW, Kim E.
 Biochem Biophys Res Commun. 2002 Jul 12;295(2):495-500. [PMID: 12150977] 

Functional Description

 Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. 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. Shows restriction activity towards human cytomegalovirus (HCMV). 

Sequence Annotation

 REGION 1 160 Necessary for interaction with USP7.
 REGION 347 570 Necessary for interaction with USP7.
 REGION 501 625 Interaction with MAP3K5.
 REGION 626 740 Interaction with SPOP.
 REGION 733 740 Sumo interaction motif (SIM).
 MOTIF 391 395 Nuclear localization signal (Potential).
 MOTIF 628 634 Nuclear localization signal (Potential).
 MOD_RES 178 178 Phosphoserine.
 MOD_RES 213 213 Phosphoserine.
 MOD_RES 459 459 Phosphothreonine (By similarity).
 MOD_RES 495 495 Phosphoserine.
 MOD_RES 512 512 N6-acetyllysine.
 MOD_RES 668 668 Phosphoserine.
 MOD_RES 671 671 Phosphoserine.
 MOD_RES 688 688 Phosphoserine.
 MOD_RES 702 702 Phosphoserine.
 MOD_RES 737 737 Phosphoserine.
 MOD_RES 739 739 Phosphoserine.
 CROSSLNK 630 630 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 631 631 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Alternative splicing; Apoptosis; Centromere; Chromosome; Coiled coil; Complete proteome; Cytoplasm; Host-virus interaction; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 740 AA 

Protein Sequence

Gene Ontology

 GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; ISS:UniProtKB.
 GO:0000792; C:heterochromatin; IEA:Compara.
 GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
 GO:0016605; C:PML body; IDA:UniProtKB.
 GO:0031072; F:heat shock protein binding; TAS:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0005057; F:receptor signaling protein activity; TAS:ProtInc.
 GO:0008134; F:transcription factor binding; IDA:UniProtKB.
 GO:0007257; P:activation of JUN kinase activity; TAS:ProtInc.
 GO:0030521; P:androgen receptor signaling pathway; IDA:UniProtKB.
 GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS:ProtInc.
 GO:0006917; P:induction of apoptosis; ISS:UniProtKB.
 GO:0000281; P:mitotic cytokinesis; IEA:Compara.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:0031396; P:regulation of protein ubiquitination; IDA:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR005012; Daxx. 

Pfam

 PF03344; Daxx 

SMART

  

PROSITE

  

PRINTS