Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000747
UniProt IDQ9UER7
Primary gene name(s)DAXX
Synonym gene name(s)BING2, DAP6
Protein nameDeath domain-associated protein 6
Protein functionTranscription 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 activation 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. Upon neuronal activation associates 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. In case of overexpression of centromeric histone variant CENPA, as found in various tumors is involved in its mislocalization to chromosomes; the ectopic localization involves a heterotypic tetramer containing CENPA, and histones H3.3 and H4 and decreases binding of CTCF to 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. Shows restriction activity towards human cytomegalovirus, HCMV. {ECO:0000269|PubMed:12140263, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:15364927, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:17081986, ECO:0000269|PubMed:17942542, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:23222847, ECO:0000269|PubMed:24200965, ECO:0000269|PubMed:24530302}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:11495919, ECO:0000269|PubMed:11842083, ECO:0000269|PubMed:12968034, ECO:0000269|PubMed:9407001}. Nucleus, nucleoplasm {ECO:0000269|PubMed:10669754, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:23222847, ECO:0000269|PubMed:9407001}. Nucleus, PML body {ECO:0000269|PubMed:10669754, ECO:0000269|PubMed:11842083, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:17081986, ECO:0000269|PubMed:21482821, ECO:0000269|PubMed:23222847, ECO:0000269|PubMed:24200965, ECO:0000269|PubMed:25275136}. Nucleus, nucleolus {ECO:0000269|PubMed:23222847}. Chromosome, centromere {ECO:0000269|PubMed:24200965, ECO:0000269|PubMed:9645950}. Note=Dispersed throughout the nucleoplasm, in PML/POD/ND10 nuclear bodies, and in nucleoli, Probable. Colocalizes with histone H3.3, ATRX, HIRA and ASF1A at PML-nuclear bodies, PubMed:12953102, PubMed:14990586, PubMed:23222847, PubMed:24200965. Colocalizes with a subset of interphase centromeres, but is absent from mitotic centromeres, PubMed:9645950. Detected in cytoplasmic punctate structures, PubMed:11842083. Translocates from the nucleus to the cytoplasm upon glucose deprivation or oxidative stress, PubMed:12968034. Colocalizes with RASSF1 in the nucleus, PubMed:18566590. Colocalizes with USP7 in nucleoplasma with accumulation in speckled structures, PubMed:16845383. {ECO:0000269|PubMed:11842083, ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:12968034, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:23222847, ECO:0000269|PubMed:24200965, ECO:0000269|PubMed:9645950, ECO:0000305|PubMed:10669754}.;
SUBCELLULAR LOCATION: Isoform beta: Nucleus {ECO:0000269|PubMed:21482821}. Note=Diffuse nuclear distribution pattern and no comparable dot-like accumulation of isoform 1. {ECO:0000269|PubMed:21482821}.;
SUBCELLULAR LOCATION: Isoform gamma: Nucleus {ECO:0000269|PubMed:21482821}. Note=Diffuse nuclear distribution pattern and no comparable dot-like accumulation of isoform 1. {ECO:0000269|PubMed:21482821}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9UER7
Gene Ontology
(Biological Process)
Complete annatation
activation of JUN kinase activity [GO:0007257];
androgen receptor signaling pathway [GO:0030521];
apoptotic process [GO:0006915];
chromatin remodeling [GO:0006338];
covalent chromatin modification [GO:0016569];
extrinsic apoptotic signaling pathway via death domain receptors [GO:0008625];
negative regulation of transcription, DNA-templated [GO:0045892];
nucleosome assembly [GO:0006334];
positive regulation of neuron death [GO:1901216];
positive regulation of protein kinase activity [GO:0045860];
positive regulation of protein phosphorylation [GO:0001934];
regulation of protein ubiquitination [GO:0031396];
regulation of transcription, DNA-templated [GO:0006355];
transcription, DNA-templated [GO:0006351];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
androgen receptor binding [GO:0050681];
enzyme binding [GO:0019899];
heat shock protein binding [GO:0031072];
histone binding [GO:0042393];
p53 binding [GO:0002039];
protein homodimerization activity [GO:0042803];
protein kinase activator activity [GO:0030295];
protein kinase binding [GO:0019901];
protein N-terminus binding [GO:0047485];
receptor signaling protein activity [GO:0005057];
transcription corepressor activity [GO:0003714];
transcription factor binding [GO:0008134];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
cell body [GO:0044297];
cell cortex [GO:0005938];
chromosome, centromeric region [GO:0000775];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
microtubule [GO:0005874];
neuron projection [GO:0043005];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
PML body [GO:0016605];
SWI/SNF superfamily-type complex [GO:0070603];
XY body [GO:0001741]
Protein-protein interaction107985
Phylogenetic treeQ9UER7
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-0.004772266895305890.9883752924701570.992061295159178
AZA vs. DISU-0.1089793822063060.6663524842156190.962297595817978
AZA vs. IL70.06093013842466740.7511944603319910.999311006273513
AZA vs. SAHA-0.1486670989020070.5420752112368850.844253962329433
DISU vs. CD3-0.11614045607880.748842671878990.82520080418865
DISU vs. IL70.1603534775337490.5241592679305230.839623946876276
DISU vs. SAHA-0.03745218330640150.8976351024007330.974619934229746
DMSO vs. AZA0.02974651533892230.859041532806721
DMSO vs. CD30.02429971676204030.9395385365173470.957898724047415
DMSO vs. DISU0.1372098129260160.5736285539073030.930932477407238
DMSO vs. IL70.03833359405312630.8310641597535960.963051812112721
DMSO vs. SAHA-0.184457509037230.4337838668280460.768509344471904
HIV vs. Mock in Activation0.1353612917610960.828040114770180.999983755607037
HIV vs. Mock in Latency0.04634918892776380.7789068047629530.999834320637052
IL7 vs. CD30.07184972712758620.8233926238895340.885235165469825
SAHA vs. CD3-0.1673817362207620.6360997343963230.727591878356932
SAHA vs. IL7-0.2118408972266850.3841955858046190.634255163710988
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.140439 0.356974
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.987 0.98 0.923 0.896 1.008
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2KQS NMR - B=721-740.
2KZS NMR - A=55-144.
2KZU NMR - A=55-144.
4H9N X-ray 1.9Å C=178-389.
4H9O X-ray 2.0Å C=178-389.
4H9P X-ray 2.2Å C=178-389.
4H9Q X-ray 1.9Å C=178-389.
4H9R X-ray 2.2Å C=178-389.
4H9S X-ray 2.6Å E/F=183-398.
4HGA X-ray 2.8Å A=184-390.
5KDM X-ray 3.5Å C=178-389.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
integrase interacts with 18558084

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa05014 Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)