DAXX_CHLAE
ID DAXX_CHLAE Reviewed; 736 AA.
AC O18805;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Death domain-associated protein 6;
DE AltName: Full=Daxx;
GN Name=DAXX;
OS Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9407001; DOI=10.1089/dna.1997.16.1289;
RA Kiriakidou M., Driscoll D.A., Lopez-Guisa J.M., Strauss J.F. III;
RT "Cloning and expression of primate Daxx cDNAs and mapping of the human gene
RT to chromosome 6p21.3 in the MHC region.";
RL DNA Cell Biol. 16:1289-1298(1997).
CC -!- FUNCTION: Transcription corepressor known to repress transcriptional
CC potential of several sumoylated transcription factors. Down-regulates
CC basal and activated transcription. Its transcription repressor activity
CC is modulated by recruiting it to subnuclear compartments like the
CC nucleolus or PML/POD/ND10 nuclear bodies through interactions with
CC MCSR1 and PML, respectively. Seems to regulate transcription in
CC PML/POD/ND10 nuclear bodies together with PML and may influence
CC TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional
CC activation of PAX3 and ETS1 through direct protein-protein
CC interactions. Modulates PAX5 activity; the function seems to involve
CC CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by
CC regulating the RING-finger E3 ligase MDM2 ubiquitination activity.
CC Under non-stress condition, in association with the deubiquitinating
CC USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3
CC ligase activity of MDM2 towards TP53, thereby promoting TP53
CC ubiquitination and subsequent proteasomal degradation. Upon DNA damage,
CC its association with MDM2 and USP7 is disrupted, resulting in increased
CC MDM2 autoubiquitination and consequently, MDM2 degradation, which leads
CC to TP53 stabilization. Acts as histone chaperone that facilitates
CC deposition of histone H3.3. Acts as targeting component of the
CC chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA
CC translocase activity and catalyzes the replication-independent
CC deposition of histone H3.3 in pericentric DNA repeats outside S-phase
CC and telomeres, and the in vitro remodeling of H3.3-containing
CC nucleosomes. Does not affect the ATPase activity of ATRX but alleviates
CC its transcription repression activity. Upon neuronal activation
CC associates with regulatory elements of selected immediate early genes
CC where it promotes deposition of histone H3.3 which may be linked to
CC transcriptional induction of these genes. Required for the recruitment
CC of histone H3.3:H4 dimers to PML-nuclear bodies (PML-NBs); the process
CC is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested
CC to function as regulatory sites for the incorporation of newly
CC synthesized histone H3.3 into chromatin. Proposed to mediate activation
CC of the JNK pathway and apoptosis via MAP3K5 in response to signaling
CC from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent
CC interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis.
CC In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated
CC apoptosis may not involve DAXX (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homomultimer. Interacts (via C-terminus) with TNFRSF6 (via
CC death domain). Interacts with PAX5, SLC2A4/GLUT4, MAP3K5, TGFBR2,
CC phosphorylated dimeric HSPB1/HSP27, CENPC, ETS1, sumoylated PML, UBE2I,
CC MCRS1 and TP53. Interacts (via N-terminus) with HIPK2 and HIPK3.
CC Interacts with HIPK1, which induces translocation from PML/POD/ND10
CC nuclear bodies to chromatin and enhances association with HDAC1.
CC Interacts (non-phosphorylated) with PAX3, PAX7, DEK, HDAC1, HDAC2,
CC HDAC3, acetylated histone H4 and histones H2A, H2B, H3, H3.3 and H4.
CC Interacts with SPOP; mediating CUL3-dependent proteosomal degradation.
CC Interacts with CBP; the interaction is dependent the sumoylation of CBP
CC and suppresses CBP transcriptional activity via recruitment of HDAC2
CC directly in the complex with TP53 and HIPK2. Interacts with AXIN1; the
CC interaction stimulates the interaction of DAXX with TP53, stimulates
CC 'Ser-46' phosphorylation of TP53 on and induces cell death on UV
CC irradiation. Interacts with MDM2; the interaction is direct. Interacts
CC with USP7; the interaction is direct and independent of MDM2 and TP53.
CC Part of a complex with DAXX, MDM2 and USP7 under non-stress conditions.
CC Interacts (via N-terminus) with RASSF1 (via C-terminus); the
CC interaction is independent of MDM2 and TP53; RASSF1 isoform A disrupts
CC interactions among MDM2, DAXX and USP7, thus contributing to the
CC efficient activation of TP53 by promoting MDM2 self-ubiquitination in
CC cell-cycle checkpoint control in response to DNA damage. Interacts with
CC ATRX to form the chromatin remodeling complex ATRX:DAXX (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UER7}.
CC Nucleus, nucleoplasm {ECO:0000250|UniProtKB:Q9UER7}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:Q9UER7}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q9UER7}. Chromosome, centromere
CC {ECO:0000250|UniProtKB:Q9UER7}. Note=Dispersed throughout the
CC nucleoplasm, in PML/POD/ND10 nuclear bodies, and in nucleoli.
CC Colocalizes with histone H3.3, ATRX, HIRA and ASF1A at PML-nuclear
CC bodies. Colocalizes with a subset of interphase centromeres, but is
CC absent from mitotic centromeres. Detected in cytoplasmic punctate
CC structures. Translocates from the nucleus to the cytoplasm upon glucose
CC deprivation or oxidative stress. Colocalizes with RASSF1 in the
CC nucleus. Colocalizes with USP7 in nucleoplasma with accumulation in
CC speckled structures. {ECO:0000250|UniProtKB:Q9UER7}.
CC -!- DOMAIN: The Sumo interaction motif mediates Sumo binding, and is
CC required both for sumoylation and binding to sumoylated targets.
CC {ECO:0000250}.
CC -!- PTM: Sumoylated with SUMO1 on multiple lysine residues. {ECO:0000250}.
CC -!- PTM: Polyubiquitinated; which is promoted by CUL3 and SPOP and results
CC in proteasomal degradation. Ubiquitinated by MDM2; inducing its
CC degradation. Deubiquitinated by USP7; leading to stabilize it (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the DAXX family. {ECO:0000305}.
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DR EMBL; AF015957; AAB66586.1; -; mRNA.
DR PIR; T03849; T03849.
DR AlphaFoldDB; O18805; -.
DR BMRB; O18805; -.
DR SMR; O18805; -.
DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:CAFA.
DR GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IMP:CAFA.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071276; P:cellular response to cadmium ion; ISS:UniProtKB.
DR GO; GO:0071280; P:cellular response to copper ion; ISS:UniProtKB.
DR GO; GO:0072738; P:cellular response to diamide; ISS:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
DR GO; GO:1903936; P:cellular response to sodium arsenite; ISS:UniProtKB.
DR GO; GO:0034620; P:cellular response to unfolded protein; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0031396; P:regulation of protein ubiquitination; ISS:UniProtKB.
DR CDD; cd13151; DAXX_helical_bundle; 1.
DR CDD; cd13150; DAXX_histone_binding; 1.
DR Gene3D; 1.10.8.810; -; 1.
DR Gene3D; 1.20.58.2170; -; 1.
DR InterPro; IPR005012; Daxx.
DR InterPro; IPR046378; DAXX_histone_binding.
DR InterPro; IPR046426; DAXX_histone_binding_sf.
DR InterPro; IPR031333; Daxx_N.
DR InterPro; IPR038298; Daxx_N_sf.
DR PANTHER; PTHR12766:SF7; PTHR12766:SF7; 1.
DR Pfam; PF03344; Daxx; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Apoptosis; Centromere; Chaperone; Chromatin regulator;
KW Chromosome; Coiled coil; Cytoplasm; Isopeptide bond; Nucleus;
KW Phosphoprotein; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..736
FT /note="Death domain-associated protein 6"
FT /id="PRO_0000151257"
FT REGION 1..160
FT /note="Necessary for interaction with USP7 and ATRX"
FT /evidence="ECO:0000250"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 148..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 183..417
FT /note="Interaction with histone H3.3"
FT /evidence="ECO:0000250"
FT REGION 347..566
FT /note="Necessary for interaction with USP7"
FT /evidence="ECO:0000250"
FT REGION 387..558
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 602..736
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 622..736
FT /note="Interaction with SPOP"
FT /evidence="ECO:0000250"
FT REGION 729..736
FT /note="Sumo interaction motif (SIM)"
FT /evidence="ECO:0000250"
FT COILED 180..216
FT /evidence="ECO:0000255"
FT COILED 430..490
FT /evidence="ECO:0000255"
FT MOTIF 391..395
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 624..630
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 34..49
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 148..184
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 434..488
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 495..527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 673..722
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 459
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O35613"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 497
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VIB2"
FT MOD_RES 511
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VIB2"
FT MOD_RES 576
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VIB2"
FT MOD_RES 664
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 667
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 698
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 733
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT CROSSLNK 142
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT CROSSLNK 626
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT CROSSLNK 627
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
SQ SEQUENCE 736 AA; 81316 MW; D06039EA82E55D65 CRC64;
MATANSIIVL DDDDENEAAA QPGPSHPLPS TASPEAEAPS SSEPHGARGS SSSGGKKCYK
LENEKLFQEF LELCKTQTAD HPEVVPFLCN RQQRAHSLFL ASAEFCNILS RVLSRAQSRP
FKLYVYINEL CTVLKGHSAK KKLNLAPVAT TSNEPSGNNP PTHLSLDPTN AENTASQAPR
TRGSRRQIQR LEQLLALYVA EIRRLQEREL DLSELDDPDS TYLQEARLKR KLIRLFGRLC
ELKDCSSLTG RVIKQRIPYR GTRYPKVNRR IERLINKPGP DTFPDYGDVL RAVKKAAARH
SLGLPRQQLQ LMAQDAFRNV GIRLQEQRHL DLIYNFGCHL TNDYRPGVDP ALSYPVLARR
LRENRILALI RLDQVISFYA MLQDGGEEGK KKKRRARLHG PSSHSANPPE PSLDSGEGPI
GMASQGCPSA SRAETDDEDD EESDEEEEEE EEEEEEEATD FEEEEDLEQM QEGQEDDEEE
EEEEEAAGKD GDGSPMSSPQ ISTEKNLEPG KQISRSSGEQ QNKVSPLLLS EEPLAPSSID
AESNGEQPEE LTLEEESPVS QLFELEIEAL PLDTPSFVEM DISFFRKQSE EPFTTVLENG
AGMVSSTSFN GGVSPHNWGD SGPPCKKSRK EKKQTGSGPL GNSYVERQRS VHEKNGKKIC
TLPSPPSPLA SLAPVADSST RVDSPSHGLV TSSLCNPSPA QLSQTPQSQP PRPSTYKTSV
ATQCDPEEII VLSDSD
