DAXX_RAT
ID DAXX_RAT Reviewed; 731 AA.
AC Q8VIB2;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Death domain-associated protein 6;
DE AltName: Full=Daxx;
GN Name=Daxx;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Mizuta H., Usui T., Nakamura Y., Murabe H., Nakao K.;
RT "Cloning and characterization of rat Daxx that enhances the transcription
RT activity of hERalpha.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488; SER-490; SER-527;
RP SER-551 AND SER-571, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Plays a role as a positive regulator of
CC the heat shock transcription factor HSF1 activity during the stress
CC protein response (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9UER7}.
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). Interacts with HSF1 (via homotrimeric form
CC preferentially); this interaction relieves homotrimeric HSF1 from
CC repression of its transcriptional activity by HSP90-dependent
CC multichaperone complex upon heat shock (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9UER7}.
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: Repressor activity is down-regulated upon Ser-661 phosphorylation.
CC Upon neuronal activation dephosphorylated by calcineurin in a Ca2+
CC dependent manner at Ser-661; dephosphorylation positively affects
CC histone H3.3 loading and transcriptional activation (By similarity).
CC {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; AB064671; BAB83524.1; -; mRNA.
DR AlphaFoldDB; Q8VIB2; -.
DR BMRB; Q8VIB2; -.
DR SMR; Q8VIB2; -.
DR IntAct; Q8VIB2; 4.
DR MINT; Q8VIB2; -.
DR STRING; 10116.ENSRNOP00000000559; -.
DR iPTMnet; Q8VIB2; -.
DR PhosphoSitePlus; Q8VIB2; -.
DR PaxDb; Q8VIB2; -.
DR UCSC; RGD:621227; rat.
DR RGD; 621227; Daxx.
DR eggNOG; ENOG502QRS6; Eukaryota.
DR InParanoid; Q8VIB2; -.
DR PhylomeDB; Q8VIB2; -.
DR Reactome; R-RNO-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-RNO-6804757; Regulation of TP53 Degradation.
DR Reactome; R-RNO-9670095; Inhibition of DNA recombination at telomere.
DR PRO; PR:Q8VIB2; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0044297; C:cell body; IDA:RGD.
DR GO; GO:0005938; C:cell cortex; IDA:RGD.
DR GO; GO:0000775; C:chromosome, centromeric region; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0000792; C:heterochromatin; ISO:RGD.
DR GO; GO:0005874; C:microtubule; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0016605; C:PML body; IDA:RGD.
DR GO; GO:0001741; C:XY body; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042393; F:histone binding; ISO:RGD.
DR GO; GO:0008432; F:JUN kinase binding; IPI:RGD.
DR GO; GO:0019894; F:kinesin binding; IPI:RGD.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IPI:RGD.
DR GO; GO:0002039; F:p53 binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030295; F:protein kinase activator activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISS:UniProtKB.
DR GO; GO:0140037; F:sumo-dependent protein binding; ISO:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0030521; P:androgen receptor signaling pathway; ISO:RGD.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071454; P:cellular response to anoxia; IEP:RGD.
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:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0034620; P:cellular response to unfolded protein; ISS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISO:RGD.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0007254; P:JNK cascade; ISO:RGD.
DR GO; GO:0000281; P:mitotic cytokinesis; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IDA:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0006334; P:nucleosome assembly; ISO:RGD.
DR GO; GO:0030578; P:PML body organization; IMP:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0033129; P:positive regulation of histone phosphorylation; IMP:RGD.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:RGD.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0071168; P:protein localization to chromatin; ISO:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0031396; P:regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0010038; P:response to metal ion; IEP:RGD.
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 1: Evidence at protein level;
KW Acetylation; Apoptosis; Centromere; Chaperone; Chromatin regulator;
KW Chromosome; Coiled coil; Cytoplasm; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..731
FT /note="Death domain-associated protein 6"
FT /id="PRO_0000151260"
FT REGION 1..158
FT /note="Necessary for interaction with USP7 and ATRX"
FT /evidence="ECO:0000250"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 181..414
FT /note="Interaction with histone H3.3"
FT /evidence="ECO:0000250"
FT REGION 345..560
FT /note="Necessary for interaction with USP7"
FT /evidence="ECO:0000250"
FT REGION 381..639
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 617..731
FT /note="Interaction with SPOP"
FT /evidence="ECO:0000250"
FT REGION 663..688
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 724..731
FT /note="Sumo interaction motif (SIM)"
FT /evidence="ECO:0000250"
FT COILED 177..215
FT /evidence="ECO:0000255"
FT COILED 368..395
FT /evidence="ECO:0000255"
FT COILED 428..485
FT /evidence="ECO:0000255"
FT MOTIF 391..395
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 622..628
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 150..180
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..395
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 396..426
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..482
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 501..518
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 582..610
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 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 421
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 456
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O35613"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35613"
FT MOD_RES 503
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 527
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 551
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 571
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 617
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35613"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35613"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 679
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 693
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 728
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 730
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 621
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
SQ SEQUENCE 731 AA; 80687 MW; 17EEBAAB5AA73157 CRC64;
MATDDSIIVL DDDDEDEAAA QPGPSNPASN PVSPGPEASG PSESHGDGGS SNSGSRKCYK
LENEKLFEEF LELCKMQTSD HPEVVPFLHK LQQRAQSAFL ASAEFRNILS RVLSRSRNRP
AKLYVYINEL CTVLKAHSIK KKLNLAPAAS AESSGDNPPT DPPSDLTNTE TTASEASRTR
GSRRQIQRLE QLLALYVAEI QRLQEKELDL SELDDPDSSY LQEARLKRKL IRLFGRLCDL
KDCSSLTGKV IEQRIPYRGT RYPEVNRRIE RLINKPGPDT FPDYGDVLRA VEKAATRHSL
GLPRQQLQLL AQDAFRDVGV RLQERRHLDL IYNFGCHLTD DYRPGVDPAL TDPTLARRLR
ENRTLAMSRL DEVISKYAMM QDKSEEGERQ KRRARLLATS QSSDLPKASS DSGEGPSGVA
SQEDPTTPKA ETEDEEDDEE SDDEEEEEEE EEEEATEDED EDLEQLQEDQ DDEEEEEGDN
EDDKSPASPS PIFRRKEFSN PQKGSGPQEE QQERGLTGTP ASPLEASPGL PSTDAESSGE
QLQERLLAGE SPVSQLSELD MEALPEETIP SPEERGISSS RRKSDSSLPT ILENGAAMVT
STSFNGRVSS HPCRDASPPS KRFRKEKKQL GPGPLGNSYV KKQTMAQQDS GWKISVLSTP
SSPLASVGPV ADSSTRVDSP SHELVTSSLC NPSPSLILQT PQSQSPRPCI YKTSVATQCD
PEEIIVLSDS D
