DAXX_CANLF
ID DAXX_CANLF Reviewed; 737 AA.
AC Q5TJE1;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Death domain-associated protein 6;
DE AltName: Full=Daxx;
GN Name=DAXX;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Doberman pinscher;
RX PubMed=15607421; DOI=10.1016/j.ygeno.2004.09.009;
RA Debenham S.L., Hart E.A., Ashurst J.L., Howe K.L., Quail M.A.,
RA Ollier W.E.R., Binns M.M.;
RT "Genomic sequence of the class II region of the canine MHC: comparison with
RT the MHC of other mammalian species.";
RL Genomics 85:48-59(2005).
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). Plays a role as a
CC positive regulator of the heat shock transcription factor HSF1 activity
CC during the stress 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: 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; AJ630366; CAI11447.1; -; Genomic_DNA.
DR AlphaFoldDB; Q5TJE1; -.
DR SMR; Q5TJE1; -.
DR STRING; 9612.ENSCAFP00000001395; -.
DR PaxDb; Q5TJE1; -.
DR Ensembl; ENSCAFT00845038086; ENSCAFP00845029838; ENSCAFG00845021574.
DR VEuPathDB; HostDB:ENSCAFG00845021574; -.
DR eggNOG; ENOG502QRS6; Eukaryota.
DR GeneTree; ENSGT00390000009448; -.
DR InParanoid; Q5TJE1; -.
DR Proteomes; UP000002254; Chromosome 12.
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; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IEA:Ensembl.
DR GO; GO:0002039; F:p53 binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030295; F:protein kinase activator activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0030521; P:androgen receptor signaling pathway; IEA:Ensembl.
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:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0006334; P:nucleosome assembly; IBA:GO_Central.
DR GO; GO:1901216; P:positive regulation of neuron death; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
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 3: Inferred from homology;
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..737
FT /note="Death domain-associated protein 6"
FT /id="PRO_0000151256"
FT REGION 1..159
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 145..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..417
FT /note="Interaction with histone H3.3"
FT /evidence="ECO:0000250"
FT REGION 346..567
FT /note="Necessary for interaction with USP7"
FT /evidence="ECO:0000250"
FT REGION 382..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 569..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 624..737
FT /note="Interaction with SPOP"
FT /evidence="ECO:0000250"
FT REGION 730..737
FT /note="Sumo interaction motif (SIM)"
FT /evidence="ECO:0000250"
FT COILED 179..216
FT /evidence="ECO:0000255"
FT COILED 432..474
FT /evidence="ECO:0000255"
FT MOTIF 390..394
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 626..632
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 36..50
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 148..181
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 382..396
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 433..489
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 499..545
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 590..617
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 672..719
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 212
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 558
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VIB2"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VIB2"
FT MOD_RES 665
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 668
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 699
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 734
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT MOD_RES 736
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 628
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
FT CROSSLNK 629
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q9UER7"
SQ SEQUENCE 737 AA; 81479 MW; E321EB2C160C3946 CRC64;
MATANSIIVL DDDDEDEAAA QPGPSHPPPN PASPQAEAPG SSQPHGAGGS SSSGGKKCYK
LENEKLFEEF LELCKMQTAD HPEVVPFLYN RQQRAHSLFL ASAEFCNILS RVLSRAQSRP
AKLYVYINEL CTVLKAHSAK KKLNLAPAAT SSEPSGNNPP TDPSSDPTNA ETTASEAPRT
RGSRRQIQRL EQLLALYVAE IRRLQEKELD LSELDDPDST YLQEARLKRK LIRLFGRLCE
LKDCSSLTGR VIEQRIPYRG TRYPEVNRRI ERLINKPGPD TFPDYGDVLR AVEKAAARHS
LGLPRQQLQL MAQDAFRDVG IRLQERRHLD LIYNFGCHLT DDYRPGIDPA LSDPALARRL
RENRSLAMSR LDEVISKYAM MQDKSEEGER QKRRARLPQA TSSHSTDPLK ASLDSGEGPS
GMASQECPTT SKPETDDEED EESEEEEEEE EEEEEEEATD SEEEEDLEQM QEGQGDDEEE
EEEEEEAGQD GDKSPMSPPR ISTEKNLEPS KGISRSMGEQ QNKEFTVSPS SEEPLAPSSI
DAESNGENLE ELLLEEESPI SQLFELEIEA LPLDTTPSPE ERDISSSRKQ SEEPLTTVLE
NGAAMVTSTS FNGGVSPHTW GDSCPPCKKS RKEKETGAEP LGNSYVERQR SVHEKNGRKI
PTLPSPPSPL TSMAPVADSS TRVDSPSHGL VTSSLCSASQ ARLSQTPHSQ PSRPGTYKMS
VATQCDPEEI IVLSDSD
