ATRX_NOTEU
ID ATRX_NOTEU Reviewed; 497 AA.
AC P82798;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 1.
DT 25-MAY-2022, entry version 77.
DE RecName: Full=Transcriptional regulator ATRX;
DE EC=3.6.4.12;
DE AltName: Full=ATP-dependent helicase ATRX;
DE AltName: Full=X-linked nuclear protein;
DE Flags: Fragment;
GN Name=ATRX;
OS Notamacropus eugenii (Tammar wallaby) (Macropus eugenii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Diprotodontia; Macropodidae; Notamacropus.
OX NCBI_TaxID=9315;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE, AND TISSUE SPECIFICITY.
RX PubMed=11069290; DOI=10.1073/pnas.230424497;
RA Pask A., Renfree M.B., Marshall Graves J.A.;
RT "The human sex-reversing ATRX gene has a homologue on the marsupial Y
RT chromosome, ATRY: implications for the evolution of mammalian sex
RT determination.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13198-13202(2000).
CC -!- FUNCTION: Involved in transcriptional regulation and chromatin
CC remodeling. Facilitates DNA replication in multiple cellular
CC environments and is required for efficient replication of a subset of
CC genomic loci. Binds to DNA tandem repeat sequences in both telomeres
CC and euchromatin and in vitro binds DNA quadruplex structures. May help
CC stabilizing G-rich regions into regular chromatin structures by
CC remodeling G4 DNA and incorporating H3.3-containing nucleosomes.
CC Catalytic component of the chromatin remodeling complex ATRX:DAXX which
CC has ATP-dependent DNA translocase activity and catalyzes the
CC replication-independent deposition of histone H3.3 in pericentric DNA
CC repeats outside S-phase and telomeres, and the in vitro remodeling of
CC H3.3-containing nucleosomes. Its heterochromatin targeting is proposed
CC to involve a combinatorial readout of histone H3 modifications
CC (specifically methylation states of H3K9 and H3K4) and association with
CC CBX5. May be involved in transcriptional regulation of telomeric
CC repeat-containing RNA (TERRA). Acts as negative regulator of chromatin
CC incorporation of transcriptionally repressive histone MACROH2A1,
CC particularily at telomeres. Binds to zinc-finger coding genes with
CC atypical chromatin signatures and regulates its H3K9me3 levels. Forms a
CC complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and
CC maintenance of H3K9me3 at the 3' exons of zinc-finger genes (By
CC similarity). {ECO:0000250|UniProtKB:P46100}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC -!- SUBUNIT: Interacts with DAXX to form the chromatin remodeling complex
CC ATRX:DAXX. Probably binds EZH2. Binds annexin V in a calcium and
CC phosphatidylcholine/phosphatidylserine-dependent manner. Interacts
CC directly with CBX5 via the PxVxL motif. Interacts with RAD50, MRE11 and
CC NBN; indicative for an association with the MRN complex. Interacts with
CC histone MACROH2A1. Interacts with histone H3 peptides methylated at
CC 'Lys-10' with preferences H3K9me3 > H3K9me2 > H3K9me1. Interacts with
CC histone H3 peptides unmethylated at 'Lys-5' (H3K4me0). Interacts with
CC MECP2, SMC1 and SMC3. Interacts with SETDB1, TRIM28 and ZNF274 (By
CC similarity). {ECO:0000250|UniProtKB:P46100}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Chromosome, telomere
CC {ECO:0000250}. Nucleus, PML body {ECO:0000250}. Note=Associated with
CC pericentromeric heterochromatin during interphase and mitosis, probably
CC by interacting with CBX5/HP1 alpha. Colocalizes with histone H3.3,
CC DAXX, HIRA and ASF1A at PML-nuclear bodies (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues except developing testis.
CC {ECO:0000269|PubMed:11069290}.
CC -!- DOMAIN: The ADD domain predominantly interacts with histone H3
CC trimethylated at 'Lys-10'(H3K9me3) (and to a lesser extent H3 mono- or
CC dimethylated at 'Lys-10') and simultanously to histone H3 unmethylated
CC at 'Lys-5' (H3K4me0). The interaction with H3K9me3 is disrupted by the
CC presence of H3K4me3 suggesting a readout of the combined histone H3
CC methylation state (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. {ECO:0000305}.
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DR AlphaFoldDB; P82798; -.
DR SMR; P82798; -.
DR GO; GO:0000781; C:chromosome, telomeric region; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0072711; P:cellular response to hydroxyurea; ISS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0006336; P:DNA replication-independent chromatin assembly; ISS:UniProtKB.
DR GO; GO:1901581; P:negative regulation of telomeric RNA transcription from RNA pol II promoter; ISS:UniProtKB.
DR GO; GO:0006334; P:nucleosome assembly; ISS:UniProtKB.
DR GO; GO:0010571; P:positive regulation of nuclear cell cycle DNA replication; ISS:UniProtKB.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:1900112; P:regulation of histone H3-K9 trimethylation; ISS:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR025766; ADD.
DR InterPro; IPR041430; ADD_ATRX.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF17981; ADD_ATRX; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51533; ADD; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Chromatin regulator; Chromosome; DNA damage; DNA repair;
KW DNA-binding; Helicase; Hydrolase; Isopeptide bond; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Telomere; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN <1..>497
FT /note="Transcriptional regulator ATRX"
FT /id="PRO_0000074302"
FT DOMAIN 21..158
FT /note="ADD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT ZN_FING 32..68
FT /note="GATA-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT ZN_FING 79..134
FT /note="PHD-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT REGION 346..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 350..368
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT CROSSLNK 1
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT CROSSLNK 5
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT CROSSLNK 161
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT CROSSLNK 300
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT NON_TER 1
FT /evidence="ECO:0000303|PubMed:11069290"
FT NON_TER 497
FT /evidence="ECO:0000303|PubMed:11069290"
SQ SEQUENCE 497 AA; 57057 MW; 994F6C9ED9BC1370 CRC64;
KDDFKGPEFR SRSKMKTENL KKRGEGLHGI VSCTACGQQV NHFQKDSIYR HPTLKVLICK
NCYKYYMSDD ISRDADGMDE QCRWCAEGGN LICCDFCHNA FCKKCILRNL GRKELSAIMD
ENSQWYCYIC RPEPLLDLVT ACHSVFKNLE QLLQQNKKKI KVESEKSNKL FEHTHRFSPK
KNVSSCNGEE KKSDDAYSGS VTYSFTALMV PKDIVKKTKK LVETTASMNT SFVRFLKQAS
ENPEVSPVTK LRQLKAFKSV LNDVKKVHLA LEGSLNVEIR TLEALNKETV TKEHKAEGVK
PDTEVTKVEV YCAPKKKDFS KCATKLSVKQ VDSEINGQSL PVVGQPVHKT TSAEDKKSSR
KDPHFEPANT SEALDMDFSL LIFPLIFIFF ELSSCYFLLS SSFLFQSCFS LTSIFLLQIV
DLLFFKFYFF FKISLISIFL LQIVHLLFSL NLFSSKLFFL FLNFFSFFKL STFQIPNFSS
KMLFPDFYLP LPILLFL
