ATRX_RAT
ID ATRX_RAT Reviewed; 527 AA.
AC P70486;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 118.
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 AltName: Full=pABP-2;
DE Flags: Fragment;
GN Name=Atrx;
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], AND CHARACTERIZATION.
RC STRAIN=Wistar; TISSUE=Embryonic brain;
RX PubMed=8667030; DOI=10.1046/j.1471-4159.1996.67010089.x;
RA Ohsawa K., Imai Y., Ito D., Kohsaka S.;
RT "Molecular cloning and characterization of annexin V-binding proteins with
RT highly hydrophilic peptide structure.";
RL J. Neurochem. 67:89-97(1996).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112; SER-113; SER-114;
RP SER-162; SER-345 AND SER-346, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE 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: 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. Involved in maintaining telomere structural integrity in
CC embryonic stem cells probably implying recruitment of CBX5 to
CC telomeres. 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. Participates in the allele-specific gene
CC expression at the imprinted IGF2/H19 gene locus. On the maternal
CC allele, required for the chromatin occupancy of SMC1 and CTCTF within
CC the H19 imprinting control region (ICR) and involved in esatblishment
CC of histone tails modifications in the ICR. Binds to zinc-finger coding
CC genes with atypical chromatin signatures and regulates its H3K9me3
CC levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate
CC the deposition and maintenance of H3K9me3 at the 3' exons of zinc-
CC finger genes (By 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 -!- 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 -!- DOMAIN: Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is
CC required for interaction with chromoshadow domains. This motif requires
CC additional residues -7, -6, +4 and +5 of the central Val which contact
CC the chromoshadow domain.
CC -!- PTM: Citrullinated by PADI4. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. {ECO:0000305}.
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DR EMBL; D64059; BAA10936.1; -; mRNA.
DR AlphaFoldDB; P70486; -.
DR IntAct; P70486; 1.
DR iPTMnet; P70486; -.
DR PhosphoSitePlus; P70486; -.
DR jPOST; P70486; -.
DR PaxDb; P70486; -.
DR PRIDE; P70486; -.
DR UCSC; RGD:619795; rat.
DR RGD; 619795; Atrx.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0099115; C:chromosome, subtelomeric region; ISO:RGD.
DR GO; GO:0000781; C:chromosome, telomeric region; ISS:UniProtKB.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0000792; C:heterochromatin; ISO:RGD.
DR GO; GO:0000228; C:nuclear chromosome; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005721; C:pericentric heterochromatin; ISO:RGD.
DR GO; GO:0016605; C:PML body; ISO:RGD.
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:0031490; F:chromatin DNA binding; IBA:GO_Central.
DR GO; GO:0070087; F:chromo shadow domain binding; ISO:RGD.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0015616; F:DNA translocase activity; ISO:RGD.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; ISO:RGD.
DR GO; GO:0072711; P:cellular response to hydroxyurea; ISS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0070192; P:chromosome organization involved in meiotic cell cycle; ISO:RGD.
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:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0000212; P:meiotic spindle organization; ISO:RGD.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:1904908; P:negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric; ISO:RGD.
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:1901582; P:positive regulation of telomeric RNA transcription from RNA pol II promoter; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0035128; P:post-embryonic forelimb morphogenesis; ISO:RGD.
DR GO; GO:0070198; P:protein localization to chromosome, telomeric region; ISO:RGD.
DR GO; GO:1900112; P:regulation of histone H3-K9 trimethylation; ISS:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR GO; GO:0072520; P:seminiferous tubule development; ISO:RGD.
DR GO; GO:0060009; P:Sertoli cell development; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
PE 1: Evidence at protein level;
KW ATP-binding; Chromatin regulator; Chromosome; Citrullination; DNA damage;
KW DNA repair; DNA-binding; Helicase; Hydrolase; Isopeptide bond;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Telomere;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN <1..>527
FT /note="Transcriptional regulator ATRX"
FT /id="PRO_0000074306"
FT REGION 1..527
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 290..427
FT /note="Interaction with DAXX"
FT /evidence="ECO:0000250"
FT COMPBIAS 28..45
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..125
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..245
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..293
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 296..312
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..411
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..463
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 495..520
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 184
FT /note="Citrulline"
FT /evidence="ECO:0000250"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61687"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46100"
FT CROSSLNK 105
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 NON_TER 527
SQ SEQUENCE 527 AA; 59259 MW; ABEF4B10C086D638 CRC64;
GRSVVEFGDM VCKRQQSAVS SAGSEKPSGK EENVHSPEDK RVTKSKEKSK HLRTRTGRKV
KSDVTDRFRK KEQSSESSEG EKKQGRQRTG TRGKKSTDLK EEKVKREREY ESSSDGTEKL
PEGEEIGLFS KGVKQNKNDT TDEAKKGKKW KDKSCEKKEE LSDSVDRLPV KGESCDSSED
KKTRNRVSLR EKKQFSLPAK SSGKRPECSS SDTERSVKGE CCDSTDKRVK RIDLRERRSS
NSKRSTKEVK SGSSSSDAEG SSEDAKKQKK QRMSAKKKNS NTKERKRKSL RATTTKRKQA
DITSSSSDIG DDDQNSAGEE SSDEQKIKPV TENLVLPSHT GFCQSSGDEA FSKSVPATVD
DDDDDNDPEN RIAKKMLLEE IKANLSSDED GSSDDEPKEG EKKRIGKQSE ETPGDDGSNQ
VNSESDSDSE ESKKPRYRHR LLRHKLSLSD GESGGEKKTK PKEHKETKGR NRRKVSSEDS
EDTDFQESGV SEEVSESEDE QRPRTRSAKK AELEENQRSY KQKKKRR
