Chromatin remodeler ATRX

UniProt P46100 Organism Homo sapiens Gene ATRX, RAD54L, XH2 EC 3.6.4.-

Also known as: ATRX, RAD54L, XH2

Function

Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts. May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCF within the H19 imprinting control region (ICR) and involved in establishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes.

Classification

Family (Pfam): PF17981 ADD_ATRX, PF26143 ATRX_C, PF00271 Helicase_C, PF00176 SNF2-rel_dom
InterPro: ADD, ADD_ATRX, ATRX_C, ATRX_domain-containing, Helicase_ATP-bd, Helicase_C-like, P-loop_NTPase, SNF2-like_sf, SNF2/RAD54-like_C, SNF2_N, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
Functional cluster: Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 12

2JM1 NMR
2LBM NMR
2LD1 NMR
3QL9 X-ray 0.93A
3QLA X-ray 1.60A
3QLC X-ray 2.50A
3QLN X-ray 1.90A
4W5A X-ray 2.60A
5GRQ X-ray 1.58A
5Y18 X-ray 2.20A
5Y6O X-ray 3.10A
6G0O X-ray 1.40A

A predicted model is available from AlphaFold.

Gene Ontology · 35

Disease associations

alpha-thalassemia-myelodysplastic syndrome MONDO:0010328
alpha thalassemia-X-linked intellectual disability syndrome MONDO:0010519
intellectual disability-hypotonic facies syndrome, X-linked, 1 MONDO:0010663

Neighborhood · nearest proteins

Nearest neighbours of Chromatin remodeler ATRX: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Chromatin remodeler ATRX 1.00
Chromatin remodeler ATRX 1.00
Chromatin remodeler ATRX 0.96
PHD finger protein 3 0.83
ATPase family AAA domain-containing protein 5 0.82
ATPase family AAA domain-containing protein 5 0.81
Biorientation of chromosomes in cell division protein 1-like 1 0.80
Mis18-binding protein 1 0.79
CASP8-associated protein 2 0.79
ORC ubiquitin ligase 1 0.79
Protein SCAF11 0.79
ORC ubiquitin ligase 1 0.78

Co-cited proteins · studied together in the literature

Chromatin remodeler ATRX 7 shared papers
Death domain-associated protein 6 5 shared papers
Death domain-associated protein 6 2 shared papers
Neurotrophin receptor-interacting factor homolog 1 shared papers
Methyl-CpG-binding protein 2 1 shared papers
Histone-lysine N-methyltransferase EZH2 1 shared papers
Methyl-CpG-binding protein 2 1 shared papers
Transcription intermediary factor 1-beta 2 shared papers
Methyl-CpG-binding protein 2 1 shared papers
Signal transducing adapter molecule 2 1 shared papers
Histone-lysine N-methyltransferase SETDB1 1 shared papers
Delta(14)-sterol reductase LBR 1 shared papers

Literature · 58 cited papers

Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
ATRX binds to atypical chromatin domains at the 3' exons of zinc finger genes to preserve H3K9me3 enrichment. Epigenetics · 2016
SUMO-2 orchestrates chromatin modifiers in response to DNA damage. Cell Rep. · 2015
Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. Proc. Natl. Acad. Sci. U.S.A. · 2014
ATRX dysfunction induces replication defects in primary mouse cells. PLoS ONE · 2014
Alternative lengthening of telomeres is characterized by reduced compaction of telomeric chromatin. Nucleic Acids Res. · 2014
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
DAXX-dependent supply of soluble (H3.3-H4) dimers to PML bodies pending deposition into chromatin. Genome Res. · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway. PLoS Genet. · 2012
ATRX-mediated chromatin association of histone variant macroH2A1 regulates alpha-globin expression. Genes Dev. · 2012
… and 46 more in the literature graph

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