ATRX

Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) is a protein that in humans is encoded by the ATRX gene.^[5][6][7]

ATRX
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JM1, 2LBM, 2LD1, 3QL9, 3QLA, 3QLC, 3QLN, 4W5A
Identifiers
Aliases	ATRX, ATR2, JMS, MRXHF1, RAD54, RAD54L, SFM1, SHS, XH2, XNP, ZNF-HX, MRX52, alpha thalassemia/mental retardation syndrome X-linked, chromatin remodeler, ATRX chromatin remodeler
External IDs	OMIM: 300032; MGI: 103067; HomoloGene: 416; GeneCards: ATRX; OMA:ATRX - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xq21.1 Start 77,504,880 bp[1] End 77,786,233 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X D|X 47.26 cM Start 104,841,221 bp[2] End 104,973,009 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell Achilles tendon epithelium of colon cerebellar vermis Brodmann area 23 Epithelium of choroid plexus pylorus tibia sural nerve Region I of hippocampus proper Top expressed in genital tubercle tail of embryo pineal gland medullary collecting duct vestibular sensory epithelium condyle fossa lobe of cerebellum Gonadal ridge ciliary body More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding nucleotide binding chromo shadow domain binding helicase activity histone binding metal ion binding DNA translocase activity methylated histone binding DNA helicase activity protein binding hydrolase activity ATP binding chromatin binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component PML body SWI/SNF superfamily-type complex pericentric heterochromatin chromosome heterochromatin nuclear chromosome telomere nucleus nucleoplasm nuclear body Biological process chromatin remodeling nucleosome assembly DNA recombination post-embryonic forelimb morphogenesis regulation of transcription, DNA-templated multicellular organism growth DNA damage response, signal transduction by p53 class mediator positive regulation of nuclear cell cycle DNA replication Sertoli cell development transcription, DNA-templated protein localization to chromosome, telomeric region cellular response to DNA damage stimulus positive regulation of telomeric RNA transcription from RNA pol II promoter positive regulation of telomere maintenance DNA methylation negative regulation of telomeric RNA transcription from RNA pol II promoter seminiferous tubule development spermatogenesis replication fork processing negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric forebrain development DNA repair cellular response to hydroxyurea positive regulation of transcription by RNA polymerase II DNA duplex unwinding regulation of histone H3-K9 trimethylation meiotic spindle organization chromosome organization involved in meiotic cell cycle chromatin organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 546 22589 Ensembl ENSG00000085224 ENSMUSG00000031229 UniProt P46100 Q61687 RefSeq (mRNA) NM_000489 NM_138270 NM_138271 NM_009530 RefSeq (protein) NP_000480 NP_612114 NP_033556 Location (UCSC) Chr X: 77.5 – 77.79 Mb Chr X: 104.84 – 104.97 Mb PubMed search [3] [4]
Wikidata
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Function

Transcriptional regulator ATRX contains an ATPase / helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. ATRX is required for deposition of the histone variant H3.3 at telomeres and other genomic repeats.^[8] These interactions are important for maintaining silencing at these sites.^[9][10][11]

In addition, ATRX undergoes cell cycle-dependent phosphorylation, which regulates its nuclear matrix and chromatin association, and suggests its involvement in the gene regulation at interphase and chromosomal segregation in mitosis.^[7]

Clinical significance

Inherited mutations

Inherited mutations of the ATRX gene are associated with an X-linked mental retardation (XLMR) syndrome most often accompanied by alpha-thalassemia (ATR-X) syndrome. These mutations have been shown to cause diverse changes in the pattern of DNA methylation, which may provide a link between chromatin remodeling, DNA methylation, and gene expression in developmental processes. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. Female carriers may demonstrate skewed X chromosome inactivation.^[7]

Somatic mutations

Acquired mutations in ATRX have been reported in a number of human cancers including pancreatic neuroendocrine tumours,^[12] gliomas,^{[13] [14]} osteosarcomas,^[15] soft-tissue sarcomas,^[16] and malignant pheochromocytomas.^[17] There is a strong correlation between ATRX mutations and an Alternative Lengthening of Telomeres (ALT)^{[broken anchor]} phenotype in cancers.^[12]

Interactions

ATRX forms a complex with DAXX which is an histone H3.3 chaperone.^[18]

ATRX has been also shown to interact with EZH2.^[19]

See also

• Alpha-thalassemia mental retardation syndrome