ATRX

Alpha thalassemia/mental retardation syndrome X-linked
Identifiers
Symbols	ATRX; ATR2; JMS; MGC2094; MRXHF1; RAD54; RAD54L; SFM1; SHS; XH2; XNP; ZNF-HX
External IDs	OMIM: 300032 MGI: 103067 HomoloGene: 416 GeneCards: ATRX Gene
EC number	3.6.4.12
Gene Ontology Molecular function • nucleotide binding • DNA binding • DNA helicase activity • chromatin binding • helicase activity • protein binding • ATP binding • zinc ion binding • hydrolase activity • metal ion binding • chromo shadow domain binding Cellular component • nuclear chromosome • nucleus • nuclear heterochromatin Biological process • DNA repair • DNA methylation • DNA recombination • regulation of transcription, DNA-dependent • forebrain development Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	546	22589
Ensembl	ENSG00000085224	ENSMUSG00000031229
UniProt	P46100	Q3TP53
RefSeq (mRNA)	NM_000489.3	NM_009530.2
RefSeq (protein)	NP_000480.2	NP_033556.2
Location (UCSC)	Chr X: 76.76 – 77.04 Mb	Chr X: 102.99 – 103.12 Mb
PubMed search	[1]	[2]

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.

Function

Transcriptional regulator ATRX contains an ATPase / helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. This protein is found to undergo 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.

Clinical significance

Mutations of the ATRX gene are associated with an X-linked mental retardation (XLMR) syndrome most often accompanied by alpha-thalassemia (ATRX) 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.

See also

• X-linked alpha thalassemia mental retardation syndrome

Interactions

ATRX has been shown to interact with EZH2 and RAD51.

Further reading

• Mulley JC, Kerr B, Stevenson R, Lubs H (1992). "Nomenclature guidelines for X-linked mental retardation". Am. J. Med. Genet. 43 (1–2): 383–91. doi:10.1002/ajmg.1320430159. PMID 1605216. 
• Tang P, Park DJ, Marshall Graves JA, Harley VR (2005). "ATRX and sex differentiation". Trends Endocrinol. Metab. 15 (7): 339–44. doi:10.1016/j.tem.2004.07.006. PMID 15350606. 
• Forget BG (2006). "De novo and acquired forms of alpha thalassemia". Curr. Hematol. Rep. 5 (1): 11–4. PMID 16537041. 
• Adès LC, Kerr B, Turner G, Wise G (1992). "Smith-Fineman-Myers syndrome in two brothers". Am. J. Med. Genet. 40 (4): 467–70. doi:10.1002/ajmg.1320400419. PMID 1684092. 
• Sutherland GR, Gedeon AK, Haan EA, et al. (1988). "Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia (MRX2)". Am. J. Med. Genet. 30 (1–2): 493–508. doi:10.1002/ajmg.1320300152. PMID 3177467. 
• Shapiro MB, Senapathy P (1987). "RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression". Nucleic Acids Res. 15 (17): 7155–74. doi:10.1093/nar/15.17.7155. PMC 306199. PMID 3658675. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=306199. 
• Gibbons RJ, Picketts DJ, Villard L, Higgs DR (1995). "Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome)". Cell 80 (6): 837–45. doi:10.1016/0092-8674(95)90287-2. PMID 7697714. 
• Wang LH, Collins A, Lawrence S, et al. (1995). "Integration of gene maps: chromosome X". Genomics 22 (3): 590–604. doi:10.1006/geno.1994.1432. PMID 8001970. 
• Gecz J, Pollard H, Consalez G, et al. (1994). "Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3". Hum. Mol. Genet. 3 (1): 39–44. doi:10.1093/hmg/3.1.39. PMID 8162050. 
• Villard L, Gecz J, Mattéi JF, et al. (1996). "XNP mutation in a large family with Juberg-Marsidi syndrome". Nat. Genet. 12 (4): 359–60. doi:10.1038/ng0496-359. PMID 8630485. 
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
• Picketts DJ, Higgs DR, Bachoo S, et al. (1997). "ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome". Hum. Mol. Genet. 5 (12): 1899–907. doi:10.1093/hmg/5.12.1899. PMID 8968741. 
• Villard L, Lacombe D, Fontés M (1997). "A point mutation in the XNP gene, associated with an ATR-X phenotype without alpha-thalassemia". Eur. J. Hum. Genet. 4 (6): 316–20. PMID 9043863. 
• Villard L, Lossi AM, Cardoso C, et al. (1997). "Determination of the genomic structure of the XNP/ATRX gene encoding a potential zinc finger helicase". Genomics 43 (2): 149–55. doi:10.1006/geno.1997.4793. PMID 9244431. 
• Golub EI, Kovalenko OV, Gupta RC, et al. (1997). "Interaction of human recombination proteins Rad51 and Rad54". Nucleic Acids Res. 25 (20): 4106–10. doi:10.1093/nar/25.20.4106. PMC 147015. PMID 9321665. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=147015. 
• Gibbons RJ, Bachoo S, Picketts DJ, et al. (1997). "Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain". Nat. Genet. 17 (2): 146–8. doi:10.1038/ng1097-146. PMID 9326931. 
• Cardoso C, Timsit S, Villard L, et al. (1998). "Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein". Hum. Mol. Genet. 7 (4): 679–84. doi:10.1093/hmg/7.4.679. PMID 9499421. 
• Bérubé NG, Mangelsdorf M, Jagla Met al. (2005). "The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis". J. Clin. Invest. 115 (2): 258–267. doi:10.1172/JCI200522329. PMC 544602. PMID 15668733. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=544602. 

External Links

• GeneReviews/NCBI/NIH/UW entry on Alpha-Thalassemia X-Linked Mental Retardation Syndrome; ATRX Syndrome; Alpha Thalassemia/Mental Retardation, X-Linked; XLMR-Hypotonic Face Syndrome
• OMIM entries on Alpha-Thalassemia X-Linked Mental Retardation Syndrome