ATRX

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
External IDs	MGI: 103067 HomoloGene: 416 GeneCards: ATRX
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 Cellular component • telomeric heterochromatin • PML body • nuclear subtelomeric heterochromatin • SWI/SNF superfamily-type complex • pericentric heterochromatin • chromosome • nuclear heterochromatin • heterochromatin • nuclear chromosome • chromosome, telomeric region • nuclear chromosome, telomeric region • nucleus 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 • DNA replication-independent nucleosome assembly • forebrain development • DNA repair • cellular response to hydroxyurea • positive regulation of transcription from RNA polymerase II promoter • DNA duplex unwinding • regulation of histone H3-K9 trimethylation • covalent chromatin modification 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_000480.3 NP_612114.2	NP_033556.2
Location (UCSC)	Chr X: 77.5 – 77.79 Mb	Chr X: 105.8 – 105.93 Mb
PubMed search	[1]	[2]
Wikidata

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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.^[3][4][5]

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.^[5]

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.^[5]

Interactions

ATRX has been shown to interact with EZH2.^[6]

See also

• Alpha-thalassemia mental retardation syndrome

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Stayton CL, Dabovic B, Gulisano M, Gecz J, Broccoli V, Giovanazzi S, Bossolasco M, Monaco L, Rastan S, Boncinelli E (April 1995). "Cloning and characterization of a new human Xq13 gene, encoding a putative helicase". Hum Mol Genet. 3 (11): 1957–64. doi:10.1093/hmg/3.11.1957. PMID 7874112.
4. Gibbons RJ, Suthers GK, Wilkie AO, Buckle VJ, Higgs DR (November 1992). "X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis". Am J Hum Genet. 51 (5): 1136–49. PMC 1682840. PMID 1415255.
5. "Entrez Gene: ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae)".
6. Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L (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.

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, Woodroffe P, Mulley JC (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.
• 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, Keats BJ, Morton NE (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, Villard L, Stayton C, Millasseau P, Khrestchatisky M, Fontes M (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, Fontés M, Saugier-Veber P, Munnich A, Lyonnet S (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, Blake DJ, Quarrell OW, Gibbons RJ (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, Proud V, Chiaroni P, Colleaux L, Schwartz C, Fontés M (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, Ward DC, Radding CM (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.
• Gibbons RJ, Bachoo S, Picketts DJ, Aftimos S, Asenbauer B, Bergoffen J, Berry SA, Dahl N, Fryer A, Keppler K, Kurosawa K, Levin ML, Masuno M, Neri G, Pierpont ME, Slaney SF, Higgs DR (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, Khrestchatisky M, Fontès M, Colleaux L (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 M, Vanderluit J, Garrick D, Gibbons RJ, Higgs DR, Slack RS, Picketts DJ (2005). "The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis". J. Clin. Invest. 115 (2): 258–267. doi:10.1172/JCI22329. PMC 544602. PMID 15668733.

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