The reference OMIM entry for this protein is 300032

Atr-x gene; atrx
Helicase 2, x-linked; xh2
X-linked nuclear protein gene; xnp

CLONING

Stayton et al. (1994) described the cloning and characterization of a gene, provisionally called X-linked helicase-2 (XH2), located on chromosome Xq13. The gene undergoes X inactivation, contains a 4-kb open reading frame, and encodes a putative NTP-binding nuclear protein homologous to several members of the helicase II superfamily. In situ hybridization studies in the mouse revealed precocious, widespread expression of the murine homolog of XH2 at early stages of embryogenesis, and more restricted expression during late developmental stages and at birth. XH2 shares 6 conserved, collinear domains with other members of the family of proven and putative helicases. In particular, the XH2 protein shows homology with RAD54. Type II helicases have been implicated in nucleotide excision repair and initiation of transcription. Picketts et al. (1996) established the full-length sequence of the ATRX cDNA and predicted the structure of the ATRX protein. Their comparative analysis showed that ATRX is a member of the SNF2-like subgroup of a superfamily of proteins with similar ATPase and helicase domains (see 300012). The N-terminal region contains a nuclear localization signal and antibody studies indicated a nuclear localization of the protein. The C-terminal region is glutamine rich, a common attribute of other transcription factors. In addition, a 15-amino acid segment (the P element) in the C-terminal region shows 35 to 50% similarity to SNF2-like proteins which are involved in gene expression. Villard et al. (1997) determined that the ATRX gene encodes a predicted protein of 2,492 amino acids. Three zinc finger motifs were found within the 5-prime end of the gene. Expression analysis in different tissues identified an alternative splicing event that involves exon 6. One of these alternatively spliced transcripts is expressed predominantly in embryonic tissues. Gibbons et al. (1998) used the N-terminal sequence of ATRX, as identified by Picketts et al. (1996), to identify a cysteine-rich motif, similar to a putative zinc finger domain (cys4-his-cys3), called the PHD finger. PHD motifs span 50 to 80 amino acids and had been identified in more than 40 proteins, many of which are implicated in chromatin-mediated transcriptional control. Picketts et al. (1998) showed that the mouse Atrx gene shows structural features similar to those of the human gene. Two highly conserved and functionally important regions were identified: a potential finger domain at the N terminus and a catalytic domain at the C terminus. Gibbons and Higgs (2000) stated that the XH2 gene encodes at least 2 alternatively spliced mRNA transcripts that differ at the 5-prime ends and give rise to slightly different proteins of 265 and 280 kD, respectively.

GENE STRUCTURE

Stayton et al. (1994) determined that the genomic length of XH2 is more than 220 kb. Picketts et al. (1996) determined that the XH2 gene contains 36 exons and spans approximately 300 kb. Using a vectorette strategy, Villard et al. (1997) identified and sequenced the intron/exon boundaries of the ATRX gene.

MAPPING

Stayton et al. (1994) mapped the XH2 gene to chromosome Xq13, between the gene for Menkes disease (MNK; 309400) and DXS56. They showed that the murine homolog maps to the homologous genetic interval between Pgk1 and Xist.

GENE FUNCTION

Gibbons et al. (1995) showed that mutations in the XH2 gene cause the alpha-thalassemia/mental retardation syndrome (ATR ... More on the omim web site

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May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300032 was added.