title: FXY2/MID2, a gene related to the X-linked Opitz syndrome gene FXY/MID1, maps to Xq22 and encodes a FNIII domain-containing protein that associates with microtubules.
abstract: Opitz G/BBB syndrome (OS) is a genetically heterogeneous disorder with an X-linked locus and an autosomal locus linked to 22q11.2. OS affects multiple organ systems with often variable severity even between siblings. The clinical features, which include hypertelorism, cleft lip and palate, defects of cardiac septation, hypospadias, and anorectal anomalies, indicate an underlying disturbance of the developing ventral midline of the embryo. The gene responsible for X-linked OS, FXY/MID1, is located on the short arm of the human X chromosome within Xp22.3 and encodes a protein with both an RBCC (RING finger, B-box, coiled coil) and a B30.2 domain. The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species. Here we describe a gene closely related to FXY/MID1, called FXY2, which also maps to the X chromosome within Xq22. The mouse Fxy2 gene is located on the distal part of the mouse X chromosome within a region syntenic to Xq22. Analysis of genes flanking both FXY/MID1 and FXY2 (as well as their counterparts in mouse) suggests that these regions may have arisen as a result of an intrachromosomal duplication on an ancestral X chromosome. We have also identified in both FXY2 and FXY/MID1 proteins a conserved fibronectin type III domain located between the RBCC and B30.2 domains that has implications for understanding protein function. The FXY/MID1 protein has previously been shown to colocalize with microtubules, and here we show that the FXY2 protein similarly associates with microtubules in a manner that is dependent on the carboxy-terminal B30.2 domain.
authors.affiliation: Section of Gene Function and Regulation, Chester Beatty Laboratories, The Institute of Cancer Research, Fulham Road, London, SW3 6JB, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Perry
authors.forename: K M
authors.initials: KM
authors.lastname: Short
authors.forename: J T
authors.initials: JT
authors.lastname: Romer
authors.forename: S
authors.initials: S
authors.lastname: Swift
authors.forename: T C
authors.initials: TC
authors.lastname: Cox
authors.forename: A
authors.initials: A
authors.lastname: Ashworth
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D015870:Gene Expression; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009928:Organ Specificity; D017434:Protein Structure, Tertiary / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D014960:X Chromosome / Q000235:genetics*
chemical_list: C121118:MID2 protein, human; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases