Fig 1.

Mutations of Trr and MLL3/4. Amino acid alignment of Trr, MLL3, and MLL4 was generated using CLC Sequence Viewer 6. Known protein domains are indicated. Sequence conservation between Trr, MLL3, and MLL4 is shown beneath the alignment. Yellow represents highly conserved regions, whereas blue indicates regions of poor sequence conservation between the 3 related proteins. Reported nonsense mutations of Trr, including those reported by Kanda et al. (25), are shown. Missense mutations of MLL3 and MLL4 were obtained from the Catalogue of Somatic Mutations in Cancer (COSMIC) database (http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/) (35). Note that the COSMIC website reports sites of MLL4 mutations relative to an alternatively spliced transcript encoding a shortened 5,268-amino-acid protein. In the figure presented here, these positions were adjusted to match the 5,537-amino-acid protein that is most commonly reported in the literature.