Alignment of Catalytic Region of Myotubularin Domain Sequences. Human myotubularin sequences were obtained from the literature and database keyword searches. For the other species represented, candidate myotubularin sequences were obtained by either utilizing BLASTP at NCBI  or searching the protein datasets of fully sequenced eukaryotic genomes, as detailed in Methods. The contiguous sequence encompassing the PH-GRAM domain and the myotubularin phosphatase domain was identified as detailed in Methods, and multiple alignment was performed as detailed in Methods. Sequences are presented in the general order of taxonomic groups specified in Figure 1, with the exception that Choanoflagellate/Metazoan sequences are grouped according to phylogenetic classification as in Table 2. Non-human sequences in the alignment are generally designated by an organism prefix followed by numerals. This Figure presents the portion of the alignment around the catalytic loop region. The full alignment is presented as Additional File 1. At the top of the alignment, in the line designated "SS", is depicted the secondary structure of the solved structure of human MTMR2 (PDB:1LW3). "H" indicates alpha helix, "C" indicates random coil, "E" indicates beta strand. Above the alignment a blue bar (positions 1380 - 1389) indicates the location of the catalytic motif of the myotubularin phosphatase domain (HCSDGWDR for active subunits). The sequences for all myotubularin homologues, along with their database accession numbers, and designations used in this Figure, are presented in Additional File 5. The URLs for all web sites used to obtain organism specific databases, plus original literature citations, are presented in Additional File 4.