Alignment of Zebrafish, Xenopus, Murine, and Human FOXH1 Proteins
Identical residues are shown in blue, and similar residues are shown in yellow. Considerable sequence identity is seen in known functional domains, including the DNA-binding forkhead domain and the SMAD interaction domain. The SMAD interaction domain contains three motifs: FM1, FM2, and the core Smad-interaction motif (SIM). 31,32 Note that the extreme C terminus after the SIM is poorly conserved, but it contains a significant fraction of detectable variations of both patients and controls. Most of these variants are inadequately studied to draw definitive conclusions (scored as blue and, therefore, do not contribute to the tabulations in Table 1). Mutations are annotated by amino acid position and colored as in previous figures (red, less than 50%; orange, 50%–99%; blue, not adequately tested; black, normal activity; frameshift, blue or black with no fill).