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. 2017 Nov 28;9(8):8165–8178. doi: 10.18632/oncotarget.22742

Figure 1. FOXC1 schematic structure and FOXC1 missense mutations.

Figure 1

FOXC1 protein contains two activation domains (AD) that are located at the N-terminus 1-51 aa, and the C-terminus 435-553 aa, both of which play a main role in FOXC1 activation. Engineered FOXC1 proteins that lack either the N- or/and C- terminus have reduce activity and improper functions. FOXC1 protein localizes to the cell nucleus via two nuclear localization sequences (NLS), and binds to DNA via the forkhead domain (FHD) 73-176 aa. To date 28 point mutations have been identified in the FHD of FOXC1, most of which are linked to ocular defects and malformations. Deletion of the inhibitory domain (ID) 435-533 aa.significantly increases FOXC1 activity. In contrast to the two ADs that activate FOXC1, specific residues in the ID experience post-translational phosphorylation and as a result inhibit FOXC1function.