Supplementary Figure 2: Sequence alignment of Sky1–353 with the TBC domain of human TBC1D24 and representative RabGAP proteins for which the crystal structure has been reported.
From: Skywalker-TBC1D24 has a lipid-binding pocket mutated in epilepsy and required for synaptic function
The residues corresponding to the arginine and glutamine fingers in conventional TBC Rab-GAP proteins are highlighted in green. The residues corresponding to the cationic pocket residues in Sky are highlighted in blue. Residues corresponding to patient mutations are red, with those located in the cationic pocket additionally indicated by a red star. The α-helices determined from the Sky1-353 structure are indicated above the alignment, with the numbering corresponding to the numbering used in the Gyp1 structure. The sequences used are human TBC1D24 (UniProt: Q9ULP9), Gyp1 from Saccharomyces cerevisiae (UniProt: Q08484), human TBC1D1 (UniProt: Q86TI0), human TBC1D4 (Uniprot: O60343), human TBC1D7 (UniProt: Q9P0N9), human TBC1D11 (UniProt: Q9Y3P9), human TBC1D14 (UniProt: Q9P2M4), human TBC1D18 (UniProt: Q5R372), human TBC1D20 (UniProt: Q96BZ9), human TBC1D22A (UniProt: Q8WUA7), human TBC1D22B (UniProt: Q9NU19), CrfRabGAP from Chlamydomonas reinhardtii (UniProt: A8JCA4).
