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Figure 5. BPPS-SIPRIS analysis of synaptojanin/EEP domains within INPP5 proteins. ; Color code: EEP-residues, yellow sidechains; INPP5 residues, red sidechains; INPP5B-, INPP5E- and SHIP2-subfamily residues, orange sidechains; ligands, cyan; atoms involved in hydrogen bonds, CPK coloring. (A). Human INPP5B in complex with phosphatidylinositol 3,4-bisphosphate (pdb: 4cml) (Trésaugues et al., 2014), which is associated with cytosolic and mitochondrial membranes (Speed et al., 1995). BPPS-SIPRIS results: EEP spherical cluster, p=5.8 × 10−13; INPP5 spherical cluster, p=3.9 × 10−7; INPP5B spherical cluster, p=0.0021. (B). INPP5 hydrogen bond network within human INPP5B (pdb: 3mtc) (unpublished). (C). View of INPP5-residues (in 3mtc) that bind the 4-phosphate group required for substrate recognition. (D). Human INPP5B with phosphate bound to a possible membrane interaction or allosteric site (Mills et al., 2016). (E). Human INPP5B Ocrl with glycerol bound to the same site as indicated in (D) (Trésaugues et al., 2014). (F). INPP5 subgroups within the BPPS-defined hierarchy. (G). Human INPP5E (pdb: 2xsw) (unpublished), which is associated with the primary cilium, an organelle involved in signal transduction (Jacoby et al., 2009) (spherical cluster, p=3.6 × 10−4). (H). Human SHIP2 (pdb: 4a9c) (Mills et al., 2012), which is associated with membrane ruffle formation (Hasegawa et al., 2011) (spherical cluster, p=0.30). The following source data are available for Figure 5.

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