3.A.3.8.13
P4 phospholipid (phosphatidyl serine)-transporting ATPase 8A1 (EC 3.6.3.1) (ATPase class I type 8A member 1) (Chromaffin granule ATPase II).  Also found in the liver canicular membrane (Chaubey et al. 2016). The 3-D strcutures of 6 distinct intermediates (2.6 - 3.3 Å resolution) of the complex of this protein with CDC50A (TC# 8.A.27.1.5) have been solved, revealing the transport cycle for lipid flipping (Hiraizumi et al. 2019). ATP-dependent phosphorylation induces a large rotational movement of the actuator domain around the phosphorylation site in the phosphorylation domain, accompanied by lateral shifts of the first and second TMSs, thereby allowing phosphatidylserine binding. The phospholipid head group passes through the hydrophilic cleft, while the acyl chain is exposed toward the lipid environment (Hiraizumi et al. 2019). The phospholipid binds to ATP8A1-CDC50 at an early stage when ATP8A1-CDC50 changes from E2P to E2Pi-PL state (Zhang et al. 2023). TMEM30A is an essential subunit of P4-ATPase phospholipid flippases (Li et al. 2023). Distinct domains in Ndc1 mediate its interaction with the Nup84 complex and the nuclear membrane (Amm et al. 2023). Ndc1 functions in NPC assembly at the fused inner and outer nuclear membranes. A direct interaction of Ndc1's transmembrane domain with Nup120 and Nup133, members of the pore membrane coating Y-complex. An amphipathic helix in Ndc1's C-terminal domain binds highly curved liposomes. Ndc1's amphipathic motif functionally interacts with related motifs in the C-terminus of the nucleoporins Nup53 and Nup59, important for pore membrane binding and interconnecting NPC modules. The essential function of Ndc1 can be suppressed by deleting the amphipathic helix from Nup53 (Amm et al. 2023). It is a possible drug target for pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors (Vit et al. 2023).