PT  - JOURNAL ARTICLE
AU  - Kuanxiang Sun
AU  - Wanli Tian
AU  - Wenjing Liu
AU  - Yeming Yang
AU  - Xianjun Zhu
TI  - Disease mutation study identifies essential residues for phosphatidylserine flippase ATP11A
AID  - 10.1101/2020.01.13.904045
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.13.904045
4099  - http://biorxiv.org/content/early/2020/01/13/2020.01.13.904045.short
4100  - http://biorxiv.org/content/early/2020/01/13/2020.01.13.904045.full
AB  - PS flippase (P4-ATPase) transports PS from the outer to the inner leaflet of the lipid bilayer in the membrane to maintain PS asymmetry, which is important for biological activity of the cell. ATP11A is expressed in multiple tissues and plays a role in myotube formation. However, detailed cellular function of ATP11A remains elusive. Mutation analysis revealed that I91, L308 and E897 residues in ATP8A2 are important for flippase activity. In order to investigate the roles of these corresponding amino acid residues in ATP11A, we assessed the expression and flippase activity of the respective ATP11A mutant proteins. ATP11A mainly localizes to the Golgi when co-expressed with TMEM30A, the β-subunit of the complex. Y300F and D913K mutations affect correct Golgi localization and PS stimulated flippase activity. In addition, Y300F mutation causes reduced ATP11A expression. Our data provides insight into essential residues for expression and flippase activity of ATP11A.