9qm9

Structural highlights

Function

PP4P1_HUMAN Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P) (PubMed:16365287). Does not hydrolyze phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-bisphosphate, inositol 3,5-bisphosphate, inositol 3,4-bisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3-monophosphate (PubMed:16365287). Regulates lysosomal positioning by recruiting JIP4 to lysosomal membranes, thus inducing retrograde transport of lysosomes along microtubules (PubMed:29146937). Contributes to assembly of the V-ATPase complex in lipid rafts of the lysosomal membrane and to subsequent amino acid-dependent activation of mTORC1 (PubMed:29644770). May play a role in the regulation of cellular cholesterol metabolism (PubMed:25035345).^{[1] [2] [3] [4]}

References

1. ↑ Ungewickell A, Hugge C, Kisseleva M, Chang SC, Zou J, Feng Y, Galyov EE, Wilson M, Majerus PW. The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18854-9. PMID:16365287 doi:10.1073/pnas.0509740102
2. ↑ Medina MW, Bauzon F, Naidoo D, Theusch E, Stevens K, Schilde J, Schubert C, Mangravite LM, Rudel LL, Temel RE, Runz H, Krauss RM. Transmembrane protein 55B is a novel regulator of cellular cholesterol metabolism. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1917-23. PMID:25035345 doi:10.1161/ATVBAHA.113.302806
3. ↑ Willett R, Martina JA, Zewe JP, Wills R, Hammond GRV, Puertollano R. TFEB regulates lysosomal positioning by modulating TMEM55B expression and JIP4 recruitment to lysosomes. Nat Commun. 2017 Nov 17;8(1):1580. PMID:29146937 doi:10.1038/s41467-017-01871-z
4. ↑ Hashimoto Y, Shirane M, Nakayama KI. TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1 activation. Genes Cells. 2018 Jun;23(6):418-434. PMID:29644770 doi:10.1111/gtc.12583