Gene Symbol: Drs2p
Description: aminophospholipid-translocating P4-type ATPase DRS2
Alias: FUN38, SWA3, aminophospholipid-translocating P4-type ATPase DRS2
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Baldridge R, Xu P, Graham T. Type IV P-type ATPases distinguish mono- versus diacyl phosphatidylserine using a cytofacial exit gate in the membrane domain. J Biol Chem. 2013;288:19516-27 pubmed publisher
    ..These studies indicate that Dnf1 poorly recognizes diacylated phospholipid and define key substitutions enabling recognition of endogenous PS. ..
  2. Hanamatsu H, Fujimura Kamada K, Yamamoto T, Furuta N, Tanaka K. Interaction of the phospholipid flippase Drs2p with the F-box protein Rcy1p plays an important role in early endosome to trans-Golgi network vesicle transport in yeast. J Biochem. 2014;155:51-62 pubmed publisher
    ..The type 4 P-type ATPases are phospholipid flippases that generate such membrane phospholipid asymmetry. Drs2p, a flippase in budding yeast, is involved in the endocytic recycling pathway...
  3. Zhou X, Graham T. Reconstitution of phospholipid translocase activity with purified Drs2p, a type-IV P-type ATPase from budding yeast. Proc Natl Acad Sci U S A. 2009;106:16586-91 pubmed publisher
    ..In addition, the activity of Drs2p, a P4-ATPase from Saccharomyces cerevisiae, is required for vesicle-mediated protein transport from the Golgi and ..
  4. Furuta N, Fujimura Kamada K, Saito K, Yamamoto T, Tanaka K. Endocytic recycling in yeast is regulated by putative phospholipid translocases and the Ypt31p/32p-Rcy1p pathway. Mol Biol Cell. 2007;18:295-312 pubmed
    ..The homologous proteins Cdc50p, Lem3p, and Crf1p are potential noncatalytic subunits of Drs2p, Dnf1p and Dnf2p, and Dnf3p, respectively; these putative heteromeric PLTs share an essential function for cell ..
  5. Pomorski T, Lombardi R, Riezman H, Devaux P, van Meer G, Holthuis J. Drs2p-related P-type ATPases Dnf1p and Dnf2p are required for phospholipid translocation across the yeast plasma membrane and serve a role in endocytosis. Mol Biol Cell. 2003;14:1240-54 pubmed
    ..Phosphatidylethanolamine exposure by Deltadnf1Deltadnf2 cells further increased upon removal of Drs2p, an ATPase II homolog in the yeast Golgi...
  6. Zhou X, Sebastian T, Graham T. Auto-inhibition of Drs2p, a yeast phospholipid flippase, by its carboxyl-terminal tail. J Biol Chem. 2013;288:31807-15 pubmed publisher
    b>Drs2p, a yeast type IV P-type ATPase (P4-ATPase), or flippase, couples ATP hydrolysis to phosphatidylserine translocation and the establishment of membrane asymmetry...
  7. Lenoir G, Williamson P, Puts C, Holthuis J. Cdc50p plays a vital role in the ATPase reaction cycle of the putative aminophospholipid transporter Drs2p. J Biol Chem. 2009;284:17956-67 pubmed publisher
    ..Here, we show that the affinity of yeast P(4)-ATPase Drs2p for its Cdc50-binding partner fluctuates during the transport cycle, with the strongest interaction occurring at a ..
  8. Hua Z, Fatheddin P, Graham T. An essential subfamily of Drs2p-related P-type ATPases is required for protein trafficking between Golgi complex and endosomal/vacuolar system. Mol Biol Cell. 2002;13:3162-77 pubmed
    ..We have previously implicated Drs2p in clathrin function at the trans-Golgi network...
  9. Takahashi Y, Fujimura Kamada K, Kondo S, Tanaka K. Isolation and characterization of novel mutations in CDC50, the non-catalytic subunit of the Drs2p phospholipid flippase. J Biochem. 2011;149:423-32 pubmed publisher
    ..previously showed that a conserved membrane protein, Cdc50p, is required for the endoplasmic reticulum exit of the Drs2p flippase in yeast...

More Information


  1. Alder Baerens N, Lisman Q, Luong L, Pomorski T, Holthuis J. Loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles. Mol Biol Cell. 2006;17:1632-42 pubmed
    ..This activity is independent of Dnf1p and Dnf2p but requires two other P4 ATPases, Drs2p and Dnf3p, that reside primarily in the trans-Golgi network...
  2. Baldridge R, Graham T. Identification of residues defining phospholipid flippase substrate specificity of type IV P-type ATPases. Proc Natl Acad Sci U S A. 2012;109:E290-8 pubmed publisher
    ..Modeling of residues involved in substrate selection suggests a novel P-type ATPase transport pathway at the protein/lipid interface and a potential solution to the giant substrate problem. ..
  3. Ripmaster T, Vaughn G, Woolford J. DRS1 to DRS7, novel genes required for ribosome assembly and function in Saccharomyces cerevisiae. Mol Cell Biol. 1993;13:7901-12 pubmed
    ..Identification of gene products affecting ribosome assembly and function among the DNAs complementing the drs mutations validates the feasibility of this approach. ..
  4. Takeda M, Yamagami K, Tanaka K. Role of phosphatidylserine in phospholipid flippase-mediated vesicle transport in Saccharomyces cerevisiae. Eukaryot Cell. 2014;13:363-75 pubmed publisher
    ..The genome of budding yeast encodes four heteromeric flippases (Drs2p, Dnf1p, Dnf2p, and Dnf3p), which associate with the Cdc50 family noncatalytic subunit, and one monomeric flippase ..
  5. Chen S, Wang J, Muthusamy B, Liu K, Zare S, Andersen R, et al. Roles for the Drs2p-Cdc50p complex in protein transport and phosphatidylserine asymmetry of the yeast plasma membrane. Traffic. 2006;7:1503-17 pubmed
    b>Drs2p, a P-type adenosine triphosphatase required for a phosphatidylserine (PS) flippase activity in the yeast trans Golgi network (TGN), was first implicated in protein trafficking by a screen for mutations synthetically lethal with ..
  6. Liu K, Hua Z, Nepute J, Graham T. Yeast P4-ATPases Drs2p and Dnf1p are essential cargos of the NPFXD/Sla1p endocytic pathway. Mol Biol Cell. 2007;18:487-500 pubmed
    b>Drs2p family P-type ATPases (P4-ATPases) are required in multiple vesicle-mediated protein transport steps and are proposed to be phospholipid translocases (flippases)...
  7. Liu K, Surendhran K, Nothwehr S, Graham T. P4-ATPase requirement for AP-1/clathrin function in protein transport from the trans-Golgi network and early endosomes. Mol Biol Cell. 2008;19:3526-35 pubmed publisher
    b>Drs2p is a resident type 4 P-type ATPase (P4-ATPase) and potential phospholipid translocase of the trans-Golgi network (TGN) where it has been implicated in clathrin function...
  8. Sakane H, Yamamoto T, Tanaka K. The functional relationship between the Cdc50p-Drs2p putative aminophospholipid translocase and the Arf GAP Gcs1p in vesicle formation in the retrieval pathway from yeast early endosomes to the TGN. Cell Struct Funct. 2006;31:87-108 pubmed
    b>Drs2p, the catalytic subunit of the Cdc50p-Drs2p putative aminophospholipid translocase, has been implicated in conjunction with the Arf1 signaling pathway in the formation of clathrin-coated vesicles (CCVs) from the TGN...
  9. Tang X, Halleck M, Schlegel R, Williamson P. A subfamily of P-type ATPases with aminophospholipid transporting activity. Science. 1996;272:1495-7 pubmed
    ..Studies in Saccharomyces cerevisiae suggest that aminophospholipid translocation is a general function of members of this family. ..
  10. Jacquot A, Montigny C, Hennrich H, Barry R, le Maire M, Jaxel C, et al. Phosphatidylserine stimulation of Drs2p·Cdc50p lipid translocase dephosphorylation is controlled by phosphatidylinositol-4-phosphate. J Biol Chem. 2012;287:13249-61 pubmed publisher
    Here, Drs2p, a yeast lipid translocase that belongs to the family of P(4)-type ATPases, was overexpressed in the yeast Saccharomyces cerevisiae together with Cdc50p, its glycosylated partner, as a result of the design of a novel co-..
  11. Chen C, Ingram M, Rosal P, Graham T. Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. J Cell Biol. 1999;147:1223-36 pubmed
    ..Subcellular fractionation and immunofluorescence analysis indicate that Drs2p localizes to late Golgi membranes containing Kex2p...
  12. Natarajan P, Wang J, Hua Z, Graham T. Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and relationship to in vivo function. Proc Natl Acad Sci U S A. 2004;101:10614-9 pubmed
    ..The identities of APLTs remain unknown, although candidate proteins include the Drs2p/ATPase II subfamily of P-type ATPases...
  13. Muthusamy B, Raychaudhuri S, Natarajan P, Abe F, Liu K, Prinz W, et al. Control of protein and sterol trafficking by antagonistic activities of a type IV P-type ATPase and oxysterol binding protein homologue. Mol Biol Cell. 2009;20:2920-31 pubmed publisher
    ..defect of drs2Delta, which correlates with an enhanced ability of Dnf P4-ATPases to functionally substitute for Drs2p. Loss of Kes1p also suppresses a drs2-ts allele in a strain deficient for Dnf P4-ATPases, suggesting that Kes1p ..
  14. Natarajan P, Liu K, Patil D, Sciorra V, Jackson C, Graham T. Regulation of a Golgi flippase by phosphoinositides and an ArfGEF. Nat Cell Biol. 2009;11:1421-6 pubmed publisher
    ..However, the identity of downstream effectors of PtdIns(4)P in this system has been elusive. Here, we show that Drs2p, a type IV P-type ATPase required for phospholipid translocase (flippase) activity and transport vesicle budding ..
  15. Saito K, Fujimura Kamada K, Furuta N, Kato U, Umeda M, Tanaka K. Cdc50p, a protein required for polarized growth, associates with the Drs2p P-type ATPase implicated in phospholipid translocation in Saccharomyces cerevisiae. Mol Biol Cell. 2004;15:3418-32 pubmed
    ..Both Cdc50p and Drs2p were localized to the trans-Golgi network and late endosome...
  16. Chantalat S, Park S, Hua Z, Liu K, Gobin R, Peyroche A, et al. The Arf activator Gea2p and the P-type ATPase Drs2p interact at the Golgi in Saccharomyces cerevisiae. J Cell Sci. 2004;117:711-22 pubmed
    ..This process is highly conserved at the morphological level from yeast to mammalian cells. Drs2p, a multi-span transmembrane domain protein and putative aminophospholipid translocase, is required for the ..
  17. Gall W, Geething N, Hua Z, Ingram M, Liu K, Chen S, et al. Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo. Curr Biol. 2002;12:1623-7 pubmed
    ..b>Drs2p/Swa3p is a P-type ATPase and a potential aminophospholipid translocase that localizes to the trans-Golgi network (..
  18. Kishimoto T, Yamamoto T, Tanaka K. Defects in structural integrity of ergosterol and the Cdc50p-Drs2p putative phospholipid translocase cause accumulation of endocytic membranes, onto which actin patches are assembled in yeast. Mol Biol Cell. 2005;16:5592-609 pubmed
    ..Cdc50p, a membrane protein in the endosomal/trans-Golgi network compartments, is a noncatalytic subunit of Drs2p, which is implicated in translocation of phospholipids across lipid bilayers...
  19. Yamamoto T, Fujimura Kamada K, Shioji E, Suzuki R, Tanaka K. Cfs1p, a Novel Membrane Protein in the PQ-Loop Family, Is Involved in Phospholipid Flippase Functions in Yeast. G3 (Bethesda). 2017;7:179-192 pubmed publisher
    ..The budding yeast Saccharomyces cerevisiae has four heteromeric flippases (Drs2p, Dnf1p, Dnf2p, and Dnf3p), associated with the Cdc50p family noncatalytic subunit, and one monomeric flippase, ..
  20. Puts C, Panatala R, Hennrich H, Tsareva A, Williamson P, Holthuis J. Mapping functional interactions in a heterodimeric phospholipid pump. J Biol Chem. 2012;287:30529-40 pubmed publisher
    ..Collectively, our data indicate that a dynamic association between subunit and transporter is crucial for the transport reaction cycle of the heterodimer. ..
  21. Xu P, Baldridge R, Chi R, Burd C, Graham T. Phosphatidylserine flipping enhances membrane curvature and negative charge required for vesicular transport. J Cell Biol. 2013;202:875-86 pubmed publisher
  22. Thomas L, Fromme J. GTPase cross talk regulates TRAPPII activation of Rab11 homologues during vesicle biogenesis. J Cell Biol. 2016;215:499-513 pubmed
    ..By coordinating simultaneous activation of two essential GTPase pathways, this mechanism ensures recruitment of the complete set of effectors needed for vesicle formation, transport, and tethering. ..
  23. Tsai P, Hsu J, Liu Y, Chen K, Lee F. Arl1p regulates spatial membrane organization at the trans-Golgi network through interaction with Arf-GEF Gea2p and flippase Drs2p. Proc Natl Acad Sci U S A. 2013;110:E668-77 pubmed publisher
    ..factor (GEF) Gea2p has been shown to bind to and stimulate the activity of the flippase Drs2p. Here, we provide evidence for the interaction and activation of Drs2p by Arf-like protein Arl1p in yeast...
  24. Sartorel E, Barrey E, Lau R, Thorner J. Plasma membrane aminoglycerolipid flippase function is required for signaling competence in the yeast mating pheromone response pathway. Mol Biol Cell. 2015;26:134-50 pubmed publisher
    ..Thus proper remodeling of plasma membrane aminoglycerolipids and phosphoinositides is necessary for efficient recruitment, stability, and function of the pheromone signaling apparatus. ..
  25. Puts C, Lenoir G, Krijgsveld J, Williamson P, Holthuis J. A P4-ATPase protein interaction network reveals a link between aminophospholipid transport and phosphoinositide metabolism. J Proteome Res. 2010;9:833-42 pubmed publisher
    ..We applied this method to identify binding partners of the yeast Golgi P(4)-ATPase Drs2p, a member of a conserved family of putative aminophospholipid transporters...
  26. Hsu J, Chen Z, Liu Y, Lee F. Mechanism of action of the flippase Drs2p in modulating GTP hydrolysis of Arl1p. J Cell Sci. 2014;127:2615-20 pubmed publisher
    ..Here, we demonstrate that another Arl1p effector, the lipid flippase Drs2p, is required for Gcs1p-stimulated inactivation of Arl1p...
  27. Azouaoui H, Montigny C, Dieudonné T, Champeil P, Jacquot A, Vázquez Ibar J, et al. High phosphatidylinositol 4-phosphate (PI4P)-dependent ATPase activity for the Drs2p-Cdc50p flippase after removal of its N- and C-terminal extensions. J Biol Chem. 2017;292:7954-7970 pubmed publisher
    ..to investigate the role of the N and C termini in ATP hydrolysis and auto-inhibition of the yeast flippase Drs2p-Cdc50p...
  28. Azouaoui H, Montigny C, Ash M, Fijalkowski F, Jacquot A, Grønberg C, et al. A high-yield co-expression system for the purification of an intact Drs2p-Cdc50p lipid flippase complex, critically dependent on and stabilized by phosphatidylinositol-4-phosphate. PLoS ONE. 2014;9:e112176 pubmed publisher
    ..In this report, we present a procedure for high-yield co-expression of a yeast flippase, the Drs2p-Cdc50p complex...
  29. Hua Z, Graham T. Requirement for neo1p in retrograde transport from the Golgi complex to the endoplasmic reticulum. Mol Biol Cell. 2003;14:4971-83 pubmed
    ..cerevisiae is an essential P-type ATPase and potential aminophospholipid translocase (flippase) in the Drs2p family...
  30. Azouaoui H, Montigny C, Jacquot A, Barry R, Champeil P, Lenoir G. Coordinated Overexpression in Yeast of a P4-ATPase and Its Associated Cdc50 Subunit: The Case of the Drs2p/Cdc50p Lipid Flippase Complex. Methods Mol Biol. 2016;1377:37-55 pubmed publisher
    ..Here, we describe the overexpression of a yeast lipid flippase complex, namely the P4-ATPase Drs2p and its associated subunit Cdc50p, in a coordinated manner...
  31. Kinzy T, Ripmaster T, Woolford J. Multiple genes encode the translation elongation factor EF-1 gamma in Saccharomyces cerevisiae. Nucleic Acids Res. 1994;22:2703-7 pubmed
    ..Low-stringency genomic Southern hybridization analysis indicates there may be additional yeast genes related to TEF3 and TEF4. ..
  32. Takar M, Wu Y, Graham T. The Essential Neo1 Protein from Budding Yeast Plays a Role in Establishing Aminophospholipid Asymmetry of the Plasma Membrane. J Biol Chem. 2016;291:15727-39 pubmed publisher
    ..These results indicate that Neo1 plays an important role in establishing PS and PE plasma membrane asymmetry in budding yeast. ..
  33. Hankins H, Sere Y, Diab N, Menon A, Graham T. Phosphatidylserine translocation at the yeast trans-Golgi network regulates protein sorting into exocytic vesicles. Mol Biol Cell. 2015;26:4674-85 pubmed publisher
    ..We propose that PS flip is part of a homeostatic mechanism that controls sterol loading and lateral segregation of protein and lipid domains at the TGN. ..
  34. García Marqués S, Randez Gil F, Dupont S, Garre E, Prieto J. Sng1 associates with Nce102 to regulate the yeast Pkh-Ypk signalling module in response to sphingolipid status. Biochim Biophys Acta. 2016;1863:1319-33 pubmed publisher
    ..Hence, both Nce102p and Sng1p participate in a regulatory circuit that controls the activity of the Pkh/Ypk module and their function is required in response to sphingolipid status. ..
  35. Marx U, Polakowski T, Pomorski T, Lang C, Nelson H, Nelson N, et al. Rapid transbilayer movement of fluorescent phospholipid analogues in the plasma membrane of endocytosis-deficient yeast cells does not require the Drs2 protein. Eur J Biochem. 1999;263:254-63 pubmed
    ..Thus, lipid asymmetry, at least of aminophospholipids, was preserved in S. cerevisiae end4 cells independently of the presence of the Drs2 protein. ..