ID ATC3_YEAST Reviewed; 1355 AA. AC P39524; D6VPJ2; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 220. DE RecName: Full=Phospholipid-transporting ATPase DRS2; DE EC=7.6.2.1 {ECO:0000269|PubMed:19805341, ECO:0000269|PubMed:24045945, ECO:0000305|PubMed:15249668, ECO:0000305|PubMed:16452632, ECO:0000305|PubMed:19898464, ECO:0000305|PubMed:22308393, ECO:0000305|PubMed:25393116}; GN Name=DRS2 {ECO:0000303|PubMed:8247005}; GN Synonyms=SWA3 {ECO:0000303|PubMed:24374639}; GN OrderedLocusNames=YAL026C; ORFNames=FUN38; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8247005; DOI=10.1128/mcb.13.12.7901-7912.1993; RA Ripmaster T.L., Vaughn G.P., Woolford J.L. Jr.; RT "DRS1 to DRS7, novel genes required for ribosome assembly and function in RT Saccharomyces cerevisiae."; RL Mol. Cell. Biol. 13:7901-7912(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=7731988; DOI=10.1073/pnas.92.9.3809; RA Bussey H., Kaback D.B., Zhong W.-W., Vo D.H., Clark M.W., Fortin N., RA Hall J., Ouellette B.F.F., Keng T., Barton A.B., Su Y., Davies C.J., RA Storms R.K.; RT "The nucleotide sequence of chromosome I from Saccharomyces cerevisiae."; RL Proc. Natl. Acad. Sci. U.S.A. 92:3809-3813(1995). RN [3] RP GENOME REANNOTATION, AND SEQUENCE REVISION TO 45-46; 450; 674; 891-892; RP 953-954 AND 987. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [4] RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF RP ASP-560. RX PubMed=10601336; DOI=10.1083/jcb.147.6.1223; RA Chen C.Y., Ingram M.F., Rosal P.H., Graham T.R.; RT "Role for Drs2p, a P-type ATPase and potential aminophospholipid RT translocase, in yeast late Golgi function."; RL J. Cell Biol. 147:1223-1236(1999). RN [5] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12372257; DOI=10.1016/s0960-9822(02)01148-x; RA Gall W.E., Geething N.C., Hua Z., Ingram M.F., Liu K., Chen S.I., RA Graham T.R.; RT "Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo."; RL Curr. Biol. 12:1623-1627(2002). RN [6] RP SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE. RX PubMed=12631737; DOI=10.1091/mbc.e02-08-0501; RA Pomorski T., Lombardi R., Riezman H., Devaux P.F., van Meer G., RA Holthuis J.C.; RT "Drs2p-related P-type ATPases Dnf1p and Dnf2p are required for phospholipid RT translocation across the yeast plasma membrane and serve a role in RT endocytosis."; RL Mol. Biol. Cell 14:1240-1254(2003). RN [7] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [8] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [9] RP INTERACTION WITH GEA2 AND GEA1, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF RP 1259-ALA--GLU-1282. RX PubMed=14734650; DOI=10.1242/jcs.00896; RA Chantalat S., Park S.K., Hua Z., Liu K., Gobin R., Peyroche A., RA Rambourg A., Graham T.R., Jackson C.L.; RT "The Arf activator Gea2p and the P-type ATPase Drs2p interact at the Golgi RT in Saccharomyces cerevisiae."; RL J. Cell Sci. 117:711-722(2004). RN [10] RP INTERACTION WITH CDC50. RX PubMed=15090616; DOI=10.1091/mbc.e03-11-0829; RA Saito K., Fujimura-Kamada K., Furuta N., Kato U., Umeda M., Tanaka K.; RT "Cdc50p, a protein required for polarized growth, associates with the Drs2p RT P-type ATPase implicated in phospholipid translocation in Saccharomyces RT cerevisiae."; RL Mol. Biol. Cell 15:3418-3432(2004). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBCELLULAR LOCATION. RX PubMed=15249668; DOI=10.1073/pnas.0404146101; RA Natarajan P., Wang J., Hua Z., Graham T.R.; RT "Drs2p-coupled aminophospholipid translocase activity in yeast Golgi RT membranes and relationship to in vivo function."; RL Proc. Natl. Acad. Sci. U.S.A. 101:10614-10619(2004). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DISRUPTION RP PHENOTYPE. RX PubMed=16452632; DOI=10.1091/mbc.e05-10-0912; RA Alder-Baerens N., Lisman Q., Luong L., Pomorski T., Holthuis J.C.; RT "Loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport RT and asymmetry in yeast post-Golgi secretory vesicles."; RL Mol. Biol. Cell 17:1632-1642(2006). RN [13] RP TOPOLOGY [LARGE SCALE ANALYSIS]. RC STRAIN=ATCC 208353 / W303-1A; RX PubMed=16847258; DOI=10.1073/pnas.0604075103; RA Kim H., Melen K., Oesterberg M., von Heijne G.; RT "A global topology map of the Saccharomyces cerevisiae membrane proteome."; RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006). RN [14] RP FUNCTION, INTERACTION WITH CDC50, SUBCELLULAR LOCATION, AND DISRUPTION RP PHENOTYPE. RX PubMed=16956384; DOI=10.1111/j.1600-0854.2006.00485.x; RA Chen S., Wang J., Muthusamy B.P., Liu K., Zare S., Andersen R.J., RA Graham T.R.; RT "Roles for the Drs2p-Cdc50p complex in protein transport and RT phosphatidylserine asymmetry of the yeast plasma membrane."; RL Traffic 7:1503-1517(2006). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC STRAIN=ADR376; RX PubMed=17330950; DOI=10.1021/pr060559j; RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., RA Elias J.E., Gygi S.P.; RT "Large-scale phosphorylation analysis of alpha-factor-arrested RT Saccharomyces cerevisiae."; RL J. Proteome Res. 6:1190-1197(2007). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth phosphoproteome RT analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [17] RP FUNCTION, ACTIVITY REGULATION, IDENTIFICATION IN A COMPLEX WITH CDC50, RP INTERACTION WITH CDC50, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, ACTIVE RP SITE, AND MUTAGENESIS OF GLY-341; GLU-342 AND ASP-560. RX PubMed=19411703; DOI=10.1074/jbc.m109.013722; RA Lenoir G., Williamson P., Puts C.F., Holthuis J.C.; RT "Cdc50p plays a vital role in the ATPase reaction cycle of the putative RT aminophospholipid transporter Drs2p."; RL J. Biol. Chem. 284:17956-17967(2009). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 1250-ARG--VAL-1263; RP 1268-ARG--ARG-1273 AND 1274-GLY--GLU-1282. RX PubMed=19898464; DOI=10.1038/ncb1989; RA Natarajan P., Liu K., Patil D.V., Sciorra V.A., Jackson C.L., Graham T.R.; RT "Regulation of a Golgi flippase by phosphoinositides and an ArfGEF."; RL Nat. Cell Biol. 11:1421-1426(2009). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND DISRUPTION RP PHENOTYPE. RX PubMed=19805341; DOI=10.1073/pnas.0904293106; RA Zhou X., Graham T.R.; RT "Reconstitution of phospholipid translocase activity with purified Drs2p, a RT type-IV P-type ATPase from budding yeast."; RL Proc. Natl. Acad. Sci. U.S.A. 106:16586-16591(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights RT into evolution."; RL Science 325:1682-1686(2009). RN [21] RP FUNCTION, AND INTERACTION WITH CDC50. RX PubMed=21212072; DOI=10.1093/jb/mvq155; RA Takahashi Y., Fujimura-Kamada K., Kondo S., Tanaka K.; RT "Isolation and characterization of novel mutations in CDC50, the non- RT catalytic subunit of the Drs2p phospholipid flippase."; RL J. Biochem. 149:423-432(2011). RN [22] RP IDENTIFICATION IN A COMPLEX WITH CDC50, INTERACTION WITH CDC50, AND RP MUTAGENESIS OF GLY-341; GLU-342 AND ASP-560. RX PubMed=22791719; DOI=10.1074/jbc.m112.371088; RA Puts C.F., Panatala R., Hennrich H., Tsareva A., Williamson P., RA Holthuis J.C.; RT "Mapping functional interactions in a heterodimeric phospholipid pump."; RL J. Biol. Chem. 287:30529-30540(2012). RN [23] RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF RP PHE-511. RX PubMed=22308393; DOI=10.1073/pnas.1115725109; RA Baldridge R.D., Graham T.R.; RT "Identification of residues defining phospholipid flippase substrate RT specificity of type IV P-type ATPases."; RL Proc. Natl. Acad. Sci. U.S.A. 109:E290-E298(2012). RN [24] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND DOMAIN RP C-TERMINAL PART. RX PubMed=24045945; DOI=10.1074/jbc.m113.481986; RA Zhou X., Sebastian T.T., Graham T.R.; RT "Auto-inhibition of Drs2p, a yeast phospholipid flippase, by its carboxyl- RT terminal tail."; RL J. Biol. Chem. 288:31807-31815(2013). RN [25] RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 237-GLN-GLN-238; ASN-445; ASP-473 RP AND PHE-511. RX PubMed=23302692; DOI=10.1073/pnas.1216948110; RA Baldridge R.D., Graham T.R.; RT "Two-gate mechanism for phospholipid selection and transport by type IV P- RT type ATPases."; RL Proc. Natl. Acad. Sci. U.S.A. 110:E358-E367(2013). RN [26] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, IDENTIFICATION IN A RP COMPLEX WITH CDC50, INTERACTION WITH CDC50, IDENTIFICATION BY MASS RP SPECTROMETRY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLU-342 AND ASP-560. RX PubMed=25393116; DOI=10.1371/journal.pone.0112176; RA Azouaoui H., Montigny C., Ash M.R., Fijalkowski F., Jacquot A., RA Groenberg C., Lopez-Marques R.L., Palmgren M.G., Garrigos M., le Maire M., RA Decottignies P., Gourdon P., Nissen P., Champeil P., Lenoir G.; RT "A high-yield co-expression system for the purification of an intact Drs2p- RT Cdc50p lipid flippase complex, critically dependent on and stabilized by RT phosphatidylinositol-4-phosphate."; RL PLoS ONE 9:e112176-e112176(2014). RN [27] RP DISRUPTION PHENOTYPE. RX PubMed=27235400; DOI=10.1074/jbc.m115.686253; RA Takar M., Wu Y., Graham T.R.; RT "The Essential Neo1 Protein from Budding Yeast Plays a Role in Establishing RT Aminophospholipid Asymmetry of the Plasma Membrane."; RL J. Biol. Chem. 291:15727-15739(2016). RN [28] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, IDENTIFICATION IN A RP COMPLEX WITH CDC50, INTERACTION WITH CDC50, DOMAIN C-TERMINAL PART, MASS RP SPECTROMETRY, AND MUTAGENESIS OF GLU-342. RX PubMed=28302728; DOI=10.1074/jbc.m116.751487; RA Azouaoui H., Montigny C., Dieudonne T., Champeil P., Jacquot A., RA Vazquez-Ibar J.L., Le Marechal P., Ulstrup J., Ash M.R., Lyons J.A., RA Nissen P., Lenoir G.; RT "High phosphatidylinositol 4-phosphate (PI4P)-dependent ATPase activity for RT the Drs2p-Cdc50p flippase after removal of its N- and C-terminal RT extensions."; RL J. Biol. Chem. 292:7954-7970(2017). RN [29] RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 237-GLN-GLN-238. RX PubMed=30824614; DOI=10.1194/jlr.m093526; RA Takar M., Huang Y., Graham T.R.; RT "The PQ-loop protein Any1 segregates Drs2 and Neo1 functions required for RT viability and plasma membrane phospholipid asymmetry."; RL J. Lipid Res. 60:1032-1042(2019). RN [30] {ECO:0007744|PDB:6ROH, ECO:0007744|PDB:6ROI, ECO:0007744|PDB:6ROJ} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN COMPLEX WITH CDC50 AND RP MAGNESIUM, FUNCTION, ACTIVITY REGULATION, IDENTIFICATION IN A COMPLEX WITH RP CDC50, INTERACTION WITH CDC50, DOMAIN C-TERMINAL PART, AND RP 1,2-DIACYL-SN-GLYCERO-3-PHOSPHO-(1D-MYO-INOSITOL 4-PHOSPHATE) BINDING. RX PubMed=31243363; DOI=10.1038/s41586-019-1344-7; RA Timcenko M., Lyons J.A., Januliene D., Ulstrup J.J., Dieudonne T., RA Montigny C., Ash M.R., Karlsen J.L., Boesen T., Kuhlbrandt W., Lenoir G., RA Moeller A., Nissen P.; RT "Structure and autoregulation of a P4-ATPase lipid flippase."; RL Nature 571:366-370(2019). RN [31] {ECO:0007744|PDB:6PSX, ECO:0007744|PDB:6PSY} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN COMPLEX WITH CDC50, RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, IDENTIFICATION IN A RP COMPLEX WITH CDC50, INTERACTION WITH CDC50, DOMAIN C-TERMINAL PART, AND RP MUTAGENESIS OF ARG-1228; TYR-1235 AND HIS-1236. RX PubMed=31515475; DOI=10.1038/s41467-019-12191-9; RA Bai L., Kovach A., You Q., Hsu H.C., Zhao G., Li H.; RT "Autoinhibition and activation mechanisms of the eukaryotic lipid flippase RT Drs2p-Cdc50p."; RL Nat. Commun. 10:4142-4142(2019). RN [32] {ECO:0007744|PDB:7OH4, ECO:0007744|PDB:7OH5, ECO:0007744|PDB:7OH6, ECO:0007744|PDB:7OH7} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) IN COMPLEX WITH CDC50; RP 1,2-DIACYL-SN-GLYCERO-3-PHOSPHO-(1D-MYO-INOSITOL 4-PHOSPHATE); MAGNESIUM RP AND ADP, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, COFACTOR, RP IDENTIFICATION IN A COMPLEX WITH CDC50, INTERACTION WITH CDC50, RP 1,2-DIACYL-SN-GLYCERO-3-PHOSPHO-(1D-MYO-INOSITOL 4-PHOSPHATE) BINDING, AND RP MUTAGENESIS OF TYR-380. RX PubMed=34023399; DOI=10.1016/j.jmb.2021.167062; RA Timcenko M., Dieudonne T., Montigny C., Boesen T., Lyons J.A., Lenoir G., RA Nissen P.; RT "Structural Basis of Substrate-Independent Phosphorylation in a P4-ATPase RT Lipid Flippase."; RL J. Mol. Biol. 433:167062-167062(2021). RN [33] {ECO:0007744|PDB:7PEM} RP STRUCTURE BY ELECTRON MICROSCOPY (3.10 ANGSTROMS) IN COMPLEX WITH CDC50, RP IDENTIFICATION IN A COMPLEX WITH CDC50, AND INTERACTION WITH CDC50. RA Wang Y., Lyons J.A., Timcenko M., Kummerer F., de Groot B.L., Nissen P., RA Gapsys V., Lindorff-Larsen K.; RT "Substrate Transport and Specificity in a Phospholipid Flippase."; RL Submitted (AUG-2021) to the PDB data bank. CC -!- FUNCTION: Catalytic component of a P4-ATPase flippase complex which CC catalyzes the hydrolysis of ATP coupled to the transport of CC phosphatidylserine and small amounts of ethanolamine from the lumen to CC the cytosolic leaflet of the trans-Golgi network and ensures the CC maintenance of asymmetric distribution of phospholipids CC (PubMed:15249668, PubMed:16452632, PubMed:16956384, PubMed:19411703, CC PubMed:19898464, PubMed:19805341, PubMed:22308393, PubMed:24045945, CC PubMed:25393116, PubMed:28302728, PubMed:30824614, PubMed:31243363, CC PubMed:31515475, PubMed:34023399). Contributes to clathrin-coated CC vesicle formation, endocytosis, and protein trafficking between the CC Golgi and endosomal system (PubMed:15249668, PubMed:12372257, CC PubMed:10601336, PubMed:8247005, PubMed:16452632, PubMed:16956384, CC PubMed:21212072). Does not appear to transport phosphatidylcholine or CC sphingomyelin (PubMed:19805341, PubMed:24045945, PubMed:15249668). CC {ECO:0000269|PubMed:10601336, ECO:0000269|PubMed:12372257, CC ECO:0000269|PubMed:15249668, ECO:0000269|PubMed:16452632, CC ECO:0000269|PubMed:16956384, ECO:0000269|PubMed:19411703, CC ECO:0000269|PubMed:19805341, ECO:0000269|PubMed:19898464, CC ECO:0000269|PubMed:21212072, ECO:0000269|PubMed:22308393, CC ECO:0000269|PubMed:24045945, ECO:0000269|PubMed:25393116, CC ECO:0000269|PubMed:28302728, ECO:0000269|PubMed:30824614, CC ECO:0000269|PubMed:31243363, ECO:0000269|PubMed:31515475, CC ECO:0000269|PubMed:34023399, ECO:0000269|PubMed:8247005}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate + CC phospholipidSide 2.; EC=7.6.2.1; CC Evidence={ECO:0000269|PubMed:19805341, ECO:0000269|PubMed:24045945, CC ECO:0000305|PubMed:15249668, ECO:0000305|PubMed:16452632, CC ECO:0000305|PubMed:19898464, ECO:0000305|PubMed:22308393, CC ECO:0000305|PubMed:25393116, ECO:0000305|PubMed:28302728, CC ECO:0000305|PubMed:31515475, ECO:0000305|PubMed:34023399}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O = CC a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + H(+) + CC phosphate; Xref=Rhea:RHEA:38567, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:57262, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:19805341, ECO:0000269|PubMed:24045945, CC ECO:0000305|PubMed:15249668, ECO:0000305|PubMed:16452632, CC ECO:0000305|PubMed:19898464, ECO:0000305|PubMed:22308393, CC ECO:0000305|PubMed:25393116}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568; CC Evidence={ECO:0000269|PubMed:19805341, ECO:0000269|PubMed:24045945, CC ECO:0000305|PubMed:15249668, ECO:0000305|PubMed:16452632, CC ECO:0000305|PubMed:19898464, ECO:0000305|PubMed:22308393, CC ECO:0000305|PubMed:25393116}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ATP + H2O CC = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ADP + H(+) + CC phosphate; Xref=Rhea:RHEA:66132, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:64612, ChEBI:CHEBI:456216; CC Evidence={ECO:0000305|PubMed:16452632}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66133; CC Evidence={ECO:0000305|PubMed:16452632}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:19805341, ECO:0000269|PubMed:34023399, CC ECO:0000305|PubMed:15249668, ECO:0000305|PubMed:24045945}; CC -!- ACTIVITY REGULATION: Allosterically activated by binding 1,2-diacyl-sn- CC glycero-3-phospho-(1D-myo-inositol 4-phosphate) (phosphatidylinositol CC 4-phosphate) (PubMed:24045945, PubMed:25393116, PubMed:28302728, CC PubMed:31243363, PubMed:31515475, PubMed:34023399). Inhibited by CC orthovanadate, N-ethylmaleimide, trifluoroberyllate and CC tetrafluoroaluminate; orthovanadate and N-ethylmaleimide inhibit CC phosphorylation of the active site aspartic acid (PubMed:24045945, CC PubMed:19805341, PubMed:25393116, PubMed:19411703). The ATPase activity CC is not potently stimulated by phosphatidylinositol 3-phosphate and CC phosphatidylinositol 5-phosphate, phosphatidylinositol 4,5-bisphosphate CC or phosphatidylcholine (PubMed:24045945, PubMed:19805341, CC PubMed:19898464). Not inhibited by azide (PubMed:19805341). CC {ECO:0000269|PubMed:19411703, ECO:0000269|PubMed:19805341, CC ECO:0000269|PubMed:19898464, ECO:0000269|PubMed:24045945, CC ECO:0000269|PubMed:25393116, ECO:0000269|PubMed:28302728, CC ECO:0000269|PubMed:31243363, ECO:0000269|PubMed:31515475, CC ECO:0000269|PubMed:34023399}. CC -!- SUBUNIT: Component of a flippase complex consisting of DRS2 and CDC50 CC (PubMed:19411703, PubMed:22791719, PubMed:25393116, PubMed:28302728, CC PubMed:31243363, PubMed:31515475, Ref.33). Interacts with CDC50; the CC interaction is direct, is required for their mutual export from the CC endoplasmic reticulum, and preferentially occurs when DRS2 is in the CC E2P state (PubMed:15090616, PubMed:16956384, PubMed:19411703, CC PubMed:21212072, PubMed:22791719, PubMed:25393116, PubMed:28302728, CC PubMed:31243363, PubMed:31515475, Ref.33). Interacts (via C-terminus) CC with GEA2 (via SEC7 domain); the interaction is direct CC (PubMed:14734650). Interacts with GEA1 (PubMed:14734650). CC {ECO:0000269|PubMed:14734650, ECO:0000269|PubMed:15090616, CC ECO:0000269|PubMed:16956384, ECO:0000269|PubMed:19411703, CC ECO:0000269|PubMed:21212072, ECO:0000269|PubMed:22791719, CC ECO:0000269|PubMed:25393116, ECO:0000269|PubMed:28302728, CC ECO:0000269|PubMed:31243363, ECO:0000269|PubMed:31515475, CC ECO:0000269|Ref.33}. CC -!- INTERACTION: CC P39524; P25656: CDC50; NbExp=10; IntAct=EBI-3106, EBI-22014; CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane CC {ECO:0000269|PubMed:10601336, ECO:0000269|PubMed:12372257, CC ECO:0000269|PubMed:12631737, ECO:0000269|PubMed:14562095, CC ECO:0000269|PubMed:15249668, ECO:0000269|PubMed:16956384, CC ECO:0000269|PubMed:19411703, ECO:0000269|PubMed:19898464}; Multi-pass CC membrane protein {ECO:0000269|PubMed:12372257, CC ECO:0000269|PubMed:14562095}. Endosome membrane CC {ECO:0000269|PubMed:16452632}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- DOMAIN: The C-terminal part (1231-1309) serves an autoinhibitory CC function and is dislodged upon substrate binding. CC {ECO:0000269|PubMed:24045945, ECO:0000269|PubMed:28302728, CC ECO:0000269|PubMed:31515475}. CC -!- MASS SPECTROMETRY: Mass=153900; Method=MALDI; CC Evidence={ECO:0000269|PubMed:28302728}; CC -!- DISRUPTION PHENOTYPE: Decreases phosphatidylserine and CC phosphatidylethanolamine flippase activity in secretory vesicles; CC simultaneous knockout of DNF3 exacerbates the effect (PubMed:16452632). CC Abnormal vesicle-mediated transport to vacuole (PubMed:10601336). CC Abnormal proteolytic processing of proteins in the trans-Golgi network CC (PubMed:10601336). Contains abnormal clathrin-coated vesicles and leads CC to an accumulation of aberrant membranous material probably derived CC from the Golgi (PubMed:10601336, PubMed:14734650). Increases CC phosphatidylserine and phosphatidylethanolamine levels in the outer CC leaflet of the cell membrane (PubMed:16956384, PubMed:12631737). CC Abnormal endocytosis (PubMed:12631737). Sensitive to cold, duramycin CC and cinnamycin (phosphatidylethanolamine-binding cytoxins), papuamide A CC and B (phosphatidylserine-binding cytotoxins), cobalt, nickel, zinc, CC calcium, and magnesium ions (PubMed:10601336, PubMed:16956384, CC PubMed:19411703, PubMed:19898464, PubMed:19805341, PubMed:22308393, CC PubMed:23302692, PubMed:25393116, PubMed:27235400, PubMed:30824614). CC Simultaneous knockout of ARF1 results in inviability, and simultaneous CC knockout of GEA2 exacerbates cold sensitivity (PubMed:10601336, CC PubMed:14734650). {ECO:0000269|PubMed:10601336, CC ECO:0000269|PubMed:12631737, ECO:0000269|PubMed:14734650, CC ECO:0000269|PubMed:16452632, ECO:0000269|PubMed:16956384, CC ECO:0000269|PubMed:19411703, ECO:0000269|PubMed:19805341, CC ECO:0000269|PubMed:19898464, ECO:0000269|PubMed:22308393, CC ECO:0000269|PubMed:23302692, ECO:0000269|PubMed:25393116, CC ECO:0000269|PubMed:27235400, ECO:0000269|PubMed:30824614}. CC -!- MISCELLANEOUS: Present with 606 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) CC family. Type IV subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L01795; AAA16891.1; -; Unassigned_RNA. DR EMBL; U12980; AAC05006.1; -; Genomic_DNA. DR EMBL; BK006935; DAA06962.2; -; Genomic_DNA. DR PIR; S51995; S51995. DR RefSeq; NP_009376.2; NM_001178171.2. DR PDB; 6PSX; EM; 3.30 A; A=1-1355. DR PDB; 6PSY; EM; 2.80 A; A=1-1355. DR PDB; 6ROH; EM; 2.80 A; A=1-1355. DR PDB; 6ROI; EM; 3.70 A; A=1-1355. DR PDB; 6ROJ; EM; 2.90 A; A=1-1355. DR PDB; 7OH4; EM; 3.00 A; A=1-1355. DR PDB; 7OH5; EM; 2.90 A; A=1-1355. DR PDB; 7OH6; EM; 3.00 A; A=1-1355. DR PDB; 7OH7; EM; 3.80 A; A=1-1355. DR PDB; 7PEM; EM; 3.10 A; A=1-1355. DR PDBsum; 6PSX; -. DR PDBsum; 6PSY; -. DR PDBsum; 6ROH; -. DR PDBsum; 6ROI; -. DR PDBsum; 6ROJ; -. DR PDBsum; 7OH4; -. DR PDBsum; 7OH5; -. DR PDBsum; 7OH6; -. DR PDBsum; 7OH7; -. DR PDBsum; 7PEM; -. DR AlphaFoldDB; P39524; -. DR EMDB; EMD-12893; -. DR EMDB; EMD-12894; -. DR EMDB; EMD-12895; -. DR EMDB; EMD-12896; -. DR EMDB; EMD-13353; -. DR EMDB; EMD-20467; -. DR EMDB; EMD-20468; -. DR EMDB; EMD-4972; -. DR EMDB; EMD-4973; -. DR EMDB; EMD-4974; -. DR SMR; P39524; -. DR BioGRID; 31740; 627. DR ComplexPortal; CPX-1018; DRS2-CDC50 P4-ATPase complex. DR DIP; DIP-2216N; -. DR IntAct; P39524; 11. DR MINT; P39524; -. DR STRING; 4932.YAL026C; -. DR TCDB; 3.A.3.8.2; the p-type atpase (p-atpase) superfamily. DR iPTMnet; P39524; -. DR MaxQB; P39524; -. DR PaxDb; 4932-YAL026C; -. DR PeptideAtlas; P39524; -. DR EnsemblFungi; YAL026C_mRNA; YAL026C; YAL026C. DR GeneID; 851207; -. DR KEGG; sce:YAL026C; -. DR AGR; SGD:S000000024; -. DR SGD; S000000024; DRS2. DR VEuPathDB; FungiDB:YAL026C; -. DR eggNOG; KOG0206; Eukaryota. DR GeneTree; ENSGT00940000168736; -. DR HOGENOM; CLU_000846_3_0_1; -. DR InParanoid; P39524; -. DR OMA; MHSFWSW; -. DR OrthoDB; 275833at2759; -. DR BioCyc; YEAST:G3O-28837-MONOMER; -. DR BRENDA; 7.6.2.1; 984. DR Reactome; R-SCE-6798695; Neutrophil degranulation. DR Reactome; R-SCE-936837; Ion transport by P-type ATPases. DR BioGRID-ORCS; 851207; 4 hits in 10 CRISPR screens. DR PRO; PR:P39524; -. DR Proteomes; UP000002311; Chromosome I. DR RNAct; P39524; Protein. DR GO; GO:1990530; C:Cdc50p-Drs2p complex; IPI:SGD. DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; NAS:ComplexPortal. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005802; C:trans-Golgi network; IDA:SGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0140326; F:ATPase-coupled intramembrane lipid transporter activity; IBA:GO_Central. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0140345; F:phosphatidylcholine flippase activity; IGI:SGD. DR GO; GO:0090555; F:phosphatidylethanolamine flippase activity; IMP:SGD. DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB. DR GO; GO:0140346; F:phosphatidylserine flippase activity; IDA:UniProtKB. DR GO; GO:0090556; F:phosphatidylserine floppase activity; IEA:RHEA. DR GO; GO:0032456; P:endocytic recycling; IMP:SGD. DR GO; GO:0006897; P:endocytosis; IGI:SGD. DR GO; GO:0045332; P:phospholipid translocation; IDA:UniProtKB. DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; IMP:SGD. DR CDD; cd02073; P-type_ATPase_APLT_Dnf-like; 1. DR Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 1. DR Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1. DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 1. DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N. DR InterPro; IPR018303; ATPase_P-typ_P_site. DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf. DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf. DR InterPro; IPR036412; HAD-like_sf. DR InterPro; IPR023214; HAD_sf. DR InterPro; IPR006539; P-type_ATPase_IV. DR InterPro; IPR032631; P-type_ATPase_N. DR InterPro; IPR001757; P_typ_ATPase. DR InterPro; IPR032630; P_typ_ATPase_c. DR InterPro; IPR044492; P_typ_ATPase_HD_dom. DR NCBIfam; TIGR01652; ATPase-Plipid; 1. DR NCBIfam; TIGR01494; ATPase_P-type; 1. DR PANTHER; PTHR24092:SF214; PHOSPHOLIPID-TRANSPORTING ATPASE; 1. DR PANTHER; PTHR24092; PROBABLE PHOSPHOLIPID-TRANSPORTING ATPASE; 1. DR Pfam; PF13246; Cation_ATPase; 1. DR Pfam; PF16212; PhoLip_ATPase_C; 1. DR Pfam; PF16209; PhoLip_ATPase_N; 1. DR PRINTS; PR00119; CATATPASE. DR SFLD; SFLDS00003; Haloacid_Dehalogenase; 1. DR SFLD; SFLDF00027; p-type_atpase; 1. DR SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1. DR SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1. DR SUPFAM; SSF56784; HAD-like; 1. DR SUPFAM; SSF81660; Metal cation-transporting ATPase, ATP-binding domain N; 1. DR PROSITE; PS00154; ATPASE_E1_E2; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Endosome; Golgi apparatus; Lipid-binding; KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Translocase; Transmembrane; Transmembrane helix. FT CHAIN 1..1355 FT /note="Phospholipid-transporting ATPase DRS2" FT /id="PRO_0000046233" FT TOPO_DOM 1..221 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 222..242 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 243..246 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 247..267 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 268..449 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 450..470 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 471..490 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 491..511 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 512..1012 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1013..1033 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1034..1043 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1044..1064 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1065..1094 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1095..1115 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1116..1131 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1132..1152 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1153..1161 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1162..1182 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1183..1202 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 1203..1223 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1224..1355 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..104 FT /note="Involved in autoinhibition" FT /evidence="ECO:0000269|PubMed:24045945, FT ECO:0000269|PubMed:28302728" FT REGION 1..50 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 237..238 FT /note="Involved in phosphatidylserine substrate FT recognition" FT /evidence="ECO:0000269|PubMed:23302692" FT REGION 1230..1282 FT /note="Interaction with GEA2" FT /evidence="ECO:0000269|PubMed:14734650" FT REGION 1231..1309 FT /note="Involved in autoinhibition" FT /evidence="ECO:0000269|PubMed:24045945, FT ECO:0000269|PubMed:28302728, ECO:0000269|PubMed:31515475" FT REGION 1305..1355 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..19 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 25..47 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1308..1322 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1334..1348 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 560 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000305|PubMed:19411703" FT BINDING 560 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 560 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 561 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 562 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:34023399, FT ECO:0007744|PDB:7OH5, ECO:0007744|PDB:7OH7" FT BINDING 562 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 655 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 698 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 700 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P32660" FT BINDING 703 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:34023399, FT ECO:0007744|PDB:7OH5, ECO:0007744|PDB:7OH7" FT BINDING 721 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 755 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 756 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:34023399, FT ECO:0007744|PDB:7OH5" FT BINDING 835 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:34023399, FT ECO:0007744|PDB:7OH5" FT BINDING 836 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 837 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 928 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 934 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 954 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 957 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 958 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 958 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q8NB49" FT BINDING 1149 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol FT 4-phosphate)" FT /ligand_id="ChEBI:CHEBI:58178" FT /evidence="ECO:0000269|PubMed:34023399, FT ECO:0007744|PDB:7OH5" FT BINDING 1219 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol FT 4-phosphate)" FT /ligand_id="ChEBI:CHEBI:58178" FT /evidence="ECO:0000269|PubMed:31243363, FT ECO:0000269|PubMed:34023399, ECO:0007744|PDB:6ROI, FT ECO:0007744|PDB:7OH4, ECO:0007744|PDB:7OH5, FT ECO:0007744|PDB:7OH6" FT BINDING 1223 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol FT 4-phosphate)" FT /ligand_id="ChEBI:CHEBI:58178" FT /evidence="ECO:0000269|PubMed:31243363, FT ECO:0000269|PubMed:34023399, ECO:0007744|PDB:6ROI, FT ECO:0007744|PDB:7OH4, ECO:0007744|PDB:7OH7" FT BINDING 1224 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol FT 4-phosphate)" FT /ligand_id="ChEBI:CHEBI:58178" FT /evidence="ECO:0000269|PubMed:31243363, FT ECO:0000269|PubMed:34023399, ECO:0007744|PDB:6ROI, FT ECO:0007744|PDB:6ROJ, ECO:0007744|PDB:7OH4, FT ECO:0007744|PDB:7OH5, ECO:0007744|PDB:7OH6" FT BINDING 1235 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol FT 4-phosphate)" FT /ligand_id="ChEBI:CHEBI:58178" FT /evidence="ECO:0000269|PubMed:31243363, FT ECO:0000269|PubMed:34023399, ECO:0007744|PDB:6ROI, FT ECO:0007744|PDB:7OH7" FT BINDING 1236 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol FT 4-phosphate)" FT /ligand_id="ChEBI:CHEBI:58178" FT /evidence="ECO:0000269|PubMed:31243363, FT ECO:0000269|PubMed:34023399, ECO:0007744|PDB:6ROI, FT ECO:0007744|PDB:6ROJ, ECO:0007744|PDB:7OH4, FT ECO:0007744|PDB:7OH5, ECO:0007744|PDB:7OH6, FT ECO:0007744|PDB:7OH7" FT SITE 508 FT /note="Involved in the release of the transported lipid FT into the cytosolic leaflet" FT /evidence="ECO:0000250|UniProtKB:C7EXK4" FT MOD_RES 102 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18407956, FT ECO:0007744|PubMed:19779198" FT MUTAGEN 237..238 FT /note="QQ->GA: Loss of activity. Sensitive to papuamide B FT (phosphatidylserine-binding cytotoxin); the effect is FT suppressed when associated with S-445." FT /evidence="ECO:0000269|PubMed:23302692, FT ECO:0000269|PubMed:30824614" FT MUTAGEN 341 FT /note="G->L: Reduces interaction with CDC50. Sensitive to FT cold." FT /evidence="ECO:0000269|PubMed:19411703, FT ECO:0000269|PubMed:22791719" FT MUTAGEN 342 FT /note="E->Q: Loss of activity. Does not appear to reduce FT interaction with CDC50. Sensitive to cold." FT /evidence="ECO:0000269|PubMed:19411703, FT ECO:0000269|PubMed:22791719, ECO:0000269|PubMed:25393116, FT ECO:0000269|PubMed:28302728" FT MUTAGEN 380 FT /note="Y->F: Increases ATPase activity." FT /evidence="ECO:0000269|PubMed:34023399" FT MUTAGEN 445 FT /note="N->S: No sensitivity to papuamide B FT (phosphatidylserine-binding cytotoxin) or cold. No FT sensitivity to papuamide B; when associated with FT 237-G--A-238 or K-473." FT /evidence="ECO:0000269|PubMed:23302692" FT MUTAGEN 473 FT /note="D->K: Sensitive to papuamide B FT (phosphatidylserine-binding cytotoxin); the effect is FT suppressed when associated with S-445." FT /evidence="ECO:0000269|PubMed:23302692" FT MUTAGEN 511 FT /note="F->L: Sensitive to duramycin FT (phosphatidylethanolamine-binding cytoxin). Decreases FT ATPase activity." FT /evidence="ECO:0000269|PubMed:22308393" FT MUTAGEN 511 FT /note="F->Y,L: Sensitive to papuamide B FT (phosphatidylserine-binding cytotoxin)." FT /evidence="ECO:0000269|PubMed:22308393, FT ECO:0000269|PubMed:23302692" FT MUTAGEN 511 FT /note="F->Y: Normal ATPase activity. No sensitivity to FT cold." FT /evidence="ECO:0000269|PubMed:22308393, FT ECO:0000269|PubMed:23302692" FT MUTAGEN 560 FT /note="D->N,E: Sensitive to cold. Reduces interaction with FT CDC50. Decreases protein level." FT /evidence="ECO:0000269|PubMed:10601336, FT ECO:0000269|PubMed:19411703, ECO:0000269|PubMed:25393116" FT MUTAGEN 560 FT /note="D->N: Loss of activity. Sensitive to cinnamycin FT (phosphatidylethanolamine-binding cytoxin)." FT /evidence="ECO:0000269|PubMed:19411703, FT ECO:0000269|PubMed:22791719, ECO:0000269|PubMed:25393116" FT MUTAGEN 1228 FT /note="R->A: Abolishes ATPase activity and leads to cold FT sensitivity." FT /evidence="ECO:0000269|PubMed:31515475" FT MUTAGEN 1235 FT /note="Y->A: Abolishes ATPase activity and leads to cold FT sensitivity." FT /evidence="ECO:0000269|PubMed:31515475" FT MUTAGEN 1236 FT /note="H->A: Abolishes ATPase activity and leads to cold FT sensitivity." FT /evidence="ECO:0000269|PubMed:31515475" FT MUTAGEN 1250..1263 FT /note="Missing: Sensitive to cold." FT /evidence="ECO:0000269|PubMed:19898464" FT MUTAGEN 1259..1282 FT /note="Missing: Sensitive to cold." FT /evidence="ECO:0000269|PubMed:14734650" FT MUTAGEN 1268..1273 FT /note="RMKKQR->AMAAQA: Decreases phosphatidylserine FT flippase activity. No effect on interaction with GEA2. FT Sensitive to cold." FT /evidence="ECO:0000269|PubMed:19898464" FT MUTAGEN 1268..1273 FT /note="Missing: Decreases phosphatidylserine flippase FT activity and decreases interaction with GEA2. Sensitive to FT cold." FT /evidence="ECO:0000269|PubMed:19898464" FT MUTAGEN 1274..1282 FT /note="Missing: Sensitive to cold." FT /evidence="ECO:0000269|PubMed:19898464" FT CONFLICT 45..46 FT /note="AN -> GY (in Ref. 1; AAA16891 and 2; AAC05006)" FT /evidence="ECO:0000305" FT CONFLICT 450 FT /note="A -> R (in Ref. 1; AAA16891 and 2; AAC05006)" FT /evidence="ECO:0000305" FT CONFLICT 674 FT /note="P -> G (in Ref. 1; AAA16891 and 2; AAC05006)" FT /evidence="ECO:0000305" FT CONFLICT 891..892 FT /note="NT -> KS (in Ref. 1; AAA16891 and 2; AAC05006)" FT /evidence="ECO:0000305" FT CONFLICT 953..954 FT /note="GD -> AS (in Ref. 1; AAA16891 and 2; AAC05006)" FT /evidence="ECO:0000305" FT CONFLICT 987 FT /note="V -> L (in Ref. 1; AAA16891 and 2; AAC05006)" FT /evidence="ECO:0000305" FT STRAND 183..188 FT /evidence="ECO:0007829|PDB:6ROH" FT TURN 190..193 FT /evidence="ECO:0007829|PDB:6ROH" FT TURN 194..196 FT /evidence="ECO:0007829|PDB:7OH5" FT STRAND 210..212 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 213..222 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 225..235 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 240..242 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 249..280 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 283..287 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 293..299 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 307..310 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 312..315 FT /evidence="ECO:0007829|PDB:7OH4" FT STRAND 318..327 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 337..340 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 344..347 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 352..356 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 361..364 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 369..371 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 384..387 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 392..395 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 397..399 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 403..411 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 413..419 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 423..427 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 439..472 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 474..476 FT /evidence="ECO:0007829|PDB:6ROH" FT TURN 478..481 FT /evidence="ECO:0007829|PDB:6ROH" FT HELIX 487..501 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 503..505 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 508..510 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 511..525 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 529..531 FT /evidence="ECO:0007829|PDB:6ROJ" FT TURN 534..537 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 542..544 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 546..548 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 549..552 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 556..559 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 562..565 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 571..579 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 580..585 FT /evidence="ECO:0007829|PDB:6ROH" FT STRAND 588..590 FT /evidence="ECO:0007829|PDB:7PEM" FT STRAND 596..598 FT /evidence="ECO:0007829|PDB:6ROH" FT HELIX 601..611 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 612..615 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 617..619 FT /evidence="ECO:0007829|PDB:6ROJ" FT HELIX 620..632 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 637..640 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 642..644 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 646..649 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 653..663 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 664..666 FT /evidence="ECO:0007829|PDB:7OH5" FT STRAND 668..672 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 676..681 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 683..685 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 689..692 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 700..702 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 704..710 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 716..722 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 724..727 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 728..730 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 733..736 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 739..750 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 751..753 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 755..763 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 766..780 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 783..785 FT /evidence="ECO:0007829|PDB:6ROH" FT HELIX 786..796 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 800..810 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 817..825 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 826..828 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 830..834 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 839..848 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 854..858 FT /evidence="ECO:0007829|PDB:7PEM" FT STRAND 859..861 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 868..880 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 881..883 FT /evidence="ECO:0007829|PDB:6ROH" FT TURN 887..889 FT /evidence="ECO:0007829|PDB:6ROH" FT HELIX 890..892 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 894..897 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 900..903 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 908..910 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 911..918 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 921..926 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 931..943 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 949..955 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 956..958 FT /evidence="ECO:0007829|PDB:6ROH" FT HELIX 959..963 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 965..971 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 973..975 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 978..981 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 983..988 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 992..998 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 999..1001 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1002..1022 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1025..1028 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1030..1033 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1043..1049 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 1050..1053 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1056..1062 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1072..1075 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1077..1080 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1081..1084 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 1087..1089 FT /evidence="ECO:0007829|PDB:7OH5" FT HELIX 1091..1115 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 1116..1119 FT /evidence="ECO:0007829|PDB:6ROJ" FT STRAND 1124..1126 FT /evidence="ECO:0007829|PDB:6PSX" FT HELIX 1131..1152 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 1155..1157 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1161..1164 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1166..1182 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 1183..1187 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1190..1192 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1195..1199 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1203..1229 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 1233..1235 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1236..1239 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1255..1261 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 1263..1266 FT /evidence="ECO:0007829|PDB:6PSY" FT HELIX 1281..1283 FT /evidence="ECO:0007829|PDB:6PSY" FT TURN 1286..1291 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 1294..1296 FT /evidence="ECO:0007829|PDB:6PSY" FT STRAND 1300..1303 FT /evidence="ECO:0007829|PDB:6PSY" SQ SEQUENCE 1355 AA; 153765 MW; 5745B92901F8E1AE CRC64; MNDDRETPPK RKPGEDDTLF DIDFLDDTTS HSGSRSKVTN SHANANYIPP SHVLPEETID LDADDDNIEN DVHENLFMSN NHDDQTSWNA NRFDSDAYQP QSLRAVKPPG LFARFGNGLK NAFTFKRKKG PESFEMNHYN AVTNNELDDN YLDSRNKFNI KILFNRYILR KNVGDAEGNG EPRVIHINDS LANSSFGYSD NHISTTKYNF ATFLPKFLFQ EFSKYANLFF LCTSAIQQVP HVSPTNRYTT IGTLLVVLIV SAMKECIEDI KRANSDKELN NSTAEIFSEA HDDFVEKRWI DIRVGDIIRV KSEEPIPADT IILSSSEPEG LCYIETANLD GETNLKIKQS RVETAKFIDV KTLKNMNGKV VSEQPNSSLY TYEGTMTLND RQIPLSPDQM ILRGATLRNT AWIFGLVIFT GHETKLLRNA TATPIKRTAV EKIINRQIIA LFTVLIVLIL ISSIGNVIMS TADAKHLSYL YLEGTNKAGL FFKDFLTFWI LFSNLVPISL FVTVELIKYY QAFMIGSDLD LYYEKTDTPT VVRTSSLVEE LGQIEYIFSD KTGTLTRNIM EFKSCSIAGH CYIDKIPEDK TATVEDGIEV GYRKFDDLKK KLNDPSDEDS PIINDFLTLL ATCHTVIPEF QSDGSIKYQA ASPDEGALVQ GGADLGYKFI IRKPNSVTVL LEETGEEKEY QLLNICEFNS TRKRMSAIFR FPDGSIKLFC KGADTVILER LDDEANQYVE ATMRHLEDYA SEGLRTLCLA MRDISEGEYE EWNSIYNEAA TTLDNRAEKL DEAANLIEKN LILIGATAIE DKLQDGVPET IHTLQEAGIK IWVLTGDRQE TAINIGMSCR LLSEDMNLLI INEETRDDTE RNLLEKINAL NEHQLSTHDM NTLALVIDGK SLGFALEPEL EDYLLTVAKL CKAVICCRVS PLQKALVVKM VKRKSSSLLL AIGDGANDVS MIQAAHVGVG ISGMEGMQAA RSADIAVGQF KFLKKLLLVH GSWSYQRISV AILYSFYKNT ALYMTQFWYV FANAFSGQSI MESWTMSFYN LFFTVWPPFV IGVFDQFVSS RLLERYPQLY KLGQKGQFFS VYIFWGWIIN GFFHSAIVFI GTILIYRYGF ALNMHGELAD HWSWGVTVYT TSVIIVLGKA ALVTNQWTKF TLIAIPGSLL FWLIFFPIYA SIFPHANISR EYYGVVKHTY GSGVFWLTLI VLPIFALVRD FLWKYYKRMY EPETYHVIQE MQKYNISDSR PHVQQFQNAI RKVRQVQRMK KQRGFAFSQA EEGGQEKIVR MYDTTQKRGK YGELQDASAN PFNDNNGLGS NDFESAEPFI ENPFADGNQN SNRFSSSRDD ISFDI //