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3.A.3.8.4
Inwardly directed phospholipid and lysophospholipid (phosphatidylcholine, phosphatidyl serine and lysophosphoethanolamine) flippase, Dnf1 or ATP11C (functions with the β-subunit, Lem3 or CDC50A (TC# 8.A.27.1.5) (Elvington et al., 2005; Pomorski et al., 2003; Riekhof and Voelker, 2006; Riekhof et al., 2007) Also transports the anti-neoplastic and anti-parasitic ether lipid substrates related to edelfosine (Riekhof and Voelker, 2009) (not required for phosphotidyl serine inwardly directed flipping (Stevens et al. 2008)). Transports diacyl phospholipids in preference to lyso (monoacyl) phospholipids (Baldridge et al. 2013).  A conserved asparagine (N220) in the first transmembrane segment specifies glycerophospholipid binding and transport, but specific substitutions at this site allow transport of sphingomyelin (Roland and Graham 2016). It transports glycosphingolipids (Roland et al. 2019). Nakanishi et al. 2020 presented the crystal structures of a human plasma membrane flippase, the ATP11C-CDC50A complex, in a stabilized E2P conformation. The structure revealed a deep longitudinal crevice along transmembrane helices continuing from the cell surface to the phospholipid occlusion site in the middle of the membrane. The extension of the crevice on the exoplasmic side was open, and the complex was therefore in an outward-open E2P state, similar to a cryo-EM structure of the yeast flippase Drs2p-Cdc50p complex. Phosphatidylserines were in the crevice and in its extension to the extracellular side. One was close to the phosphatidylserine occlusion site as previously reported for the human ATP8A1-CDC50A complex, and the other in a cavity at the surface of the exoplasmic leaflet of the bilayer. Substitutions in either of the binding sites or along the path between them impaired ATPase and transport activities. Thus, the crevice is the conduit along which phosphatidylserine traverses the membrane (Nakanishi et al. 2020).

Accession Number:P32660
Protein Name:Dnf1 aka Yer166W aka SygP-ORF7
Length:1571
Molecular Weight:177798.00
Species:Saccharomyces cerevisiae (Baker's yeast) [4932]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate sphingomyelin d18:1, phospholipid, 1,2-diacyl-sn-glycero-3-phosphocholine(1+), phosphatidyl-L-serine, monoacylglycerol phosphate

Cross database links:

DIP: DIP-7949N
RefSeq: NP_011093.1   
Entrez Gene ID: 856913   
Pfam: PF00122   
KEGG: sce:YER166W   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005739 C:mitochondrion
GO:0005886 C:plasma membrane
GO:0005524 F:ATP binding
GO:0015662 F:ATPase activity, coupled to transmembrane m...
GO:0042802 F:identical protein binding
GO:0000287 F:magnesium ion binding
GO:0004012 F:phospholipid-translocating ATPase activity
GO:0006754 P:ATP biosynthetic process
GO:0006897 P:endocytosis
GO:0007163 P:establishment or maintenance of cell polarity
GO:0006886 P:intracellular protein transport
GO:0045332 P:phospholipid translocation

References (6)

[1] “The nucleotide sequence of Saccharomyces cerevisiae chromosome V.”  Dietrich F.S.et.al.   9169868
[2] “A global topology map of the Saccharomyces cerevisiae membrane proteome.”  Kim H.et.al.   16847258
[3] “Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae.”  Li X.et.al.   17330950
[4] “Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry.”  Chi A.et.al.   17287358
[5] “Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases.”  Smolka M.B.et.al.   17563356
[6] “A multidimensional chromatography technology for in-depth phosphoproteome analysis.”  Albuquerque C.P.et.al.   18407956

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MSGTFHGDGH APMSPFEDTF QFEDNSSNED THIAPTHFDD GATSNKYSRP QVSFNDETPK 
61:	NKREDAEEFT FNDDTEYDNH SFQPTPKLNN GSGTFDDVEL DNDSGEPHTN YDGMKRFRMG 
121:	TKRNKKGNPI MGRSKTLKWA RKNIPNPFED FTKDDIDPGA INRAQELRTV YYNMPLPKDM 
181:	IDEEGNPIMQ YPRNKIRTTK YTPLTFLPKN ILFQFHNFAN VYFLVLIILG AFQIFGVTNP 
241:	GLSAVPLVVI VIITAIKDAI EDSRRTVLDL EVNNTKTHIL EGVENENVST DNISLWRRFK 
301:	KANSRLLFKF IQYCKEHLTE EGKKKRMQRK RHELRVQKTV GTSGPRSSLD SIDSYRVSAD 
361:	YGRPSLDYDN LEQGAGEANI VDRSLPPRTD CKFAKNYWKG VKVGDIVRIH NNDEIPADII 
421:	LLSTSDTDGA CYVETKNLDG ETNLKVRQSL KCTNTIRTSK DIARTKFWIE SEGPHSNLYT 
481:	YQGNMKWRNL ADGEIRNEPI TINNVLLRGC TLRNTKWAMG VVMFTGGDTK IMLNSGITPT 
541:	KKSRISRELN FSVVINFVLL FILCFVSGIA NGVYYDKKGR SRFSYEFGTI AGSAATNGFV 
601:	SFWVAVILYQ SLVPISLYIS VEIIKTAQAA FIYGDVLLYN AKLDYPCTPK SWNISDDLGQ 
661:	VEYIFSDKTG TLTQNVMEFK KCTINGVSYG RAYTEALAGL RKRQGIDVET EGRREKAEIA 
721:	KDRDTMIDEL RALSGNSQFY PEEVTFVSKE FVRDLKGASG EVQQRCCEHF MLALALCHSV 
781:	LVEANPDNPK KLDLKAQSPD EAALVATARD VGFSFVGKTK KGLIIEMQGI QKEFEILNIL 
841:	EFNSSRKRMS CIVKIPGLNP GDEPRALLIC KGADSIIYSR LSRQSGSNSE AILEKTALHL 
901:	EQYATEGLRT LCIAQRELSW SEYEKWNEKY DIAAASLANR EDELEVVADS IERELILLGG 
961:	TAIEDRLQDG VPDCIELLAE AGIKLWVLTG DKVETAINIG FSCNLLNNEM ELLVIKTTGD 
1021:	DVKEFGSEPS EIVDALLSKY LKEYFNLTGS EEEIFEAKKD HEFPKGNYAI VIDGDALKLA 
1081:	LYGEDIRRKF LLLCKNCRAV LCCRVSPSQK AAVVKLVKDS LDVMTLAIGD GSNDVAMIQS 
1141:	ADVGIGIAGE EGRQAVMCSD YAIGQFRYLA RLVLVHGRWS YKRLAEMIPE FFYKNMIFAL 
1201:	ALFWYGIYND FDGSYLYEYT YMMFYNLAFT SLPVIFLGIL DQDVNDTISL VVPQLYRVGI 
1261:	LRKEWNQRKF LWYMLDGLYQ SIICFFFPYL VYHKNMIVTS NGLGLDHRYF VGVYVTTIAV 
1321:	ISCNTYVLLH QYRWDWFSGL FIALSCLVVF AWTGIWSSAI ASREFFKAAA RIYGAPSFWA 
1381:	VFFVAVLFCL LPRFTYDSFQ KFFYPTDVEI VREMWQHGHF DHYPPGYDPT DPNRPKVTKA 
1441:	GQHGEKIIEG IALSDNLGGS NYSRDSVVTE EIPMTFMHGE DGSPSGYQKQ ETWMTSPKET 
1501:	QDLLQSPQFQ QAQTFGRGPS TNVRSSLDRT REQMIATNQL DNRYSVERAR TSLDLPGVTN 
1561:	AASLIGTQQN N