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3.A.3.8.14
ATP11C (ATPIG, ATPIQ) aminophospholipid (phosphatidyl serine and phosphatidyl ethanolamine, but not phosphatidyl choline) flippase of 1132 aas and 10 TMSs.  It is dependent on CDC50A (1232 aas and 9 TMSs, Anoctamin-8, Ano8; TC#1.A.17.1.30), for proper localization to the plasma membrane, and possibly also for activity (Segawa et al. 2014).  Present in liver basolateral membranes (Chaubey et al. 2016). It is the only phospholipid flipping ATPase in the human red blood cell (Liou et al. 2019). In the cell membrane of erythrocytes, it is required to maintain phosphatidylserine (PS) in the inner leaflet preventing its exposure on the surface. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized PS is a phagocytic signal for splenic macrophages (Arashiki et al. 2016). Phospholipid translocation seems also to be implicated in vesicle formation and in the uptake of lipid signaling molecules, and is required for B cell differentiation past the pro-B cell stage It seems to mediate PS flipping in pro-B cells and may be involved in the transport of cholestatic bile acids.  Caspase-dependent inactivation of ATP11C is essential for an apoptotic "eat me" signal, phosphatidylserine exposure, which prompts phagocytes to engulf cells. Nakanishi et al. 2020 presented six cryo-EM structures of ATP11C at 3.0-4.0 A resolution in five different states of the transport cycle. A structural comparison revealed phosphorylation-driven domain movements coupled with phospholipid binding. Three structures of phospholipid-bound states visualize phospholipid translocation accompanied by the rearrangement of transmembrane helices and an unwound portion at the occlusion site. They thus detail the basis for head group recognition and the locality of the protein-bound acyl chains in transmembrane grooves. Invariant Lys880 and the surrounding hydrogen-bond network serve as a pivot point for helix bending and precise P domain inclination, which is crucial for dephosphorylation. The structures detail key features of phospholipid translocation by ATP11C; a common basic mechanism for flippases is emerging (Nakanishi et al. 2020).  

Accession Number:Q8NB49
Protein Name:Probable phospholipid-transporting ATPase IG
Length:1132
Molecular Weight:129477.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate Aminophospholipids

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Structure:
6LKN     

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FASTA formatted sequence
1:	MQMVPSLPPA SECAGEEKRV GTRTVFVGNH PVSETEAYIA QRFCDNRIVS SKYTLWNFLP 
61:	KNLFEQFRRI ANFYFLIIFL VQVTVDTPTS PVTSGLPLFF VITVTAIKQG YEDCLRHRAD 
121:	NEVNKSTVYI IENAKRVRKE SEKIKVGDVV EVQADETFPC DLILLSSCTT DGTCYVTTAS 
181:	LDGESNCKTH YAVRDTIALC TAESIDTLRA AIECEQPQPD LYKFVGRINI YSNSLEAVAR 
241:	SLGPENLLLK GATLKNTEKI YGVAVYTGME TKMALNYQGK SQKRSAVEKS INAFLIVYLF 
301:	ILLTKAAVCT TLKYVWQSTP YNDEPWYNQK TQKERETLKV LKMFTDFLSF MVLFNFIIPV 
361:	SMYVTVEMQK FLGSFFISWD KDFYDEEINE GALVNTSDLN EELGQVDYVF TDKTGTLTEN 
421:	SMEFIECCID GHKYKGVTQE VDGLSQTDGT LTYFDKVDKN REELFLRALC LCHTVEIKTN 
481:	DAVDGATESA ELTYISSSPD EIALVKGAKR YGFTFLGNRN GYMRVENQRK EIEEYELLHT 
541:	LNFDAVRRRM SVIVKTQEGD ILLFCKGADS AVFPRVQNHE IELTKVHVER NAMDGYRTLC 
601:	VAFKEIAPDD YERINRQLIE AKMALQDREE KMEKVFDDIE TNMNLIGATA VEDKLQDQAA 
661:	ETIEALHAAG LKVWVLTGDK METAKSTCYA CRLFQTNTEL LELTTKTIEE SERKEDRLHE 
721:	LLIEYRKKLL HEFPKSTRSF KKAWTEHQEY GLIIDGSTLS LILNSSQDSS SNNYKSIFLQ 
781:	ICMKCTAVLC CRMAPLQKAQ IVRMVKNLKG SPITLSIGDG ANDVSMILES HVGIGIKGKE 
841:	GRQAARNSDY SVPKFKHLKK LLLAHGHLYY VRIAHLVQYF FYKNLCFILP QFLYQFFCGF 
901:	SQQPLYDAAY LTMYNICFTS LPILAYSLLE QHINIDTLTS DPRLYMKISG NAMLQLGPFL 
961:	YWTFLAAFEG TVFFFGTYFL FQTASLEENG KVYGNWTFGT IVFTVLVFTV TLKLALDTRF 
1021:	WTWINHFVIW GSLAFYVFFS FFWGGIIWPF LKQQRMYFVF AQMLSSVSTW LAIILLIFIS 
1081:	LFPEILLIVL KNVRRRSARR NLSCRRASDS LSARPSVRPL LLRTFSDESN VL