ID AT11C_HUMAN Reviewed; 1132 AA. AC Q8NB49; Q5JT69; Q5JT70; Q5JT71; Q5JT72; Q5JT73; Q6ZND5; Q6ZU50; Q6ZUP7; AC Q70IJ9; Q70IK0; Q8WX24; DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 12-APR-2005, sequence version 3. DT 24-JAN-2024, entry version 185. DE RecName: Full=Phospholipid-transporting ATPase IG; DE EC=7.6.2.1 {ECO:0000269|PubMed:24904167, ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:32493773}; DE AltName: Full=ATPase IQ; DE AltName: Full=ATPase class VI type 11C; DE AltName: Full=P4-ATPase flippase complex alpha subunit ATP11C; GN Name=ATP11C {ECO:0000303|PubMed:26944472}; Synonyms=ATPIG, ATPIQ; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY, AND RP VARIANT TRP-114. RC TISSUE=Liver; RX PubMed=15533723; DOI=10.1016/j.ygeno.2004.08.003; RA Andrew-Nesbit M., Bowl M.R., Harding B., Schlessinger D., Whyte M.P., RA Thakker R.V.; RT "X-linked hypoparathyroidism region on Xq27 is evolutionarily conserved RT with regions on 3q26 and 13q34 and contains a novel P-type ATPase."; RL Genomics 84:1060-1070(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 305-1132 (ISOFORM 4), NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 543-1132 (ISOFORM 1), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 777-1132 (ISOFORM 2). RC TISSUE=Brain, Fetal brain, Testis, and Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1108, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [9] RP INTERACTION WITH TMEM30A, AND SUBCELLULAR LOCATION. RX PubMed=21914794; DOI=10.1074/jbc.m111.281006; RA Takatsu H., Baba K., Shima T., Umino H., Kato U., Umeda M., Nakayama K., RA Shin H.W.; RT "ATP9B, a P4-ATPase (a putative aminophospholipid translocase), localizes RT to the trans-Golgi network in a CDC50 protein-independent manner."; RL J. Biol. Chem. 286:38159-38167(2011). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445; SER-1108; SER-1116 AND RP SER-1126, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP VARIANTS [LARGE SCALE ANALYSIS] ILE-157 AND PRO-931. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP GLU-184 AND ASP-412. RX PubMed=25315773; DOI=10.1074/jbc.m114.593012; RA Takatsu H., Tanaka G., Segawa K., Suzuki J., Nagata S., Nakayama K., RA Shin H.W.; RT "Phospholipid flippase activities and substrate specificities of human type RT IV P-type ATPases localized to the plasma membrane."; RL J. Biol. Chem. 289:33543-33556(2014). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PROTEOLYTIC CLEAVAGE, RP AND MUTAGENESIS OF ASP-442; ASP-448 AND ASP-484. RX PubMed=24904167; DOI=10.1126/science.1252809; RA Segawa K., Kurata S., Yanagihashi Y., Brummelkamp T.R., Matsuda F., RA Nagata S.; RT "Caspase-mediated cleavage of phospholipid flippase for apoptotic RT phosphatidylserine exposure."; RL Science 344:1164-1168(2014). RN [16] RP FUNCTION IN PHOSPHATIDYLSERINE FLIPPING, INVOLVEMENT IN HACXL, VARIANT RP HACXL ASN-418, AND CHARACTERIZATION OF VARIANT HACXL ASN-418. RX PubMed=26944472; DOI=10.3324/haematol.2016.142273; RA Arashiki N., Takakuwa Y., Mohandas N., Hale J., Yoshida K., Ogura H., RA Utsugisawa T., Ohga S., Miyano S., Ogawa S., Kojima S., Kanno H.; RT "ATP11C is a major flippase in human erythrocytes and its defect causes RT congenital hemolytic anemia."; RL Haematologica 101:559-565(2016). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, AND TISSUE SPECIFICITY. RX PubMed=26567335; DOI=10.1074/jbc.m115.690727; RA Segawa K., Kurata S., Nagata S.; RT "Human Type IV P-type ATPases That Work as Plasma Membrane Phospholipid RT Flippases and Their Regulation by Caspase and Calcium."; RL J. Biol. Chem. 291:762-772(2016). RN [18] RP SUBCELLULAR LOCATION, DOMAIN, PHOSPHORYLATION AT SER-1116, AND MUTAGENESIS RP OF SER-1116; LEU-1120; LEU-1121; LEU-1122 AND SER-1126. RX PubMed=29123098; DOI=10.1038/s41467-017-01338-1; RA Takatsu H., Takayama M., Naito T., Takada N., Tsumagari K., Ishihama Y., RA Nakayama K., Shin H.W.; RT "Phospholipid flippase ATP11C is endocytosed and downregulated following RT Ca2+-mediated protein kinase C activation."; RL Nat. Commun. 8:1423-1423(2017). RN [19] RP X-RAY CRYSTALLOGRAPHY (3.90 ANGSTROMS) OF 13-1132 IN COMPLEX WITH TMEM30A RP AND MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLN-66; RP ARG-69; ASN-72; PHE-75; THR-93; VAL-101; VAL-352; LEU-353; ASN-355; RP PHE-356; VAL-360; LYS-883; ASN-884 AND ASN-915. RX PubMed=32493773; DOI=10.1074/jbc.ra120.014144; RA Nakanishi H., Irie K., Segawa K., Hasegawa K., Fujiyoshi Y., Nagata S., RA Abe K.; RT "Crystal structure of a human plasma membrane phospholipid flippase."; RL J. Biol. Chem. 295:10180-10194(2020). CC -!- FUNCTION: Catalytic component of a P4-ATPase flippase complex which CC catalyzes the hydrolysis of ATP coupled to the transport of CC aminophospholipids, phosphatidylserines (PS) and CC phosphatidylethanolamines (PE), from the outer to the inner leaflet of CC the plasma membrane (PubMed:25315773, PubMed:32493773, PubMed:24904167, CC PubMed:26567335). Major PS-flippase in immune cell subsets. In CC erythrocyte plasma membrane, it is required to maintain PS in the inner CC leaflet preventing its exposure on the surface. This asymmetric CC distribution is critical for the survival of erythrocytes in CC circulation since externalized PS is a phagocytic signal for CC erythrocyte clearance by splenic macrophages (PubMed:26944472). CC Required for B cell differentiation past the pro-B cell stage (By CC similarity). Seems to mediate PS flipping in pro-B cells (By CC similarity). May be involved in the transport of cholestatic bile acids CC (By similarity). {ECO:0000250|UniProtKB:Q9QZW0, CC ECO:0000269|PubMed:24904167, ECO:0000269|PubMed:25315773, CC ECO:0000269|PubMed:26944472, ECO:0000269|PubMed:32493773}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate + CC phospholipidSide 2.; EC=7.6.2.1; CC Evidence={ECO:0000269|PubMed:24904167, ECO:0000269|PubMed:25315773, CC ECO:0000269|PubMed:26567335, ECO:0000269|PubMed:32493773}; 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:24904167, ECO:0000269|PubMed:25315773, CC ECO:0000269|PubMed:26567335, ECO:0000269|PubMed:32493773}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568; CC Evidence={ECO:0000305|PubMed:24904167, ECO:0000305|PubMed:25315773, CC ECO:0000305|PubMed:26567335, ECO:0000305|PubMed:32493773}; 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:0000269|PubMed:24904167, ECO:0000269|PubMed:25315773, CC ECO:0000269|PubMed:26567335, ECO:0000269|PubMed:32493773}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66133; CC Evidence={ECO:0000305|PubMed:24904167, ECO:0000305|PubMed:25315773, CC ECO:0000305|PubMed:26567335, ECO:0000305|PubMed:32493773}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:Q9Y2Q0}; CC -!- ACTIVITY REGULATION: The flippase activity is inactivated by caspase- CC mediated cleavage in apoptotic cells, allowing for PS exposure on the CC cell surface and engulfment of apoptotic cells by macrophages. The CC ATPase activity is up-regulated by aminophospholipids PS and PE and CC down-regulated by Increasing intracellular Ca2+ levels. CC {ECO:0000269|PubMed:24904167, ECO:0000269|PubMed:26567335}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.3 uM for ATP (in the presence of PS) CC {ECO:0000269|PubMed:26567335}; CC KM=11 uM for ATP (in the presence of PE) CC {ECO:0000269|PubMed:26567335}; CC Vmax=8.9 nmol/min/ug enzyme toward ATP (in the presence of PS) CC {ECO:0000269|PubMed:26567335}; CC Vmax=6.7 nmol/min/ug enzyme toward ATP (in the presence of PE) CC {ECO:0000269|PubMed:26567335}; CC -!- SUBUNIT: Component of a P4-ATPase flippase complex which consists of a CC catalytic alpha subunit ATP11C and an accessory beta subunit TMEM30A. CC {ECO:0000269|PubMed:21914794, ECO:0000269|PubMed:32493773}. CC -!- INTERACTION: CC Q8NB49; Q9NV96: TMEM30A; NbExp=2; IntAct=EBI-11279131, EBI-2836942; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21914794, CC ECO:0000269|PubMed:25315773}; Multi-pass membrane protein CC {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:21914794, ECO:0000269|PubMed:25315773}; Multi-pass CC membrane protein {ECO:0000255}. Early endosome membrane CC {ECO:0000269|PubMed:29123098}; Multi-pass membrane protein CC {ECO:0000255}. Recycling endosome membrane CC {ECO:0000269|PubMed:29123098}; Multi-pass membrane protein CC {ECO:0000255}. Note=Efficient exit from the endoplasmic reticulum CC requires the presence of TMEM30A. Internalized via clathrin-dependent CC endocytosis in response to ca(2+) signaling induced by G-protein CC coupled serotonin and histamine receptors. CC {ECO:0000269|PubMed:29123098}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q8NB49-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8NB49-2; Sequence=VSP_007309; CC Name=3; CC IsoId=Q8NB49-3; Sequence=VSP_013373; CC Name=4; CC IsoId=Q8NB49-4; Sequence=VSP_013374; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:15533723, CC ECO:0000269|PubMed:26567335}. CC -!- DOMAIN: The di-leucine motif is required for sorting to clathrin-coated CC endosomes upon ca(2+)-dependent PRKCA activation. CC {ECO:0000269|PubMed:29123098}. CC -!- PTM: Proteolytically cleaved by CASP3, CASP6 and CASP7. CC {ECO:0000269|PubMed:24904167}. CC -!- PTM: Phosphorylated at Ser-1116 likely by PRKCA; this creates a CC functional di-leucine motif that is sufficient for endocytosis. CC {ECO:0000269|PubMed:29123098}. CC -!- DISEASE: Hemolytic anemia, congenital, X-linked (HACXL) [MIM:301015]: CC An X-linked hematologic disease characterized by shortened survival of CC erythrocytes due to congenital hemolysis that cannot be compensated by CC bone marrow activity. Clinical features are mild jaundice and anemia. CC Red cells morphology is normal. {ECO:0000269|PubMed:26944472}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) CC family. Type IV subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC03692.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAC86172.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAC86377.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAD18440.1; Type=Erroneous initiation; Evidence={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; AJ580093; CAE30472.1; -; mRNA. DR EMBL; AJ580094; CAE30473.1; -; mRNA. DR EMBL; AL161777; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL356785; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590077; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK091552; BAC03692.1; ALT_INIT; mRNA. DR EMBL; AK125474; BAC86172.1; ALT_INIT; mRNA. DR EMBL; AK125986; BAC86377.1; ALT_INIT; mRNA. DR EMBL; AK131262; BAD18440.1; ALT_INIT; mRNA. DR CCDS; CCDS14668.1; -. [Q8NB49-1] DR CCDS; CCDS35410.1; -. [Q8NB49-3] DR RefSeq; NP_001010986.1; NM_001010986.2. [Q8NB49-3] DR RefSeq; NP_775965.2; NM_173694.4. [Q8NB49-1] DR PDB; 6LKN; X-ray; 3.90 A; A/E/I/M=13-1132. DR PDB; 7BSP; EM; 4.00 A; A=13-1094. DR PDB; 7BSQ; EM; 3.20 A; A=13-1094. DR PDB; 7BSS; EM; 3.30 A; A=13-1094. DR PDB; 7BSU; EM; 3.20 A; A=13-1094. DR PDB; 7BSV; EM; 3.00 A; A=13-1094. DR PDB; 7BSW; EM; 3.90 A; A=13-1094. DR PDB; 7VSG; EM; 3.90 A; A=13-1094. DR PDB; 7VSH; EM; 3.40 A; A=13-1094. DR PDBsum; 6LKN; -. DR PDBsum; 7BSP; -. DR PDBsum; 7BSQ; -. DR PDBsum; 7BSS; -. DR PDBsum; 7BSU; -. DR PDBsum; 7BSV; -. DR PDBsum; 7BSW; -. DR PDBsum; 7VSG; -. DR PDBsum; 7VSH; -. DR AlphaFoldDB; Q8NB49; -. DR EMDB; EMD-30163; -. DR EMDB; EMD-30164; -. DR EMDB; EMD-30165; -. DR EMDB; EMD-30167; -. DR EMDB; EMD-30168; -. DR EMDB; EMD-30169; -. DR EMDB; EMD-32110; -. DR EMDB; EMD-32111; -. DR SMR; Q8NB49; -. DR BioGRID; 130370; 95. DR ComplexPortal; CPX-6312; ATP11C-CDC50A P4-ATPase complex. DR IntAct; Q8NB49; 37. DR MINT; Q8NB49; -. DR STRING; 9606.ENSP00000332756; -. DR TCDB; 3.A.3.8.14; the p-type atpase (p-atpase) superfamily. DR iPTMnet; Q8NB49; -. DR PhosphoSitePlus; Q8NB49; -. DR SwissPalm; Q8NB49; -. DR BioMuta; ATP11C; -. DR DMDM; 62512178; -. DR EPD; Q8NB49; -. DR jPOST; Q8NB49; -. DR MassIVE; Q8NB49; -. DR MaxQB; Q8NB49; -. DR PaxDb; 9606-ENSP00000332756; -. DR PeptideAtlas; Q8NB49; -. DR ProteomicsDB; 72731; -. [Q8NB49-1] DR ProteomicsDB; 72732; -. [Q8NB49-2] DR ProteomicsDB; 72733; -. [Q8NB49-3] DR ProteomicsDB; 72734; -. [Q8NB49-4] DR Pumba; Q8NB49; -. DR Antibodypedia; 30516; 110 antibodies from 23 providers. DR DNASU; 286410; -. DR Ensembl; ENST00000327569.7; ENSP00000332756.3; ENSG00000101974.15. [Q8NB49-1] DR Ensembl; ENST00000361648.6; ENSP00000355165.2; ENSG00000101974.15. [Q8NB49-3] DR GeneID; 286410; -. DR KEGG; hsa:286410; -. DR UCSC; uc004faz.4; human. [Q8NB49-1] DR AGR; HGNC:13554; -. DR CTD; 286410; -. DR DisGeNET; 286410; -. DR GeneCards; ATP11C; -. DR HGNC; HGNC:13554; ATP11C. DR HPA; ENSG00000101974; Tissue enhanced (liver). DR MalaCards; ATP11C; -. DR MIM; 300516; gene. DR MIM; 301015; phenotype. DR neXtProt; NX_Q8NB49; -. DR OpenTargets; ENSG00000101974; -. DR PharmGKB; PA25103; -. DR VEuPathDB; HostDB:ENSG00000101974; -. DR eggNOG; KOG0206; Eukaryota. DR GeneTree; ENSGT00940000158878; -. DR HOGENOM; CLU_000846_3_1_1; -. DR InParanoid; Q8NB49; -. DR OMA; RNLNCRR; -. DR OrthoDB; 275833at2759; -. DR PhylomeDB; Q8NB49; -. DR TreeFam; TF326897; -. DR BRENDA; 7.6.2.1; 2681. DR PathwayCommons; Q8NB49; -. DR Reactome; R-HSA-936837; Ion transport by P-type ATPases. DR SignaLink; Q8NB49; -. DR BioGRID-ORCS; 286410; 20 hits in 786 CRISPR screens. DR ChiTaRS; ATP11C; human. DR GenomeRNAi; 286410; -. DR Pharos; Q8NB49; Tbio. DR PRO; PR:Q8NB49; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q8NB49; Protein. DR Bgee; ENSG00000101974; Expressed in seminal vesicle and 187 other cell types or tissues. DR ExpressionAtlas; Q8NB49; baseline and differential. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB. DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; IDA:FlyBase. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0055037; C:recycling endosome; IBA:GO_Central. DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell. 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:0090555; F:phosphatidylethanolamine flippase activity; 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:0034220; P:monoatomic ion transmembrane transport; TAS:Reactome. DR GO; GO:0045332; P:phospholipid translocation; IDA:FlyBase. 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; 3. DR PANTHER; PTHR24092:SF38; PHOSPHOLIPID-TRANSPORTING ATPASE IG; 1. DR PANTHER; PTHR24092; PROBABLE PHOSPHOLIPID-TRANSPORTING ATPASE; 1. DR Pfam; PF13246; Cation_ATPase; 1. DR Pfam; PF00122; E1-E2_ATPase; 1. DR Pfam; PF16212; PhoLip_ATPase_C; 1. DR Pfam; PF16209; PhoLip_ATPase_N; 1. 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. DR Genevisible; Q8NB49; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Disease variant; Endoplasmic reticulum; Endosome; KW Hereditary hemolytic anemia; Lipid transport; Magnesium; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Translocase; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..1132 FT /note="Phospholipid-transporting ATPase IG" FT /id="PRO_0000046373" FT TOPO_DOM 1..66 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 67..85 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 86 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 87..107 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 108..290 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 291..311 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 312..346 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 347..367 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 368..879 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 880..900 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 901..908 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 909..929 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 930..955 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 956..976 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 977..995 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 996..1016 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1017..1026 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1027..1047 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1048..1069 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1070..1090 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1091..1132 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOTIF 1116..1121 FT /note="Di-leucine motif" FT /evidence="ECO:0000269|PubMed:29123098" FT ACT_SITE 412 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 412 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 412 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 413 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 414 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 414 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 501 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 543 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 566 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 597 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 677 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 678 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 679 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 792 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 798 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 819 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:32493773, FT ECO:0007744|PDB:6LKN" FT BINDING 822 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 823 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 823 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:32493773, FT ECO:0007744|PDB:6LKN" FT SITE 442..443 FT /note="Cleavage; by CASP3, CASP6 and CASP7" FT /evidence="ECO:0000269|PubMed:24904167" FT SITE 448..449 FT /note="Cleavage; by CASP3" FT /evidence="ECO:0000269|PubMed:24904167" FT SITE 484..485 FT /note="Cleavage; by CASP3 and CASP7" FT /evidence="ECO:0000269|PubMed:24904167" FT MOD_RES 445 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1108 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1116 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:29123098, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1126 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1100..1132 FT /note="RNLSCRRASDSLSARPSVRPLLLRTFSDESNVL -> VHHLISSSA (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_007309" FT VAR_SEQ 1100..1132 FT /note="RNLSCRRASDSLSARPSVRPLLLRTFSDESNVL -> NPNLELPMLLSYKHT FT DSGYS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15533723" FT /id="VSP_013373" FT VAR_SEQ 1100..1132 FT /note="RNLSCRRASDSLSARPSVRPLLLRTFSDESNVL -> VTKRLPSSGTSAIFM FT LSQTSSNHSFSWSE (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_013374" FT VARIANT 114 FT /note="C -> W (in dbSNP:rs2491014)" FT /evidence="ECO:0000269|PubMed:15533723" FT /id="VAR_021827" FT VARIANT 157 FT /note="T -> I (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036501" FT VARIANT 418 FT /note="T -> N (in HACXL; decreased phosphatidylserine FT translocation from the outer to the inner leaflet of FT erythrocytes cell membrane; dbSNP:rs1556323334)" FT /evidence="ECO:0000269|PubMed:26944472" FT /id="VAR_081016" FT VARIANT 522 FT /note="Y -> C (in dbSNP:rs17281983)" FT /id="VAR_055546" FT VARIANT 931 FT /note="Q -> P (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036502" FT VARIANT 972 FT /note="V -> M (in dbSNP:rs55724992)" FT /id="VAR_061036" FT MUTAGEN 66 FT /note="Q->A: Decreases ATPase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 69 FT /note="R->A: Decreases ATPase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 72 FT /note="N->A: Decreases ATPase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 75 FT /note="F->A: Impairs ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 93 FT /note="T->A: Decreases ATPase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 101 FT /note="V->A: Impairs ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 184 FT /note="E->Q: Has no effect on endoplasmic reticulum to FT plasma membrane trafficking. Impairs ATPase flippase FT activity." FT /evidence="ECO:0000269|PubMed:25315773" FT MUTAGEN 352 FT /note="V->F: Impairs ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 353 FT /note="L->F: Decreases ATPase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 355 FT /note="N->A: Impairs ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 356 FT /note="F->N: Has no effect on ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 360 FT /note="V->F: Decreases ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 360 FT /note="V->I: Has minor effect on ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 412 FT /note="D->N: Impairs endoplasmic reticulum to plasma FT membrane trafficking." FT /evidence="ECO:0000269|PubMed:25315773" FT MUTAGEN 442 FT /note="D->A: Impairs caspase-mediated cleavage; when FT associated with A-448 and A-484." FT /evidence="ECO:0000269|PubMed:24904167" FT MUTAGEN 448 FT /note="D->A: Impairs caspase-mediated cleavage; when FT associated with A-442 and A-484." FT /evidence="ECO:0000269|PubMed:24904167" FT MUTAGEN 484 FT /note="D->A: Impairs caspase-mediated cleavage; when FT associated with A-442 and A-448." FT /evidence="ECO:0000269|PubMed:24904167" FT MUTAGEN 883 FT /note="K->A: Decreases ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 884 FT /note="N->A: Decreases ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 915 FT /note="N->A: Decreases ATPase flippase activity." FT /evidence="ECO:0000269|PubMed:32493773" FT MUTAGEN 1116 FT /note="S->A: Impairs sorting to endosomal compartments in FT response to ca(2+) signaling." FT /evidence="ECO:0000269|PubMed:29123098" FT MUTAGEN 1116 FT /note="S->D: Localizes to endosomal compartments in the FT absence of ca(2+) signaling." FT /evidence="ECO:0000269|PubMed:29123098" FT MUTAGEN 1120 FT /note="L->A: Impairs sorting to endosomal compartments in FT response to ca(2+) signaling." FT /evidence="ECO:0000269|PubMed:29123098" FT MUTAGEN 1121 FT /note="L->A: Impairs sorting to endosomal compartments in FT response to ca(2+) signaling." FT /evidence="ECO:0000269|PubMed:29123098" FT MUTAGEN 1122 FT /note="L->A: Has no effect on sorting to endosomal FT compartments in response to ca(2+) signaling." FT /evidence="ECO:0000269|PubMed:29123098" FT MUTAGEN 1126 FT /note="S->A: Decreases sorting to endosomal compartments in FT response to ca(2+) signaling." FT /evidence="ECO:0000269|PubMed:29123098" FT CONFLICT 537 FT /note="L -> P (in Ref. 3; BAC86377)" FT /evidence="ECO:0000305" FT CONFLICT 873 FT /note="I -> V (in Ref. 3; BAC86377)" FT /evidence="ECO:0000305" FT STRAND 23..26 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 55..57 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 58..66 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 70..84 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 92..123 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 127..131 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 133..140 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 141..143 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 149..151 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 159..163 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 166..171 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 173..177 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 179..181 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 188..191 FT /evidence="ECO:0007829|PDB:7BSQ" FT HELIX 194..196 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 200..203 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 211..214 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 226..228 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 233..235 FT /evidence="ECO:0007829|PDB:7VSH" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 244..246 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 253..256 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 258..263 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 268..271 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 272..275 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 286..316 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 320..322 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 326..328 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 333..336 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 339..354 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 355..357 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 360..373 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 375..379 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 381..385 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 386..389 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 393..395 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 397..402 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 408..411 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 415..417 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 423..429 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 459..461 FT /evidence="ECO:0007829|PDB:7BSQ" FT HELIX 462..470 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 471..473 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 486..489 FT /evidence="ECO:0007829|PDB:7BSQ" FT HELIX 499..510 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 519..523 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 528..530 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 535..541 FT /evidence="ECO:0007829|PDB:7BSQ" FT TURN 545..547 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 549..555 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 561..567 FT /evidence="ECO:0007829|PDB:7BSQ" FT TURN 570..572 FT /evidence="ECO:0007829|PDB:7BSQ" FT TURN 573..575 FT /evidence="ECO:0007829|PDB:7VSH" FT HELIX 578..580 FT /evidence="ECO:0007829|PDB:7BSQ" FT HELIX 581..593 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 597..606 FT /evidence="ECO:0007829|PDB:7BSQ" FT HELIX 608..622 FT /evidence="ECO:0007829|PDB:7BSQ" FT HELIX 628..636 FT /evidence="ECO:0007829|PDB:7BSQ" FT STRAND 639..652 FT /evidence="ECO:0007829|PDB:7BSQ" FT HELIX 659..668 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 672..676 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 681..688 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 689..692 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 699..702 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 705..707 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 710..712 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 713..722 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 723..728 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 747..749 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 750..755 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 756..764 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 765..767 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 770..772 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 774..783 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 788..792 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 797..805 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 808..810 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 814..821 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 824..827 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 830..835 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 843..847 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 848..851 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 853..855 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 857..862 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 865..893 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 894..896 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 897..899 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 908..913 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 914..918 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 922..926 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 935..938 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 942..948 FT /evidence="ECO:0007829|PDB:7BSV" FT TURN 949..951 FT /evidence="ECO:0007829|PDB:7BSU" FT HELIX 952..954 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 956..980 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 982..984 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 986..989 FT /evidence="ECO:0007829|PDB:7BSQ" FT HELIX 995..1017 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 1023..1043 FT /evidence="ECO:0007829|PDB:7BSV" FT STRAND 1049..1052 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 1059..1062 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 1063..1065 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 1067..1079 FT /evidence="ECO:0007829|PDB:7BSV" FT HELIX 1082..1090 FT /evidence="ECO:0007829|PDB:7BSV" SQ SEQUENCE 1132 AA; 129477 MW; 74B63B20A5C6E49D CRC64; MQMVPSLPPA SECAGEEKRV GTRTVFVGNH PVSETEAYIA QRFCDNRIVS SKYTLWNFLP KNLFEQFRRI ANFYFLIIFL VQVTVDTPTS PVTSGLPLFF VITVTAIKQG YEDCLRHRAD NEVNKSTVYI IENAKRVRKE SEKIKVGDVV EVQADETFPC DLILLSSCTT DGTCYVTTAS LDGESNCKTH YAVRDTIALC TAESIDTLRA AIECEQPQPD LYKFVGRINI YSNSLEAVAR SLGPENLLLK GATLKNTEKI YGVAVYTGME TKMALNYQGK SQKRSAVEKS INAFLIVYLF ILLTKAAVCT TLKYVWQSTP YNDEPWYNQK TQKERETLKV LKMFTDFLSF MVLFNFIIPV SMYVTVEMQK FLGSFFISWD KDFYDEEINE GALVNTSDLN EELGQVDYVF TDKTGTLTEN SMEFIECCID GHKYKGVTQE VDGLSQTDGT LTYFDKVDKN REELFLRALC LCHTVEIKTN DAVDGATESA ELTYISSSPD EIALVKGAKR YGFTFLGNRN GYMRVENQRK EIEEYELLHT LNFDAVRRRM SVIVKTQEGD ILLFCKGADS AVFPRVQNHE IELTKVHVER NAMDGYRTLC VAFKEIAPDD YERINRQLIE AKMALQDREE KMEKVFDDIE TNMNLIGATA VEDKLQDQAA ETIEALHAAG LKVWVLTGDK METAKSTCYA CRLFQTNTEL LELTTKTIEE SERKEDRLHE LLIEYRKKLL HEFPKSTRSF KKAWTEHQEY GLIIDGSTLS LILNSSQDSS SNNYKSIFLQ ICMKCTAVLC CRMAPLQKAQ IVRMVKNLKG SPITLSIGDG ANDVSMILES HVGIGIKGKE GRQAARNSDY SVPKFKHLKK LLLAHGHLYY VRIAHLVQYF FYKNLCFILP QFLYQFFCGF SQQPLYDAAY LTMYNICFTS LPILAYSLLE QHINIDTLTS DPRLYMKISG NAMLQLGPFL YWTFLAAFEG TVFFFGTYFL FQTASLEENG KVYGNWTFGT IVFTVLVFTV TLKLALDTRF WTWINHFVIW GSLAFYVFFS FFWGGIIWPF LKQQRMYFVF AQMLSSVSTW LAIILLIFIS LFPEILLIVL KNVRRRSARR NLSCRRASDS LSARPSVRPL LLRTFSDESN VL //