AT11A_HUMAN
ID AT11A_HUMAN Reviewed; 1134 AA.
AC P98196; Q5VXT2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Phospholipid-transporting ATPase IH;
DE EC=7.6.2.1 {ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:25947375, ECO:0000269|PubMed:26567335, ECO:0000269|PubMed:30018401};
DE AltName: Full=ATPase IS;
DE AltName: Full=ATPase class VI type 11A;
DE AltName: Full=P4-ATPase flippase complex alpha subunit ATP11A;
GN Name=ATP11A; Synonyms=ATPIH, ATPIS, KIAA1021;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 33-1134, AND VARIANT VAL-317.
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [3]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=15860663; DOI=10.1182/blood-2004-09-3655;
RA Zhang B., Groffen J., Heisterkamp N.;
RT "Resistance to farnesyltransferase inhibitors in Bcr/Abl-positive
RT lymphoblastic leukemia by increased expression of a novel ABC transporter
RT homolog ATP11a.";
RL Blood 106:1355-1361(2005).
RN [5]
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-738, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLU-186 AND ASP-414.
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH
RP TMEM30A, AND MUTAGENESIS OF GLU-186.
RX PubMed=25947375; DOI=10.1074/jbc.m115.655191;
RA Naito T., Takatsu H., Miyano R., Takada N., Nakayama K., Shin H.W.;
RT "Phospholipid Flippase ATP10A Translocates Phosphatidylcholine and Is
RT Involved in Plasma Membrane Dynamics.";
RL J. Biol. Chem. 290:15004-15017(2015).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, PROTEOLYTIC CLEAVAGE, MUTAGENESIS OF ASP-454; ASP-457; ASP-487
RP AND ASP-490, 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 [10]
RP FUNCTION, INTERACTION WITH TMEM30A, AND TISSUE SPECIFICITY.
RX PubMed=29799007; DOI=10.1038/s41467-018-04436-w;
RA Tsuchiya M., Hara Y., Okuda M., Itoh K., Nishioka R., Shiomi A., Nagao K.,
RA Mori M., Mori Y., Ikenouchi J., Suzuki R., Tanaka M., Ohwada T., Aoki J.,
RA Kanagawa M., Toda T., Nagata Y., Matsuda R., Takayama Y., Tominaga M.,
RA Umeda M.;
RT "Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-
RT mediated myotube formation.";
RL Nat. Commun. 9:2049-2049(2018).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP GLU-186.
RX PubMed=30018401; DOI=10.1038/s41598-018-29108-z;
RA Wang J., Molday L.L., Hii T., Coleman J.A., Wen T., Andersen J.P.,
RA Molday R.S.;
RT "Proteomic Analysis and Functional Characterization of P4-ATPase
RT Phospholipid Flippases from Murine Tissues.";
RL Sci. Rep. 8:10795-10795(2018).
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:25947375, PubMed:26567335,
CC PubMed:29799007, PubMed:30018401). Contributes to the maintenance of
CC membrane lipid asymmetry with a specific role in morphogenesis of
CC muscle cells. In myoblasts, mediates PS enrichment at the inner leaflet
CC of plasma membrane, triggering PIEZO1-dependent Ca2+ influx and Rho
CC GTPases signal transduction, subsequently leading to the assembly of
CC cortical actomyosin fibers and myotube formation (PubMed:29799007). May
CC be involved in the uptake of farnesyltransferase inhibitor drugs, such
CC as lonafarnib. {ECO:0000269|PubMed:15860663,
CC ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:25947375,
CC ECO:0000269|PubMed:26567335, ECO:0000269|PubMed:29799007,
CC ECO:0000269|PubMed:30018401, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:25947375,
CC ECO:0000269|PubMed:26567335, ECO:0000269|PubMed:30018401};
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:25315773, ECO:0000269|PubMed:25947375,
CC ECO:0000269|PubMed:26567335, ECO:0000269|PubMed:30018401};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568;
CC Evidence={ECO:0000305|PubMed:25315773, ECO:0000305|PubMed:25947375,
CC ECO:0000305|PubMed:26567335, ECO:0000305|PubMed:30018401};
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:25315773, ECO:0000269|PubMed:25947375,
CC ECO:0000269|PubMed:26567335, ECO:0000269|PubMed:30018401};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66133;
CC Evidence={ECO:0000305|PubMed:25315773, ECO:0000305|PubMed:25947375,
CC ECO:0000305|PubMed:26567335, ECO:0000305|PubMed:30018401};
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:26567335, ECO:0000269|PubMed:30018401}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.9 uM for ATP (in the presence of PS)
CC {ECO:0000269|PubMed:26567335};
CC KM=6.1 uM for ATP (in the presence of PE)
CC {ECO:0000269|PubMed:26567335};
CC Vmax=6.5 nmol/min/ug enzyme toward ATP (in the presence of PS)
CC {ECO:0000269|PubMed:26567335};
CC Vmax=4.9 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 ATP11A and an accessory beta subunit TMEM30A.
CC {ECO:0000269|PubMed:21914794, ECO:0000269|PubMed:25947375,
CC ECO:0000269|PubMed:29799007}.
CC -!- INTERACTION:
CC P98196; Q9NV96: TMEM30A; NbExp=4; IntAct=EBI-21519640, EBI-2836942;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21914794,
CC ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:25947375}; Multi-pass
CC membrane protein {ECO:0000255}. Early endosome
CC {ECO:0000269|PubMed:21914794}. Recycling endosome
CC {ECO:0000269|PubMed:21914794}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:21914794, ECO:0000269|PubMed:25315773,
CC ECO:0000269|PubMed:25947375}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Efficient exit from the endoplasmic reticulum
CC requires the presence of TMEM30A. {ECO:0000269|PubMed:25315773,
CC ECO:0000269|PubMed:25947375}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:26567335). Expressed in
CC myoblasts (PubMed:29799007). {ECO:0000269|PubMed:26567335,
CC ECO:0000269|PubMed:29799007}.
CC -!- PTM: Proteolytically cleaved by CASP3. {ECO:0000269|PubMed:26567335}.
CC -!- MISCELLANEOUS: Overexpression of ATP11A confers resistance to
CC lonafarnib.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IV subfamily. {ECO:0000305}.
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DR EMBL; AL356740; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139384; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB028944; BAA82973.2; -; mRNA.
DR CCDS; CCDS32011.1; -.
DR RefSeq; NP_056020.2; NM_015205.2.
DR RefSeq; NP_115565.3; NM_032189.3.
DR RefSeq; XP_005268362.1; XM_005268305.4.
DR RefSeq; XP_005268363.1; XM_005268306.4.
DR RefSeq; XP_016875981.1; XM_017020492.1.
DR AlphaFoldDB; P98196; -.
DR SMR; P98196; -.
DR BioGRID; 116854; 33.
DR ComplexPortal; CPX-6310; ATP11A-CDC50A P4-ATPase complex.
DR IntAct; P98196; 3.
DR STRING; 9606.ENSP00000420387; -.
DR TCDB; 3.A.3.8.17; the p-type atpase (p-atpase) superfamily.
DR iPTMnet; P98196; -.
DR PhosphoSitePlus; P98196; -.
DR SwissPalm; P98196; -.
DR BioMuta; ATP11A; -.
DR DMDM; 85700404; -.
DR EPD; P98196; -.
DR jPOST; P98196; -.
DR MassIVE; P98196; -.
DR MaxQB; P98196; -.
DR PaxDb; P98196; -.
DR PeptideAtlas; P98196; -.
DR PRIDE; P98196; -.
DR ProteomicsDB; 57826; -.
DR Antibodypedia; 48747; 59 antibodies from 23 providers.
DR DNASU; 23250; -.
DR Ensembl; ENST00000375645.8; ENSP00000364796.3; ENSG00000068650.19.
DR Ensembl; ENST00000487903.5; ENSP00000420387.1; ENSG00000068650.19.
DR GeneID; 23250; -.
DR KEGG; hsa:23250; -.
DR MANE-Select; ENST00000375645.8; ENSP00000364796.3; NM_015205.3; NP_056020.2.
DR UCSC; uc001vsi.4; human.
DR CTD; 23250; -.
DR DisGeNET; 23250; -.
DR GeneCards; ATP11A; -.
DR HGNC; HGNC:13552; ATP11A.
DR HPA; ENSG00000068650; Low tissue specificity.
DR MalaCards; ATP11A; -.
DR MIM; 605868; gene.
DR neXtProt; NX_P98196; -.
DR OpenTargets; ENSG00000068650; -.
DR Orphanet; 2032; Idiopathic pulmonary fibrosis.
DR PharmGKB; PA25101; -.
DR VEuPathDB; HostDB:ENSG00000068650; -.
DR eggNOG; KOG0206; Eukaryota.
DR GeneTree; ENSGT00940000157849; -.
DR HOGENOM; CLU_000846_3_2_1; -.
DR InParanoid; P98196; -.
DR OMA; DAQITEY; -.
DR OrthoDB; 587717at2759; -.
DR PhylomeDB; P98196; -.
DR TreeFam; TF326897; -.
DR BRENDA; 7.6.2.1; 2681.
DR PathwayCommons; P98196; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; P98196; -.
DR BioGRID-ORCS; 23250; 12 hits in 1076 CRISPR screens.
DR ChiTaRS; ATP11A; human.
DR GenomeRNAi; 23250; -.
DR Pharos; P98196; Tbio.
DR PRO; PR:P98196; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P98196; protein.
DR Bgee; ENSG00000068650; Expressed in germinal epithelium of ovary and 185 other tissues.
DR ExpressionAtlas; P98196; baseline and differential.
DR Genevisible; P98196; HS.
DR GO; GO:0005769; C:early endosome; 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:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ComplexPortal.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
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:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0045332; P:phospholipid translocation; IBA:GO_Central.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; IMP:UniProtKB.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR030361; ATP11A.
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 PANTHER; PTHR24092:SF33; PTHR24092:SF33; 1.
DR Pfam; PF16212; PhoLip_ATPase_C; 1.
DR Pfam; PF16209; PhoLip_ATPase_N; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01652; ATPase-Plipid; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 3.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Endoplasmic reticulum; Endosome;
KW Lipid transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1134
FT /note="Phospholipid-transporting ATPase IH"
FT /id="PRO_0000046369"
FT TOPO_DOM 1..61
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 62..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 83..88
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 89..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..296
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 297..318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 319..349
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..372
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 373..881
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 882..902
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 903..914
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 915..934
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 935..964
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 965..986
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 987..1000
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1001..1023
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1024..1029
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1030..1050
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1051..1068
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1069..1093
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1094..1134
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 414
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9HD20"
FT BINDING 825
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8NB49"
FT BINDING 829
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8NB49"
FT SITE 457..458
FT /note="Cleavage; by CASP3"
FT /evidence="ECO:0000269|PubMed:26567335"
FT SITE 490..491
FT /note="Cleavage; by CASP3"
FT /evidence="ECO:0000269|PubMed:26567335"
FT MOD_RES 738
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 317
FT /note="M -> V (in dbSNP:rs368865)"
FT /evidence="ECO:0000269|PubMed:10470851"
FT /id="VAR_059139"
FT VARIANT 1091
FT /note="V -> I (in dbSNP:rs11616795)"
FT /id="VAR_048379"
FT MUTAGEN 186
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 ECO:0000269|PubMed:25947375, ECO:0000269|PubMed:30018401"
FT MUTAGEN 414
FT /note="D->N: Impairs endoplasmic reticulum to plasma
FT membrane trafficking."
FT /evidence="ECO:0000269|PubMed:25315773"
FT MUTAGEN 454
FT /note="D->A: Impairs caspase-mediated cleavage; when
FT associated with A-457, A-487 and A-490."
FT /evidence="ECO:0000269|PubMed:26567335"
FT MUTAGEN 457
FT /note="D->A: Impairs caspase-mediated cleavage; when
FT associated with A-454, A-487 and A-490."
FT /evidence="ECO:0000269|PubMed:26567335"
FT MUTAGEN 487
FT /note="D->A: Impairs caspase-mediated cleavage; when
FT associated with A-454, A-457 and A-490."
FT /evidence="ECO:0000269|PubMed:26567335"
FT MUTAGEN 490
FT /note="D->A: Impairs caspase-mediated cleavage; when
FT associated with A-454, A-457 and A-487."
FT /evidence="ECO:0000269|PubMed:26567335"
SQ SEQUENCE 1134 AA; 129756 MW; A486BDFC85D6D3B2 CRC64;
MDCSLVRTLV HRYCAGEENW VDSRTIYVGH REPPPGAEAY IPQRYPDNRI VSSKYTFWNF
IPKNLFEQFR RVANFYFLII FLVQLIIDTP TSPVTSGLPL FFVITVTAIK QGYEDWLRHK
ADNAMNQCPV HFIQHGKLVR KQSRKLRVGD IVMVKEDETF PCDLIFLSSN RGDGTCHVTT
ASLDGESSHK THYAVQDTKG FHTEEDIGGL HATIECEQPQ PDLYKFVGRI NVYSDLNDPV
VRPLGSENLL LRGATLKNTE KIFGVAIYTG METKMALNYQ SKSQKRSAVE KSMNAFLIVY
LCILISKALI NTVLKYMWQS EPFRDEPWYN QKTESERQRN LFLKAFTDFL AFMVLFNYII
PVSMYVTVEM QKFLGSYFIT WDEDMFDEET GEGPLVNTSD LNEELGQVEY IFTDKTGTLT
ENNMEFKECC IEGHVYVPHV ICNGQVLPES SGIDMIDSSP SVNGREREEL FFRALCLCHT
VQVKDDDSVD GPRKSPDGGK SCVYISSSPD EVALVEGVQR LGFTYLRLKD NYMEILNREN
HIERFELLEI LSFDSVRRRM SVIVKSATGE IYLFCKGADS SIFPRVIEGK VDQIRARVER
NAVEGLRTLC VAYKRLIQEE YEGICKLLQA AKVALQDREK KLAEAYEQIE KDLTLLGATA
VEDRLQEKAA DTIEALQKAG IKVWVLTGDK METAAATCYA CKLFRRNTQL LELTTKRIEE
QSLHDVLFEL SKTVLRHSGS LTRDNLSGLS ADMQDYGLII DGAALSLIMK PREDGSSGNY
RELFLEICRS CSAVLCCRMA PLQKAQIVKL IKFSKEHPIT LAIGDGANDV SMILEAHVGI
GVIGKEGRQA ARNSDYAIPK FKHLKKMLLV HGHFYYIRIS ELVQYFFYKN VCFIFPQFLY
QFFCGFSQQT LYDTAYLTLY NISFTSLPIL LYSLMEQHVG IDVLKRDPTL YRDVAKNALL
RWRVFIYWTL LGLFDALVFF FGAYFVFENT TVTSNGQIFG NWTFGTLVFT VMVFTVTLKL
ALDTHYWTWI NHFVIWGSLL FYVVFSLLWG GVIWPFLNYQ RMYYVFIQML SSGPAWLAIV
LLVTISLLPD VLKKVLCRQL WPTATERVQT KSQCLSVEQS TIFMLSQTSS SLSF
