AT8A1_HUMAN
ID AT8A1_HUMAN Reviewed; 1164 AA.
AC Q9Y2Q0; Q32M35; Q32M36; Q4W5J7; Q4W5P2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Phospholipid-transporting ATPase IA {ECO:0000305};
DE EC=7.6.2.1 {ECO:0000250|UniProtKB:P70704};
DE AltName: Full=ATPase class I type 8A member 1;
DE AltName: Full=Chromaffin granule ATPase II;
DE AltName: Full=P4-ATPase flippase complex alpha subunit ATP8A1;
GN Name=ATP8A1 {ECO:0000312|HGNC:HGNC:13531}; Synonyms=ATPIA;
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 2).
RC TISSUE=Skeletal muscle;
RX PubMed=10198212; DOI=10.1006/bbrc.1999.0347;
RA Mouro I., Halleck M.S., Schlegel R.A., Mattei M.-G., Williamson P.L.,
RA Zachowski A., Devaux P., Cartron J.-P., Colin Y.;
RT "Cloning, expression, and chromosomal mapping of a human ATPase II gene,
RT member of the third subfamily of P-type ATPases and orthologous to the
RT presumed bovine and murine aminophospholipid translocase.";
RL Biochem. Biophys. Res. Commun. 257:333-339(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-1164 (ISOFORM 1).
RC TISSUE=Brain;
RA Osada S., Nakanishi Y.;
RT "cDNA cloning of human ATPaseII.";
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
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 INTERACTION WITH TMEM30A, AND SUBCELLULAR LOCATION.
RX PubMed=20947505; DOI=10.1074/jbc.m110.139006;
RA van der Velden L.M., Wichers C.G., van Breevoort A.E., Coleman J.A.,
RA Molday R.S., Berger R., Klomp L.W., van de Graaf S.F.;
RT "Heteromeric interactions required for abundance and subcellular
RT localization of human CDC50 proteins and class 1 P4-ATPases.";
RL J. Biol. Chem. 285:40088-40096(2010).
RN [9]
RP INTERACTION WITH TMEM30A AND TMEM30B.
RX PubMed=20961850; DOI=10.1074/jbc.m110.139543;
RA Bryde S., Hennrich H., Verhulst P.M., Devaux P.F., Lenoir G.,
RA Holthuis J.C.;
RT "CDC50 proteins are critical components of the human class-1 P4-ATPase
RT transport machinery.";
RL J. Biol. Chem. 285:40562-40572(2010).
RN [10]
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 [11]
RP PROCESSING BY CALPAIN, AND TISSUE SPECIFICITY.
RX PubMed=30674456; DOI=10.1182/bloodadvances.2018023473;
RA Jing W., Yabas M., Broeer A., Coupland L., Gardiner E.E., Enders A.,
RA Broeer S.;
RT "Calpain cleaves phospholipid flippase ATP8A1 during apoptosis in
RT platelets.";
RL Blood Adv. 3:219-229(2019).
RN [12] {ECO:0007744|PDB:6K7G, ECO:0007744|PDB:6K7H, ECO:0007744|PDB:6K7I, ECO:0007744|PDB:6K7J, ECO:0007744|PDB:6K7K, ECO:0007744|PDB:6K7L, ECO:0007744|PDB:6K7M, ECO:0007744|PDB:6K7N}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.83 ANGSTROMS) IN COMPLEX WITH TMEM30A;
RP ATP ANALOGS; MAGNESIUM AND INHIBITOR, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, INTERACTION WITH
RP TMEM30A, AND ACTIVE SITE.
RX PubMed=31416931; DOI=10.1126/science.aay3353;
RA Hiraizumi M., Yamashita K., Nishizawa T., Nureki O.;
RT "Cryo-EM structures capture the transport cycle of the P4-ATPase
RT flippase.";
RL Science 365:1149-1155(2019).
CC -!- FUNCTION: Catalytic component of a P4-ATPase flippase complex which
CC catalyzes the hydrolysis of ATP coupled to the transport of
CC aminophospholipids from the outer to the inner leaflet of various
CC membranes and ensures the maintenance of asymmetric distribution of
CC phospholipids (PubMed:31416931). Phospholipid translocation seems also
CC to be implicated in vesicle formation and in uptake of lipid signaling
CC molecules. In vitro, its ATPase activity is selectively and
CC stereospecifically stimulated by phosphatidylserine (PS)
CC (PubMed:31416931). The flippase complex ATP8A1:TMEM30A seems to play a
CC role in regulation of cell migration probably involving flippase-
CC mediated translocation of phosphatidylethanolamine (PE) at the plasma
CC membrane (By similarity). Acts as aminophospholipid translocase at the
CC plasma membrane in neuronal cells (By similarity).
CC {ECO:0000250|UniProtKB:P70704, ECO:0000269|PubMed:31416931}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000269|PubMed:31416931};
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:31416931};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568;
CC Evidence={ECO:0000305|PubMed:31416931};
CC -!- ACTIVITY REGULATION: ATPase activity is stimulated by
CC phosphatidylserine (PS) and minimally by phosphatidylethanolamine (PE).
CC ATPase activity is inhibited by beryllium fluoride and aluminum
CC trifluoride (PubMed:31416931). {ECO:0000250,
CC ECO:0000269|PubMed:31416931}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=111 uM for 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine
CC (POPS) {ECO:0000269|PubMed:31416931};
CC Vmax=99.7 nmol/min/ug enzyme toward ATP
CC {ECO:0000269|PubMed:31416931};
CC -!- SUBUNIT: Component of a P4-ATPase flippase complex which consists of a
CC catalytic alpha subunit and an accessory beta subunit
CC (PubMed:31416931). Interacts with TMEM30A to form a flippase complex;
CC this complex forms an intermediate phosphoenzyme (PubMed:20947505,
CC PubMed:20961850, PubMed:21914794, PubMed:31416931). Interacts with
CC TMEM30B; this interaction is reported conflictingly (PubMed:20961850).
CC {ECO:0000269|PubMed:20947505, ECO:0000269|PubMed:20961850,
CC ECO:0000269|PubMed:21914794, ECO:0000269|PubMed:31416931}.
CC -!- INTERACTION:
CC Q9Y2Q0; Q9NV96: TMEM30A; NbExp=5; IntAct=EBI-9539324, EBI-2836942;
CC Q9Y2Q0-2; Q9NV96: TMEM30A; NbExp=2; IntAct=EBI-21654619, EBI-2836942;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule membrane {ECO:0000250|UniProtKB:P70704}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P70704}. Cytoplasmic granule
CC {ECO:0000269|PubMed:20947505}. Cell membrane
CC {ECO:0000269|PubMed:20947505, ECO:0000269|PubMed:21914794}. Endoplasmic
CC reticulum {ECO:0000269|PubMed:20947505, ECO:0000269|PubMed:21914794}.
CC Golgi apparatus {ECO:0000269|PubMed:20947505,
CC ECO:0000269|PubMed:21914794}. Note=Exit from the endoplasmic reticulum
CC requires the presence of TMEM30A, but not TMEM30B (PubMed:20947505). In
CC the presence of TMEM30A, predominantly located in cytoplasmic punctate
CC structures and localizes to the plasma membrane (PubMed:20947505).
CC Localizes to plasma membranes of red blood cells (By similarity).
CC {ECO:0000250|UniProtKB:P70704, ECO:0000269|PubMed:20947505}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long;
CC IsoId=Q9Y2Q0-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q9Y2Q0-2; Sequence=VSP_000431;
CC Name=3;
CC IsoId=Q9Y2Q0-3; Sequence=VSP_040977, VSP_000431;
CC -!- TISSUE SPECIFICITY: Found in most adult tissues except liver, testis
CC and placenta. Most abundant in heart, brain and skeletal muscle. Also
CC detected in fetal tissues. Isoform 1 is only detected in brain,
CC skeletal muscle and heart and is the most abundant form in skeletal
CC muscle. Highly expressed in platelets (PubMed:30674456).
CC {ECO:0000269|PubMed:30674456}.
CC -!- PTM: Cleaved by calpain in a caspase- and calcium influx-dependent
CC manner during platelet apoptosis leading to a 100 kDa polypeptide.
CC {ECO:0000269|PubMed:30674456}.
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=AAI09318.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA77248.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF067820; AAD34706.1; -; mRNA.
DR EMBL; AC084010; AAY40980.1; -; Genomic_DNA.
DR EMBL; AC096734; AAY40924.1; -; Genomic_DNA.
DR EMBL; AC110788; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC139717; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471069; EAW93003.1; -; Genomic_DNA.
DR EMBL; BC109317; AAI09318.1; ALT_INIT; mRNA.
DR EMBL; BC109318; AAI09319.1; -; mRNA.
DR EMBL; AB013452; BAA77248.1; ALT_INIT; mRNA.
DR CCDS; CCDS3466.1; -. [Q9Y2Q0-1]
DR CCDS; CCDS47049.1; -. [Q9Y2Q0-3]
DR RefSeq; NP_001098999.1; NM_001105529.1. [Q9Y2Q0-3]
DR RefSeq; NP_006086.1; NM_006095.2. [Q9Y2Q0-1]
DR RefSeq; XP_016863134.1; XM_017007645.1. [Q9Y2Q0-2]
DR PDB; 6K7G; EM; 3.30 A; A=1-1164.
DR PDB; 6K7H; EM; 3.22 A; A=1-1164.
DR PDB; 6K7I; EM; 3.22 A; A=1-1164.
DR PDB; 6K7J; EM; 3.08 A; A=1-1164.
DR PDB; 6K7K; EM; 3.04 A; A=1-1164.
DR PDB; 6K7L; EM; 2.83 A; A=1-1164.
DR PDB; 6K7M; EM; 2.95 A; A=1-1164.
DR PDB; 6K7N; EM; 2.84 A; A=1-1164.
DR PDBsum; 6K7G; -.
DR PDBsum; 6K7H; -.
DR PDBsum; 6K7I; -.
DR PDBsum; 6K7J; -.
DR PDBsum; 6K7K; -.
DR PDBsum; 6K7L; -.
DR PDBsum; 6K7M; -.
DR PDBsum; 6K7N; -.
DR AlphaFoldDB; Q9Y2Q0; -.
DR SMR; Q9Y2Q0; -.
DR BioGRID; 115668; 8.
DR ComplexPortal; CPX-6285; ATP8A1-CDC50A P4-ATPase complex.
DR ComplexPortal; CPX-6286; ATP8A1-CDC50B P4-ATPase complex.
DR IntAct; Q9Y2Q0; 3.
DR STRING; 9606.ENSP00000371084; -.
DR DrugBank; DB00144; Phosphatidyl serine.
DR TCDB; 3.A.3.8.13; the p-type atpase (p-atpase) superfamily.
DR GlyGen; Q9Y2Q0; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9Y2Q0; -.
DR PhosphoSitePlus; Q9Y2Q0; -.
DR BioMuta; ATP8A1; -.
DR DMDM; 8134331; -.
DR EPD; Q9Y2Q0; -.
DR jPOST; Q9Y2Q0; -.
DR MassIVE; Q9Y2Q0; -.
DR MaxQB; Q9Y2Q0; -.
DR PaxDb; Q9Y2Q0; -.
DR PeptideAtlas; Q9Y2Q0; -.
DR PRIDE; Q9Y2Q0; -.
DR ProteomicsDB; 85858; -. [Q9Y2Q0-1]
DR ProteomicsDB; 85859; -. [Q9Y2Q0-2]
DR ProteomicsDB; 85860; -. [Q9Y2Q0-3]
DR Antibodypedia; 43947; 88 antibodies from 19 providers.
DR DNASU; 10396; -.
DR Ensembl; ENST00000264449.14; ENSP00000264449.10; ENSG00000124406.16. [Q9Y2Q0-3]
DR Ensembl; ENST00000381668.9; ENSP00000371084.5; ENSG00000124406.16. [Q9Y2Q0-1]
DR GeneID; 10396; -.
DR KEGG; hsa:10396; -.
DR MANE-Select; ENST00000381668.9; ENSP00000371084.5; NM_006095.2; NP_006086.1.
DR UCSC; uc003gwr.3; human. [Q9Y2Q0-1]
DR CTD; 10396; -.
DR DisGeNET; 10396; -.
DR GeneCards; ATP8A1; -.
DR HGNC; HGNC:13531; ATP8A1.
DR HPA; ENSG00000124406; Tissue enhanced (brain).
DR MIM; 609542; gene.
DR neXtProt; NX_Q9Y2Q0; -.
DR OpenTargets; ENSG00000124406; -.
DR PharmGKB; PA25165; -.
DR VEuPathDB; HostDB:ENSG00000124406; -.
DR eggNOG; KOG0206; Eukaryota.
DR GeneTree; ENSGT00940000157110; -.
DR HOGENOM; CLU_000846_3_0_1; -.
DR InParanoid; Q9Y2Q0; -.
DR OMA; QFWYSFQ; -.
DR OrthoDB; 587717at2759; -.
DR PhylomeDB; Q9Y2Q0; -.
DR TreeFam; TF300654; -.
DR BRENDA; 7.6.2.1; 2681.
DR PathwayCommons; Q9Y2Q0; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; Q9Y2Q0; -.
DR BioGRID-ORCS; 10396; 9 hits in 1077 CRISPR screens.
DR ChiTaRS; ATP8A1; human.
DR GenomeRNAi; 10396; -.
DR Pharos; Q9Y2Q0; Tbio.
DR PRO; PR:Q9Y2Q0; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9Y2Q0; protein.
DR Bgee; ENSG00000124406; Expressed in Brodmann (1909) area 23 and 202 other tissues.
DR ExpressionAtlas; Q9Y2Q0; baseline and differential.
DR Genevisible; Q9Y2Q0; HS.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0042584; C:chromaffin granule membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0031090; C:organelle membrane; ISS:UniProtKB.
DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0035579; C:specific 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:0019829; F:ATPase-coupled cation transmembrane transporter activity; NAS:UniProtKB.
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:0140346; F:phosphatidylserine flippase activity; IDA:UniProtKB.
DR GO; GO:0090556; F:phosphatidylserine floppase activity; IEA:RHEA.
DR GO; GO:0140331; P:aminophospholipid translocation; IDA:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0045332; P:phospholipid translocation; IBA:GO_Central.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0061092; P:positive regulation of phospholipid translocation; IEA:Ensembl.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 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 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 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Golgi apparatus;
KW Lipid transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1164
FT /note="Phospholipid-transporting ATPase IA"
FT /id="PRO_0000046360"
FT TOPO_DOM 1..65
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 66..86
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 87..92
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..297
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..319
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..344
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 345..366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 367..857
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 858..878
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 879..890
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 891..910
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 911..940
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 941..962
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 963..976
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 977..999
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1000..1005
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1006..1026
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1027..1044
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 1045..1070
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1071..1164
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 409
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000269|PubMed:31416931"
FT BINDING 409..411
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31416931"
FT BINDING 409
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31416931"
FT BINDING 411
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31416931"
FT BINDING 549
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31416931"
FT BINDING 741..748
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 801
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31416931"
FT BINDING 804..805
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31416931"
FT BINDING 805
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 1095..1102
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT MOD_RES 28
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P70704"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70704"
FT MOD_RES 443
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70704"
FT MOD_RES 1126
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70704"
FT VAR_SEQ 152..171
FT /note="AVGEIVKVTNGEHLPADLIS -> NVGDIVIIKGKEYIPADTVL (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040977"
FT VAR_SEQ 433..447
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10198212,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_000431"
FT VARIANT 673
FT /note="T -> M (in dbSNP:rs3792687)"
FT /id="VAR_022003"
FT CONFLICT 364
FT /note="E -> K (in Ref. 4; BAA77248)"
FT /evidence="ECO:0000305"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 61..73
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 77..87
FT /evidence="ECO:0007829|PDB:6K7L"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:6K7M"
FT HELIX 102..131
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:6K7M"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:6K7M"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:6K7M"
FT STRAND 156..164
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 167..176
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 193..198
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 201..204
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 209..214
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:6K7N"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 261..269
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:6K7N"
FT HELIX 276..279
FT /evidence="ECO:0007829|PDB:6K7N"
FT HELIX 289..322
FT /evidence="ECO:0007829|PDB:6K7L"
FT TURN 324..326
FT /evidence="ECO:0007829|PDB:6K7L"
FT TURN 328..330
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 340..350
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 359..376
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:6K7L"
FT TURN 383..386
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 394..396
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 399..401
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 402..408
FT /evidence="ECO:0007829|PDB:6K7L"
FT TURN 412..414
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 415..426
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 464..469
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:6K7N"
FT HELIX 474..486
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 495..498
FT /evidence="ECO:0007829|PDB:6K7M"
FT HELIX 506..517
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 521..524
FT /evidence="ECO:0007829|PDB:6K7K"
FT STRAND 527..532
FT /evidence="ECO:0007829|PDB:6K7L"
FT TURN 534..536
FT /evidence="ECO:0007829|PDB:6K7J"
FT STRAND 538..541
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 551..553
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 556..562
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 565..573
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 575..578
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 579..581
FT /evidence="ECO:0007829|PDB:6K7N"
FT HELIX 589..602
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 608..613
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 616..631
FT /evidence="ECO:0007829|PDB:6K7L"
FT TURN 632..636
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 637..646
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 656..663
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 667..676
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 680..684
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 689..698
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 704..706
FT /evidence="ECO:0007829|PDB:6K7H"
FT STRAND 709..711
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 742..745
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 746..753
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 754..757
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 758..767
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 771..775
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 778..789
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 794..800
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 803..805
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 806..811
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 812..818
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 820..822
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 825..829
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 831..836
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 839..845
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 847..870
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 872..880
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 891..895
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 896..900
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 903..910
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 917..922
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 926..933
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 938..962
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 964..966
FT /evidence="ECO:0007829|PDB:6K7N"
FT HELIX 977..999
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 1001..1003
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 1005..1025
FT /evidence="ECO:0007829|PDB:6K7L"
FT TURN 1029..1031
FT /evidence="ECO:0007829|PDB:6K7L"
FT STRAND 1032..1034
FT /evidence="ECO:0007829|PDB:6K7N"
FT HELIX 1036..1038
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 1041..1046
FT /evidence="ECO:0007829|PDB:6K7L"
FT HELIX 1049..1076
FT /evidence="ECO:0007829|PDB:6K7L"
FT TURN 1147..1149
FT /evidence="ECO:0007829|PDB:6K7L"
SQ SEQUENCE 1164 AA; 131369 MW; CE1EAF0206CD36F7 CRC64;
MPTMRRTVSE IRSRAEGYEK TDDVSEKTSL ADQEEVRTIF INQPQLTKFC NNHVSTAKYN
IITFLPRFLY SQFRRAANSF FLFIALLQQI PDVSPTGRYT TLVPLLFILA VAAIKEIIED
IKRHKADNAV NKKQTQVLRN GAWEIVHWEK VAVGEIVKVT NGEHLPADLI SLSSSEPQAM
CYIETSNLDG ETNLKIRQGL PATSDIKDVD SLMRISGRIE CESPNRHLYD FVGNIRLDGH
GTVPLGADQI LLRGAQLRNT QWVHGIVVYT GHDTKLMQNS TSPPLKLSNV ERITNVQILI
LFCILIAMSL VCSVGSAIWN RRHSGKDWYL NLNYGGASNF GLNFLTFIIL FNNLIPISLL
VTLEVVKFTQ AYFINWDLDM HYEPTDTAAM ARTSNLNEEL GQVKYIFSDK TGTLTCNVMQ
FKKCTIAGVA YGHVPEPEDY GCSPDEWQNS QFGDEKTFSD SSLLENLQNN HPTAPIICEF
LTMMAVCHTA VPEREGDKII YQAASPDEGA LVRAAKQLNF VFTGRTPDSV IIDSLGQEER
YELLNVLEFT SARKRMSVIV RTPSGKLRLY CKGADTVIYD RLAETSKYKE ITLKHLEQFA
TEGLRTLCFA VAEISESDFQ EWRAVYQRAS TSVQNRLLKL EESYELIEKN LQLLGATAIE
DKLQDQVPET IETLMKADIK IWILTGDKQE TAINIGHSCK LLKKNMGMIV INEGSLDGTR
ETLSRHCTTL GDALRKENDF ALIIDGKTLK YALTFGVRQY FLDLALSCKA VICCRVSPLQ
KSEVVEMVKK QVKVVTLAIG DGANDVSMIQ TAHVGVGISG NEGLQAANSS DYSIAQFKYL
KNLLMIHGAW NYNRVSKCIL YCFYKNIVLY IIEIWFAFVN GFSGQILFER WCIGLYNVMF
TAMPPLTLGI FERSCRKENM LKYPELYKTS QNALDFNTKV FWVHCLNGLF HSVILFWFPL
KALQYGTAFG NGKTSDYLLL GNFVYTFVVI TVCLKAGLET SYWTWFSHIA IWGSIALWVV
FFGIYSSLWP AIPMAPDMSG EAAMLFSSGV FWMGLLFIPV ASLLLDVVYK VIKRTAFKTL
VDEVQELEAK SQDPGAVVLG KSLTERAQLL KNVFKKNHVN LYRSESLQQN LLHGYAFSQD
ENGIVSQSEV IRAYDTTKQR PDEW
