ID   AT10B_HUMAN             Reviewed;        1461 AA.
AC   O94823; Q9H725;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   30-APR-2003, sequence version 2.
DT   27-MAR-2024, entry version 193.
DE   RecName: Full=Phospholipid-transporting ATPase VB;
DE            EC=7.6.2.1 {ECO:0000269|PubMed:32172343};
DE   AltName: Full=ATPase class V type 10B;
DE   AltName: Full=P4-ATPase flippase complex alpha subunit ATP10B;
GN   Name=ATP10B {ECO:0000303|PubMed:32172343}; Synonyms=ATPVB, KIAA0715;
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 MRNA] (ISOFORM A).
RC   TISSUE=Brain;
RX   PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA   Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA   Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XI. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 5:277-286(1998).
RN   [2]
RP   SEQUENCE REVISION.
RA   Ohara O., Suyama M., Nagase T., Ishikawa K., Kikuno R.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS B AND C), AND VARIANT
RP   ARG-217.
RC   TISSUE=Amygdala, and Colon;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [5]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH TMEM30A.
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   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP   PTM, ACTIVE SITE, VARIANTS SER-105; 153-ARG--ILE-1461 DEL; ASN-161;
RP   TRP-393; VAL-558; ARG-648; ARG-671; LEU-748; LYS-865; ALA-993; THR-1038;
RP   THR-1222 AND PHE-1421, AND MUTAGENESIS OF GLU-210 AND ASP-433.
RX   PubMed=32172343; DOI=10.1007/s00401-020-02145-7;
RG   BELNEU consortium;
RA   Martin S., Smolders S., Van den Haute C., Heeman B., van Veen S.,
RA   Crosiers D., Beletchi I., Verstraeten A., Gossye H., Gelders G., Pals P.,
RA   Hamouda N.N., Engelborghs S., Martin J.J., Eggermont J., De Deyn P.P.,
RA   Cras P., Baekelandt V., Vangheluwe P., Van Broeckhoven C.;
RT   "Mutated ATP10B increases Parkinson's disease risk by compromising
RT   lysosomal glucosylceramide export.";
RL   Acta Neuropathol. 139:1001-1024(2020).
RN   [7]
RP   VARIANTS MET-219; THR-540; ARG-671; LYS-865 AND PHE-1421.
RX   PubMed=32892229; DOI=10.1007/s00401-020-02219-6;
RA   Tesson C., Lohmann E., Devos D., Bertrand H., Lesage S., Brice A.;
RT   "Segregation of ATP10B variants in families with autosomal recessive
RT   parkinsonism.";
RL   Acta Neuropathol. 140:783-785(2020).
CC   -!- FUNCTION: Catalytic component of a P4-ATPase flippase complex, which
CC       catalyzes the hydrolysis of ATP coupled to the transport of
CC       glucosylceramide (GlcCer) from the outer to the inner leaflet of
CC       lysosome membranes. Plays an important role in the maintenance of
CC       lysosome membrane integrity and function in cortical neurons.
CC       {ECO:0000269|PubMed:32172343}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC         phospholipidSide 2.; EC=7.6.2.1;
CC         Evidence={ECO:0000269|PubMed:32172343};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine(out) + ATP +
CC         H2O = a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine(in) + ADP +
CC         H(+) + phosphate; Xref=Rhea:RHEA:66036, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:22801, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC         Evidence={ECO:0000269|PubMed:32172343};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66037;
CC         Evidence={ECO:0000305|PubMed:32172343};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q9Y2Q0};
CC   -!- SUBUNIT: Component of a P4-ATPase flippase complex which consists of a
CC       catalytic alpha subunit ATP10B and an accessory beta subunit TMEM30A.
CC       {ECO:0000269|PubMed:25947375}.
CC   -!- INTERACTION:
CC       O94823-1; Q9NV96-1: TMEM30A; NbExp=2; IntAct=EBI-26444823, EBI-26444832;
CC   -!- SUBCELLULAR LOCATION: Late endosome membrane
CC       {ECO:0000269|PubMed:25947375, ECO:0000269|PubMed:32172343}; Multi-pass
CC       membrane protein {ECO:0000255}. Lysosome membrane
CC       {ECO:0000269|PubMed:25947375, ECO:0000269|PubMed:32172343}; Multi-pass
CC       membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:25947375}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Exit from the endoplasmic reticulum requires the
CC       presence of TMEM30A, but not TMEM30B.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=A;
CC         IsoId=O94823-1; Sequence=Displayed;
CC       Name=B;
CC         IsoId=O94823-2; Sequence=VSP_007306, VSP_007307;
CC       Name=C;
CC         IsoId=O94823-3; Sequence=VSP_007305, VSP_007306, VSP_007307;
CC   -!- TISSUE SPECIFICITY: Expressed in predominantly in brain structures
CC       including medulla oblongata, substantia nigra and basal ganglia.
CC       Expressed in the gastrointestinal system with highest levels in the
CC       small intestine and colon. Also expressed at low levels in testis and
CC       thymus. {ECO:0000269|PubMed:32172343}.
CC   -!- PTM: Autophosphorylated at the conserved aspartate of the P-type ATPase
CC       signature sequence. {ECO:0000269|PubMed:32172343}.
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=BAA34435.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AB018258; BAA34435.2; ALT_INIT; mRNA.
DR   EMBL; AK090832; BAC03528.1; -; mRNA.
DR   EMBL; AK025130; BAB15074.1; -; mRNA.
DR   EMBL; AC008456; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS43394.1; -. [O94823-1]
DR   RefSeq; NP_079429.2; NM_025153.2. [O94823-1]
DR   RefSeq; XP_006714896.1; XM_006714833.2.
DR   RefSeq; XP_011532770.1; XM_011534468.2. [O94823-1]
DR   RefSeq; XP_011532771.1; XM_011534469.1. [O94823-1]
DR   AlphaFoldDB; O94823; -.
DR   SMR; O94823; -.
DR   BioGRID; 116742; 3.
DR   ComplexPortal; CPX-6308; ATP10B-CDC50A P4-ATPase complex.
DR   IntAct; O94823; 2.
DR   STRING; 9606.ENSP00000313600; -.
DR   GlyGen; O94823; 3 sites, 1 O-linked glycan (3 sites).
DR   iPTMnet; O94823; -.
DR   PhosphoSitePlus; O94823; -.
DR   BioMuta; ATP10B; -.
DR   jPOST; O94823; -.
DR   MassIVE; O94823; -.
DR   PaxDb; 9606-ENSP00000313600; -.
DR   PeptideAtlas; O94823; -.
DR   ProteomicsDB; 50465; -. [O94823-1]
DR   ProteomicsDB; 50466; -. [O94823-2]
DR   ProteomicsDB; 50467; -. [O94823-3]
DR   Antibodypedia; 48726; 13 antibodies from 7 providers.
DR   DNASU; 23120; -.
DR   Ensembl; ENST00000327245.10; ENSP00000313600.5; ENSG00000118322.14. [O94823-1]
DR   GeneID; 23120; -.
DR   KEGG; hsa:23120; -.
DR   MANE-Select; ENST00000327245.10; ENSP00000313600.5; NM_025153.3; NP_079429.2.
DR   UCSC; uc003lym.1; human. [O94823-1]
DR   AGR; HGNC:13543; -.
DR   CTD; 23120; -.
DR   GeneCards; ATP10B; -.
DR   HGNC; HGNC:13543; ATP10B.
DR   HPA; ENSG00000118322; Tissue enhanced (gallbladder, intestine).
DR   MIM; 619791; gene.
DR   neXtProt; NX_O94823; -.
DR   OpenTargets; ENSG00000118322; -.
DR   PharmGKB; PA25098; -.
DR   VEuPathDB; HostDB:ENSG00000118322; -.
DR   eggNOG; KOG0206; Eukaryota.
DR   GeneTree; ENSGT00940000159531; -.
DR   InParanoid; O94823; -.
DR   OMA; CDRPDTN; -.
DR   OrthoDB; 275833at2759; -.
DR   PhylomeDB; O94823; -.
DR   TreeFam; TF354252; -.
DR   BRENDA; 7.6.2.1; 2681.
DR   PathwayCommons; O94823; -.
DR   Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR   SignaLink; O94823; -.
DR   BioGRID-ORCS; 23120; 48 hits in 1144 CRISPR screens.
DR   ChiTaRS; ATP10B; human.
DR   GenomeRNAi; 23120; -.
DR   Pharos; O94823; Tdark.
DR   PRO; PR:O94823; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; O94823; Protein.
DR   Bgee; ENSG00000118322; Expressed in mucosa of sigmoid colon and 157 other cell types or tissues.
DR   ExpressionAtlas; O94823; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0031902; C:late endosome membrane; IDA:ComplexPortal.
DR   GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:ComplexPortal.
DR   GO; GO:1990531; C:phospholipid-translocating ATPase complex; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; 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:0140351; F:glycosylceramide flippase activity; IDA:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0140345; F:phosphatidylcholine flippase activity; IDA:UniProtKB.
DR   GO; GO:0097212; P:lysosomal membrane organization; IDA:UniProtKB.
DR   GO; GO:0045332; P:phospholipid translocation; IBA:GO_Central.
DR   CDD; cd02073; P-type_ATPase_APLT_Dnf-like; 1.
DR   Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 2.
DR   Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1.
DR   Gene3D; 1.20.1110.10; Calcium-transporting ATPase, transmembrane domain; 1.
DR   Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 2.
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; 2.
DR   NCBIfam; TIGR01494; ATPase_P-type; 2.
DR   PANTHER; PTHR24092:SF79; PHOSPHOLIPID-TRANSPORTING ATPASE VB; 1.
DR   PANTHER; PTHR24092; PROBABLE PHOSPHOLIPID-TRANSPORTING ATPASE; 1.
DR   Pfam; PF13246; Cation_ATPase; 1.
DR   Pfam; PF16212; PhoLip_ATPase_C; 1.
DR   Pfam; PF16209; PhoLip_ATPase_N; 1.
DR   PRINTS; PR00119; CATATPASE.
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; O94823; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; ATP-binding; Endoplasmic reticulum; Endosome;
KW   Lipid transport; Lysosome; Magnesium; Membrane; Metal-binding;
KW   Nucleotide-binding; Reference proteome; Translocase; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..1461
FT                   /note="Phospholipid-transporting ATPase VB"
FT                   /id="PRO_0000046381"
FT   TOPO_DOM        1..82
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        83..104
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        105..110
FT                   /note="Exoplasmic loop"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        111..132
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        133..316
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        317..338
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        339..368
FT                   /note="Exoplasmic loop"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        369..390
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        391..1111
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1112..1132
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1133..1144
FT                   /note="Exoplasmic loop"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1145..1164
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1165..1194
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1195..1216
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1217..1223
FT                   /note="Exoplasmic loop"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1224..1246
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1247..1252
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1253..1273
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1274..1291
FT                   /note="Exoplasmic loop"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1292..1316
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1317..1461
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          496..541
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          639..687
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1346..1397
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        496..516
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        526..541
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        639..657
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1368..1386
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        433
FT                   /note="4-aspartylphosphate intermediate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HD20,
FT                   ECO:0000305|PubMed:32172343"
FT   BINDING         433
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT   BINDING         433
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT   BINDING         434
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT   BINDING         435
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT   BINDING         435
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT   BINDING         724
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P04191"
FT   BINDING         766
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT   BINDING         790
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P04191"
FT   BINDING         835
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P04191"
FT   BINDING         915
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P04191"
FT   BINDING         916
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P04191"
FT   BINDING         917
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P04191"
FT   BINDING         1029
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P04191"
FT   BINDING         1035
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P04191"
FT   BINDING         1055
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NB49"
FT   BINDING         1058
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT   BINDING         1059
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT   BINDING         1059
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NB49"
FT   VAR_SEQ         1..156
FT                   /note="MALSVDSSWHRWQWRVRDGFPHCPSETTPLLSPEKGRQSYNLTQQRVVFPNN
FT                   SIFHQDWEEVSRRYPGNRTCTTKYTLFTFLPRNLFEQFHRWANLYFLFLVILNWMPSME
FT                   VFHREITMLPLAIVLFVIMIKDGMEDFKRHRFDKAINCSNIRIYE -> MKKEGRKRWK
FT                   RKEDKKRVVVSNLLFEGWSHKENPNRHHRGNQIKTSKYTVLSFVPKNIFEQLHRFANLY
FT                   FVGIAVLNFIPVVNAFQPEVSMIPICVILAVTAIKDAWEDLRRYKSDKVINNRECLIYS
FT                   (in isoform C)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_007305"
FT   VAR_SEQ         461..529
FT                   /note="AKRLETPKELDSDGEEWTQYQCLSFSARWAQDPATMRSQKGAQPLRRSQSAR
FT                   VPIQGHYRQRSMGHRES -> GIEAPKGSIPLSKRKYPALLRNEEIKDILLALLEAVWH
FT                   FHKLLPVSLWSSLSQIRAVPITCKLSFVYKG (in isoform B and isoform
FT                   C)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_007306"
FT   VAR_SEQ         530..1461
FT                   /note="Missing (in isoform B and isoform C)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_007307"
FT   VARIANT         105
FT                   /note="N -> S (found in a patient with early-onset
FT                   Parkinson disease; uncertain significance;
FT                   dbSNP:rs184217288)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084141"
FT   VARIANT         153..1461
FT                   /note="Missing (found in a patient with early-onset
FT                   Parkinson disease; uncertain significance; loss of protein
FT                   expression and loss-of-function)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084142"
FT   VARIANT         161
FT                   /note="T -> N (found in patients with early-onset Parkinson
FT                   disease; uncertain significance; impaired ATPase flippase
FT                   activity; dbSNP:rs73306687)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084143"
FT   VARIANT         217
FT                   /note="C -> R (in dbSNP:rs958912)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_048384"
FT   VARIANT         219
FT                   /note="V -> M (found in a family with Parkinson disease;
FT                   uncertain significance; dbSNP:rs139187738)"
FT                   /evidence="ECO:0000269|PubMed:32892229"
FT                   /id="VAR_084190"
FT   VARIANT         393
FT                   /note="G -> W (impaired ATPase flippase activity;
FT                   dbSNP:rs149397148)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084144"
FT   VARIANT         540
FT                   /note="I -> T (found in a family with Parkinson disease;
FT                   uncertain significance; dbSNP:rs56340994)"
FT                   /evidence="ECO:0000269|PubMed:32892229"
FT                   /id="VAR_084191"
FT   VARIANT         558
FT                   /note="A -> V (found in a patient with early-onset
FT                   Parkinson disease; uncertain significance;
FT                   dbSNP:rs770267845)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084145"
FT   VARIANT         648
FT                   /note="G -> R (found in patients with early-onset Parkinson
FT                   disease; uncertain significance; impaired ATPase flippase
FT                   activity; dbSNP:rs188580726)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084146"
FT   VARIANT         671
FT                   /note="G -> R (found in patients with early-onset Parkinson
FT                   disease; uncertain significance; impaired ATPase flippase
FT                   activity; dbSNP:rs61734666)"
FT                   /evidence="ECO:0000269|PubMed:32172343,
FT                   ECO:0000269|PubMed:32892229"
FT                   /id="VAR_084147"
FT   VARIANT         748
FT                   /note="V -> L (found in a patient with early-onset
FT                   Parkinson disease; uncertain significance; impaired ATPase
FT                   flippase activity; dbSNP:rs192890224)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084148"
FT   VARIANT         865
FT                   /note="N -> K (found in patients with early-onset Parkinson
FT                   disease; uncertain significance; impaired ATPase flippase
FT                   activity; dbSNP:rs61734665)"
FT                   /evidence="ECO:0000269|PubMed:32172343,
FT                   ECO:0000269|PubMed:32892229"
FT                   /id="VAR_084149"
FT   VARIANT         993
FT                   /note="E -> A (found in a patient with early-onset
FT                   Parkinson disease; uncertain significance; impaired ATPase
FT                   flippase activity; dbSNP:rs761562566)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084150"
FT   VARIANT         1038
FT                   /note="I -> T (found in a patient with early-onset
FT                   Parkinson disease; uncertain significance; impaired ATPase
FT                   flippase activity)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084151"
FT   VARIANT         1222
FT                   /note="I -> T (found in a patient with early-onset
FT                   Parkinson disease; uncertain significance; has no effect on
FT                   ATPase flippase activity; dbSNP:rs144497343)"
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT                   /id="VAR_084152"
FT   VARIANT         1421
FT                   /note="L -> F (found in patients with Parkinson disease;
FT                   uncertain significance; dbSNP:rs61734664)"
FT                   /evidence="ECO:0000269|PubMed:32172343,
FT                   ECO:0000269|PubMed:32892229"
FT                   /id="VAR_084153"
FT   MUTAGEN         210
FT                   /note="E->A: Loss of ATPase flippase activity."
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT   MUTAGEN         433
FT                   /note="D->N: Abolishes autophosphorylation and ATPase
FT                   flippase activity."
FT                   /evidence="ECO:0000269|PubMed:32172343"
FT   CONFLICT        234
FT                   /note="F -> S (in Ref. 3; BAC03528)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1461 AA;  165391 MW;  2676B90416B6B541 CRC64;
     MALSVDSSWH RWQWRVRDGF PHCPSETTPL LSPEKGRQSY NLTQQRVVFP NNSIFHQDWE
     EVSRRYPGNR TCTTKYTLFT FLPRNLFEQF HRWANLYFLF LVILNWMPSM EVFHREITML
     PLAIVLFVIM IKDGMEDFKR HRFDKAINCS NIRIYERKEQ TYVQKCWKDV RVGDFIQMKC
     NEIVPADILL LFSSDPNGIC HLETASLDGE TNLKQRCVVK GFSQQEVQFE PELFHNTIVC
     EKPNNHLNKF KGYMEHPDQT RTGFGCESLL LRGCTIRNTE MAVGIVIYAG HETKAMLNNS
     GPRYKRSKIE RRMNIDIFFC IGILILMCLI GAVGHSIWNG TFEEHPPFDV PDANGSFLPS
     ALGGFYMFLT MIILLQVLIP ISLYVSIELV KLGQVFFLSN DLDLYDEETD LSIQCRALNI
     AEDLGQIQYI FSDKTGTLTE NKMVFRRCTI MGSEYSHQEN AKRLETPKEL DSDGEEWTQY
     QCLSFSARWA QDPATMRSQK GAQPLRRSQS ARVPIQGHYR QRSMGHRESS QPPVAFSSSI
     EKDVTPDKNL LTKVRDAALW LETLSDSRPA KASLSTTSSI ADFFLALTIC NSVMVSTTTE
     PRQRVTIKPS SKALGTSLEK IQQLFQKLKL LSLSQSFSST APSDTDLGES LGANVATTDS
     DERDDASVCS GGDSTDDGGY RSSMWDQGDI LESGSGTSLE EALEAPATDL ARPEFCYEAE
     SPDEAALVHA AHAYSFTLVS RTPEQVTVRL PQGTCLTFSL LCTLGFDSVR KRMSVVVRHP
     LTGEIVVYTK GADSVIMDLL EDPACVPDIN MEKKLRKIRA RTQKHLDLYA RDGLRTLCIA
     KKVVSEEDFR RWASFRREAE ASLDNRDELL METAQHLENQ LTLLGATGIE DRLQEGVPDT
     IATLREAGIQ LWVLTGDKQE TAVNIAHSCR LLNQTDTVYT INTENQETCE SILNCALEEL
     KQFRELQKPD RKLFGFRLPS KTPSITSEAV VPEAGLVIDG KTLNAIFQGK LEKKFLELTQ
     YCRSVLCCRS TPLQKSMIVK LVRDKLRVMT LSIGDGANDV SMIQAADIGI GISGQEGMQA
     VMSSDFAITR FKHLKKLLLV HGHWCYSRLA RMVVYYLYKN VCYVNLLFWY QFFCGFSSST
     MIDYWQMIFF NLFFTSLPPL VFGVLDKDIS AETLLALPEL YKSGQNSECY NLSTFWISMV
     DAFYQSLICF FIPYLAYKGS DIDVFTFGTP INTISLTTIL LHQAMEMKTW TIFHGVVLLG
     SFLMYFLVSL LYNATCVICN SPTNPYWVME GQLSNPTFYL VCFLTPVVAL LPRYFFLSLQ
     GTCGKSLISK AQKIDKLPPD KRNLEIQSWR SRQRPAPVPE VARPTHHPVS SITGQDFSAS
     TPKSSNPPKR KHVEESVLHE QRCGTECMRD DSCSGDSSAQ LSSGEHLLGP NRIMAYSRGQ
     TDMCRCSKRS SHRRSQSSLT I
//