AT10B_HUMAN
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 03-AUG-2022, entry version 185.
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 -!- 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; 2.
DR ComplexPortal; CPX-6308; ATP10B-CDC50A P4-ATPase complex.
DR IntAct; O94823; 3.
DR STRING; 9606.ENSP00000313600; -.
DR iPTMnet; O94823; -.
DR PhosphoSitePlus; O94823; -.
DR BioMuta; ATP10B; -.
DR jPOST; O94823; -.
DR MassIVE; O94823; -.
DR PaxDb; O94823; -.
DR PeptideAtlas; O94823; -.
DR PRIDE; 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 CTD; 23120; -.
DR GeneCards; ATP10B; -.
DR HGNC; HGNC:13543; ATP10B.
DR HPA; ENSG00000118322; Tissue enhanced (brain, 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; PRFFIFA; -.
DR OrthoDB; 587717at2759; -.
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; 47 hits in 1066 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 156 other tissues.
DR ExpressionAtlas; O94823; baseline and differential.
DR Genevisible; O94823; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1905103; C:integral component of lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IDA:ComplexPortal.
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 Gene3D; 3.40.1110.10; -; 2.
DR Gene3D; 3.40.50.1000; -; 2.
DR InterPro; IPR030359; ATP10B.
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:SF79; PTHR24092:SF79; 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; 2.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
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 1055
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8NB49"
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; unknown pathological 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; unknown pathological significance; loss
FT of protein 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; unknown pathological significance; impaired ATPase
FT flippase 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 unknown pathological 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 unknown pathological 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; unknown pathological 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; unknown pathological significance; impaired ATPase
FT flippase 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; unknown pathological significance; impaired ATPase
FT flippase 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; unknown pathological significance;
FT impaired ATPase 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; unknown pathological significance; impaired ATPase
FT flippase 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; unknown pathological significance;
FT impaired ATPase 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; unknown pathological significance;
FT impaired ATPase 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; unknown pathological significance; has
FT no effect on 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 unknown pathological 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
