AT10B_MOUSE
ID AT10B_MOUSE Reviewed; 1474 AA.
AC B1AWN4;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Phospholipid-transporting ATPase VB;
DE EC=7.6.2.1 {ECO:0000250|UniProtKB:O94823};
GN Name=Atp10b {ECO:0000312|MGI:MGI:2442688};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
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).
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 (By similarity). Plays an important role in the
CC maintenance of lysosome membrane integrity and function in cortical
CC neurons (PubMed:32172343). {ECO:0000250|UniProtKB:O94823,
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:0000250|UniProtKB:O94823};
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:0000250|UniProtKB:O94823};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66037;
CC Evidence={ECO:0000250|UniProtKB:O94823};
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:0000250|UniProtKB:O94823}.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:32172343}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:32172343}; Multi-
CC pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O94823}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Exit from the endoplasmic reticulum requires the
CC presence of TMEM30A, but not TMEM30B. {ECO:0000250|UniProtKB:O94823}.
CC -!- TISSUE SPECIFICITY: Expressed in cortical neuron (at protein level).
CC {ECO:0000269|PubMed:32172343}.
CC -!- PTM: Autophosphorylated at the conserved aspartate of the P-type ATPase
CC signature sequence. {ECO:0000250|UniProtKB:O94823}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IV subfamily.
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DR EMBL; AL772227; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL935157; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS36129.1; -.
DR RefSeq; NP_795973.2; NM_176999.3.
DR RefSeq; XP_017170095.1; XM_017314606.1.
DR AlphaFoldDB; B1AWN4; -.
DR SMR; B1AWN4; -.
DR STRING; 10090.ENSMUSP00000076844; -.
DR iPTMnet; B1AWN4; -.
DR PhosphoSitePlus; B1AWN4; -.
DR MaxQB; B1AWN4; -.
DR PaxDb; B1AWN4; -.
DR PRIDE; B1AWN4; -.
DR ProteomicsDB; 351695; -.
DR Antibodypedia; 48726; 13 antibodies from 7 providers.
DR DNASU; 319767; -.
DR Ensembl; ENSMUST00000077659; ENSMUSP00000076844; ENSMUSG00000055415.
DR GeneID; 319767; -.
DR KEGG; mmu:319767; -.
DR UCSC; uc007imk.2; mouse.
DR CTD; 23120; -.
DR MGI; MGI:2442688; Atp10b.
DR VEuPathDB; HostDB:ENSMUSG00000055415; -.
DR eggNOG; KOG0206; Eukaryota.
DR GeneTree; ENSGT00940000159531; -.
DR HOGENOM; CLU_000846_3_4_1; -.
DR InParanoid; B1AWN4; -.
DR OMA; PRFFIFA; -.
DR OrthoDB; 587717at2759; -.
DR PhylomeDB; B1AWN4; -.
DR TreeFam; TF354252; -.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 319767; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Atp10b; mouse.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; B1AWN4; protein.
DR Bgee; ENSMUSG00000055415; Expressed in left colon and 78 other tissues.
DR ExpressionAtlas; B1AWN4; baseline and differential.
DR Genevisible; B1AWN4; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1905103; C:integral component of lysosomal membrane; ISO:MGI.
DR GO; GO:0031902; C:late endosome membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0140345; F:phosphatidylcholine flippase activity; ISO:MGI.
DR GO; GO:0097212; P:lysosomal membrane organization; ISO:MGI.
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 ATP-binding; Endoplasmic reticulum; Endosome; Lysosome; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Reference proteome;
KW Translocase; Transmembrane; Transmembrane helix.
FT CHAIN 1..1474
FT /note="Phospholipid-transporting ATPase VB"
FT /id="PRO_0000452096"
FT TOPO_DOM 1..92
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 93..113
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 114..115
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..316
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 317..337
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 338..360
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 361..381
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 382..1119
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1120..1140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1141..1142
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1143..1163
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1164..1192
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1193..1213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1214..1219
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1220..1240
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1241..1249
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1250..1270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1271..1294
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1295..1315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1316..1474
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 19..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 638..707
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1348..1421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1434..1474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 669..702
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1348..1368
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1398..1421
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 433
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9HD20"
FT BINDING 1053
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8NB49"
FT BINDING 1057
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8NB49"
SQ SEQUENCE 1474 AA; 166437 MW; 11B8914E95D73151 CRC64;
MTCSLDFSWL RWKWRTQDGF SQSPSETTPL LSPETDRQSH NTAEQRVVYP NNSMCHQDWK
KVCRRYPGNS ICTTKYTLLT FLPQNLFEQF HRWANLYFLF LVILNWMPSM EVFHREITIF
PLATVLLIIM VKDGIEDFKR YCFDREMNSA SIQIYERKEQ RYMLKRWQDV RVGDFVQMQC
NEIVPADILL LFSSDPSGVC HLETANLDGE TNLKQRRVVK GFSQPEVQFQ PEHFHSTIVC
EKPNNHLSKF KGYMEHPDQT RTGFGSESLL LRGCTIRNTE VAAGIVIYAG HETKAMLNNS
GPRYKRSKIE RRINTDIFFC IGLLFLMCLI GAVGHSLWNG TFKEHPPFDV PDADGNFLSL
ALGGFYMFLT MIILLQVLIP ISLYVSIELV KLGQVFLLHN DLDLYDEETD LSIQCRALNI
TEDLGQIQYI FSDKTGTLTE NKMVFRRCTI VGSEYCHQEN AKRLEMPKEL DSDGEEWTQY
QCLSFPPRWA QGSTTMRSQG GAQPLRRCHS ARVPIQSHCR QRSVGRWETS QPPVAFSSSI
EKDVTPDKNL LSKVRDAALW LETSDTRPAK PSHSTTASIA DFFLALTICN SVMVSTTTEP
RKRVTTPPAN KALGTSLEKI QQLFQRLKLL SLSQSFSSTA PSDTDLGESL GPNLPTIDSD
EKDDTSVCSG DCSTDGGYRS STWEQGDILG SESGTSLEEG LEAPTLSQDE PELCYEAESP
DEAALVHAAR AYSFTLVSRT PEQVTVRLPQ GICLTFDLLF TLGFDSVRKR MSVVVRHPLT
DEIIVYTKGA DSVIMDLLED PACESNIDVE KKLKRIRART QKHLDLYARD GLRTLCIAKK
VVDEEDFQRW ASFRREAEAS LDNREELLME TAQHLENHLT LLGATGIEDR LQEGVPDTIA
ALREAGIQLW VLTGDKQETA VNIAYSCKLL DQTDTVYSIN TENQETCESI LNCTLEDIKR
FHEPQQPARK LCGHRIPPKM PSVNSGAMAP EIGLVIDGKT LNAIFQGKLE NKFLELTQYC
RSVLCCRSTP LQKSMIVKLV RDKLSVMTLS IGDGANDVSM IQAADIGIGI SGQEGMQAVM
SSDFAIARFS HLKKLLLVHG HWCYSRLARM VVYYFYKNVC YVNLLFWYQF FCGFSGSTMI
DYWQMIFFNL FFTSLPPIIF GVLDKDVSAE TLLALPELYK SGQNSECYNL PTFWVSMADA
FYQSLICFFI PYLTYRGSDI DVFTFGTPIN TISLTTILLH QAMEMKTWTV LHGLVLLGSF
LMYFVVSLIY NATCVTCNSP TNPYWVMERQ LSDPTFYLIC LLTPVVALLP RYFLLSLQGT
YGKSLISKAQ KIDKLPIDKR NLEIQNWRSK QRPAPASASA SASAPATGTV HTRPPCHPVP
PEAQQNFGAS TSKSSGPPRQ KHVEDRVLQD PRCSREHSRD DTCTVDTLAK LSSGECLLDP
NRTVAPTAYS RGQKDVSRHS SKGSHRRSQS SLTI
