AT131_MOUSE
ID AT131_MOUSE Reviewed; 1200 AA.
AC Q9EPE9; B2RS54;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Endoplasmic reticulum transmembrane helix translocase {ECO:0000305};
DE EC=7.4.2.- {ECO:0000250|UniProtKB:Q9HD20};
DE AltName: Full=Endoplasmic reticulum P5A-ATPase {ECO:0000250|UniProtKB:Q9HD20};
GN Name=Atp13a1 {ECO:0000312|MGI:MGI:2180801};
GN Synonyms=Atp13a {ECO:0000312|MGI:MGI:2180801};
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 [MRNA].
RA Inoue S., Ohta M.;
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Testis;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-896, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUBCELLULAR LOCATION, ACTIVE SITE, AND MUTAGENESIS OF ASP-530.
RX PubMed=29505581; DOI=10.1371/journal.pone.0193228;
RA Soerensen D.M., Holemans T., van Veen S., Martin S., Arslan T.,
RA Haagendahl I.W., Holen H.W., Hamouda N.N., Eggermont J., Palmgren M.,
RA Vangheluwe P.;
RT "Parkinson disease related ATP13A2 evolved early in animal evolution.";
RL PLoS ONE 13:e0193228-e0193228(2018).
CC -!- FUNCTION: Endoplasmic reticulum translocase required to remove
CC mitochondrial transmembrane proteins mistargeted to the endoplasmic
CC reticulum. Acts as a dislocase that mediates the ATP-dependent
CC extraction of mislocalized mitochondrial transmembrane proteins from
CC the endoplasmic reticulum membrane. Specifically binds mitochondrial
CC tail-anchored transmembrane proteins: has an atypically large
CC substrate-binding pocket that recognizes and binds moderately
CC hydrophobic transmembranes with short hydrophilic lumenal domains.
CC {ECO:0000250|UniProtKB:Q9HD20}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-with a C-terminal TM segment(out) + ATP + H2O =
CC [protein]-with a C-terminal TM segment(in) + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:66168, Rhea:RHEA-COMP:16963, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:90782, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9HD20};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:29505581}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9HD20}.
CC -!- DOMAIN: Contains a large substrate-binding pocket that recognizes
CC alpha-helical transmembranes, which alternately faces the endoplasmic
CC reticulum lumen and cytosol, while remaining accessible to the lipid
CC bilayer through a lateral opening. The translocase alternates between
CC two conformations: inward-open (E1) and outward-open (E2) states.
CC Undergoes a series of conformational changes with ATP-binding,
CC phosphorylation of the Asp active site and subsequent dephosphorylation
CC in a Post-Albers cycle (i.e., E1 -> E1-ATP -> E1P-ADP -> E1P -> E2P ->
CC E2-Pi -> E1). A substrate transmembrane helix with a short,
CC preferentially positively charged lumenal segment binds to the outward-
CC open pocket and the E2P-to-E1 transition flips the transmembrane by a
CC switch from the outward-open to inward-open conformation.
CC {ECO:0000250|UniProtKB:P39986}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type V subfamily. {ECO:0000305}.
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DR EMBL; AB035381; BAB20095.1; -; mRNA.
DR EMBL; CH466569; EDL28752.1; -; Genomic_DNA.
DR EMBL; BC138721; AAI38722.1; -; mRNA.
DR EMBL; BC138722; AAI38723.1; -; mRNA.
DR CCDS; CCDS22349.1; -.
DR RefSeq; NP_573487.2; NM_133224.2.
DR AlphaFoldDB; Q9EPE9; -.
DR SMR; Q9EPE9; -.
DR BioGRID; 228421; 6.
DR IntAct; Q9EPE9; 2.
DR STRING; 10090.ENSMUSP00000034326; -.
DR GlyGen; Q9EPE9; 2 sites.
DR iPTMnet; Q9EPE9; -.
DR PhosphoSitePlus; Q9EPE9; -.
DR SwissPalm; Q9EPE9; -.
DR EPD; Q9EPE9; -.
DR jPOST; Q9EPE9; -.
DR MaxQB; Q9EPE9; -.
DR PaxDb; Q9EPE9; -.
DR PeptideAtlas; Q9EPE9; -.
DR PRIDE; Q9EPE9; -.
DR ProteomicsDB; 277082; -.
DR Antibodypedia; 28529; 84 antibodies from 27 providers.
DR DNASU; 170759; -.
DR Ensembl; ENSMUST00000034326; ENSMUSP00000034326; ENSMUSG00000031862.
DR GeneID; 170759; -.
DR KEGG; mmu:170759; -.
DR UCSC; uc009lxr.2; mouse.
DR CTD; 57130; -.
DR MGI; MGI:2180801; Atp13a1.
DR VEuPathDB; HostDB:ENSMUSG00000031862; -.
DR eggNOG; KOG0209; Eukaryota.
DR GeneTree; ENSGT00550000075064; -.
DR HOGENOM; CLU_001828_4_1_1; -.
DR InParanoid; Q9EPE9; -.
DR OMA; RFAPKQK; -.
DR OrthoDB; 172453at2759; -.
DR PhylomeDB; Q9EPE9; -.
DR TreeFam; TF300725; -.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 170759; 11 hits in 72 CRISPR screens.
DR ChiTaRS; Atp13a1; mouse.
DR PRO; PR:Q9EPE9; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9EPE9; protein.
DR Bgee; ENSMUSG00000031862; Expressed in lacrimal gland and 266 other tissues.
DR ExpressionAtlas; Q9EPE9; baseline and differential.
DR Genevisible; Q9EPE9; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016020; C: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:0019829; F:ATPase-coupled cation transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0015662; F:P-type ion transporter activity; IBA:GO_Central.
DR GO; GO:0140567; F:transmembrane protein dislocase activity; ISS:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0140569; P:extraction of mislocalized protein from ER membrane; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
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; IPR006544; P-type_TPase_V.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
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; TIGR01494; ATPase_P-type; 2.
DR TIGRFAMs; TIGR01657; P-ATPase-V; 1.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Endoplasmic reticulum; Glycoprotein; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Protein transport;
KW Reference proteome; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..1200
FT /note="Endoplasmic reticulum transmembrane helix
FT translocase"
FT /id="PRO_0000046422"
FT TOPO_DOM 1..63
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 64..84
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 85..92
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..113
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 114..240
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 262..440
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 441..461
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 462..985
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 986..1006
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1007
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1008..1028
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1029..1047
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1048..1068
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1069..1092
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1093..1113
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1114..1128
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1129..1149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1150..1162
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1163..1183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1184..1200
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 196..227
FT /note="A-domain; part 1"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT REGION 292..432
FT /note="A-domain; part 2"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT REGION 509..538
FT /note="P-domain; part 1"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT REGION 540..721
FT /note="N-domain"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT REGION 724..882
FT /note="P-domain; part 2"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT REGION 883..945
FT /note="Arm-like"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT REGION 886..928
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 946..961
FT /note="P-domain; part 3"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT COMPBIAS 900..916
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 530
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000305|PubMed:29505581"
FT BINDING 530..532
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT BINDING 530
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT BINDING 532
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT BINDING 623
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT BINDING 681
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT BINDING 746
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT BINDING 861..865
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT BINDING 861
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P39986"
FT MOD_RES 896
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 902
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HD20"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 530
FT /note="D->N: Loss of ATPase activity."
FT /evidence="ECO:0000269|PubMed:29505581"
FT CONFLICT 188
FT /note="P -> S (in Ref. 1; BAB20095)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1200 AA; 132388 MW; 059C366D63030B82 CRC64;
MAVVGNAVPC GARPGGARDN GSPQPGSRLR PGLAAGPALI ANGDELVAAV WPYRRLALLR
RLTVLPFAGL LYPAWLGAAA SGCWGWGSSW TQIPEAALLA LATICLAHAL TVLSGHWSVH
AHCALTCTPE YDPNKVTFVK VVPTPNNGST ELVALHRDKG EDGLEVLSFE FQKIKYSYDA
LEKKQFLPVA FPVGNAFSYY QSNRGFQEDS EIRAAEKKFG SNKAEMVVPD FSELFKERAT
APFFVFQVFC VGLWCLDEYW YYSVFTLSML VAFEASLVQQ QMRNMSEIRK MGNKPHMIQV
YRSRKWRPVA SDDIVPGDIV SIGRSPQENL VPCDVLLLRG RCIVDEAMLT GESVPQMKEP
IEDLSPDRVL DLQADARLHV IFGGTKVVQH IPPQKATSGL KPVDNGCVAF VLRTGFNTSQ
GRLLRTILFG VKRVTANNLE TFIFILFLLV FAIAAAAYVW VEGTKDPSRN RYKLFLECTL
ILTSVVPPEL PIELSLAVNT SLIALAKLYM YCTEPFRIPF AGKVEVCCFD KTGTLTSDSL
VVRGVAGLRD GKEVTPVSSI PIETHRALAS CHSLMQLDDG TLVGDPLEKA MLTAVDWTLT
KDEKVFPRSI KTQGLKIHQR FHFASALKRM SVLASYEKLG STDLCYIAAV KGAPETLHSM
FSQCPPDYHH IHTEISREGA RVLALGYKEL GHLTHQQARE IKREALECSL KFVGFIVVSC
PLKADSKAVI REIQNASHRV VMITGDNPLT ACHVAQELHF IDKAHTLILH PPSEKGQPCE
WRSIDSSIVL PLTLGSPKAL ALEHALCLTG DGLAHLQAVD PQQLLCLIPH VQVFARVAPK
QKEFVITSLK ELGYVTLMCG DGTNDVGALK HADVGVALLA NAPERVVERR RRPRDSPVLS
NSGPRVSRST KQKSALLSPE EPPASHRDRL SQVLRDLEEE STPIVKLGDA SIAAPFTSKL
SSIQCICHVI KQGRCTLVTT LQMFKILALN ALILAYSQSV LYLEGVKFSD FQATLQGLLL
AGCFLFISRS KPLKTLSRER PLPNIFNLYT ILTVMLQFSV HFLSLVYLYR EAQARSPEKQ
EQFVDLYKEF EPSLVNSTVY IMAMAMQMAT FAINYKGPPF MESLPENKPL VWSLAVSLLA
IIGLLLGSSP DFNSQFGLVD IPVEFKLVIG QVLALDFCLA LLADRVLQFF LGTPKLRVPS
