MDR1_RAT
ID MDR1_RAT Reviewed; 1277 AA.
AC P43245; Q63426; Q63427;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=ATP-dependent translocase ABCB1 {ECO:0000250|UniProtKB:P08183};
DE AltName: Full=ATP-binding cassette sub-family B member 1;
DE AltName: Full=Multidrug resistance protein 1;
DE EC=7.6.2.2;
DE AltName: Full=P-glycoprotein 1;
DE AltName: Full=Phospholipid transporter ABCB1 {ECO:0000305};
DE EC=7.6.2.1 {ECO:0000250|UniProtKB:P08183};
DE AltName: CD_antigen=CD243;
GN Name=Abcb1 {ECO:0000312|RGD:3318}; Synonyms=Mdr1, Mdr1b, Pgy1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1682220; DOI=10.1016/0378-1119(91)90203-n;
RA Silverman J.A., Raunio H., Gant T.W., Thorgeirsson S.S.;
RT "Cloning and characterization of a member of the rat multidrug resistance
RT (mdr) gene family.";
RL Gene 106:229-236(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1212-1277.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1348630; DOI=10.1016/0167-4781(92)90523-3;
RA Deuchars K.L., Duthie M., Ling V.;
RT "Identification of distinct P-glycoprotein gene sequences in rat.";
RL Biochim. Biophys. Acta 1130:157-165(1992).
CC -!- FUNCTION: Translocates drugs and phospholipids across the membrane.
CC Catalyzes the flop of phospholipids from the cytoplasmic to the
CC exoplasmic leaflet of the apical membrane. Participates mainly to the
CC flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-
CC glucosylceramides and sphingomyelins. Energy-dependent efflux pump
CC responsible for decreased drug accumulation in multidrug-resistant
CC cells. {ECO:0000250|UniProtKB:P08183}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2;
CC Evidence={ECO:0000250|UniProtKB:P08183};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000250|UniProtKB:P08183};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ATP + H2O
CC = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:36439, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:64612, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P08183};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ATP + H2O = a
CC 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:38583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57643,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P08183};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine(in) + ATP +
CC H2O = a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine(out) + ADP +
CC H(+) + phosphate; Xref=Rhea:RHEA:38943, 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:P08183};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP +
CC H(+) + phosphate; Xref=Rhea:RHEA:38903, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P08183};
CC -!- ACTIVITY REGULATION: Translocase activity is inhibited by verapamil and
CC is sensitive to energy depletion. {ECO:0000250|UniProtKB:P08183}.
CC -!- SUBUNIT: Interacts with PSMB5. Finds in a complex with ABCB1, TFPI2 and
CC PPP2R3C; leading to the dephosphorylation of ABCB1.
CC {ECO:0000250|UniProtKB:P08183}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein
CC {ECO:0000255|PROSITE-ProRule:PRU00441}. Apical cell membrane
CC {ECO:0000250|UniProtKB:P08183}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Multidrug resistance exporter (TC 3.A.1.201) subfamily. {ECO:0000305}.
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DR EMBL; M81855; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; X61103; CAA43415.1; -; Genomic_DNA.
DR EMBL; X61104; CAA43416.1; -; Genomic_DNA.
DR PIR; JH0502; JH0502.
DR AlphaFoldDB; P43245; -.
DR SMR; P43245; -.
DR STRING; 10116.ENSRNOP00000049952; -.
DR ChEMBL; CHEMBL1075229; -.
DR GlyGen; P43245; 2 sites.
DR PaxDb; P43245; -.
DR PRIDE; P43245; -.
DR RGD; 3318; Abcb1.
DR eggNOG; KOG0055; Eukaryota.
DR InParanoid; P43245; -.
DR PhylomeDB; P43245; -.
DR Reactome; R-RNO-382556; ABC-family proteins mediated transport.
DR Reactome; R-RNO-9754706; Atorvastatin ADME.
DR PRO; PR:P43245; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0098591; C:external side of apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0000139; C:Golgi membrane; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0046581; C:intercellular canaliculus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0099038; F:ceramide floppase activity; IBA:GO_Central.
DR GO; GO:0140328; F:floppase activity; ISS:UniProtKB.
DR GO; GO:0090554; F:phosphatidylcholine floppase activity; IBA:GO_Central.
DR GO; GO:0090555; F:phosphatidylethanolamine flippase activity; IBA:GO_Central.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0071217; P:cellular response to external biotic stimulus; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0099040; P:ceramide translocation; IBA:GO_Central.
DR GO; GO:0014045; P:establishment of endothelial blood-brain barrier; IMP:RGD.
DR GO; GO:0007595; P:lactation; IEP:RGD.
DR GO; GO:0045332; P:phospholipid translocation; IBA:GO_Central.
DR GO; GO:0001890; P:placenta development; IEP:RGD.
DR GO; GO:0097327; P:response to antineoplastic agent; IEP:RGD.
DR GO; GO:0046685; P:response to arsenic-containing substance; IEP:RGD.
DR GO; GO:0033595; P:response to genistein; IEP:RGD.
DR GO; GO:1903416; P:response to glycoside; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0010212; P:response to ionizing radiation; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0010046; P:response to mycotoxin; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0033189; P:response to vitamin A; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:RGD.
DR GO; GO:0061843; P:Sertoli cell barrier remodeling; IMP:RGD.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Glycoprotein; Lipid transport; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1277
FT /note="ATP-dependent translocase ABCB1"
FT /id="PRO_0000093335"
FT TOPO_DOM 1..42
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 43..65
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 66..115
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 137..185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 186..207
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 208..214
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 215..235
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 236..293
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 294..315
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 316..329
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 330..351
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 352..709
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 710..730
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 731..754
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 755..775
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 776..830
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 831..853
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 854
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 855..874
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 875..934
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 935..957
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 958..973
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 974..995
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 996..1277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 49..356
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 391..627
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 709..1000
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1035..1272
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 633..660
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 633..656
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 426..433
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1070..1077
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 641
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P06795"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06795"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 1227
FT /note="V -> I (in Ref. 2; CAA43415/CAA43416)"
FT /evidence="ECO:0000305"
FT CONFLICT 1270
FT /note="V -> VSV (in Ref. 2; CAA43415)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1277 AA; 141387 MW; 8AFDDD619D2934C1 CRC64;
MEFEEGLNGR ADKNFSKMGK KSKKEKEKKP AVGIFGMFRY ADWLDKLCMA LGTLAAIIHG
TLLPLLMLVF GYMTDSFTPS RDPHSDRAIT NQSEINSTHT VSDTSLEEDM AMYAYYYTGI
GAGVLIVAYI QVSLWCLAAG RQIHKIRQKF FHAIMNQEIG WFDVNDAGEL NTRLTDDVSK
INDGIGDKLG MFFQSITTFS AGFIIGFISG WKLTLVILAV SPLIGLSSAM WAKVLTSFTN
KELQAYAKAG AVAEEVLAAI RTVIAFGGQK KELERYNKNL EEAKRVGIKK AITANISIGI
AYLLVYASYA LAFWYGTSLV LSNEYSIGQV LTVFFSILLG TFSIGHLAPN IEAFANARGA
AYEIFKIIDN EPSIDSFSTK GHKPDSIMGN LEFKNVYFNY PSRSEVKILK GLNLKVKSGQ
TVALVGNSGC GKSTTVQLLQ RLYDPIEGEV SIDGQDIRTI NVRYLREIIG VVSQEPVLFA
TTIAENIRYG RENVTMDEIE KAVKEANAYD FIMKLPHKFD TLVGERGAQL SGGQKQRIAI
ARALVRNPKI LLLDEATSAL DTESEAVVQA ALDKAREGRT TIVIAHRLST VRNADVIAGF
DGGVIVEQGN HEELMKEKGI YFKLVMTQTR GNEIEPGNNA YESQSDTGAS ELTSEESKSP
LIRRSIRRSI HRRQDQERRL SSKEDVDEDV PMVSFWQILK LNISEWPYLV VGVLCAVING
CIQPVFAIVF SKIVGVFSRD DDHETKQRNC NLFSLLFLVM GMISFVTYFF QGFTFGKAGE
ILTKRLRYMV FKSMLRQDIS WFDDHKNTTG SLTTRLASDA SNVKGAMGSR LAVVTQNVAN
LGTGIILSLV LVYGWQLTLL LVVIIPLIVL GGIIEMKLLS GQALKDKKEL EISGKIATEA
IENFRTVVSL TREQKFETMY AQSLQIPYRN ALKKAHVFGI TFAFTQAMIY FSYAACFRFG
AYLVARELMT FENVMLVFSA VVFGAMAAGN TSSFAPDYAK AKVSASHIIG IIEKIPEIDS
YSTEGLKPNW LEGNVKFNGV KFNYPTRPNI PVLQGLSFEV KKGQTLRLVG SSGCGKSTVV
QLLERFYNPM AGTVFLDGKE IKQLNVQCVR ALGIVSQEPI LFDCSIAENI AYGDNSRVVS
HEEIVRAARE ANIHQFIDSL PEKYNTRVGD KGTQLSGGQK QRIAIARALV RQPHILLLDE
ATSALDTESE KVVQEALDKA REGRTCVVIA HRLSTIQNAD LIVVIQNGQV KEHGTHQQLL
AQKGIYFSMV QAGAKRS
