MDR1_CRIGR
ID MDR1_CRIGR Reviewed; 1276 AA.
AC P21448; G3HRY0; Q80W58;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 2.
DT 03-AUG-2022, entry version 144.
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:0000250|UniProtKB:P08183}; Synonyms=PGP1, PGY1;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1685679; DOI=10.3109/10425179109039677;
RA Endicott J.A., Sarangi F., Ling V.;
RT "Complete cDNA sequences encoding the Chinese hamster P-glycoprotein gene
RT family.";
RL DNA Seq. 2:89-101(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1671863; DOI=10.1016/s0021-9258(20)64357-5;
RA Devine S.E., Hussain A., Davide J.P., Melera P.W.;
RT "Full length and alternatively spliced pgp1 transcripts in multidrug-
RT resistant Chinese hamster lung cells.";
RL J. Biol. Chem. 266:4545-4555(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21804562; DOI=10.1038/nbt.1932;
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan H.C., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.";
RL Nat. Biotechnol. 29:735-741(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21, AND TISSUE SPECIFICITY.
RX PubMed=1661134;
RA Teeter L.D., Eckersberg T., Tsai Y., Kuo M.T.;
RT "Analysis of the Chinese hamster P-glycoprotein/multidrug resistance gene
RT pgp1 reveals that the AP-1 site is essential for full promoter activity.";
RL Cell Growth Differ. 2:429-437(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RC TISSUE=Ovary;
RX PubMed=8100449; DOI=10.1016/0167-4781(93)90128-z;
RA Zastawny R.L., Ling V.;
RT "Structural and functional analysis of 5' flanking and intron 1 sequences
RT of the hamster P-glycoprotein pgp1 and pgp2 genes.";
RL Biochim. Biophys. Acta 1173:303-313(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 706-1276.
RX PubMed=2893255; DOI=10.1128/mcb.7.11.4075-4081.1987;
RA Endicott J.A., Juranka P.F., Sarangi F., Gerlach J.H., Deuchars K.L.,
RA Ling V.;
RT "Simultaneous expression of two P-glycoprotein genes in drug-sensitive
RT Chinese hamster ovary cells.";
RL Mol. Cell. Biol. 7:4075-4081(1987).
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 -!- TISSUE SPECIFICITY: Expressed at a higher level in intestines than in
CC kidney and liver. {ECO:0000269|PubMed:1661134}.
CC -!- MISCELLANEOUS: PGP isoforms differ in their drug transport
CC capabilities: PGP1 and PGP2 can mediate MDR, while PGP3 apparently
CC cannot.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Multidrug resistance exporter (TC 3.A.1.201) subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EGW07208.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; M60040; AAA68883.1; -; mRNA.
DR EMBL; M59253; AAA37004.1; -; mRNA.
DR EMBL; JH000645; EGW07208.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AH003795; AAP32275.1; -; Genomic_DNA.
DR EMBL; L03286; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M17897; AAA37006.1; -; mRNA.
DR PIR; A38696; DVHY1C.
DR RefSeq; NP_001230917.1; NM_001243988.1.
DR PDB; 1MVU; X-ray; 1.78 A; P=1210-1222.
DR PDB; 2AP2; X-ray; 2.40 A; P/Q=1210-1223.
DR PDBsum; 1MVU; -.
DR PDBsum; 2AP2; -.
DR AlphaFoldDB; P21448; -.
DR SMR; P21448; -.
DR STRING; 10029.NP_001230917.1; -.
DR ABCD; P21448; 2 sequenced antibodies.
DR Ensembl; ENSCGRT00001017943; ENSCGRP00001013706; ENSCGRG00001014754.
DR GeneID; 100682536; -.
DR KEGG; cge:100682536; -.
DR CTD; 5243; -.
DR eggNOG; KOG0055; Eukaryota.
DR GeneTree; ENSGT00940000155287; -.
DR InParanoid; P21448; -.
DR OrthoDB; 186078at2759; -.
DR EvolutionaryTrace; P21448; -.
DR Proteomes; UP000001075; Unassembled WGS sequence.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046581; C:intercellular canaliculus; IEA:Ensembl.
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:0016887; F:ATP hydrolysis activity; IEA:Ensembl.
DR GO; GO:0099038; F:ceramide floppase activity; IEA:Ensembl.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0140328; F:floppase activity; ISS:UniProtKB.
DR GO; GO:0090554; F:phosphatidylcholine floppase activity; IEA:Ensembl.
DR GO; GO:0090555; F:phosphatidylethanolamine flippase activity; IEA:Ensembl.
DR GO; GO:0045332; P:phospholipid translocation; IEA:Ensembl.
DR GO; GO:0046865; P:terpenoid transport; IEA:Ensembl.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IEA:Ensembl.
DR GO; GO:1990962; P:xenobiotic transport across blood-brain barrier; IEA:Ensembl.
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; IPR030258; MDR1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR PANTHER; PTHR24221:SF251; PTHR24221:SF251; 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 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Glycoprotein; Lipid transport;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1276
FT /note="ATP-dependent translocase ABCB1"
FT /id="PRO_0000093339"
FT TOPO_DOM 1..43
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 44..66
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 67..113
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 135..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 184..205
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 206..212
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 234..291
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 292..313
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 314..327
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 328..349
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 350..708
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 709..729
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 730..753
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 754..774
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 775..829
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 830..850
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 851
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 852..871
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 872..931
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 932..954
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 955..970
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 971..992
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 993..1276
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 50..354
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 389..625
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 708..997
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1032..1270
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 653..682
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 424..431
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1067..1074
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06795"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 338..339
FT /note="GA -> AP (in Ref. 2; AAA37004)"
FT /evidence="ECO:0000305"
FT HELIX 1211..1220
FT /evidence="ECO:0007829|PDB:1MVU"
SQ SEQUENCE 1276 AA; 140926 MW; 44F3F92A186B4DFF CRC64;
MEFEEDFSGR KDKNFLKMGR KSKKEKKEKK PVVSVFTMFR YAGWLDRLYM LVGTLAAIIH
GVALPLMMLV FGDMTDSFAS VGNIPTNATN NATQVNASDI FGKLEEEMTT YAYYYTGIGA
GVLIVAYIQV SFWCLAAGRQ IHKIRQKFFH AIMNQEIGWF DVHDVGELNT RLTDDVSKIN
EGIGDKIGMF FQAMATFFGG FIIGFTRGWK LTLVILAISP VLGLSAGIWA KILSSFTDKE
LQAYAKAGAV AEEVLAAIRT VIAFGGQKKE LERYNNNLEE AKRLGIKKAI TANISMGAAF
LLIYASYALA FWYGTSLVIS KEYSIGQVLT VFFAVLIGAF SIGQASPNIE AFANARGAAY
EIFNIIDNKP SIDSFSKNGY KPDNIKGNLE FKNIHFSYPS RKDVQILKGL NLKVQSGQTV
ALVGNSGCGK STTVQLLQRL YDPTEGVVSI DGQDIRTINV RYLREIIGVV SQEPVLFATT
IAENIRYGRE NVTMDEIEKA VKEANAYDFI MKLPHKFDTL VGERGAQLSG GQKQRIAIAR
ALVRNPKILL LDEATSALDT ESEAVVQAAL DKAREGRTTI VIAHRLSTVR NADIIAGFDG
GVIVEQGNHE ELMREKGIYF KLVMTQTAGN EIELGNEVGE SKNEIDNLDM SSKDSASSLI
RRRSTRRSIR GPHDQDRKLS TKEALDEDVP PISFWRILKL NSSEWPYFVV GIFCAIVNGA
LQPAFSIIFS KVVGVFTRNT DDETKRHDSN LFSLLFLILG VISFITFFLQ GFTFGKAGEI
LTKRLRYMVF KSMLRQDVSW FDNPKNTTGA LTTRLANDAG QVKGATGARL AVITQNIANL
GTGIIISLIY GWQLTLLLLA IVPIIAIAGV VEMKMLSGQA LKDKKELEGS GKIATEAIEN
FRTVVSLTRE QKFENMYAQS LQIPYRNALK KAHVFGITFS FTQAMMYFSY AACFRFGAYL
VARELMTFEN VLLVFSAIVF GAMAVGQVSS FAPDYAKAKV SASHIIMIIE KVPSIDSYST
GGLKPNTLEG NVKFNEVVFN YPTRPDIPVL QGLNLEVKKG QTLALVGSSG CGKSTVVQLL
ERFYDPMAGT VFLDGKEVNQ LNVQWLRAHL GIVSQEPILF DCSIAENIAY GDNSRVVSQD
EIERAAKEAN IHQFIESLPD KYNTRVGDKG TQLSGGQKQR IAIARALVRQ PHILLLDEAT
SALDTESEKV VQEALDKARE GRTCIVIAHR LSTIQNADLI VVIQNGKVKE HGTHQQLLAQ
KGIYFSMVSV QAGAKR
