MRP1_MACFA
ID MRP1_MACFA Reviewed; 1531 AA.
AC Q864R9; Q864S0;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Multidrug resistance-associated protein 1 {ECO:0000250|UniProtKB:P33527};
DE EC=7.6.2.2 {ECO:0000269|PubMed:12657726};
DE AltName: Full=ATP-binding cassette sub-family C member 1;
DE AltName: Full=Glutathione-S-conjugate-translocating ATPase ABCC1 {ECO:0000250|UniProtKB:O35379};
DE EC=7.6.2.3 {ECO:0000250|UniProtKB:O35379};
DE AltName: Full=Leukotriene C(4) transporter;
DE Short=LTC4 transporter;
GN Name=ABCC1 {ECO:0000250|UniProtKB:P33527}; Synonyms=MRP1;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, VARIANTS
RP ILE-173; ILE-704 AND TYR-1047, AND CATALYTIC ACTIVITY.
RX PubMed=12657726;
RA Godinot N., Iversen P.W., Tabas L., Xia X., Williams D.C., Dantzig A.H.,
RA Perry W.L. III;
RT "Cloning and functional characterization of the multidrug resistance-
RT associated protein (MRP1/ABCC1) from the cynomolgus monkey.";
RL Mol. Cancer Ther. 2:307-316(2003).
CC -!- FUNCTION: Mediates export of organic anions and drugs from the
CC cytoplasm. Mediates ATP-dependent transport of glutathione and
CC glutathione conjugates, leukotriene C4, estradiol-17-beta-o-
CC glucuronide, methotrexate, antiviral drugs and other xenobiotics.
CC Confers resistance to anticancer drugs by decreasing accumulation of
CC drug in cells, and by mediating ATP- and GSH-dependent drug export
CC (PubMed:12657726). Hydrolyzes ATP with low efficiency. Catalyzes the
CC export of sphingosine 1-phosphate from mast cells independently of
CC their degranulation (By similarity). Participates in inflammatory
CC response by allowing export of leukotriene C4 from leukotriene C4-
CC synthezing cells (By similarity). {ECO:0000250|UniProtKB:O35379,
CC ECO:0000250|UniProtKB:P33527, ECO:0000269|PubMed:12657726}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2;
CC Evidence={ECO:0000269|PubMed:12657726};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an S-substituted glutathione(in) + ATP + H2O = ADP + an S-
CC substituted glutathione(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:19121, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:90779,
CC ChEBI:CHEBI:456216; EC=7.6.2.3;
CC Evidence={ECO:0000250|UniProtKB:O35379};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122;
CC Evidence={ECO:0000250|UniProtKB:O35379};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + sphing-4-enine 1-phosphate(in) = ADP + H(+) +
CC phosphate + sphing-4-enine 1-phosphate(out); Xref=Rhea:RHEA:38951,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:60119, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P33527};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38952;
CC Evidence={ECO:0000250|UniProtKB:P33527};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + leukotriene C4(in) = ADP + H(+) + leukotriene
CC C4(out) + phosphate; Xref=Rhea:RHEA:38963, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57973, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:12657726};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964;
CC Evidence={ECO:0000269|PubMed:12657726};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O =
CC 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:60128, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:82961, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P33527};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129;
CC Evidence={ECO:0000250|UniProtKB:P33527};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + daunorubicin(in) + H2O = ADP + daunorubicin(out) + H(+)
CC + phosphate; Xref=Rhea:RHEA:33147, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:64677, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P33527};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33148;
CC Evidence={ECO:0000250|UniProtKB:P33527};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + vincristine(in) = ADP + H(+) + phosphate +
CC vincristine(out); Xref=Rhea:RHEA:60160, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:143658, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P33527};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60161;
CC Evidence={ECO:0000250|UniProtKB:P33527};
CC -!- ACTIVITY REGULATION: MK 571 inhibits sphingosine 1-phosphate and
CC leukotriene C4 export. {ECO:0000250|UniProtKB:P33527}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12657726};
CC Multi-pass membrane protein {ECO:0000255|PROSITE-ProRule:PRU00441,
CC ECO:0000269|PubMed:12657726}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC Conjugate transporter (TC 3.A.1.208) subfamily. {ECO:0000305}.
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DR EMBL; AY146672; AAN65348.1; -; mRNA.
DR EMBL; AY146673; AAN65349.1; -; mRNA.
DR RefSeq; NP_001271100.1; NM_001284171.1.
DR AlphaFoldDB; Q864R9; -.
DR SMR; Q864R9; -.
DR STRING; 9541.XP_005591397.1; -.
DR GeneID; 102133648; -.
DR CTD; 4363; -.
DR eggNOG; KOG0054; Eukaryota.
DR OrthoDB; 138195at2759; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015431; F:ABC-type glutathione S-conjugate transporter activity; ISS:UniProtKB.
DR GO; GO:0140359; F:ABC-type transporter activity; ISS:UniProtKB.
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:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0071716; P:leukotriene transport; ISS:UniProtKB.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISS:UniProtKB.
DR Gene3D; 1.20.1560.10; -; 2.
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; IPR005292; Multidrug-R_assoc.
DR InterPro; IPR027417; P-loop_NTPase.
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 TIGRFAMs; TIGR00957; MRP_assoc_pro; 1.
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 ATP-binding; Cell membrane; Glycoprotein; Hydrolase; Lipid transport;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1531
FT /note="Multidrug resistance-associated protein 1"
FT /id="PRO_0000093352"
FT TOPO_DOM 1..33
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 34..54
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 55..74
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 75..95
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 96..100
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 101..121
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 122..133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 134..154
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 155..172
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 173..193
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 194..316
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 317..337
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 338..363
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 364..384
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 385..440
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 441..461
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 462..464
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 465..485
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 486..547
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 548..568
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 569..590
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 591..611
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 612..967
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 968..988
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 989..1025
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1026..1046
FT /note="Helical; Name=13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1047..1089
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1090..1110
FT /note="Helical; Name=14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1111
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1112..1132
FT /note="Helical; Name=15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1133..1203
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 1204..1224
FT /note="Helical; Name=16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1225..1226
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1227..1247
FT /note="Helical; Name=17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1248..1531
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 325..608
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 644..868
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 975..1256
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1293..1527
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 871..893
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 917..938
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 917..932
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 678..685
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1327..1334
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 277
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O35379"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35379"
FT MOD_RES 503
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35379"
FT MOD_RES 905
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33527"
FT MOD_RES 915
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33527"
FT MOD_RES 930
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33527"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1006
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 173
FT /note="M -> I"
FT /evidence="ECO:0000269|PubMed:12657726"
FT VARIANT 704
FT /note="L -> I"
FT /evidence="ECO:0000269|PubMed:12657726"
FT VARIANT 1047
FT /note="C -> Y"
FT /evidence="ECO:0000269|PubMed:12657726"
SQ SEQUENCE 1531 AA; 171659 MW; 1AE788EFDF9EF459 CRC64;
MALRGFCSAD GSDPLWDWNV TWYTSNPDFT KCFQNTVLVW VPCFYLWACF PFYFLYLSRH
DRGYIQMTLL NKTKTALGFL LWIVCWADLF YSFWERSRGI FLAPVFLVSP TLLGITMLLA
TFLIQLERRK GVQSSGIMLT FWLVALLCAL AILRSKIMTA LKEDVQVDLF RDMTFYVYFS
LVLIQLVLSC FSDRSPLFSE TIHDPNPCPE SSASFLSRIT FWWITGLIVR GYRQPLEGSD
LWSLNKEDTS EQVVPVLVKN WKKECAKTRK QPVKVVYSSK DPAQPKDSSK VDANEEVEAL
IVKSPQKEWN PSLFKVLYKT FGPYFLMSFF FKAIHDLMMF SGPEILKLLI NFVNDTKAPD
WQGYFYTALL FVAACLQTLV LHQYFHICFV SGMRIKTAVI GAVYRKALVI TNAARKSSTV
GEIVNLMSVD AQRFMDLATY INMIWSAPLQ VILALYLLWR NLGPPILAGV AVMVLMVPVN
AVMAMKTKTY QVAHMKSKDN RIKLMNEILN GIKVLKLYAW ELAFKDKVLA IRQEELKVLK
KSAYLAAVGT FTWVCTPFLV ALCTFAVYVT IDKNNVLDAQ KAFVSLALFN ILRFPLNILP
MVISSIVQAS VSLKRLRIFL SHEELEPDSI ERRPVKDGGD TNSITVRNAT FTWARSDPPT
LNGITFSIPE GALVAVVGQV GCGKSSLLSA LLAEMDKVEG HVALKGSVAY VPQQAWIQND
SLQENILFGC QLEEPYYRSV IQACALLPDL EILPSGDRTE IGEKGVNLSG GQKQRVSLAR
AVYCNADIYL FDDPLSAVDA HVGKHIFENV IGPKGMLKNK TRILVTHSMS YLPQVDVIIV
MSGGKISEMG SYQELLARDG AFAEFLRTYA SAEQEQDPED NGVTGVSGPG KEAKQMENGM
LVTDSAGKQL QRQLSSSSSY SGDVSRQHNS TAELQKDGAK KEETWKLMEA DKAQTGQVKL
SVYWDYMKAI GLFISFLSIF LFICNHVAAL ASNYWLSLWT DDPIVNGTQE HTKVRLSVYG
ALGISQGIAV FGYSMAVSIG GILASRCLHV DLLHSILRSP MSFFERTPSG NLVNRFSKEL
DTVDSMIPEV IKMFMGSLFN VIGACIVILL ATPIAAIIIP PLGLIYFFVQ RFYVASSRQL
KRLESVSRSP VYSHFNETLL GVSVIRAFEE QERFIHQSDL KVDENQKAYY PSIVANRWLA
VRLECVGNCI VLFAALFAVI SRHSLSAGLV GLSVSYSLQV TTYLNWLVRM SSEMETNIVA
VERLKEYSET EKEAPWQIQE TAPPSNWPQV GRVEFRNYCL RYREDLDFVL RHINVTINGG
EKVGIVGRTG AGKSSLTLGL FRINESAEGE IIIDGINIAR IGLHDLRFKI TIIPQDPVLF
SGSLRMNLDP FSQYSDEEVW TSLELAHLKG FVSALPDKLD HECAEGGENL SVGQRQLVCL
ARALLRKTKI LVLDEATAAV DLETDDLIQS TIRTQFEDCT VLTIAHRLNT IMDYTRVIVL
DKGEIQEYGA PSDLLQQRGL FYNMARDAGL V
