MRP1_CANLF
ID MRP1_CANLF Reviewed; 1531 AA.
AC Q6UR05;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Multidrug resistance-associated protein 1 {ECO:0000250|UniProtKB:P33527};
DE EC=7.6.2.2 {ECO:0000269|PubMed:12516967};
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANT SER-149, AND CATALYTIC
RP ACTIVITY.
RC STRAIN=Beagle; TISSUE=Heart, and Kidney;
RX PubMed=12516967;
RA Ma L., Pratt S.E., Cao J., Dantzig A.H., Moore R.E., Slapak C.A.;
RT "Identification and characterization of the canine multidrug resistance-
RT associated protein.";
RL Mol. Cancer Ther. 1:1335-1342(2002).
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 (By
CC similarity) (PubMed:12516967). Hydrolyzes ATP with low efficiency.
CC Catalyzes the export of sphingosine 1-phosphate from mast cells
CC independently of their degranulation (By similarity). Participates in
CC inflammatory response by allowing export of leukotriene C4 from
CC leukotriene C4-synthezing cells (By similarity).
CC {ECO:0000250|UniProtKB:O35379, ECO:0000250|UniProtKB:P33527,
CC ECO:0000269|PubMed:12516967}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2;
CC Evidence={ECO:0000269|PubMed:12516967};
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:12516967};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964;
CC Evidence={ECO:0000269|PubMed:12516967};
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:0000250}; Multi-pass membrane
CC protein {ECO:0000255|PROSITE-ProRule:PRU00441}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC Conjugate transporter (TC 3.A.1.208) subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY363728; AAQ23148.1; -; mRNA.
DR RefSeq; NP_001002971.1; NM_001002971.1.
DR AlphaFoldDB; Q6UR05; -.
DR SMR; Q6UR05; -.
DR STRING; 9612.ENSCAFP00000025361; -.
DR ChEMBL; CHEMBL4739692; -.
DR PaxDb; Q6UR05; -.
DR PRIDE; Q6UR05; -.
DR Ensembl; ENSCAFT00040003892; ENSCAFP00040003340; ENSCAFG00040002016.
DR GeneID; 403453; -.
DR KEGG; cfa:403453; -.
DR CTD; 4363; -.
DR eggNOG; KOG0054; Eukaryota.
DR InParanoid; Q6UR05; -.
DR OrthoDB; 138195at2759; -.
DR BRENDA; 7.6.2.3; 1153.
DR Reactome; R-CFA-189483; Heme degradation.
DR Reactome; R-CFA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-CFA-382556; ABC-family proteins mediated transport.
DR Reactome; R-CFA-9707564; Cytoprotection by HMOX1.
DR Reactome; R-CFA-9753281; Paracetamol ADME.
DR Reactome; R-CFA-9758890; Transport of RCbl within the body.
DR Proteomes; UP000002254; 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_0000093350"
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 917..938
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 917..936
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 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 1006
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 149
FT /note="A -> S"
FT /evidence="ECO:0000269|PubMed:12516967"
SQ SEQUENCE 1531 AA; 171792 MW; 746361A71C6158BD CRC64;
MALRGFCSAD GSDPFWEWDV SWNTSNPDFT KCFQNTVLVW VPCCYLWLCF PFYFLYLSRH
DRGYIQMTYL NKTKTALGFV LWIVCWADLF YSFWERSWGK ILAPVFLVSP TLLGITMLLA
TFLIQLERRK GVQSSGIMLT FWLIALLCAL AILRSKIMTA LKEDAEIDVF RDVTFYIYFS
LVLIQLVLSC FSDRPPLFSE TIHDLNPCPE SSASFLSRVT FWWITGLMVR GYRQPLESTD
LWSLNKEDTS EQVVPVLVKN WKKECAKSKR QQRKITYSSK DPAKPKGGSQ VDVNEEAEVL
IVKTPQKERE PSLFKVLYKT FGPYFLMSFL FKALHDLMMF AGPEILKLLI NFVNDKKAPD
WQGYLYTALL FICACLQTLV LHQYFHICFV SGMRIKTAVI GAVYRKALVI TNSARKSSTV
GEIVNLMSVD AQRFMDLATY INMIWSAPLQ VILALYLLWL NLGPSVLAGV AVMILMVPLN
AVMAMKTKTY QVAHMKSKDN RIKLMNEILN GIKVLKLYAW ELAFKDKVLA IRQEELKVLK
KSAYLAAVGT FTWVCTPFLV ALSTFAVYVT VDKNNILDAQ KAFVSLALFN ILRFPLNILP
MVISSIVQAS VSLKRLRIFL SHEELEPDSI ERRPVKDGGG ANSITVKNAT FTWARSDPPT
LSGITFSIPE GSLVAVVGQV GCGKSSLLSA LLAEMDKVEG HVAIKGSVAY VPQQAWIQND
SLRENILFGR QLQERYYKAV IEACALLPDL EILPSGDRTE IGEKGVNLSG GQKQRVSLAR
AVYCDSDIYL FDDPLSAVDA HVGKHIFENV IGPKGMLKNK TRLLVTHSIS YLPQVDVIIV
MTGGKISEMG SYQELLARDG AFAEFLRTYA SGDQEQAEQD DGLTGVSSPG KEVKQMENGM
LVTDVAGKQL QRQLSNSSSY SGDVSRHHTS TAELQKAGPK NEDAWKLVEA DKAQTGQVKL
SVYWDYMKAI GLFISFLSIF LFLCNHVASL VSNYWLSLWT DDPIVNGTQE HTKIRLSVYG
ALGISQGITV FGYSMAVSIG GIFASRRLHV DLLQNVLRSP MSFFERTPSG NLVNRFSKEL
DTVDSMIPQV IKMFMGSLFN VIGACIIILL ATPIASIIIP PLGLIYFFVQ RFYVASSRQL
KRLESVSRSP VYSHFNETLL GVSVIRAFEE QERFIRQSDL KVDENQKAYY PSIVANRWLA
VRLECVGNCI VLFAALFSVI SRHSLSAGLV GLSVSYSLQV TTYLNWLVRM SSEMETNIVA
VERLKEYSET EKEAPWQIQE MAPPSTWPQV GRVEFRDYGL RYRENLDLVL KHINITINGG
EKVGIVGRTG AGKSSLTLGL FRINESAEGE IIIDDINIAK IGLHDLRVKI TIIPQDPVLF
SGSLRMNLDP FSQYSDEEVW TSLELAHLKD FVSGLPDKLN QECAEGGENL SVGQRQLVCL
ARALLRKTKI LVLDEATAAV DLETDDLIQS TIRTQFDDCT VLTIAHRLNT IMDYTRVIVL
DKGEIRECGQ PSDLLQQRGL FYSMAKDAGL V
