RBCC Red Blood Cell Collection

ABCC1 (MRP, MRP1) [Confidence: high (present in two of the MS resources)]
Multidrug resistance-associated protein 1 (ATP-binding cassette sub-family C member 1; Leukotriene C(4) transporter; LTC4 transporter)

hRBCD IPI00008338
IPI00008338 Splice isoform Delexon-17 of P33527 Multidrug resistance-associated protein 1 Splice isoform Delexon-17 of P33527 Multidrug resistance-associated protein 1 membrane n/a n/a 1 n/a 2 1 n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a 1 integral membrane protein different splice isoforms found at its expected molecular weight found at molecular weight

UniProt P33527
ID MRP1_HUMAN Reviewed; 1531 AA.
AC P33527; A3RJX2; C9JPJ4; O14819; O43333; P78419; Q59GI9; Q9UQ97;
read moreAC Q9UQ99; Q9UQA0;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Multidrug resistance-associated protein 1;
DE AltName: Full=ATP-binding cassette sub-family C member 1;
DE AltName: Full=Leukotriene C(4) transporter;
DE Short=LTC4 transporter;
GN Name=ABCC1; Synonyms=MRP, MRP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-117.
RX PubMed=1360704; DOI=10.1126/science.1360704;
RA Cole S.P.C., Bhardwaj G., Gerlach J.H., Mackie J.E., Grant C.E.,
RA Almquist K.C., Stewart A.J., Kurz E.U., Duncan A.M.V., Deeley R.G.;
RT "Overexpression of a transporter gene in a multidrug-resistant human
RT lung cancer cell line.";
RL Science 258:1650-1654(1992).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=8098549; DOI=10.1126/science.8098549;
RA Cole S.P.C., Deeley R.G.;
RT "Multidrug resistance-associated protein: sequence correction.";
RL Science 260:879-879(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND VARIANT
RP THR-117.
RX PubMed=9344662; DOI=10.1006/geno.1997.4950;
RA Grant C.E., Kurz E.U., Cole S.P.C., Deeley R.G.;
RT "Analysis of the intron-exon organization of the human multidrug-
RT resistance protein gene (MRP) and alternative splicing of its mRNA.";
RL Genomics 45:368-378(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-671; GLN-723;
RP THR-861; SER-1047 AND ILE-1146.
RG NIEHS SNPs program;
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 103-1531 (ISOFORM 9).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 516-1531.
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R.,
RA Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
RA Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
RA Harris P.C., Venter J.C., Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from
RT human chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [8]
RP TOPOLOGY, AND GLYCOSYLATION AT ASN-19; ASN-23 AND ASN-1006.
RX PubMed=9295302; DOI=10.1074/jbc.272.38.23623;
RA Hipfner D.R., Almquist K.C., Leslie E.M., Gerlach J.H., Grant C.E.,
RA Deeley R.G., Cole S.P.C.;
RT "Membrane topology of the multidrug resistance protein (MRP). A study
RT of glycosylation-site mutants reveals an extracytosolic NH2
RT terminus.";
RL J. Biol. Chem. 272:23623-23630(1997).
RN [9]
RP TOPOLOGY.
RX PubMed=9334225; DOI=10.1074/jbc.272.42.26479;
RA Kast C., Gros P.;
RT "Topology mapping of the amino-terminal half of multidrug resistance-
RT associated protein by epitope insertion and immunofluorescence.";
RL J. Biol. Chem. 272:26479-26487(1997).
RN [10]
RP TOPOLOGY.
RX PubMed=9485377; DOI=10.1021/bi972332v;
RA Kast C., Gros P.;
RT "Epitope insertion favors a six transmembrane domain model for the
RT carboxy-terminal portion of the multidrug resistance-associated
RT protein.";
RL Biochemistry 37:2305-2313(1998).
RN [11]
RP FUNCTION.
RX PubMed=10064732;
RA Sjoelinder M., Tornhamre S., Claesson H.-E., Hydman J., Lindgren J.A.;
RT "Characterization of a leukotriene C4 export mechanism in human
RT platelets: possible involvement of multidrug resistance-associated
RT protein 1.";
RL J. Lipid Res. 40:439-446(1999).
RN [12]
RP FUNCTION.
RX PubMed=11114332; DOI=10.1016/S0092-8674(00)00179-3;
RA Robbiani D.F., Finch R.A., Jaeger D., Muller W.A., Sartorelli A.C.,
RA Randolph G.J.;
RT "The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta,
RT ELC)-dependent mobilization of dendritic cells to lymph nodes.";
RL Cell 103:757-768(2000).
RN [13]
RP MUTAGENESIS OF ASP-792; ASP-793; LYS-1333 AND 1454-ASP-GLU-1455.
RX PubMed=11469806; DOI=10.1006/abbi.2001.2441;
RA Cui L., Hou Y.-X., Riordan J.R., Chang X.-B.;
RT "Mutations of the Walker B motif in the first nucleotide binding
RT domain of multidrug resistance protein MRP1 prevent conformational
RT maturation.";
RL Arch. Biochem. Biophys. 392:153-161(2001).
RN [14]
RP MUTAGENESIS OF TRP-1246.
RX PubMed=11278867; DOI=10.1074/jbc.M011246200;
RA Ito K., Olsen S.L., Qiu W., Deeley R.G., Cole S.P.C.;
RT "Mutation of a single conserved tryptophan in multidrug resistance
RT protein 1 (MRP1/ABCC1) results in loss of drug resistance and
RT selective loss of organic anion transport.";
RL J. Biol. Chem. 276:15616-15624(2001).
RN [15]
RP MUTAGENESIS OF GLU-1089.
RX PubMed=11278596; DOI=10.1074/jbc.M010008200;
RA Zhang D.-W., Cole S.P.C., Deeley R.G.;
RT "Identification of an amino acid residue in multidrug resistance
RT protein 1 critical for conferring resistance to anthracyclines.";
RL J. Biol. Chem. 276:13231-13239(2001).
RN [16]
RP MUTAGENESIS OF ARG-1046; ASP-1084 AND ARG-1131.
RX PubMed=15208328; DOI=10.1074/jbc.M403832200;
RA Situ D., Haimeur A., Conseil G., Sparks K.E., Zhang D.-W.,
RA Deeley R.G., Cole S.P.C.;
RT "Mutational analysis of ionizable residues proximal to the cytoplasmic
RT interface of membrane spanning domain 3 of the multidrug resistance
RT protein, MRP1 (ABCC1): glutamate 1204 is important for both the
RT expression and catalytic activity of the transporter.";
RL J. Biol. Chem. 279:38871-38880(2004).
RN [17]
RP MUTAGENESIS OF GLN-580; THR-581; SER-585; ASN-597; SER-604 AND
RP SER-605.
RX PubMed=15260484; DOI=10.1021/bi0495230;
RA Zhang D.-W., Nunoya K., Vasa M., Gu H.-M., Theis A., Cole S.P.C.,
RA Deeley R.G.;
RT "Transmembrane helix 11 of multidrug resistance protein 1
RT (MRP1/ABCC1): identification of polar amino acids important for
RT substrate specificity and binding of ATP at nucleotide binding domain
RT 1.";
RL Biochemistry 43:9413-9425(2004).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [19]
RP FUNCTION, MUTAGENESIS OF ARG-1138; LYS-1141 AND ARG-1142, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16230346; DOI=10.1074/jbc.M510143200;
RA Conseil G., Deeley R.G., Cole S.P.;
RT "Functional importance of three basic residues clustered at the
RT cytosolic interface of transmembrane helix 15 in the multidrug and
RT organic anion transporter MRP1 (ABCC1).";
RL J. Biol. Chem. 281:43-50(2006).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-915, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-905 AND SER-930, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-930, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 642-871 IN COMPLEX WITH
RP MG-ATP.
RX PubMed=16697012; DOI=10.1016/j.jmb.2006.04.005;
RA Ramaen O., Leulliot N., Sizun C., Ulryck N., Pamlard O.,
RA Lallemand J.-Y., Tilbeurgh H., Jacquet E.;
RT "Structure of the human multidrug resistance protein 1 nucleotide
RT binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic
RT site.";
RL J. Mol. Biol. 359:940-949(2006).
RN [27]
RP VARIANTS GLN-633 AND VAL-671.
RX PubMed=10835642; DOI=10.1038/76102;
RA Le Saux O., Urban Z., Tschuch C., Csiszar K., Bacchelli B.,
RA Quaglino D., Pasquali-Ronchetti I., Pope F.M., Richards A., Terry S.,
RA Bercovitch L., de Paepe A., Boyd C.D.;
RT "Mutations in a gene encoding an ABC transporter cause pseudoxanthoma
RT elasticum.";
RL Nat. Genet. 25:223-227(2000).
RN [28]
RP VARIANT VAL-671.
RX PubMed=10811882; DOI=10.1073/pnas.100041297;
RA Ringpfeil F., Lebwohl M.G., Christiano A.M., Uitto J.;
RT "Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a
RT transmembrane ATP-binding cassette (ABC) transporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6001-6006(2000).
RN [29]
RP VARIANT SER-433, AND CHARACTERIZATION OF VARIANT VAL-671.
RX PubMed=11721885; DOI=10.1007/s100380170017;
RA Conrad S., Kauffmann H.-M., Ito K., Deeley R.G., Cole S.P.C.,
RA Schrenk D.;
RT "Identification of human multidrug resistance protein 1 (MRP1)
RT mutations and characterization of a G671V substitution.";
RL J. Hum. Genet. 46:656-663(2001).
RN [30]
RP VARIANTS THR-117 AND LEU-1512.
RX PubMed=11139250;
RX DOI=10.1002/1098-1004(2001)17:1<74::AID-HUMU14>3.0.CO;2-F;
RA Perdu J., Germain D.P.;
RT "Identification of novel polymorphisms in the pM5 and MRP1 (ABCC1)
RT genes at locus 16p13.1 and exclusion of both genes as responsible for
RT pseudoxanthoma elasticum.";
RL Hum. Mutat. 17:74-75(2001).
RN [31]
RP VARIANTS SER-43; ILE-73; GLN-723 AND GLN-1058.
RX PubMed=11266082; DOI=10.1097/00008571-200103000-00008;
RA Ito S., Ieiri I., Tanabe M., Suzuki A., Higuchi S., Otsubo K.;
RT "Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT,
RT in healthy Japanese subjects.";
RL Pharmacogenetics 11:175-184(2001).
RN [32]
RP VARIANT [LARGE SCALE ANALYSIS] SER-433.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J.,
RA Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C.,
RA Graubert T.A., DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
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. Hydrolyzes ATP with low
CC efficiency.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Comment=Additional isoforms seem to exist. Experimental
CC confirmation may be lacking for some isoforms;
CC Name=1; Synonyms=Allexons;
CC IsoId=P33527-1; Sequence=Displayed;
CC Name=2; Synonyms=Delexon-17;
CC IsoId=P33527-2; Sequence=VSP_000037;
CC Name=3; Synonyms=Delexon-18;
CC IsoId=P33527-3; Sequence=VSP_000038;
CC Name=4; Synonyms=Delexon-30;
CC IsoId=P33527-4; Sequence=VSP_000039;
CC Name=5; Synonyms=Delexon-17-18;
CC IsoId=P33527-5; Sequence=VSP_000037, VSP_000038;
CC Name=6; Synonyms=Delexon-17-30;
CC IsoId=P33527-6; Sequence=VSP_000037, VSP_000039;
CC Name=7; Synonyms=Delexon-18-30;
CC IsoId=P33527-7; Sequence=VSP_000038, VSP_000039;
CC Name=8; Synonyms=Delexon-17-18-30;
CC IsoId=P33527-8; Sequence=VSP_000037, VSP_000038, VSP_000039;
CC Name=9;
CC IsoId=P33527-9; Sequence=VSP_017014;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Lung, testis and peripheral blood mononuclear
CC cells.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC
CC family. Conjugate transporter (TC 3.A.1.208) subfamily.
CC -!- SIMILARITY: Contains 2 ABC transmembrane type-1 domains.
CC -!- SIMILARITY: Contains 2 ABC transporter domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MRPID106.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/abcc1/";
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC
CC proteins;
CC URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=P33527";
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DR EMBL; L05628; AAB46616.1; -; mRNA.
DR EMBL; AF022853; AAB83979.1; -; Genomic_DNA.
DR EMBL; AF022827; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022828; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022829; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022831; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022833; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022835; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022837; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022839; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022841; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022850; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022849; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022848; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022847; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022846; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022845; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022844; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022843; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022842; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022852; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022851; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022840; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022838; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022836; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022834; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022832; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022826; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022825; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022824; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022830; AAB83979.1; JOINED; Genomic_DNA.
DR EMBL; AF022853; AAB83980.1; -; Genomic_DNA.
DR EMBL; AF022824; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022825; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022826; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022828; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022830; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022832; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022834; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022836; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022838; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022848; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022847; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022846; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022845; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022844; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022843; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022842; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022841; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022839; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022852; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022851; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022850; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022849; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022837; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022835; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022833; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022831; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022829; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022827; AAB83980.1; JOINED; Genomic_DNA.
DR EMBL; AF022853; AAB83981.1; -; Genomic_DNA.
DR EMBL; AF022824; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022825; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022826; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022827; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022829; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022831; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022833; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022835; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022837; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022847; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022846; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022845; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022844; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022843; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022842; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022841; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022840; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022838; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022852; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022851; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022850; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022849; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022848; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022836; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022834; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022832; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022830; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022828; AAB83981.1; JOINED; Genomic_DNA.
DR EMBL; AF022853; AAB83983.1; -; Genomic_DNA.
DR EMBL; AF022824; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022825; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022826; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022827; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022828; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022829; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022830; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022831; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022832; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022833; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022834; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022835; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022836; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022837; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022838; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022839; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022840; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022841; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022842; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022843; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022844; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022845; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022846; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022847; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022848; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022849; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022850; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; AF022851; AAB83983.1; JOINED; Genomic_DNA.
DR EMBL; EF419769; ABN79590.1; -; Genomic_DNA.
DR EMBL; AC025778; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC130651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC136624; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB209120; BAD92357.1; -; mRNA.
DR EMBL; U91318; AAC15784.1; -; Genomic_DNA.
DR EMBL; AC003026; AAC05808.1; -; Genomic_DNA.
DR PIR; A44231; DVHUAR.
DR RefSeq; NP_004987.2; NM_004996.3.
DR RefSeq; XP_005255383.1; XM_005255326.1.
DR RefSeq; XP_005255386.1; XM_005255329.1.
DR UniGene; Hs.391464; -.
DR PDB; 2CBZ; X-ray; 1.50 A; A=642-871.
DR PDBsum; 2CBZ; -.
DR ProteinModelPortal; P33527; -.
DR SMR; P33527; 642-871.
DR IntAct; P33527; 5.
DR MINT; MINT-2802626; -.
DR ChEMBL; CHEMBL3004; -.
DR DrugBank; DB00694; Daunorubicin.
DR DrugBank; DB01016; Glibenclamide.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB01232; Saquinavir.
DR DrugBank; DB01138; Sulfinpyrazone.
DR TCDB; 3.A.1.208.8; the atp-binding cassette (abc) superfamily.
DR PhosphoSite; P33527; -.
DR DMDM; 296439301; -.
DR PaxDb; P33527; -.
DR PRIDE; P33527; -.
DR Ensembl; ENST00000345148; ENSP00000263014; ENSG00000103222.
DR Ensembl; ENST00000346370; ENSP00000263019; ENSG00000103222.
DR Ensembl; ENST00000349029; ENSP00000263016; ENSG00000103222.
DR Ensembl; ENST00000351154; ENSP00000263017; ENSG00000103222.
DR Ensembl; ENST00000399408; ENSP00000382340; ENSG00000103222.
DR Ensembl; ENST00000399410; ENSP00000382342; ENSG00000103222.
DR GeneID; 4363; -.
DR KEGG; hsa:4363; -.
DR UCSC; uc010bvi.3; human.
DR CTD; 4363; -.
DR GeneCards; GC16P016043; -.
DR H-InvDB; HIX0134370; -.
DR HGNC; HGNC:51; ABCC1.
DR HPA; CAB016097; -.
DR HPA; HPA002380; -.
DR MIM; 158343; gene.
DR neXtProt; NX_P33527; -.
DR PharmGKB; PA244; -.
DR eggNOG; COG1132; -.
DR HOVERGEN; HBG108314; -.
DR KO; K05665; -.
DR OMA; DISRHHN; -.
DR OrthoDB; EOG7MWGW0; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; ABCC1; human.
DR EvolutionaryTrace; P33527; -.
DR GeneWiki; ABCC1; -.
DR GenomeRNAi; 4363; -.
DR NextBio; 17171; -.
DR PRO; PR:P33527; -.
DR ArrayExpress; P33527; -.
DR Bgee; P33527; -.
DR CleanEx; HS_ABCC1; -.
DR Genevestigator; P33527; -.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; TAS:ProtInc.
DR GO; GO:0042626; F:ATPase activity, coupled to transmembrane movement of substances; TAS:ProtInc.
DR GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR GO; GO:0009235; P:cobalamin metabolic process; TAS:Reactome.
DR GO; GO:0006691; P:leukotriene metabolic process; TAS:Reactome.
DR GO; GO:0042493; P:response to drug; TAS:ProtInc.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR003439; ABC_transporter-like.
DR InterPro; IPR017871; ABC_transporter_CS.
DR InterPro; IPR001140; ABC_transptr_TM_dom.
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 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Complete proteome; Glycoprotein; Hydrolase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1 1531 Multidrug resistance-associated protein
FT 1.
FT /FTId=PRO_0000093351.
FT TOPO_DOM 1 33 Extracellular.
FT TRANSMEM 34 54 Helical; Name=1.
FT TOPO_DOM 55 74 Cytoplasmic.
FT TRANSMEM 75 95 Helical; Name=2.
FT TOPO_DOM 96 100 Extracellular.
FT TRANSMEM 101 121 Helical; Name=3.
FT TOPO_DOM 122 133 Cytoplasmic.
FT TRANSMEM 134 154 Helical; Name=4.
FT TOPO_DOM 155 172 Extracellular.
FT TRANSMEM 173 193 Helical; Name=5.
FT TOPO_DOM 194 316 Cytoplasmic.
FT TRANSMEM 317 337 Helical; Name=6.
FT TOPO_DOM 338 363 Extracellular.
FT TRANSMEM 364 384 Helical; Name=7.
FT TOPO_DOM 385 440 Cytoplasmic.
FT TRANSMEM 441 461 Helical; Name=8.
FT TOPO_DOM 462 464 Extracellular.
FT TRANSMEM 465 485 Helical; Name=9.
FT TOPO_DOM 486 547 Cytoplasmic.
FT TRANSMEM 548 568 Helical; Name=10.
FT TOPO_DOM 569 590 Extracellular.
FT TRANSMEM 591 611 Helical; Name=11.
FT TOPO_DOM 612 967 Cytoplasmic.
FT TRANSMEM 968 988 Helical; Name=12.
FT TOPO_DOM 989 1025 Extracellular.
FT TRANSMEM 1026 1046 Helical; Name=13.
FT TOPO_DOM 1047 1089 Cytoplasmic.
FT TRANSMEM 1090 1110 Helical; Name=14.
FT TOPO_DOM 1111 1111 Extracellular.
FT TRANSMEM 1112 1132 Helical; Name=15.
FT TOPO_DOM 1133 1203 Cytoplasmic.
FT TRANSMEM 1204 1224 Helical; Name=16.
FT TOPO_DOM 1225 1226 Extracellular.
FT TRANSMEM 1227 1247 Helical; Name=17.
FT TOPO_DOM 1248 1531 Cytoplasmic.
FT DOMAIN 325 608 ABC transmembrane type-1 1.
FT DOMAIN 644 868 ABC transporter 1.
FT DOMAIN 975 1256 ABC transmembrane type-1 2.
FT DOMAIN 1293 1527 ABC transporter 2.
FT NP_BIND 678 685 ATP 1.
FT NP_BIND 1327 1334 ATP 2 (Potential).
FT BINDING 653 653 ATP 1.
FT BINDING 713 713 ATP 1.
FT MOD_RES 905 905 Phosphoserine.
FT MOD_RES 915 915 Phosphoserine.
FT MOD_RES 930 930 Phosphoserine.
FT CARBOHYD 19 19 N-linked (GlcNAc...).
FT CARBOHYD 23 23 N-linked (GlcNAc...).
FT CARBOHYD 1006 1006 N-linked (GlcNAc...).
FT VAR_SEQ 706 764 Missing (in isoform 2, isoform 5, isoform
FT 6 and isoform 8).
FT /FTId=VSP_000037.
FT VAR_SEQ 765 820 Missing (in isoform 3, isoform 5, isoform
FT 7 and isoform 8).
FT /FTId=VSP_000038.
FT VAR_SEQ 882 882 G -> GSTVMDEEEAG (in isoform 9).
FT /FTId=VSP_017014.
FT VAR_SEQ 1431 1495 Missing (in isoform 4, isoform 6, isoform
FT 7 and isoform 8).
FT /FTId=VSP_000039.
FT VARIANT 43 43 C -> S (in dbSNP:rs41395947).
FT /FTId=VAR_013317.
FT VARIANT 73 73 T -> I (in dbSNP:rs41494447).
FT /FTId=VAR_013318.
FT VARIANT 117 117 M -> T.
FT /FTId=VAR_013319.
FT VARIANT 433 433 R -> S (in dbSNP:rs60782127).
FT /FTId=VAR_013320.
FT VARIANT 633 633 R -> Q (in dbSNP:rs112282109).
FT /FTId=VAR_011488.
FT VARIANT 671 671 G -> V (no effect on leukotriene C4 and
FT estradiol glucuronide transport;
FT dbSNP:rs45511401).
FT /FTId=VAR_011489.
FT VARIANT 723 723 R -> Q (in dbSNP:rs4148356).
FT /FTId=VAR_013321.
FT VARIANT 861 861 A -> T (in dbSNP:rs45517537).
FT /FTId=VAR_055384.
FT VARIANT 1047 1047 C -> S (in dbSNP:rs13337489).
FT /FTId=VAR_055385.
FT VARIANT 1058 1058 R -> Q (in dbSNP:rs41410450).
FT /FTId=VAR_013322.
FT VARIANT 1146 1146 V -> I (in dbSNP:rs28706727).
FT /FTId=VAR_055386.
FT VARIANT 1512 1512 S -> L.
FT /FTId=VAR_013323.
FT MUTAGEN 580 580 Q->A: No effect.
FT MUTAGEN 581 581 T->A: No effect.
FT MUTAGEN 585 585 S->A: No effect.
FT MUTAGEN 597 597 N->A: Increases resistance to vincristine
FT and decreases resistance to VP-16.
FT MUTAGEN 604 604 S->A: Increases estradiol glucuronide
FT transport.
FT MUTAGEN 605 605 S->A: Decreases resistance to
FT vincristine, VP-16 and doxorubicin.
FT MUTAGEN 792 792 D->A: Only partially affects protein
FT maturation; impairs leukotriene C4
FT transport.
FT MUTAGEN 792 792 D->L: Impairs protein maturation and
FT leukotriene C4 transport.
FT MUTAGEN 793 793 D->L: No effect on protein maturation and
FT leukotriene C4 transport.
FT MUTAGEN 1046 1046 R->D: Slightly impairs leukotriene C4 and
FT estradiol glucuronide transport.
FT MUTAGEN 1084 1084 D->R: Impairs leukotriene C4 and
FT estradiol glucuronide transport.
FT MUTAGEN 1089 1089 E->A,L,N,Q: Decreases resistance to
FT anthracyclines.
FT MUTAGEN 1089 1089 E->D: No effect.
FT MUTAGEN 1089 1089 E->K: Abolishes resistance to
FT anthracyclines.
FT MUTAGEN 1131 1131 R->E: Slightly impairs leukotriene C4 and
FT estradiol glucuronide transport.
FT MUTAGEN 1138 1138 R->E,K: Strongly reduced transport of
FT leukotriene C4, estradiol glucuronide and
FT of glutathione.
FT MUTAGEN 1141 1141 K->E: Reduced transport of leukotriene C4
FT and of glutathione.
FT MUTAGEN 1141 1141 K->R: Reduced transport of glutathione.
FT MUTAGEN 1142 1142 R->E,K: Reduced transport of leukotriene
FT C4, estradiol glucuronide and of
FT glutathione.
FT MUTAGEN 1246 1246 W->A,F,Y: Impairs estradiol glucuronide
FT transport.
FT MUTAGEN 1246 1246 W->C: Impairs estradiol glucuronide
FT transport; loss of resistance to alkaloid
FT vincristine, cationic anthracyclines,
FT epipodophyllotoxin VP-16, but not
FT potassium antimony tartrate; partial loss
FT of resistance to sodium arsenite.
FT MUTAGEN 1333 1333 K->L: Impairs leukotriene C4 transport.
FT MUTAGEN 1454 1455 DE->LL: Impairs leukotriene C4 transport.
FT STRAND 644 653
FT STRAND 660 668
FT STRAND 673 677
FT HELIX 684 691
FT STRAND 695 704
FT STRAND 708 711
FT STRAND 719 721
FT HELIX 722 727
FT HELIX 736 743
FT HELIX 747 750
FT HELIX 756 758
FT STRAND 759 762
FT HELIX 770 784
FT STRAND 787 793
FT TURN 794 797
FT HELIX 800 809
FT TURN 816 819
FT STRAND 820 825
FT HELIX 832 834
FT STRAND 835 842
FT STRAND 845 850
FT HELIX 852 858
FT HELIX 861 868
SQ SEQUENCE 1531 AA; 171591 MW; 46A7CB643B9478C4 CRC64;
MALRGFCSAD GSDPLWDWNV TWNTSNPDFT KCFQNTVLVW VPCFYLWACF PFYFLYLSRH
DRGYIQMTPL NKTKTALGFL LWIVCWADLF YSFWERSRGI FLAPVFLVSP TLLGITMLLA
TFLIQLERRK GVQSSGIMLT FWLVALVCAL AILRSKIMTA LKEDAQVDLF RDITFYVYFS
LLLIQLVLSC FSDRSPLFSE TIHDPNPCPE SSASFLSRIT FWWITGLIVR GYRQPLEGSD
LWSLNKEDTS EQVVPVLVKN WKKECAKTRK QPVKVVYSSK DPAQPKESSK VDANEEVEAL
IVKSPQKEWN PSLFKVLYKT FGPYFLMSFF FKAIHDLMMF SGPQILKLLI KFVNDTKAPD
WQGYFYTVLL FVTACLQTLV LHQYFHICFV SGMRIKTAVI GAVYRKALVI TNSARKSSTV
GEIVNLMSVD AQRFMDLATY INMIWSAPLQ VILALYLLWL NLGPSVLAGV AVMVLMVPVN
AVMAMKTKTY QVAHMKSKDN RIKLMNEILN GIKVLKLYAW ELAFKDKVLA IRQEELKVLK
KSAYLSAVGT FTWVCTPFLV ALCTFAVYVT IDENNILDAQ TAFVSLALFN ILRFPLNILP
MVISSIVQAS VSLKRLRIFL SHEELEPDSI ERRPVKDGGG TNSITVRNAT FTWARSDPPT
LNGITFSIPE GALVAVVGQV GCGKSSLLSA LLAEMDKVEG HVAIKGSVAY VPQQAWIQND
SLRENILFGC QLEEPYYRSV IQACALLPDL EILPSGDRTE IGEKGVNLSG GQKQRVSLAR
AVYSNADIYL FDDPLSAVDA HVGKHIFENV IGPKGMLKNK TRILVTHSMS YLPQVDVIIV
MSGGKISEMG SYQELLARDG AFAEFLRTYA STEQEQDAEE NGVTGVSGPG KEAKQMENGM
LVTDSAGKQL QRQLSSSSSY SGDISRHHNS TAELQKAEAK KEETWKLMEA DKAQTGQVKL
SVYWDYMKAI GLFISFLSIF LFMCNHVSAL 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 TAPPSSWPQV GRVEFRNYCL RYREDLDFVL RHINVTINGG
EKVGIVGRTG AGKSSLTLGL FRINESAEGE IIIDGINIAK IGLHDLRFKI TIIPQDPVLF
SGSLRMNLDP FSQYSDEEVW TSLELAHLKD FVSALPDKLD HECAEGGENL SVGQRQLVCL
ARALLRKTKI LVLDEATAAV DLETDDLIQS TIRTQFEDCT VLTIAHRLNT IMDYTRVIVL
DKGEIQEYGA PSDLLQQRGL FYSMAKDAGL V
//

MIM 158343
*RECORD*
*FIELD* NO
158343
*FIELD* TI
*158343 ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 1; ABCC1
;;MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 1; MRP1;;
read moreMULTIDRUG RESISTANCE-ASSOCIATED PROTEIN; MRP
*FIELD* TX

CLONING

Cole et al. (1992) identified a transporter protein whose gene is
overexpressed in a multidrug-resistant variant of the small cell lung
cancer cell line NCI-H69. Unlike most tumor cell lines that are
resistant to multiple chemotherapeutic agents, it did not overexpress
the transmembrane transport protein P-glycoprotein (MDR1; 171050). Cole
et al. (1992) isolated cDNA clones corresponding to mRNAs overexpressed
in the resistant H69 cells. One cDNA hybridized to an mRNA of 7.8 to 8.2
kb that was expressed 100- to 200-fold higher in the resistant cells
than in the drug-sensitive H69 cells. Overexpression was associated with
amplification of the cognate gene. The cDNA contained a single open
reading frame of 1,522 amino acids encoding a protein that they
designated MRP, for 'multidrug resistance-associated protein.' (Cole and
Deeley (1993) corrected the predicted protein sequence to 1,531 amino
acids.) Database analyses demonstrated similarities in primary sequence
to the adenosine triphosphate (ATP)-binding cassette (ABC) superfamily
of transport systems. Included in this superfamily are the genes for
MDR1 and for the cystic fibrosis transmembrane conductance regulator
(CFTR; 602421). Northern blot analysis readily detected MRP transcripts
in lung, testis, and peripheral blood mononuclear cells; MRP transcripts
were below the level of detection in placenta, brain, kidney, salivary
gland, uterus, liver, and spleen.

GENE FUNCTION

Zaman et al. (1994) described experiments leading them to conclude that
MRP is a plasma membrane drug-efflux pump.

Lorico et al. (2002) showed that glutathione is a cofactor in
MRP-mediated resistance to heavy metal oxyanions: human fibrosarcoma
cells overexpressing MRP1 together with the heavy (catalytic) subunit of
gamma-glutamylcysteine synthetase (606857) showed increased resistance
to sodium arsenite and antimony toxicity.

Using flow cytometric analysis, Muller et al. (2002) found that when a
FLAG epitope was introduced into the extracellular loops of
membrane-spanning domain-1 (MSD1) or MSD3 of MRP1, it was accessible on
the cell surface upon removal of N-glycosylation sites. In contrast,
FLAG epitope inserted into MSD2 was not accessible even after removal of
all 3 N-glycosylation sites, indicating that MSD2 is deeply buried in
the plasma membrane.

Using RT-PCR and Western blot analysis, Pascolo et al. (2003) found that
MRP1 and MRP3 (ABCC3; 604323) were highly expressed in placenta, but
only MRP1 was highly expressed in a trophoblastic cell line. MRP2
(ABCC2; 601107) and MRP5 (ABCC5; 605251) were only weakly expressed in
placenta and the trophoblastic cell line. Third-trimester placenta
expressed more MRP1 than first-trimester placenta. MRP1 expression
increased markedly in the trophoblastic cell line upon polarization.
Pascolo et al. (2003) concluded that MRP1 expression increases with
trophoblast maturation.

In cultured mouse astrocytes, Gennuso et al. (2004) found that
unconjugated bilirubin induced increased expression and transient
redistribution of Mrp1 from the Golgi apparatus to the plasma membrane
and throughout the cytoplasm. Blocking Mrp1 efflux pumps increased the
susceptibility of the cells to the toxic effects of unconjugated
bilirubin, suggesting that Mrp1 is an important protector in this
scenario. The authors noted the relevance of the findings to neonatal
encephalopathy caused by increased bilirubin.

Mitra et al. (2006) found that sphingosine-1-phosphate (S1P) was
released from mast cells independently of degranulation. S1P secretion
was dependent on ABCC1, but not on ABCB1 (171050), and inhibition of
ABCC1 blocked both constitutive and antigen-stimulated S1P release.
Chemotaxis assays showed that ABCC1-mediated transport of S1P influenced
mast-cell migration, but not mast-cell degranulation.

The reactivation of latent human cytomegalovirus (HCMV) infection after
transplantation is associated with high morbidity and mortality. In
vivo, myeloid cells and their progenitors are an important site of HCMV
latency, whose establishment and/or maintenance require expression of
the viral transcript UL138. Weekes et al. (2013) used stable isotope
labeling by amino acids in cell culture-based mass spectrometry to
identify a dramatic UL138-mediated loss of cell surface MRP1 and the
reduction of substrate export by this transporter. Latency-associated
loss of MRP1 and accumulation of the cytotoxic drug vincristine, an MRP1
substrate, depleted virus from naturally latent CD14+ (158120) and CD34+
(142230) progenitors, all of which are in vivo sites of latency. Weekes
et al. (2013) concluded that the UL138-mediated loss of MRP1 provides a
marker for detecting latent HCMV infection and a therapeutic target for
eliminating latently infected cells before transplantation.

GENE STRUCTURE

Grant et al. (1997) defined the intron/exon structure of MRP and
characterized a number of splicing variants of MRP mRNA. The gene spans
at least 200 kb. It contains 31 exons and a high proportion of class 0
introns, alternative splicing of which results in significant levels of
variant transcripts that maintain the original open reading frame of MRP
mRNA. (A class 0 splice occurs between 2 codons, e.g., ATG/ATG =
Met.Met. A class 1 splice would be ATGA/TG and a class 2 splice would be
ATGAT/G.) Analyses of the conservation of intron/exon organization and
protein primary structure suggested that the MRP-related transporters
evolved from a common ancestor shared with CFTR by fusion with 1 or more
genes encoding polytopic membrane proteins.

MAPPING

By isotopic in situ hybridization, Cole et al. (1992) mapped the MRP1
gene to chromosome 16p13.1. Grant et al. (1997) located the MRP1 gene
close to the short arm breakpoint of the pericentric inversion
associated with the M4Eo subclass of acute myeloid leukemia and on the
telomeric side of the MYH11 gene (160745).

MOLECULAR GENETICS

Using PCR-SSCP analysis, Conrad et al. (2001) screened 36 Caucasian
volunteers for mutations in the coding exons of the MRP1 gene, including
the adjacent intron sequences. Among several changes found, 2 were
predicted to cause amino acid substitutions. One of these mutations,
G671V, was of special interest because it is located near the first
nucleotide-binding domain. To determine whether this mutation caused a
change in the MRP1 phenotype, a mutant MRP1 expression vector was
constructed and transfected into SV40-transformed human embryonic kidney
cells and the transport properties of the mutant protein were examined.
With the substrates studied, the mutant showed no differences in organic
anion transport activities compared to wildtype MRP1.

Wang et al. (2005) scanned for genomic signatures of recent positive
selection in MRP1 in approximately 480 individuals sampled from the
Chinese, Malay, Indian, European American, and African American
populations. The genetic profile of SNPs at this locus revealed high
haplotype diversity and weak linkage disequilibrium (LD). Despite this
weak LD, the G allele of the -260G-C SNP (dbSNP rs4148330) in the
promoter region of the MRP1 gene, which was contained within a
high-frequency haplotype, exhibited extended haplotype homozygosity
across 135 kb in European Americans. Long-range haplotype and F(st)
statistic tests showed evidence of positive selection for the G allele
in the European American population. An MRP1 promoter-reporter assay
showed significantly lower activity for the G allele-containing promoter
when compared with the C allele-containing promoter in all 4 cell lines
tested (P = less than 0.01). Wang et al. (2005) suggested that dbSNP
rs4148330 may account, in part, for interindividual variations and
population differences in drug response.

ANIMAL MODEL

Robbiani et al. (2000) showed that migration of dendritic cells (DCs)
from skin to lymph nodes utilizes the leukotriene C4 (LTC4; see 246530)
transporter MRP1. DC mobilization from the epidermis and trafficking
into lymphatic vessels was greatly reduced in Mrp1 -/- mice, but
migration was restored by exogenous cysteinyl leukotrienes LTC4 or LTD4.
In vitro, these cysteinyl leukotrienes promoted optimal chemotaxis to
the chemokine CCL19 (SCYA19; 602227) but not to other related
chemokines. Antagonism of CCL19 in vivo prevented DC migration out of
the epidermis. Thus, the authors concluded that MRP1 regulates DC
migration to lymph nodes, apparently by transporting LTC4, which in turn
promotes chemotaxis to CCL19 and mobilization of DCs from the epidermis.

Schultz et al. (2001) showed that Mrp1-deficient mice had diminished
outgrowth of Streptococcus pneumoniae and strongly reduced mortality
compared with wildtype mice after intranasal infection. This advantage
could be abrogated by treatment with a 5-lipoxygenase inhibitor. Mutant
mice had low levels of LTC4 in lung because of accumulation of
intracellular LTC4 and inhibition of LTC4 synthase. On the other hand,
they had a reduced inflammatory response and high levels of LTB4 (see
LTB4R2; 605773), which was associated with increased LTA4 hydrolase
(151570) activity and was required for the protective effect. Schultz et
al. (2001) suggested that MRP1 may be a novel target for adjunctive
therapy in pneumonia.

Lorico et al. (2002) found resistance to heavy metal oxyanion toxicity
in cell cultures overexpressing MRP1, but no increase in sensitivity to
sodium arsenite and antimony in Mrp1 -/- knockout mice. The authors
stated that the redundancy of transmembrane export pumps suggests that
other pump(s) may effectively vicariate for MRP1-mediated transport of
heavy metal oxyanions.

*FIELD* RF
1. Cole, S. P. C.; Bhardwaj, G.; Gerlach, J. H.; Mackie, J. E.; Grant,
C. E.; Almquist, K. C.; Stewart, A. J.; Kurz, E. U.; Duncan, A. M.
V.; Deeley, R. G.: Overexpression of a transporter gene in a multidrug-resistant
human lung cancer cell line. Science 258: 1650-1654, 1992. Note:
Erratum: Science 260: 879 only, 1993.

2. Cole, S. P. C.; Deeley, R. G.: Multidrug resistance-associated
protein: sequence correction. (Letter) Science 260: 879 only, 1993.

3. Conrad, S.; Kauffmann, H.-M.; Ito, K.; Deeley, R. G.; Cole, S.
P. C.; Schrenk, D.: Identification of human multidrug resistance
protein 1 (MRP1) mutations and characterization of a G671V substitution. J.
Hum. Genet. 46: 656-663, 2001.

4. Gennuso, F.; Fernetti, C.; Tirolo, C.; Testa, N.; L'Episcopo, F.;
Caniglia, S.; Morale, M. C.; Ostrow, J. D.; Pascolo, L.; Tiribelli,
C.; Marchetti, B.: Bilirubin protects astrocytes from its own toxicity
by inducing up-regulation and translocation of multidrug resistance-associated
protein 1 (Mrp1). Proc. Nat. Acad. Sci. 101: 2470-2475, 2004.

5. Grant, C. E.; Kurz, E. U.; Cole, S. P. C.; Deeley, R. G.: Analysis
of the intron-exon organization of the human multidrug-resistance
protein gene (MRP) and alternative splicing of its mRNA. Genomics 45:
368-378, 1997.

6. Lorico, A.; Bertola, A.; Baum, C.; Fodstad, O.; Rappa, G.: Role
of multidrug resistance protein 1 in protection from heavy metal oxyanions:
investigations in vitro and in Mrp1-deficient mice. Biochem. Biophys.
Res. Commun. 291: 617-622, 2002.

7. Mitra, P.; Oskeritzian, C. A.; Payne, S. G.; Beaven, M. A.; Milstien,
S.; Spiegel, S.: Role of ABCC1 in export of sphingosine-1-phosphate
from mast cells. Proc. Nat. Acad. Sci. 103: 16394-16399, 2006.

8. Muller, M.; Yong, M.; Peng, X.-H.; Petre, B.; Arora, S.; Ambudkar,
S. V.: Evidence for the role of glycosylation in accessibility of
the extracellular domains of human MRP1 (ABCC1). Biochemistry 41:
10123-10132, 2002.

9. Pascolo, L.; Fernetti, C.; Pirulli, D.; Crovella, S.; Amoroso,
A.; Tiribelli, C.: Effects of maturation on RNA transcription and
protein expression of four MRP genes in human placenta and in BeWo
cells. Biochem. Biophys. Res. Commun. 303: 259-265, 2003.

10. Robbiani, D. F.; Finch, R. A.; Jager, D.; Muller, W. A.; Sartorelli,
A. C.; Randolph, G. J.: The leukotriene C4 transporter MRP1 regulates
CCL19 (MIP-3-beta, ELC)-dependent mobilization of dendritic cells
to lymph nodes. Cell 103: 757-768, 2000.

11. Schultz, M. J.; Wijnholds, J.; Peppelenbosch, M. P.; Vervoordeldonk,
M. J. B. M.; Speelman, P.; van Deventer, S. J. H.; Borst, P.; van
der Poll, T.: Mice lacking the multidrug resistance protein 1 are
resistant to Streptococcus pneumoniae-induced pneumonia. J. Immun. 166:
4059-4064, 2001.

12. Wang, Z.; Wang, B.; Tang, K.; Lee, E. J. D.; Chong, S. S.; Lee,
C. G. L.: A functional polymorphism within the MRP1 gene locus identified
through its genomic signature of positive selection. Hum. Molec.
Genet. 14: 2075-2087, 2005.

13. Weekes, M. P.; Tan, S. Y. L.; Poole, E.; Talbot, S.; Antrobus,
R.; Smith, D. L.; Montag, C.; Gygi, S. P.; Sinclair, J. H.; Lehner,
P. J.: Latency-associated degradation of the MRP1 drug transporter
during latent human cytomegalovirus infection. Science 340: 199-202,
2013.

14. Zaman, G. J. R.; Flens, M. J.; van Leusden, M. R.; de Haas, M.;
Mulder, H. S.; Lankelma, J.; Pinedo, H. M.; Scheper, R. J.; Baas,
F.; Broxterman, H. J.; Borst, P.: The human multidrug resistance-associated
protein MRP is a plasma membrane drug-efflux pump. Proc. Nat. Acad.
Sci. 91: 8822-8826, 1994.

*FIELD* CN
Ada Hamosh - updated: 05/07/2013
George E. Tiller - updated: 11/18/2008
Paul J. Converse - updated: 1/22/2007
Cassandra L. Kniffin - updated: 3/11/2004
Patricia A. Hartz - updated: 3/25/2002
Victor A. McKusick - updated: 1/8/2002
Paul J. Converse - updated: 4/27/2001
Stylianos E. Antonarakis - updated: 12/18/2000
Victor A. McKusick - updated: 1/6/1998
Victor A. McKusick - updated: 12/8/1997

*FIELD* CD
Victor A. McKusick: 1/29/1993

*FIELD* ED
alopez: 05/07/2013
carol: 12/21/2012
wwang: 11/18/2008
mgross: 1/22/2007
tkritzer: 3/12/2004
ckniffin: 3/11/2004
carol: 4/17/2002
carol: 4/15/2002
terry: 3/25/2002
carol: 2/1/2002
carol: 1/10/2002
mcapotos: 1/10/2002
terry: 1/8/2002
mgross: 4/27/2001
carol: 4/13/2001
mgross: 12/18/2000
carol: 11/9/1999
carol: 3/19/1999
carol: 3/28/1998
terry: 1/6/1998
mark: 12/11/1997
terry: 12/8/1997
carol: 11/10/1994
carol: 1/29/1993