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3.A.1.208.8
Drug resistance pump; ABCC1 (MRP1), exports chemotherapeutic agents, organic anions such as leukotriene C4 (LTC4), 17-β-estradiol 17-β-D-glucuronide, glucuronide-X (E217βG, etoposide-glucuronide), estrone-3-sulfate, folic acid and methotrexate, arsenic triglutathione, arsenic and antimonial oxyanions, glutathione (GSH), GSSG, glutathione conjugates (GSH-X; LTC4, DNP-SG, EA-SG, NEH-SG), sulfate-X (E1S, DHEAS), HIV protease inhibitors, anthracyclines, epipodophyllotoxins, and Vinca alkaloids. Changing charged residues in TMS6 (K332, H335 and D336) gave rise to specific changes in specificity (Chen et al., 2006; Haimeur et al., 2002; Leslie et al., 2004). Also exports cobalamine (Vitamin B12) (Beedholm-Ebsen et al., 2010). Also exports cytotoxic metals including antimony, mercuric ions, arsenate and arsenite, but not copper, chromium, cobalt and aluminum, often as glutathione conjugates (Aleo et al., 2005; Vernhet et al., 2000). Notch1 regulates the expression in cultured cancer cells (Cho et al., 2011).  Structural and functional properties of MRP1 have been reviewed comprehensively (He et al. 2011).  Fluorescent substrates have been identified (Strouse et al. 2013).  Pumps out sulfur mustards and nitrogen mustards (mechlorethamine, HN2), potent vesicants developed as chemical warfare agents (Udasin et al. 2015).

Accession Number:P33527
Protein Name:MRP1 aka ABCC1 aka MRP
Length:1531
Molecular Weight:171591.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:17
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate Chemotherapeutic agents, Leukotriene C4, 17-beta-estradiol 17-beta-D-glucuronide, glucuronide-X, Estrone-3-sulfate, Folic acid, methotrexate, Arsenic triglutathione, Arsenic oxyanions, Antimonial oxyanions, Glutathione, Glutathione conjugates, Cobalamine, Antimony, Mercuric ions, arsenate, arsenite, Sulfur mustards, Nitrogen mustards

Cross database links:

Genevestigator: P33527
eggNOG: prNOG15058
RefSeq: NP_004987.2   
Entrez Gene ID: 4363   
Pfam: PF00664    PF00005   
OMIM: 158343  gene
KEGG: hsa:4363   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005624 C:membrane fraction
GO:0005524 F:ATP binding
GO:0042626 F:ATPase activity, coupled to transmembrane m...
GO:0042493 P:response to drug
GO:0055085 P:transmembrane transport

References (27)

[1] “Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.”  Cole S.P.C.et.al.   1360704
[2] “Multidrug resistance-associated protein: sequence correction.”  Cole S.P.C.et.al.   8098549
[3] “Analysis of the intron-exon organization of the human multidrug-resistance protein gene (MRP) and alternative splicing of its mRNA.”  Grant C.E.et.al.   9344662
[4] “The sequence and analysis of duplication-rich human chromosome 16.”  Martin J.et.al.   15616553
[5] “Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.”  Loftus B.J.et.al.   10493829
[6] “Membrane topology of the multidrug resistance protein (MRP). A study of glycosylation-site mutants reveals an extracytosolic NH2 terminus.”  Hipfner D.R.et.al.   9295302
[7] “Topology mapping of the amino-terminal half of multidrug resistance-associated protein by epitope insertion and immunofluorescence.”  Kast C.et.al.   9334225
[8] “Epitope insertion favors a six transmembrane domain model for the carboxy-terminal portion of the multidrug resistance-associated protein.”  Kast C.et.al.   9485377
[9] “Characterization of a leukotriene C4 export mechanism in human platelets: possible involvement of multidrug resistance-associated protein 1.”  Sjoelinder M.et.al.   10064732
[10] “The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta, ELC)-dependent mobilization of dendritic cells to lymph nodes.”  Robbiani D.F.et.al.   11114332
[11] “Mutations of the Walker B motif in the first nucleotide binding domain of multidrug resistance protein MRP1 prevent conformational maturation.”  Cui L.et.al.   11469806
[12] “Mutation of a single conserved tryptophan in multidrug resistance protein 1 (MRP1/ABCC1) results in loss of drug resistance and selective loss of organic anion transport.”  Ito K.et.al.   11278867
[13] “Identification of an amino acid residue in multidrug resistance protein 1 critical for conferring resistance to anthracyclines.”  Zhang D.-W.et.al.   11278596
[14] “Mutational analysis of ionizable residues proximal to the cytoplasmic interface of membrane spanning domain 3 of the multidrug resistance protein, MRP1 (ABCC1): glutamate 1204 is important for both the expression and catalytic activity of the transporter.”  Situ D.et.al.   15208328
[15] “Transmembrane helix 11 of multidrug resistance protein 1 (MRP1/ABCC1): identification of polar amino acids important for substrate specificity and binding of ATP at nucleotide binding domain 1.”  Zhang D.-W.et.al.   15260484
[16] “Functional importance of three basic residues clustered at the cytosolic interface of transmembrane helix 15 in the multidrug and organic anion transporter MRP1 (ABCC1).”  Conseil G.et.al.   16230346
[17] “Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.”  Daub H.et.al.   18691976
[18] “Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.”  Gauci S.et.al.   19413330
[19] “Large-scale proteomics analysis of the human kinome.”  Oppermann F.S.et.al.   19369195
[20] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[21] “Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site.”  Ramaen O.et.al.   16697012
[22] “Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum.”  Le Saux O.et.al.   10835642
[23] “Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter.”  Ringpfeil F.et.al.   10811882
[24] “Identification of human multidrug resistance protein 1 (MRP1) mutations and characterization of a G671V substitution.”  Conrad S.et.al.   11721885
[25] “Identification of novel polymorphisms in the pM5 and MRP1 (ABCC1) genes at locus 16p13.1 and exclusion of both genes as responsible for pseudoxanthoma elasticum.”  Perdu J.et.al.   11139250
[26] “Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects.”  Ito S.et.al.   11266082
[27] “DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.”  Ley T.J.et.al.   18987736
Structure:
2CBZ   4C3Z     

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FASTA formatted sequence
1:	MALRGFCSAD GSDPLWDWNV TWNTSNPDFT KCFQNTVLVW VPCFYLWACF PFYFLYLSRH 
61:	DRGYIQMTPL NKTKTALGFL LWIVCWADLF YSFWERSRGI FLAPVFLVSP TLLGITMLLA 
121:	TFLIQLERRK GVQSSGIMLT FWLVALVCAL AILRSKIMTA LKEDAQVDLF RDITFYVYFS 
181:	LLLIQLVLSC FSDRSPLFSE TIHDPNPCPE SSASFLSRIT FWWITGLIVR GYRQPLEGSD 
241:	LWSLNKEDTS EQVVPVLVKN WKKECAKTRK QPVKVVYSSK DPAQPKESSK VDANEEVEAL 
301:	IVKSPQKEWN PSLFKVLYKT FGPYFLMSFF FKAIHDLMMF SGPQILKLLI KFVNDTKAPD 
361:	WQGYFYTVLL FVTACLQTLV LHQYFHICFV SGMRIKTAVI GAVYRKALVI TNSARKSSTV 
421:	GEIVNLMSVD AQRFMDLATY INMIWSAPLQ VILALYLLWL NLGPSVLAGV AVMVLMVPVN 
481:	AVMAMKTKTY QVAHMKSKDN RIKLMNEILN GIKVLKLYAW ELAFKDKVLA IRQEELKVLK 
541:	KSAYLSAVGT FTWVCTPFLV ALCTFAVYVT IDENNILDAQ TAFVSLALFN ILRFPLNILP 
601:	MVISSIVQAS VSLKRLRIFL SHEELEPDSI ERRPVKDGGG TNSITVRNAT FTWARSDPPT 
661:	LNGITFSIPE GALVAVVGQV GCGKSSLLSA LLAEMDKVEG HVAIKGSVAY VPQQAWIQND 
721:	SLRENILFGC QLEEPYYRSV IQACALLPDL EILPSGDRTE IGEKGVNLSG GQKQRVSLAR 
781:	AVYSNADIYL FDDPLSAVDA HVGKHIFENV IGPKGMLKNK TRILVTHSMS YLPQVDVIIV 
841:	MSGGKISEMG SYQELLARDG AFAEFLRTYA STEQEQDAEE NGVTGVSGPG KEAKQMENGM 
901:	LVTDSAGKQL QRQLSSSSSY SGDISRHHNS TAELQKAEAK KEETWKLMEA DKAQTGQVKL 
961:	SVYWDYMKAI GLFISFLSIF LFMCNHVSAL ASNYWLSLWT DDPIVNGTQE HTKVRLSVYG 
1021:	ALGISQGIAV FGYSMAVSIG GILASRCLHV DLLHSILRSP MSFFERTPSG NLVNRFSKEL 
1081:	DTVDSMIPEV IKMFMGSLFN VIGACIVILL ATPIAAIIIP PLGLIYFFVQ RFYVASSRQL 
1141:	KRLESVSRSP VYSHFNETLL GVSVIRAFEE QERFIHQSDL KVDENQKAYY PSIVANRWLA 
1201:	VRLECVGNCI VLFAALFAVI SRHSLSAGLV GLSVSYSLQV TTYLNWLVRM SSEMETNIVA 
1261:	VERLKEYSET EKEAPWQIQE TAPPSSWPQV GRVEFRNYCL RYREDLDFVL RHINVTINGG 
1321:	EKVGIVGRTG AGKSSLTLGL FRINESAEGE IIIDGINIAK IGLHDLRFKI TIIPQDPVLF 
1381:	SGSLRMNLDP FSQYSDEEVW TSLELAHLKD FVSALPDKLD HECAEGGENL SVGQRQLVCL 
1441:	ARALLRKTKI LVLDEATAAV DLETDDLIQS TIRTQFEDCT VLTIAHRLNT IMDYTRVIVL 
1501:	DKGEIQEYGA PSDLLQQRGL FYSMAKDAGL V