Q8CG09 (MRP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Multidrug resistance-associated protein 1

Alternative name(s):
ATP-binding cassette sub-family C member 1
Leukotriene C(4) transporter
Short name=LTC4 transporter

Gene names

Name:	Abcc1
Synonyms:	Mrp1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1532 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency. Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.7.
Tissue specificity	Skeletal muscle, brain, heart, spleen, lung and kidney. Ref.2
Post-translational modification	Glycosylated.
Sequence similarities	Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily. [View classification] Contains 2 ABC transmembrane type-1 domains. Contains 2 ABC transporter domains.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell chemotaxis Inferred from mutant phenotype PubMed 17050692. Source: RGD daunorubicin transport Inferred from mutant phenotype PubMed 18465260. Source: RGD drug export Inferred from direct assay Ref.1PubMed 15198509. Source: RGD glutathione transmembrane transport Inferred from mutant phenotype PubMed 12125073. Source: RGD negative regulation of neuron death Inferred from mutant phenotype PubMed 17141959. Source: RGD phospholipid efflux Inferred from mutant phenotype PubMed 17050692. Source: RGD plasma membrane long-chain fatty acid transport Inferred from direct assay Ref.2. Source: RGD positive regulation of cell migration Inferred from mutant phenotype PubMed 17050692. Source: RGD response to oxidative stress Inferred from mutant phenotype Ref.5. Source: RGD
Cellular_component	basolateral plasma membrane Inferred from direct assay PubMed 11804835PubMed 17854063. Source: RGD cytoplasm Inferred from direct assay PubMed 11804835. Source: RGD integral to plasma membrane Inferred from direct assay PubMed 17854063. Source: RGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW efflux transmembrane transporter activity Inferred from direct assay Ref.1. Source: RGD glutathione S-conjugate-exporting ATPase activity Inferred from mutant phenotype PubMed 19053318. Source: RGD glutathione transmembrane transporter activity Inferred from mutant phenotype PubMed 12125073. Source: RGD lipid-transporting ATPase activity Inferred from direct assay Ref.2. Source: RGD long-chain fatty acid transporter activity Inferred from direct assay Ref.2. Source: RGD oxidoreductase activity Inferred from electronic annotation. Source: InterPro sphingolipid transporter activity Inferred from mutant phenotype PubMed 17050692. Source: RGD xenobiotic-transporting ATPase activity Inferred from direct assay Ref.2. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8CG09-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8CG09-2)

The sequence of this isoform differs from the canonical sequence as follows:
     912-920: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1532	1532	Multidrug resistance-associated protein 1		PRO_0000093354
Regions
	Topological domain	1 – 33	33	Extracellular By similarity
	Transmembrane	34 – 54	21	Helical; Name=1; By similarity
	Topological domain	55 – 74	20	Cytoplasmic By similarity
	Transmembrane	75 – 95	21	Helical; Name=2; By similarity
	Topological domain	96 – 100	5	Extracellular By similarity
	Transmembrane	101 – 121	21	Helical; Name=3; By similarity
	Topological domain	122 – 133	12	Cytoplasmic By similarity
	Transmembrane	134 – 154	21	Helical; Name=4; By similarity
	Topological domain	155 – 172	18	Extracellular By similarity
	Transmembrane	173 – 193	21	Helical; Name=5; By similarity
	Topological domain	194 – 317	124	Cytoplasmic By similarity
	Transmembrane	318 – 338	21	Helical; Name=6; By similarity
	Topological domain	339 – 364	26	Extracellular By similarity
	Transmembrane	365 – 385	21	Helical; Name=7; By similarity
	Topological domain	386 – 441	56	Cytoplasmic By similarity
	Transmembrane	442 – 462	21	Helical; Name=8; By similarity
	Topological domain	463 – 465	3	Extracellular By similarity
	Transmembrane	466 – 486	21	Helical; Name=9; By similarity
	Topological domain	487 – 548	62	Cytoplasmic By similarity
	Transmembrane	549 – 569	21	Helical; Name=10; By similarity
	Topological domain	570 – 591	22	Extracellular By similarity
	Transmembrane	592 – 612	21	Helical; Name=11; By similarity
	Topological domain	613 – 967	355	Cytoplasmic By similarity
	Transmembrane	968 – 988	21	Helical; Name=12; By similarity
	Topological domain	989 – 1026	38	Extracellular By similarity
	Transmembrane	1027 – 1047	21	Helical; Name=13; By similarity
	Topological domain	1048 – 1090	43	Cytoplasmic By similarity
	Transmembrane	1091 – 1111	21	Helical; Name=14; By similarity
	Topological domain	1112	1	Extracellular By similarity
	Transmembrane	1113 – 1133	21	Helical; Name=15; By similarity
	Topological domain	1134 – 1204	71	Cytoplasmic By similarity
	Transmembrane	1205 – 1225	21	Helical; Name=16; By similarity
	Topological domain	1226 – 1227	2	Extracellular By similarity
	Transmembrane	1228 – 1248	21	Helical; Name=17; By similarity
	Topological domain	1249 – 1532	284	Cytoplasmic By similarity
	Domain	326 – 609	284	ABC transmembrane type-1 1
	Domain	645 – 869	225	ABC transporter 1
	Domain	975 – 1257	283	ABC transmembrane type-1 2
	Domain	1294 – 1528	235	ABC transporter 2
	Nucleotide binding	679 – 686	8	ATP 1 Potential
	Nucleotide binding	1328 – 1335	8	ATP 2 Potential
Amino acid modifications
	Modified residue	879	1	Phosphoserine By similarity
	Modified residue	916	1	Phosphoserine By similarity
	Modified residue	931	1	Phosphoserine By similarity
	Glycosylation	19	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	912 – 920	9	Missing in isoform 2.		VSP_017015
Experimental info
	Mutagenesis	983	1	L → M: No effect on estradiol glucuronide transport. Ref.2
	Mutagenesis	1090	1	Q → E: 7.6-fold increase of the estradiol glucuronide transport; when associated with T-1243. Increases doxorubicin inhibition. Ref.2
	Mutagenesis	1101	1	S → N: 50% increase of estradiol glucuronide transport. Ref.2
	Mutagenesis	1106	1	V → C: No effect on estradiol glucuronide transport. Ref.2
	Mutagenesis	1243	1	A → T: 7.6-fold increase of the estradiol glucuronide transport; when associated with E-1090. Ref.2
	Sequence conflict	4	1	S → R in AAN86532. Ref.1
	Sequence conflict	4	1	S → R in AAO44983. Ref.4
	Sequence conflict	480	1	F → S in AAO44983. Ref.4
	Sequence conflict	820	1	N → S in CAB97204. Ref.5
	Sequence conflict	868	1	R → P in CAB97204. Ref.5
	Sequence conflict	916	1	S → G in CAB97204. Ref.5
	Sequence conflict	1122	1	P → T in CAB97204. Ref.5
	Sequence conflict	1382	1	S → P in AAN86532. Ref.1
	Sequence conflict	1473	1	I → V in AAN86532. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 24, 2006. Version 2. Checksum: 2E6939F63F5A3F68	FASTA	1,532	171,493
	10 20 30 40 50 60 MALSSFCSSD GSDPLWDWNV TWHTSNPDFT KCFQNTVLTW VPCFYLWSCF PLYFLYLSRH 70 80 90 100 110 120 DRGYIQMTHL NKAKTALGFF LWIICWADLF YSFWERSQGM LLAPVLLVSP TLLGITMLLA 130 140 150 160 170 180 TFLIQFERRK GVQSSGIMLT FWLVALLCAL AILRSKIISA LKKDAQVDMF RDSAFYLYFT 190 200 210 220 230 240 LVFIQLVLSC FSDSSPLFSE TVRDPNPCPE SSASFLSRIT FWWITGMMVQ GYRQPLKSSD 250 260 270 280 290 300 LWSLNKEDTS EEVVPVLVNN WKKECVKSRK QPVRIVYAPP KDPTKPKGSS QLDVNEEVEA 310 320 330 340 350 360 LIVKSSHKDR DPSLFKVLYK TFGPYFLMSF LYKALHDLMM FAGPEILELI INFVNDREAP 370 380 390 400 410 420 DWQGYLYTAL LFVSACLQTL ALHQYFHICF VTGMRIKTAV VGAVYRKALV ITNSARKSST 430 440 450 460 470 480 VGEIVNLMSV DAQRFMDLAT YINMIWSAPL QVTLALYFLW LNLGPSVLAG VAVMILMVPF 490 500 510 520 530 540 NAVMAMKTKT YQVAHMKSKD NRIKLMNEIL NGIKVLKLYA WELAFQDKVM NIRQEELKVL 550 560 570 580 590 600 KKSAYLAAVG TFTWVCTPFL VALSTFAVFV TVDEKNILDA KKAFVSLALF NILRFPLNIL 610 620 630 640 650 660 PMVISSIVQA SVSLKRLRIF LSHEELEPDS IERWSIKDGG GMNSITVKNA TFTWARDEPP 670 680 690 700 710 720 TLNGITFAIP DGALVAVVGQ VGCGKSSLLS ALLAEMDKVE GHVTLKGSVA YVPQQAWIQN 730 740 750 760 770 780 DSLRENILFG RPLQEHCYKA VMEACALLPD LEILPSGDLT EIGEKGVNLS GGQKQRVSLA 790 800 810 820 830 840 RAVYCNSDIY LLDDPLSAVD AHVGKHIFEK VVGPMGLLKN KTRILVTHGI SYLPQVDVII 850 860 870 880 890 900 VMSGGKISEM GSYQELLDRD GAFAEFVRTY ANTEQDLASE DDSKNGVSGL GKESKPVENG 910 920 930 940 950 960 ILVTDAVGKP LQRHLSNSSS HSVVTNQQHS STAELQKSGV KEETWKLMEA DKAQTGQVKL 970 980 990 1000 1010 1020 SVYWNYMKAI GLCISFLSIF LFLCNHVSAL ASNYWLSLWT DDRPAVNGTQ ENRNFRLSVY 1030 1040 1050 1060 1070 1080 GALGILQGVA VFGYSMAVSI GGIFASRRLH LDLLQNVLRS PMSFFERTPS GNLVNRFSKE 1090 1100 1110 1120 1130 1140 LDTVDSMIPQ VIKMFMGSLF SVIGAVIIIL LATPIAAVII PPLGLVYFFV QRFYVASSRQ 1150 1160 1170 1180 1190 1200 LKRLESVSRS PVYSHFNETL LGVSVIRAFE EQERFIRQSD LKVDENQKAY YPSIVANRWL 1210 1220 1230 1240 1250 1260 AVRLECVGNC IVLFAALFAV ISRHSLSAGL VGLSVSYSLQ ITAYLNWLVR MSSEMETNIV 1270 1280 1290 1300 1310 1320 AVERLKEYSE TEKEASWQIQ ETAPPSTWPH SGRVEFRDYC LRYREDLDLV LKHINVTIEG 1330 1340 1350 1360 1370 1380 GEKVGIVGRT GAGKSSLTLG LFRINESAEG EIIIDGINIA KIGLHNLRFK ITIIPQDPVL 1390 1400 1410 1420 1430 1440 FSGSLRMNLD PFSQYSDEEV WMALELAHLK GFVSALPDKL NHECAEGGEN LSVGQRQLVC 1450 1460 1470 1480 1490 1500 LARALLRKTK ILVLDEATAA VDLETDDLIQ STIRTQFEDS TVLTIAHRLN TIMDYTRVIV 1510 1520 1530 LDKGEIRECG APSELLQQRG VFYSMAKDAG LV
	Isoform 2 [UniParc]. Checksum: 15FB4E9C99B7B9AC	FASTA	1,523	170,496
	10 20 30 40 50 60 MALSSFCSSD GSDPLWDWNV TWHTSNPDFT KCFQNTVLTW VPCFYLWSCF PLYFLYLSRH 70 80 90 100 110 120 DRGYIQMTHL NKAKTALGFF LWIICWADLF YSFWERSQGM LLAPVLLVSP TLLGITMLLA 130 140 150 160 170 180 TFLIQFERRK GVQSSGIMLT FWLVALLCAL AILRSKIISA LKKDAQVDMF RDSAFYLYFT 190 200 210 220 230 240 LVFIQLVLSC FSDSSPLFSE TVRDPNPCPE SSASFLSRIT FWWITGMMVQ GYRQPLKSSD 250 260 270 280 290 300 LWSLNKEDTS EEVVPVLVNN WKKECVKSRK QPVRIVYAPP KDPTKPKGSS QLDVNEEVEA 310 320 330 340 350 360 LIVKSSHKDR DPSLFKVLYK TFGPYFLMSF LYKALHDLMM FAGPEILELI INFVNDREAP 370 380 390 400 410 420 DWQGYLYTAL LFVSACLQTL ALHQYFHICF VTGMRIKTAV VGAVYRKALV ITNSARKSST 430 440 450 460 470 480 VGEIVNLMSV DAQRFMDLAT YINMIWSAPL QVTLALYFLW LNLGPSVLAG VAVMILMVPF 490 500 510 520 530 540 NAVMAMKTKT YQVAHMKSKD NRIKLMNEIL NGIKVLKLYA WELAFQDKVM NIRQEELKVL 550 560 570 580 590 600 KKSAYLAAVG TFTWVCTPFL VALSTFAVFV TVDEKNILDA KKAFVSLALF NILRFPLNIL 610 620 630 640 650 660 PMVISSIVQA SVSLKRLRIF LSHEELEPDS IERWSIKDGG GMNSITVKNA TFTWARDEPP 670 680 690 700 710 720 TLNGITFAIP DGALVAVVGQ VGCGKSSLLS ALLAEMDKVE GHVTLKGSVA YVPQQAWIQN 730 740 750 760 770 780 DSLRENILFG RPLQEHCYKA VMEACALLPD LEILPSGDLT EIGEKGVNLS GGQKQRVSLA 790 800 810 820 830 840 RAVYCNSDIY LLDDPLSAVD AHVGKHIFEK VVGPMGLLKN KTRILVTHGI SYLPQVDVII 850 860 870 880 890 900 VMSGGKISEM GSYQELLDRD GAFAEFVRTY ANTEQDLASE DDSKNGVSGL GKESKPVENG 910 920 930 940 950 960 ILVTDAVGKP LHSVVTNQQH SSTAELQKSG VKEETWKLME ADKAQTGQVK LSVYWNYMKA 970 980 990 1000 1010 1020 IGLCISFLSI FLFLCNHVSA LASNYWLSLW TDDRPAVNGT QENRNFRLSV YGALGILQGV 1030 1040 1050 1060 1070 1080 AVFGYSMAVS IGGIFASRRL HLDLLQNVLR SPMSFFERTP SGNLVNRFSK ELDTVDSMIP 1090 1100 1110 1120 1130 1140 QVIKMFMGSL FSVIGAVIII LLATPIAAVI IPPLGLVYFF VQRFYVASSR QLKRLESVSR 1150 1160 1170 1180 1190 1200 SPVYSHFNET LLGVSVIRAF EEQERFIRQS DLKVDENQKA YYPSIVANRW LAVRLECVGN 1210 1220 1230 1240 1250 1260 CIVLFAALFA VISRHSLSAG LVGLSVSYSL QITAYLNWLV RMSSEMETNI VAVERLKEYS 1270 1280 1290 1300 1310 1320 ETEKEASWQI QETAPPSTWP HSGRVEFRDY CLRYREDLDL VLKHINVTIE GGEKVGIVGR 1330 1340 1350 1360 1370 1380 TGAGKSSLTL GLFRINESAE GEIIIDGINI AKIGLHNLRF KITIIPQDPV LFSGSLRMNL 1390 1400 1410 1420 1430 1440 DPFSQYSDEE VWMALELAHL KGFVSALPDK LNHECAEGGE NLSVGQRQLV CLARALLRKT 1450 1460 1470 1480 1490 1500 KILVLDEATA AVDLETDDLI QSTIRTQFED STVLTIAHRL NTIMDYTRVI VLDKGEIREC 1510 1520 GAPSELLQQR GVFYSMAKDA GLV

References

[1]	"Cloning and characterization of the rat multidrug resistance-associated protein 1." Yang Z., Li C.S.W., Shen D.D., Ho R.J.Y. AAPS PharmSci 4:E15-E15(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: Sprague-Dawley. Tissue: Brain.
[2]	"Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1)." Nunoya K., Grant C.E., Zhang D.-W., Cole S.P.C., Deeley R.G. Drug Metab. Dispos. 31:1016-1026(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, MUTAGENESIS OF LEU-983; GLN-1090; SER-1101; VAL-1106 AND ALA-1243. Strain: Sprague-Dawley. Tissue: Skeletal muscle.
[3]	Yabuuchi H., Takayanagi S., Ishikawa T. Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: Sprague-Dawley. Tissue: Spleen.
[4]	Takayanagi S., Ishikawa T. Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: Sprague-Dawley. Tissue: Spleen.
[5]	"The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress." Hirrlinger J., Koenig J., Keppler D., Lindenau J., Schulz J.B., Dringen R. J. Neurochem. 76:627-636(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 711-1532 (ISOFORM 1).
[6]	"cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats." Buechler M., Koenig J., Brom M., Kartenbeck J., Spring H., Horie T., Keppler D. J. Biol. Chem. 271:15091-15098(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1426-1532 (ISOFORMS 1/2).
[7]	"Multidrug resistance protein 1-mediated transport of saquinavir by microglia." Dallas S., Ronaldson P.T., Bendayan M., Bendayan R. NeuroReport 15:1183-1186(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY170916 mRNA. Translation: AAN86532.1. AF487549 mRNA. Translation: AAO85437.1. AY174892 mRNA. Translation: AAO44983.1. AJ277881 mRNA. Translation: CAB97204.1. X96394 mRNA. Translation: CAA65258.1.
IPI	IPI00331756. IPI00734748.
RefSeq	NP_071617.2. NM_022281.2.
UniGene	Rn.10495.
3D structure databases
ProteinModelPortal	Q8CG09.
SMR	Q8CG09. Positions 643-872.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000045518.
PTM databases
PhosphoSite	Q8CG09.
Proteomic databases
PaxDb	Q8CG09.
PRIDE	Q8CG09.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24565.
KEGG	rno:24565.
UCSC	RGD:3112. rat.
Organism-specific databases
CTD	4363.
RGD	3112. Abcc1.
Phylogenomic databases
eggNOG	COG1132.
HOVERGEN	HBG108314.
KO	K05665.
Gene expression databases
ArrayExpress	Q8CG09.
Genevestigator	Q8CG09.
GermOnline	ENSRNOG00000032748. Rattus norvegicus.
Family and domain databases
InterPro	IPR003593. AAA+_ATPase. IPR003439. ABC_transporter-like. IPR017871. ABC_transporter_CS. IPR017940. ABC_transporter_type1. IPR001140. ABC_transptr_TM_dom. IPR011527. ABC_transptrTM_dom_typ1. IPR018170. Aldo/ket_reductase_CS. IPR005292. Multidrug-R_assoc. [Graphical view]
Pfam	PF00664. ABC_membrane. 2 hits. PF00005. ABC_tran. 2 hits. [Graphical view]
SMART	SM00382. AAA. 2 hits. [Graphical view]
SUPFAM	SSF90123. ABC_TM_1. 2 hits.
TIGRFAMs	TIGR00957. MRP_assoc_pro. 1 hit.
PROSITE	PS50929. ABC_TM1F. 2 hits. PS00211. ABC_TRANSPORTER_1. 2 hits. PS50893. ABC_TRANSPORTER_2. 2 hits. PS00063. ALDOKETO_REDUCTASE_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5680.
NextBio	603696.

Entry information

Entry name

MRP1_RAT

Accession

Primary (citable) accession number: Q8CG09
Secondary accession number(s): Q63346 , Q810E4, Q810G9, Q9JHS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2006
Last sequence update:	January 24, 2006
Last modified:	April 3, 2013
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program