Reviewed, UniProtKB/Swiss-Prot P08183 (MDR1_HUMAN)

Names and origin

Protein names

Recommended name:
    Multidrug resistance protein 1
    EC=3.6.3.44
Alternative name(s):
    ATP-binding cassette sub-family B member 1
    P-glycoprotein 1
    CD_antigen=CD243

Gene names

Name:	ABCB1
Synonyms:	MDR1, PGY1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1280 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Catalytic activity	ATP + H(2)O + xenobiotic(In) = ADP + phosphate + xenobiotic(Out).
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in liver, kidney, small intestine and brain.
Polymorphism	Genetic variation in ABCB1 may play a role in patients who do not respond to drug treatment.
Sequence similarities	Belongs to the ABC transporter family. Multidrug resistance exporter (TC 3.A.1.201) subfamily. [View classification] Contains 2 ABC transmembrane type-1 domains. Contains 2 ABC transporter domains.
Sequence caution	The sequence AAB69423.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	response to drug Traceable author statement. Source: ProtInc transport Traceable author statement. Source: ProtInc
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB integral to membrane Traceable author statement. Source: ProtInc membrane fraction Traceable author statement. Source: ProtInc
Molecular function	ATP binding Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct xenobiotic-transporting ATPase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RNF2	Q99496	1	EBI-1057359,EBI-722416

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1280	1280	Multidrug resistance protein 1		PRO_0000093332
Regions
	Topological domain	1 – 51	51	Cytoplasmic Potential
	Transmembrane	52 – 72	21	Potential
	Transmembrane	120 – 140	21	Potential
	Transmembrane	189 – 209	21	Potential
	Transmembrane	216 – 236	21	Potential
	Transmembrane	297 – 317	21	Potential
	Transmembrane	326 – 346	21	Potential
	Topological domain	347 – 710	364	Cytoplasmic Potential
	Transmembrane	711 – 731	21	Potential
	Transmembrane	757 – 777	21	Potential
	Transmembrane	833 – 853	21	Potential
	Transmembrane	854 – 874	21	Potential
	Transmembrane	937 – 957	21	Potential
	Transmembrane	974 – 994	21	Potential
	Topological domain	995 – 1280	286	Cytoplasmic Potential
	Domain	51 – 357	307	ABC transmembrane type-1 1
	Domain	392 – 628	237	ABC transporter 1
	Domain	711 – 1000	290	ABC transmembrane type-1 2
	Domain	1035 – 1273	239	ABC transporter 2
	Nucleotide binding	427 – 434	8	ATP 1 By similarity
	Nucleotide binding	1070 – 1077	8	ATP 2 By similarity
Amino acid modifications
	Glycosylation	91	1	N-linked (GlcNAc...) Potential
	Glycosylation	94	1	N-linked (GlcNAc...) Potential
	Glycosylation	99	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	17	1	F → L		VAR_022276
	Natural variant	21	1	N → D: dbSNP rs1805053.		VAR_014704
	Natural variant	103	1	F → L Rare polymorphism.		VAR_015001
	Natural variant	108	1	E → K		VAR_018351
	Natural variant	185	1	G → V in a colchicine-selected multidrug-resistant cell line; confers increased resistance to colchicine.		VAR_015002
	Natural variant	400	1	S → N		VAR_015003
	Natural variant	566	1	E → K		VAR_022277
	Natural variant	593	1	R → C		VAR_022278
	Natural variant	836	1	I → V		VAR_022279
	Natural variant	887	1	K → N in a colorectal cancer sample; somatic mutation.		VAR_035737
	Natural variant	893	1	A → S: dbSNP rs2032582.		VAR_013361
	Natural variant	893	1	A → T: dbSNP rs2032582.		VAR_013362
	Natural variant	986	1	M → V		VAR_018352
	Natural variant	999	1	A → T		VAR_015004
	Natural variant	1051	1	P → A		VAR_022280
	Natural variant	1107	1	Q → P		VAR_015005
	Natural variant	1141	1	S → T		VAR_022281
	Natural variant	1251	1	V → I		VAR_018353
Experimental info
	Sequence conflict	23	1	S → R in CAA41558. Ref.7
	Sequence conflict	336	1	Missing in AAB69423. Ref.3
	Sequence conflict	412	1	G → A Ref.3
	Sequence conflict	438	1	Q → S Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P08183-1 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: AB1C279531F43675	FASTA	1,280	141,463
	10 20 30 40 50 60 MDLEGDRNGG AKKKNFFKLN NKSEKDKKEK KPTVSVFSMF RYSNWLDKLY MVVGTLAAII 70 80 90 100 110 120 HGAGLPLMML VFGEMTDIFA NAGNLEDLMS NITNRSDIND TGFFMNLEED MTRYAYYYSG 130 140 150 160 170 180 IGAGVLVAAY IQVSFWCLAA GRQIHKIRKQ FFHAIMRQEI GWFDVHDVGE LNTRLTDDVS 190 200 210 220 230 240 KINEGIGDKI GMFFQSMATF FTGFIVGFTR GWKLTLVILA ISPVLGLSAA VWAKILSSFT 250 260 270 280 290 300 DKELLAYAKA GAVAEEVLAA IRTVIAFGGQ KKELERYNKN LEEAKRIGIK KAITANISIG 310 320 330 340 350 360 AAFLLIYASY ALAFWYGTTL VLSGEYSIGQ VLTVFFSVLI GAFSVGQASP SIEAFANARG 370 380 390 400 410 420 AAYEIFKIID NKPSIDSYSK SGHKPDNIKG NLEFRNVHFS YPSRKEVKIL KGLNLKVQSG 430 440 450 460 470 480 QTVALVGNSG CGKSTTVQLM QRLYDPTEGM VSVDGQDIRT INVRFLREII GVVSQEPVLF 490 500 510 520 530 540 ATTIAENIRY GRENVTMDEI EKAVKEANAY DFIMKLPHKF DTLVGERGAQ LSGGQKQRIA 550 560 570 580 590 600 IARALVRNPK ILLLDEATSA LDTESEAVVQ VALDKARKGR TTIVIAHRLS TVRNADVIAG 610 620 630 640 650 660 FDDGVIVEKG NHDELMKEKG IYFKLVTMQT AGNEVELENA ADESKSEIDA LEMSSNDSRS 670 680 690 700 710 720 SLIRKRSTRR SVRGSQAQDR KLSTKEALDE SIPPVSFWRI MKLNLTEWPY FVVGVFCAII 730 740 750 760 770 780 NGGLQPAFAI IFSKIIGVFT RIDDPETKRQ NSNLFSLLFL ALGIISFITF FLQGFTFGKA 790 800 810 820 830 840 GEILTKRLRY MVFRSMLRQD VSWFDDPKNT TGALTTRLAN DAAQVKGAIG SRLAVITQNI 850 860 870 880 890 900 ANLGTGIIIS FIYGWQLTLL LLAIVPIIAI AGVVEMKMLS GQALKDKKEL EGAGKIATEA 910 920 930 940 950 960 IENFRTVVSL TQEQKFEHMY AQSLQVPYRN SLRKAHIFGI TFSFTQAMMY FSYAGCFRFG 970 980 990 1000 1010 1020 AYLVAHKLMS FEDVLLVFSA VVFGAMAVGQ VSSFAPDYAK AKISAAHIIM IIEKTPLIDS 1030 1040 1050 1060 1070 1080 YSTEGLMPNT LEGNVTFGEV VFNYPTRPDI PVLQGLSLEV KKGQTLALVG SSGCGKSTVV 1090 1100 1110 1120 1130 1140 QLLERFYDPL AGKVLLDGKE IKRLNVQWLR AHLGIVSQEP ILFDCSIAEN IAYGDNSRVV 1150 1160 1170 1180 1190 1200 SQEEIVRAAK EANIHAFIES LPNKYSTKVG DKGTQLSGGQ KQRIAIARAL VRQPHILLLD 1210 1220 1230 1240 1250 1260 EATSALDTES EKVVQEALDK AREGRTCIVI AHRLSTIQNA DLIVVFQNGR VKEHGTHQQL 1270 1280 LAQKGIYFSM VSVQAGTKRQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells." Chen C.-J., Chin J.E., Ueda K., Clark D.P., Pastan I., Gottesman M.M., Roninson I.B. Cell 47:381-389(1986) [PubMed: 2876781] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-185.
[2]	"Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins." Chen C.-J., Clark D.P., Ueda K., Pastan I., Gottesman M.M., Roninson I.B. J. Biol. Chem. 265:506-514(1990) [PubMed: 1967175] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Multidrug-resistant human sarcoma cells with a mutant P-glycoprotein, altered phenotype, and resistance to cyclosporins." Chen G., Duran G.E., Steger K.A., Lacayo N.J., Jaffrezou J.P., Dumontet C., Sikic B.I. J. Biol. Chem. 272:5974-5982(1997) [PubMed: 9038218] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-185.
[4]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Rajkumar N., Downing T.K., Olson A.N., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-17; ASP-21; ASN-400; LYS-566; CYS-593; VAL-836; ALA-1051; THR-1141 AND ILE-1251.
[5]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"mdr1/P-glycoprotein gene segments analyzed from various human leukemic cell lines exhibiting different multidrug resistance profiles." Gekeler V., Weger S., Probst H. Biochem. Biophys. Res. Commun. 169:796-802(1990) [PubMed: 1972623] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 178-215 AND 800-856.
[7]	"P-glycoprotein gene (MDR1) cDNA from human adrenal: normal P-glycoprotein carries Gly185 with an altered pattern of multidrug resistance." Kioka N., Tsubota J., Kakehi Y., Komano T., Gottesman M.M., Pastan I., Ueda K. Biochem. Biophys. Res. Commun. 162:224-231(1989) [PubMed: 2568832] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-23, VARIANT SER-893.
[8]	"ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2." Kerb R., Hoffmeyer S., Brinkmann U. Pharmacogenomics 2:51-64(2001) [PubMed: 11258197] [Abstract] Cited for: REVIEW.
[9]	"An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene." Choi K.H., Chen C.-J., Kriegler M., Roninson I.B. Cell 53:519-529(1988) [PubMed: 2897240] [Abstract] Cited for: VARIANT VAL-185.
[10]	"Genetic polymorphism in MDR-1: a tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors." Mickley L.A., Lee J.-S., Weng Z., Zhan Z., Alvarez M., Wilson W., Bates S.E., Fojo T. Blood 91:1749-1756(1998) [PubMed: 9473242] [Abstract] Cited for: VARIANTS SER-893 AND THR-999.
[11]	"A new polymorphism (N21D) in the exon 2 of the human MDR1 gene encoding the P-glycoprotein." Decleves X., Chevillard S., Charpentier C., Vielh P., Laplanche J.-L. Hum. Mutat. 15:486-486(2000) [PubMed: 10790226] [Abstract] Cited for: VARIANT ASP-21.
[12]	"Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo." Hoffmeyer S., Burk O., von Richter O., Arnold H.P., Brockmoeller J., Johne A., Cascorbi I., Gerloff T., Roots I., Eichelbaum M., Brinkmann U. Proc. Natl. Acad. Sci. U.S.A. 97:3473-3478(2000) [PubMed: 10716719] [Abstract] Cited for: VARIANTS ASP-21; LEU-103 AND ASN-400.
[13]	"Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects." Cascorbi I., Gerloff T., Johne A., Meisel C., Hoffmeyer S., Schwab M., Schaeffeler E., Eichelbaum M., Brinkmann U., Roots I. Clin. Pharmacol. Ther. 69:169-174(2001) [PubMed: 11240981] [Abstract] Cited for: VARIANTS ASP-21; ASN-400; SER-893; THR-893 AND PRO-1107.
[14]	"Polymorphism of MDR1 gene in healthy Japanese subjects: a novel SNP with an amino acid substitution (Glu108Lys)." Honda T., Dan Y., Koyabu N., Ieiri I., Otsubo K., Higuchi S., Ohtani H., Sawada J. Drug Metab. Pharmacokinet. 17:479-481(2002) [PubMed: 15618700] [Abstract] Cited for: VARIANT LYS-108.
[15]	"Twelve novel single nucleotide polymorphisms in ABCB1/MDR1 among Japanese patients with ventricular tachycardia who were administered amiodarone." Itoda M., Saito Y., Komamura K., Ueno K., Kamakura S., Ozawa S., Sawada J. Drug Metab. Pharmacokinet. 17:566-571(2002) [PubMed: 15618713] [Abstract] Cited for: VARIANT ILE-1251.
[16]	"Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population." Saito S., Iida A., Sekine A., Miura Y., Ogawa C., Kawauchi S., Higuchi S., Nakamura Y. J. Hum. Genet. 47:38-50(2002) [PubMed: 11829140] [Abstract] Cited for: VARIANTS SER-893 AND THR-893.
[17]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-887.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

P-glycoprotein entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	M14758 mRNA. Translation: AAA59575.1. M29447 , M29424, M29425, M29426, M29427,