MDR1_CANAL
ID MDR1_CANAL Reviewed; 564 AA.
AC Q5ABU7; A0A1D8PQ31;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 2.
DT 25-MAY-2022, entry version 111.
DE RecName: Full=Multidrug resistance protein 1 {ECO:0000303|PubMed:7726508};
DE AltName: Full=Benomyl resistance protein 1;
GN Name=MDR1 {ECO:0000303|PubMed:7726508}; Synonyms=BEN, BMR1;
GN OrderedLocusNames=CAALFM_C603170CA; ORFNames=CaO19.13047, CaO19.5604;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP FUNCTION.
RX PubMed=2062311; DOI=10.1007/bf00259685;
RA Fling M.E., Kopf J., Tamarkin A., Gorman J.A., Smith H.A., Koltin Y.;
RT "Analysis of a Candida albicans gene that encodes a novel mechanism for
RT resistance to benomyl and methotrexate.";
RL Mol. Gen. Genet. 227:318-329(1991).
RN [5]
RP FUNCTION.
RX PubMed=8031026; DOI=10.1128/aac.38.4.648;
RA Ben-Yaacov R., Knoller S., Caldwell G.A., Becker J.M., Koltin Y.;
RT "Candida albicans gene encoding resistance to benomyl and methotrexate is a
RT multidrug resistance gene.";
RL Antimicrob. Agents Chemother. 38:648-652(1994).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=7726508; DOI=10.1128/aac.39.2.422;
RA Goldway M., Teff D., Schmidt R., Oppenheim A.B., Koltin Y.;
RT "Multidrug resistance in Candida albicans: disruption of the BENr gene.";
RL Antimicrob. Agents Chemother. 39:422-426(1995).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=8891134; DOI=10.1128/aac.40.10.2300;
RA Sanglard D., Ischer F., Monod M., Bille J.;
RT "Susceptibilities of Candida albicans multidrug transporter mutants to
RT various antifungal agents and other metabolic inhibitors.";
RL Antimicrob. Agents Chemother. 40:2300-2305(1996).
RN [8]
RP FUNCTION.
RX PubMed=9210670; DOI=10.1128/aac.41.7.1482;
RA White T.C.;
RT "Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in
RT azole resistance in Candida albicans isolates from a patient infected with
RT human immunodeficiency virus.";
RL Antimicrob. Agents Chemother. 41:1482-1487(1997).
RN [9]
RP IDENTIFICATION.
RX PubMed=9046086;
RX DOI=10.1002/(sici)1097-0061(199701)13:1<43::aid-yea56>3.0.co;2-j;
RA Goffeau A., Park J., Paulsen I.T., Jonniaux J.L., Dinh T., Mordant P.,
RA Saier M.H. Jr.;
RT "Multidrug-resistant transport proteins in yeast: complete inventory and
RT phylogenetic characterization of yeast open reading frames with the major
RT facilitator superfamily.";
RL Yeast 13:43-54(1997).
RN [10]
RP FUNCTION.
RX PubMed=9756759; DOI=10.1128/aac.42.10.2584;
RA Marr K.A., Lyons C.N., Rustad T.R., Bowden R.A., White T.C., Rustad T.;
RT "Rapid, transient fluconazole resistance in Candida albicans is associated
RT with increased mRNA levels of CDR.";
RL Antimicrob. Agents Chemother. 42:2584-2589(1998).
RN [11]
RP FUNCTION.
RX PubMed=9797228; DOI=10.1128/aac.42.11.2932;
RA Lopez-Ribot J.L., McAtee R.K., Lee L.N., Kirkpatrick W.R., White T.C.,
RA Sanglard D., Patterson T.F.;
RT "Distinct patterns of gene expression associated with development of
RT fluconazole resistance in serial candida albicans isolates from human
RT immunodeficiency virus-infected patients with oropharyngeal candidiasis.";
RL Antimicrob. Agents Chemother. 42:2932-2937(1998).
RN [12]
RP INDUCTION.
RX PubMed=9922230; DOI=10.1128/jb.181.3.700-708.1999;
RA Alarco A.M., Raymond M.;
RT "The bZip transcription factor Cap1p is involved in multidrug resistance
RT and oxidative stress response in Candida albicans.";
RL J. Bacteriol. 181:700-708(1999).
RN [13]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10844673; DOI=10.1046/j.1365-2958.2000.01899.x;
RA Wirsching S., Michel S., Morschhauser J.;
RT "Targeted gene disruption in Candida albicans wild-type strains: the role
RT of the MDR1 gene in fluconazole resistance of clinical Candida albicans
RT isolates.";
RL Mol. Microbiol. 36:856-865(2000).
RN [14]
RP FUNCTION.
RX PubMed=11568478; DOI=10.1007/bf02703742;
RA Kohli A., Gupta V., Krishnamurthy S., Hasnain S.E., Prasad R.;
RT "Specificity of drug transport mediated by CaMDR1: a major facilitator of
RT Candida albicans.";
RL J. Biosci. 26:333-339(2001).
RN [15]
RP INDUCTION.
RX PubMed=14688046; DOI=10.1093/jac/dkh040;
RA Lee M.K., Williams L.E., Warnock D.W., Arthington-Skaggs B.A.;
RT "Drug resistance genes and trailing growth in Candida albicans isolates.";
RL J. Antimicrob. Chemother. 53:217-224(2004).
RN [16]
RP INDUCTION.
RX PubMed=15980350; DOI=10.1128/aac.49.7.2785-2792.2005;
RA Harry J.B., Oliver B.G., Song J.L., Silver P.M., Little J.T., Choiniere J.,
RA White T.C.;
RT "Drug-induced regulation of the MDR1 promoter in Candida albicans.";
RL Antimicrob. Agents Chemother. 49:2785-2792(2005).
RN [17]
RP FUNCTION.
RX PubMed=16569853; DOI=10.1128/aac.50.4.1365-1371.2006;
RA Hiller D., Sanglard D., Morschhaeuser J.;
RT "Overexpression of the MDR1 gene is sufficient to confer increased
RT resistance to toxic compounds in Candida albicans.";
RL Antimicrob. Agents Chemother. 50:1365-1371(2006).
RN [18]
RP INDUCTION.
RX PubMed=16801405; DOI=10.1128/aac.00196-06;
RA Hiller D., Stahl S., Morschhaeuser J.;
RT "Multiple cis-acting sequences mediate upregulation of the MDR1 efflux pump
RT in a fluconazole-resistant clinical Candida albicans isolate.";
RL Antimicrob. Agents Chemother. 50:2300-2308(2006).
RN [19]
RP INDUCTION.
RX PubMed=17041190; DOI=10.1128/ec.00243-06;
RA Riggle P.J., Kumamoto C.A.;
RT "Transcriptional regulation of MDR1, encoding a drug efflux determinant, in
RT fluconazole-resistant Candida albicans strains through an Mcm1p binding
RT site.";
RL Eukaryot. Cell 5:1957-1968(2006).
RN [20]
RP INDUCTION.
RX PubMed=17159223; DOI=10.1099/mic.0.29277-0;
RA Rognon B., Kozovska Z., Coste A.T., Pardini G., Sanglard D.;
RT "Identification of promoter elements responsible for the regulation of MDR1
RT from Candida albicans, a major facilitator transporter involved in azole
RT resistance.";
RL Microbiology 152:3701-3722(2006).
RN [21]
RP FUNCTION.
RX PubMed=17325226; DOI=10.1128/aac.00182-07;
RA Cheng S., Clancy C.J., Nguyen K.T., Clapp W., Nguyen M.H.;
RT "A Candida albicans petite mutant strain with uncoupled oxidative
RT phosphorylation overexpresses MDR1 and has diminished susceptibility to
RT fluconazole and voriconazole.";
RL Antimicrob. Agents Chemother. 51:1855-1858(2007).
RN [22]
RP INDUCTION, AND FUNCTION.
RX PubMed=17983269; DOI=10.1371/journal.ppat.0030164;
RA Morschhauser J., Barker K.S., Liu T.T., Blass-Warmuth J., Homayouni R.,
RA Rogers P.D.;
RT "The transcription factor Mrr1p controls expression of the MDR1 efflux pump
RT and mediates multidrug resistance in Candida albicans.";
RL PLoS Pathog. 3:E164-E164(2007).
RN [23]
RP INDUCTION.
RX PubMed=18238892; DOI=10.1093/jac/dkm513;
RA Vogel M., Hartmann T., Koeberle M., Treiber M., Autenrieth I.B.,
RA Schumacher U.K.;
RT "Rifampicin induces MDR1 expression in Candida albicans.";
RL J. Antimicrob. Chemother. 61:541-547(2008).
RN [24]
RP INDUCTION.
RX PubMed=18390649; DOI=10.1128/ec.00070-08;
RA Znaidi S., Weber S., Al-Abdin O.Z., Bomme P., Saidane S., Drouin S.,
RA Lemieux S., De Deken X., Robert F., Raymond M.;
RT "Genomewide location analysis of Candida albicans Upc2p, a regulator of
RT sterol metabolism and azole drug resistance.";
RL Eukaryot. Cell 7:836-847(2008).
RN [25]
RP INDUCTION.
RX PubMed=19395663; DOI=10.1128/ec.00002-09;
RA Znaidi S., Barker K.S., Weber S., Alarco A.M., Liu T.T., Boucher G.,
RA Rogers P.D., Raymond M.;
RT "Identification of the Candida albicans Cap1p regulon.";
RL Eukaryot. Cell 8:806-820(2009).
RN [26]
RP INDUCTION.
RX PubMed=19527793; DOI=10.1016/j.fgb.2009.06.003;
RA Chen C.G., Yang Y.L., Tseng K.Y., Shih H.I., Liou C.H., Lin C.C., Lo H.J.;
RT "Rep1p negatively regulating MDR1 efflux pump involved in drug resistance
RT in Candida albicans.";
RL Fungal Genet. Biol. 46:714-720(2009).
RN [27]
RP INDUCTION.
RX PubMed=21136999; DOI=10.1002/prca.200800252;
RA Hoehamer C.F., Cummings E.D., Hilliard G.M., Morschhaeuser J., Rogers P.D.;
RT "Proteomic analysis of Mrr1p- and Tac1p-associated differential protein
RT expression in azole-resistant clinical isolates of Candida albicans.";
RL Proteomics Clin. Appl. 3:968-978(2009).
RN [28]
RP INDUCTION.
RX PubMed=19420894; DOI=10.1248/yakushi.129.623;
RA Zhang H., Gao A., Li F., Zhang G., Ho H.I., Liao W.;
RT "Mechanism of action of tetrandrine, a natural inhibitor of Candida
RT albicans drug efflux pumps.";
RL Yakugaku Zasshi 129:623-630(2009).
RN [29]
RP FUNCTION.
RX PubMed=20348384; DOI=10.1128/ec.00355-09;
RA Basso L.R. Jr., Gast C.E., Mao Y., Wong B.;
RT "Fluconazole transport into Candida albicans secretory vesicles by the
RT membrane proteins Cdr1p, Cdr2p, and Mdr1p.";
RL Eukaryot. Cell 9:960-970(2010).
RN [30]
RP INDUCTION.
RX PubMed=21343453; DOI=10.1128/aac.01467-10;
RA Mogavero S., Tavanti A., Senesi S., Rogers P.D., Morschhaeuser J.;
RT "Differential requirement of the transcription factor Mcm1 for activation
RT of the Candida albicans multidrug efflux pump MDR1 by its regulators Mrr1
RT and Cap1.";
RL Antimicrob. Agents Chemother. 55:2061-2066(2011).
RN [31]
RP INDUCTION.
RX PubMed=21402859; DOI=10.1128/aac.01343-10;
RA Schubert S., Barker K.S., Znaidi S., Schneider S., Dierolf F., Dunkel N.,
RA Aid M., Boucher G., Rogers P.D., Raymond M., Morschhaeuser J.;
RT "Regulation of efflux pump expression and drug resistance by the
RT transcription factors Mrr1, Upc2, and Cap1 in Candida albicans.";
RL Antimicrob. Agents Chemother. 55:2212-2223(2011).
RN [32]
RP INDUCTION.
RX PubMed=21685320; DOI=10.1128/ec.05100-11;
RA Schubert S., Popp C., Rogers P.D., Morschhauser J.;
RT "Functional dissection of a Candida albicans zinc cluster transcription
RT factor, the multidrug resistance regulator Mrr1.";
RL Eukaryot. Cell 10:1110-1121(2011).
RN [33]
RP SUBCELLULAR LOCATION, FUNCTION, DOMAIN, AND MUTAGENESIS OF GLU-296;
RP LYS-300; LYS-306; LYS-308; ARG-309; ASP-317; ARG-318; GLU-322; GLU-324;
RP GLU-326 AND LYS-329.
RX PubMed=22587419; DOI=10.1042/bj20120190;
RA Mandal A., Kumar A., Singh A., Lynn A.M., Kapoor K., Prasad R.;
RT "A key structural domain of the Candida albicans Mdr1 protein.";
RL Biochem. J. 445:313-322(2012).
RN [34]
RP INDUCTION.
RX PubMed=22615278; DOI=10.1128/aac.00264-12;
RA Sasse C., Schillig R., Reimund A., Merk J., Morschhauser J.;
RT "Inducible and constitutive activation of two polymorphic promoter alleles
RT of the Candida albicans multidrug efflux pump MDR1.";
RL Antimicrob. Agents Chemother. 56:4490-4494(2012).
RN [35]
RP INDUCTION.
RX PubMed=24051054; DOI=10.1016/j.ijantimicag.2013.07.013;
RA Morio F., Pagniez F., Besse M., Gay-andrieu F., Miegeville M., Le Pape P.;
RT "Deciphering azole resistance mechanisms with a focus on transcription
RT factor-encoding genes TAC1, MRR1 and UPC2 in a set of fluconazole-resistant
RT clinical isolates of Candida albicans.";
RL Int. J. Antimicrob. Agents 42:410-415(2013).
RN [36]
RP INDUCTION.
RX PubMed=23527892; DOI=10.3109/13880209.2013.764537;
RA Zhang X., Guo H., Gao L., Song Y., Li S., Zhang H.;
RT "Molecular mechanisms underlying the tetrandrine-mediated reversal of the
RT fluconazole resistance of Candida albicans.";
RL Pharm. Biol. 51:749-752(2013).
RN [37]
RP INDUCTION.
RX PubMed=24936593; DOI=10.1128/aac.03065-14;
RA Ramirez-Zavala B., Mogavero S., Schoeller E., Sasse C., Rogers P.D.,
RA Morschhaeuser J.;
RT "SAGA/ADA complex subunit Ada2 is required for Cap1- but not Mrr1-mediated
RT upregulation of the Candida albicans multidrug efflux pump MDR1.";
RL Antimicrob. Agents Chemother. 58:5102-5110(2014).
RN [38]
RP INDUCTION.
RX PubMed=24723295; DOI=10.1007/s00253-014-5719-2;
RA Shafreen R.M., Raja Mohamed B.S., Muthamil S., Subramanian M.,
RA Pandian S.K., Shunmugiah K.P.;
RT "Inhibition of Candida albicans virulence factors by novel levofloxacin
RT derivatives.";
RL Appl. Microbiol. Biotechnol. 98:6775-6785(2014).
CC -!- FUNCTION: Plasma membrane multidrug efflux pump that confers resistance
CC to numerous chemicals including azoles such as fluconazole,
CC voriconazole, and benztriazoles, as well as to benomyl, cycloheximide,
CC methotrexate, 4-nitroquinoline-N-oxide, sulfometuron methyl, cerulenin,
CC and brefeldin A. {ECO:0000269|PubMed:10844673,
CC ECO:0000269|PubMed:11568478, ECO:0000269|PubMed:16569853,
CC ECO:0000269|PubMed:17325226, ECO:0000269|PubMed:17983269,
CC ECO:0000269|PubMed:20348384, ECO:0000269|PubMed:2062311,
CC ECO:0000269|PubMed:22587419, ECO:0000269|PubMed:7726508,
CC ECO:0000269|PubMed:8031026, ECO:0000269|PubMed:8891134,
CC ECO:0000269|PubMed:9210670, ECO:0000269|PubMed:9756759,
CC ECO:0000269|PubMed:9797228, ECO:0000303|PubMed:9046086}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22587419};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Constitutive, high-level transcription is commonly observed
CC in laboratory and clinical strains of Candida albicans that are
CC resistant to the antifungal drug fluconazole. Multiple cis-acting
CC sequences within the promoter mediate its activation. One, a benomyl
CC response element (BRE), is situated at position -296 to -260. It is
CC required for benomyl-dependent MDR1 up-regulation and is also necessary
CC for constitutive high expression of MDR1. A second element, termed
CC H(2)O(2) response element (HRE), is situated at position -561 to -520.
CC The HRE is required for H(2)O(2)-dependent MDR1 up-regulation, but
CC dispensable for constitutive high expression. Two potential binding
CC sites (TTAG/CTAA) for the transcription factor CAP1 lie within the HRE.
CC Expression is induced by fluconazole, rifampicin, methotrexate,
CC diethylmaleate, diamide, 4-nitroquinoline-N-oxide, benomyl, o-
CC phenanthroline (OP), hydrogen peroxide, methyl methanesulfonate, and
CC sulfometuron methyl. Expression is down-regulated by tetrandrine and
CC levofloxacin derivatives. Transcription is positively regulated by
CC ADA2, CAP1, MRR1, UPC2, and TAC1; and negatively regulated by REP1.
CC Transcription is also regulated by the general transcription factor
CC MCM1. MCM1 is dispensable for up-regulation by H(2)O(2) but is required
CC for full induction by benomyl. {ECO:0000269|PubMed:14688046,
CC ECO:0000269|PubMed:15980350, ECO:0000269|PubMed:16801405,
CC ECO:0000269|PubMed:17041190, ECO:0000269|PubMed:17159223,
CC ECO:0000269|PubMed:17983269, ECO:0000269|PubMed:18238892,
CC ECO:0000269|PubMed:18390649, ECO:0000269|PubMed:19395663,
CC ECO:0000269|PubMed:19420894, ECO:0000269|PubMed:19527793,
CC ECO:0000269|PubMed:21136999, ECO:0000269|PubMed:21343453,
CC ECO:0000269|PubMed:21402859, ECO:0000269|PubMed:21685320,
CC ECO:0000269|PubMed:22615278, ECO:0000269|PubMed:23527892,
CC ECO:0000269|PubMed:24051054, ECO:0000269|PubMed:24723295,
CC ECO:0000269|PubMed:24936593, ECO:0000269|PubMed:9922230}.
CC -!- DOMAIN: The central cytoplasmic loop (residues 295 to 350) is critical
CC for the function, but unlike other homologous proteins, has no apparent
CC role in imparting substrate specificity or in the recruitment of the
CC transporter protein. {ECO:0000269|PubMed:22587419}.
CC -!- DISRUPTION PHENOTYPE: Leads to enhanced susceptibility against
CC fluconazole, methotrexate, 4-nitroquinoline-N-oxide, and cycloheximide.
CC {ECO:0000269|PubMed:10844673, ECO:0000269|PubMed:7726508,
CC ECO:0000269|PubMed:8891134}.
CC -!- MISCELLANEOUS: The overexpression of MDR1 is a frequent cause of
CC resistance to the widely used antimycotic agent fluconazole and other
CC toxic compounds in the pathogenic yeast Candida albicans.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. CAR1 family.
CC {ECO:0000305}.
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DR EMBL; CP017628; AOW30248.1; -; Genomic_DNA.
DR RefSeq; XP_719165.2; XM_714072.2.
DR AlphaFoldDB; Q5ABU7; -.
DR STRING; 237561.Q5ABU7; -.
DR ChEMBL; CHEMBL5336; -.
DR GeneID; 3639260; -.
DR KEGG; cal:CAALFM_C603170CA; -.
DR CGD; CAL0000173998; MDR1.
DR VEuPathDB; FungiDB:C6_03170C_A; -.
DR eggNOG; KOG0255; Eukaryota.
DR HOGENOM; CLU_008455_11_1_1; -.
DR InParanoid; Q5ABU7; -.
DR OrthoDB; 607899at2759; -.
DR PRO; PR:Q5ABU7; -.
DR Proteomes; UP000000559; Chromosome 6.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:CGD.
DR GO; GO:0015244; F:fluconazole transmembrane transporter activity; IDA:CGD.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IDA:CGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:CGD.
DR GO; GO:0015903; P:fluconazole transport; IDA:CGD.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0046898; P:response to cycloheximide; IEA:UniProtKB-KW.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IDA:CGD.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR004734; Multidrug-R.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00880; 2_A_01_02; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Antibiotic resistance; Cell membrane; Cycloheximide resistance;
KW Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..564
FT /note="Multidrug resistance protein 1"
FT /id="PRO_0000431619"
FT TOPO_DOM 1..115
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 116..136
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..151
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 152..172
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 184..204
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..206
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 207..227
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 228..242
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 243..263
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..273
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 274..294
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..350
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 351..371
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 372..390
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 391..411
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 412..428
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 429..449
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 450..455
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 456..476
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 477..503
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 504..524
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 525..528
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 529..549
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..564
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 60..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 453
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 296
FT /note="E->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 300
FT /note="K->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 306
FT /note="K->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 308
FT /note="K->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 309
FT /note="R->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 317
FT /note="D->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 318
FT /note="R->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 322
FT /note="E->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 324
FT /note="E->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 326
FT /note="E->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
FT MUTAGEN 329
FT /note="K->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22587419"
SQ SEQUENCE 564 AA; 62904 MW; BC0DF5BEA61D5C4F CRC64;
MHYRFLRDSF VGRVTYHLSK HKYFAHPEEA KDYIVPEKYL ADYKPTLADD TSINFEKEEI
DNQGEPNSSQ SSSSNNTIVD NNNNNDNDVD GDKIVVTWDG DDDPENPQNW PTLQKAFFIF
QISFLTTSVY MGSAVYTPGI EELMHDFGIG RVVATLPLTL FVIGYGVGPL VFSPMSENAI
FGRTSIYIIT LFLFVILQIP TALVNNIAGL CILRFLGGFF ASPCLATGGA SVADVVKFWN
LPVGLAAWSL GAVCGPSFGP FFGSILTVKA SWRWTFWFMC IISGFSFVML CFTLPETFGK
TLLYRKAKRL RAITGNDRIT SEGEVENSKM TSHELIIDTL WRPLEITVME PVVLLINIYI
AMVYSILYLF FEVFPIYFVG VKHFTLVELG TTYMSIVIGI VIAAFIYIPV IRQKFTKPIL
RQEQVFPEVF IPIAIVGGIL LTSGLFIFGW SANRTTHWVG PLFGAATTAS GAFLIFQTLF
NFMGASFKPH YIASVFASND LFRSVIASVF PLFGAPLFDN LATPEYPVAW GSSVLGFITL
VMIAIPVLFY LNGPKLRARS KYAN
