Product Description: multidrug resistance protein 1
SignalP Peptide: N/A
# Transmembrane Domains: 11
EC Numbers: 3.6.3.44 (Transferred entry: 7.6.2.2)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020020 | food vacuole |
| Component | GO:0005634 | nucleus |
| Function | GO:0042626 | ATPase-coupled transmembrane transporter activity |
| Function | GO:0005515 | protein binding |
| Process | GO:0042493 | response to drug |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0055085 | transmembrane transport |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | not expressed | N/A | N/A |
| Ring | expressed | 1.90 | 0.30 |
| Trophozoite | expressed | 1.15 | 0.44 |
| Schizont | expressed | 0.43 | 0.75 |
| Gametocyte | expressed | 0.64 | 0.65 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0523000
Resistome Missense Mutations: F78L, F78L, G88S, G88D, I205F, Y290F, G293V, G316R, F806L, A807T, M841I, L917F, F928L, N1042I, Y1046N, F1072L, T1073I, S1075I
Resistome Compounds with Missense Mutations: ACT-451840, BCH070, BI-2536, GNF-Pf-5310/MMV665785, GNF-Pf-5660, GNF-Pf-5668, Lopinavir, MMV006901, MMV026596, MMV982556
Resistome # Samples with Disruptive Mutations: 35 (35 missense, 34 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.128 | MFS: -2.943 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1237800)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q7K6A5
"Best" AlphaFill ligand hit: ANP (phosphoaminophosphonic acid-adenylate ester, Local RMSD=0.06) with 5D3M (Global RMSD=3.95)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.6.3.44 | xenobiotic-transporting ATPase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P08183 | ATP-dependent translocase ABCB1 | HOGENOM, OrthoDB | US11802108, Compound CSAUS9090657, DEBIO-025, 2N-(4-Bromo-phenyl)-2,4,5-trimethoxy-benzamide (10)2,4,5-Trimethoxy-N-(2-methoxy-phenyl)-benzamide (14)... | |
| P21447 | ATP-dependent translocase ABCB1 | HOGENOM, OrthoDB | VinblastineCHEMBL283438CHEMBL27536CHEMBL29631... | |
| P21439 | Phosphatidylcholine translocator ABCB4 | HOGENOM, OrthoDB | BMS-986020 | |
| O95342 | Bile salt export pump | HOGENOM, OMA, OrthoDB | US11802108, Compound CSAUS9090657, DEBIO-025, 2CHEMBL1651956CHEMBL3344501... | |
| O70127 | Bile salt export pump | Rattus norvegicus | OMA, OrthoDB | AtorvastatinRIFAMYCINCyclosporine APioglitazone... |
| P06795 | ATP-dependent translocase ABCB1 | Mus musculus | OrthoDB | CHEMBL346486CHEMBL152651CHEMBL152590CHEMBL433715... |
Ortholog Group (OrthoMCL): OG6_100059
Most Similar Human Ortholog: H7C486
TM-align score: 0.91 | RMSD: 1.07
Seq Identity: 0.42 | Length: 71 / 1419
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000004846 | ATP binding cassette subfamily B member 5 |
| ENSG00000005471 | ATP binding cassette subfamily B member 4 |
| ENSG00000073734 | ATP binding cassette subfamily B member 11 |
| ENSG00000085563 | ATP binding cassette subfamily B member 1 |
| ENSG00000135776 | ATP binding cassette subfamily B member 10 |
| ENSG00000150967 | ATP binding cassette subfamily B member 9 |
| ENSG00000197150 | ATP binding cassette subfamily B member 8 |
| ENSG00000276582 | ATP binding cassette subfamily B member 11 |
Protein Length: 1419 | Molecular Weight (kDa): 162.252
UniProt ID(s): D5L5S5, D5L5S6, F1C8M7, F1C8M8, F1C8M9, F1C8N0, F1C8N1, F1C8N2, F1C8N3, Q7K6A5, Q9NG76
PDB ID(s): 8JVH, 8JW4, 8JWF, 8JWG, 8JWI
Isoelectric Point: 9.2
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR003439 | ABC transporter-like |
| InterPro | IPR003593 | AAA+ ATPase domain |
| InterPro | IPR011527 | ABC transporter type 1, transmembrane domain |
| InterPro | IPR017871 | ABC transporter, conserved site |
| InterPro | IPR027417 | P-loop containing nucleoside triphosphate hydrolase |
| InterPro | IPR036640 | ABC transporter type 1, transmembrane domain superfamily |
| PFam | PF00005 | ABC transporter-like |
| PFam | PF00664 | ABC transporter type 1, transmembrane domain |
| Superfamily | SSF52540 | P-loop containing nucleoside triphosphate hydrolase |
| Superfamily | SSF90123 | ABC transporter type 1, transmembrane domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 15 | 67 | 47 | 94 |
| disruptive | 38 | 87 | 37 | 158 |
| missense | 27 | 72 | 32 | 128 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 25 | 148 | 60 | 89 |
| disruptive | 60 | 180 | 93 | 241 |
| missense | 38 | 140 | 69 | 182 |
PlasmoDB Total SNPs: 296
Non-coding: 206 | Synonymous: 45 | Nonsynonymous: 43 | Stop Codon: 2
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 1674943 | A P-glycoprotein homologue of Plasmodium falciparum is localized on the digestivevacuole. | Cowman AF, Karcz S, Galatis D, Culvenor JG | 10.1083/jcb.113.5.1033 |
| 10706290 | Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodiumfalciparum. | Reed MB, Saliba KJ, ..., Cowman AF | 10.1038/35002615 |
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 15673784 | Mutations in pfmdr1 modulate the sensitivity of Plasmodium falciparum to theintrinsic antiplasmodial activity of verapamil. | Hayward R, Saliba KJ, Kirk K | 10.1128/AAC.49.2.840-842.2005 |
| 15686571 | pfmdr1 mutations associated with chloroquine resistance incur a fitness cost inPlasmodium falciparum. | Hayward R, Saliba KJ, Kirk K | 10.1111/j.1365-2958.2004.04470.x |
| 15717281 | In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles byartemether-lumefantrine (Coartem). | Sisowath C, Stromberg J, ..., Gil JP | 10.1086/427997 |
| 15891133 | pfmdr1 genotyping and in vivo mefloquine resistance on the Thai-Myanmar border. | Nelson AL, Purfield A, ..., Meshnick SR | https://pubmed.ncbi.nlm.nih.gov/15891133/ |
| 16710674 | Analysis of P-glycoprotein expression in purified parasite plasma membrane andfood vacuole from Plasmodium falciparum. | Elandaloussi LM, Lindt M, Collins M, Smith PJ | 10.1007/s00436-006-0209-9 |
| 16794577 | Genetic linkage of pfmdr1 with food vacuolar solute import in Plasmodiumfalciparum. | Rohrbach P, Sanchez CP, ..., Lanzer M | 10.1038/sj.emboj.7601203 |
| 17096149 | No variation in the prevalence of point mutations in the Pfcrt and Pfmdr1 genesin isolates from Gabonese patients with uncomplicated or severe Plasmodiumfalciparum malaria. | Mayengue PI, Kalmbach Y, ..., Ntoumi F | 10.1007/s00436-006-0287-8 |
| 17124182 | Recurrent gene amplification and soft selective sweeps during evolution ofmultidrug resistance in malaria parasites. | Nair S, Nash D, ..., Anderson TJ | 10.1093/molbev/msl185 |
| 18165517 | Short report: polymorphisms in the pfcrt and pfmdr1 genes of Plasmodiumfalciparum and in vitro susceptibility to amodiaquine and desethylamodiaquine. | Echeverry DF, Holmgren G, ..., Osorio L | https://pubmed.ncbi.nlm.nih.gov/18165517/ |
| 18194156 | Dissecting the components of quinine accumulation in Plasmodium falciparum. | Sanchez CP, Stein WD, Lanzer M | 10.1111/j.1365-2958.2008.06108.x |
| 18385361 | Association of pfcrt but not pfmdr1 alleles with chloroquine resistance inIranian isolates of Plasmodium falciparum. | Zakeri S, Afsharpad M, ..., Djadid ND | https://pubmed.ncbi.nlm.nih.gov/18385361/ |
| 18513774 | pfmdr1 mutations in imported African Plasmodium falciparum isolates. | Dippmann AK, Bienzle U, Harms G, Mockenhaupt FP | 10.1016/j.trstmh.2008.04.001 |
| 18713316 | Polymorphisms within PfMDR1 alter the substrate specificity for anti-malarialdrugs in Plasmodium falciparum. | Sanchez CP, Rotmann A, Stein WD, Lanzer M | 10.1111/j.1365-2958.2008.06413.x |
| 18950599 | Association between chloroquine resistance phenotypes and point mutations inpfcrt and pfmdr1 in Plasmodium falciparum isolates from Thailand. | Rungsihirunrat K, Chaijareonkul W, ..., Thaithong S | 10.1016/j.actatropica.2008.09.011 |
| 18990178 | A polymorphic drug pump in the malaria parasite. | Saliba KJ, Lehane AM, Kirk K | 10.1111/j.1365-2958.2008.06451.x |
| 19567229 | Association of molecular markers in Plasmodium falciparum crt and mdr1 with invitro chloroquine resistance: a Philippine study. | Hatabu T, Iwagami M, ..., Kano S | 10.1016/j.parint.2009.01.010 |
| 19770282 | In vitro activities of piperaquine, lumefantrine, and dihydroartemisinin inKenyan Plasmodium falciparum isolates and polymorphisms in pfcrt and pfmdr1. | Mwai L, Kiara SM, ..., Nzila A | 10.1128/AAC.00638-09 |
| 19807279 | Plasmodium falciparum multidrug resistance protein 1 and artemisinin-basedcombination therapy in Africa. | Dahlstrom S, Ferreira PE, ..., Gil JP | 10.1086/606009 |
| 20145087 | pfmdr1 amplification and fixation of pfcrt chloroquine resistance alleles inPlasmodium falciparum in Venezuela. | Griffing S, Syphard L, ..., Udhayakumar V | 10.1128/AAC.01243-09 |
| 20199676 | Markers of anti-malarial drug resistance in Plasmodium falciparum isolates fromSwaziland: identification of pfmdr1-86F in natural parasite isolates. | Dlamini SV, Beshir K, Sutherland CJ | 10.1186/1475-2875-9-68 |
| 20350946 | Role of pfmdr1 amplification and expression in induction of resistance toartemisinin derivatives in Plasmodium falciparum. | Chavchich M, Gerena L, ..., Kyle DE | 10.1128/AAC.00947-09 |
| 20367478 | Multiple genetic backgrounds of the amplified Plasmodium falciparum multidrugresistance (pfmdr1) gene and selective sweep of 184F mutation in Cambodia. | Vinayak S, Alam MT, ..., Udhayakumar V | 10.1086/651949 |
| 20421395 | Exploring the contribution of candidate genes to artemisinin resistance inPlasmodium falciparum. | Imwong M, Dondorp AM, ..., White NJ | 10.1128/AAC.00032-10 |
| 20421397 | Deamplification of pfmdr1-containing amplicon on chromosome 5 in Plasmodiumfalciparum is associated with reduced resistance to artelinic acid in vitro. | Chen N, Chavchich M, ..., Cheng Q | 10.1128/AAC.01421-09 |
| 20427933 | Analysis of gene mutations involved in chloroquine resistance in Plasmodiumfalciparum parasites isolated from patients in the southwest of Saudi Arabia. | Bin Dajem SM, Al-Qahtani A | 10.4103/0256-4947.62826 |
| 20546803 | Purified Plasmodium falciparum multi-drug resistance protein (PfMDR 1) binds ahigh affinity chloroquine analogue. | Pleeter P, Lekostaj JK, Roepe PD | https://pubmed.ncbi.nlm.nih.gov/20546803/ |
| 20547801 | Absence of association between piperaquine in vitro responses and polymorphismsin the pfcrt, pfmdr1, pfmrp, and pfnhe genes in Plasmodium falciparum. | Briolant S, Henry M, ..., Pradines B | 10.1128/AAC.00183-10 |
| 20967251 | Chloroquine clinical failures in P. falciparum malaria are associated with mutantPfmdr-1, not Pfcrt in Madagascar. | Andriantsoanirina V, Ratsimbasoa A, ..., Menard D | 10.1371/journal.pone.0013281 |
| 21036827 | Association between the pfmdr1 gene and in vitro artemether and lumefantrinesensitivity in Thai isolates of Plasmodium falciparum. | Mungthin M, Khositnithikul R, ..., Na-Bangchang K | 10.4269/ajtmh.2010.10-0339 |
| 21136929 | Food vacuole proteome of the malarial parasite Plasmodium falciparum. | Lamarque M, Tastet C, ..., Dubremetz JF | 10.1002/prca.200700112 |
| 21340360 | Sequence analysis of coding DNA fragments of pfcrt and pfmdr-1 genes inPlasmodium falciparum isolates from Odisha, India. | 10.1590/S0074-02762011000200023 | |
| 21633513 | Novel polymorphisms in Plasmodium falciparum ABC transporter genes are associatedwith major ACT antimalarial drug resistance. | Veiga MI, Ferreira PE, ..., Gil JP | 10.1371/journal.pone.0020212 |
| 21777558 | Molecular analysis of pfatp6 and pfmdr1 polymorphisms and their association within vitro sensitivity in Plasmodium falciparum isolates from the Thai-Myanmarborder. | Phompradit P, Wisedpanichkij R, ..., Na-Bangchang K | 10.1016/j.actatropica.2011.07.003 |
| 21881128 | Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malariawith artemether-lumefantrine in Uganda. | Baliraine FN, Rosenthal PJ | 10.1093/infdis/jir486 |
| 22302850 | Different patterns of pfcrt and pfmdr1 polymorphisms in P. falciparum isolatesfrom Nigeria and Brazil: the potential role of antimalarial drug selectionpressure. | Gbotosho GO, Folarin OA, ..., Happi CT | 10.4269/ajtmh.2012.11-0368 |
| 22540925 | Artemether resistance in vitro is linked to mutations in PfATP6 that alsointeract with mutations in PfMDR1 in travellers returning with Plasmodiumfalciparum infections. | Pillai DR, Lau R, ..., Krishna S | 10.1186/1475-2875-11-131 |
| 23509121 | Association between prevalence of chloroquine resistance and unusual mutation inpfmdr-I and pfcrt genes in India. | Das S, Chakraborty SP, Hati AK, Roy S | 10.4269/ajtmh.11-0795 |
| 23697703 | Plasmodium falciparum with multidrug resistance 1 gene duplications, Senegal. | Pascual A, Fall B, ..., Pradines B | 10.3201/eid1905.121603 |
| 23836177 | The polymorphic linker domain of pfmdr1 is associated with resistance-conferringmutations in Plasmodium falciparum populations from East and West Africa. | Okombo J, Zongo I, ..., Sutherland CJ | 10.1128/AAC.00455-13 |
| 24752268 | Polymorphisms in Pfmdr1, Pfcrt, and Pfnhe1 genes are associated with reduced invitro activities of quinine in Plasmodium falciparum isolates from western Kenya. | Cheruiyot J, Ingasia LA, ..., Kamau E | 10.1128/AAC.02472-14 |
| 24889967 | Assessment of Plasmodium falciparum PfMDR1 transport rates using Fluo-4. | Friedrich O, Reiling SJ, Wunderlich J, Rohrbach P | 10.1111/jcmm.12313 |
| 25070111 | Double mutation in the pfmdr1 gene is associated with emergence ofchloroquine-resistant Plasmodium falciparum malaria in Eastern India. | Das S, Mahapatra SK, ..., Roy S | 10.1128/AAC.02762-14 |
| 25105963 | Correlation of molecular markers, Pfmdr1-N86Y and Pfcrt-K76T, with in vitrochloroquine resistant Plasmodium falciparum, isolated in the malaria endemicstates of Assam and Arunachal Pradesh, Northeast India. | Shrivastava SK, Gupta RK, Mahanta J, Dubey ML | 10.1371/journal.pone.0103848 |
| 25184337 | Molecular evidence of increased resistance to anti-folate drugs in Plasmodiumfalciparum in North-East India: a signal for potential failure of artemisininplus sulphadoxine-pyrimethamine combination therapy. | Mohapatra PK, Sarma DK, ..., Mahanta J | 10.1371/journal.pone.0105562 |
| 25199781 | Role of Pfmdr1 in in vitro Plasmodium falciparum susceptibility to chloroquine,quinine, monodesethylamodiaquine, mefloquine, lumefantrine, anddihydroartemisinin. | Wurtz N, Fall B, ..., Pradines B | 10.1128/AAC.03494-14 |
| 25318907 | Genetic mutations in pfcrt and pfmdr1 at the time of artemisinin combinationtherapy introduction in South Pacific islands of Vanuatu and Solomon Islands. | Gresty KJ, Gray KA, ..., Waters NC | 10.1186/1475-2875-13-406 |
| 26152336 | Identification of large variation in pfcrt, pfmdr-1 and pfubp-1 markers inPlasmodium falciparum isolates from Ethiopia and Tanzania. | Golassa L, Kamugisha E, ..., Swedberg G | 10.1186/s12936-015-0783-3 |
| 27031231 | Artesunate-Amodiaquine and Artemether-Lumefantrine Therapies and Selection ofPfcrt and Pfmdr1 Alleles in Nanoro, Burkina Faso. | Sondo P, Derra K, ..., Tinto H | 10.1371/journal.pone.0151565 |
| 27189525 | Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibilityto artemisinin-based combination therapies. | Veiga MI, Dhingra SK, ..., Fidock DA | 10.1038/ncomms11553 |
| 27405118 | PFMDR1 POLYMORPHISMS INFLUENCE ON IN VITRO SENSITIVITY OF THAI PLASMODIUMFALCIPARUM ISOLATES TO PRIMAQUINE, SITAMAQUINE AND TAFENOQUINE. | Kaewpruk N, Tan-ariya P, ..., Mungthin M | https://pubmed.ncbi.nlm.nih.gov/27405118/ |
| 27821443 | Altered Plasmodium falciparum Sensitivity to the Antiretroviral Protease Inhibitor Lopinavir Associated with Polymorphisms in pfmdr1 | Sonoiki E, Nsanzabana C, ..., Rosenthal PJ | 10.1128/AAC.01949-16 |
| 28044042 | Influence of the pfmdr1 Gene on In Vitro Sensitivities of Piperaquine in ThaiIsolates of Plasmodium falciparum. | Mungthin M, Watanatanasup E, ..., Ward SA | 10.4269/ajtmh.16-0668 |
| 28355493 | pfmdr1 (Plasmodium falciparum multidrug drug resistance gene 1): a pivotal factorin malaria resistance to artemisinin combination therapies. | Gil JP, Krishna S | 10.1080/14787210.2017.1313703 |
| 28376874 | Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes,pfcrt and pfmdr1, in North Sulawesi, Indonesia. | Reteng P, Vrisca V, ..., Tuda J | 10.1186/s13104-017-2468-1 |
| 29842979 | Spatio-temporal distribution of PfMDR1 polymorphism among uncomplicatedPlasmodium falciparum malaria cases along international border of north eastIndia. | Goomber S, Mishra N, ..., Valecha N | 10.1016/j.meegid.2018.05.025 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 33109270 | Molecular detection of drug resistant polymorphisms in Plasmodium falciparumisolates from Southwest, Nigeria. | Tola M, Ajibola O, ..., Amambua-Ngwa A | 10.1186/s13104-020-05334-5 |
| 33262257 | Expansion of a Specific Plasmodium falciparum Pf MDR1 Haplotype in Southeast Asiawith Increased Substrate Transport | Calcada C, Silva M, ..., Veiga MI | 10.1128/mBio.02093-20 |
| 33843972 | Plasmodium falciparum Atg18 localizes to the food vacuole via interaction withthe multi-drug resistance protein 1 and phosphatidylinositol 3-phosphate. | Sudhakar R, Das D, ..., Sijwali PS | 10.1042/BCJ20210001 |
| 33933099 | Molecular surveillance of anti-malarial resistance pfcrt, pfmdr1, and pfk13polymorphisms in African Plasmodium falciparum imported parasites to Wuhan,China. | Cheng W, Song X, ..., Li J | 10.1186/s12936-021-03737-8 |
| 34205228 | Selection of pfcrt K76 and pfmdr1 N86 Coding Alleles after Uncomplicated Malaria Treatment by Artemether-Lumefantrine in Mali | Maiga H, Grivoyannis A, ..., Djimde AA | 10.3390/ijms22116057 |
| 34666779 | Increase in the proportion of Plasmodium falciparum with kelch13 C580Y mutationand decline in pfcrt and pfmdr1 mutant alleles in Papua New Guinea. | Yoshida N, Yamauchi M, ..., Mita T | 10.1186/s12936-021-03933-6 |
| 38413566 | Deaggregation of mutant Plasmodium yoelii de-ubiquitinase UBP1 alters MDR1localization to confer multidrug resistance | Xu R, Lin L, ..., Li J | 10.1038/s41467-024-46006-3 |