Product Description: chloroquine resistance transporter
SignalP Peptide: N/A
# Transmembrane Domains: 10
EC Numbers: None
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005783 | endoplasmic reticulum |
| Component | GO:0020020 | food vacuole |
| Component | GO:0016020 | membrane |
| Function | GO:0015091 | ferric iron transmembrane transporter activity |
| Function | GO:0015093 | ferrous iron transmembrane transporter activity |
| Function | GO:0042910 | xenobiotic transmembrane transporter activity |
| Process | GO:0034635 | glutathione transport |
| Process | GO:0015833 | peptide transport |
| Process | GO:1902349 | response to chloroquine |
| Process | GO:0042493 | response to drug |
| Process | GO:0009410 | response to xenobiotic stimulus |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | possibly expressed | N/A | N/A |
| Ring | expressed | 0.42 | 0.79 |
| Trophozoite | expressed | 0.20 | 0.87 |
| Schizont | expressed | 0.05 | 0.97 |
| Gametocyte | expressed | 0.08 | 0.95 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0709000
Resistome Missense Mutations: S65R, K76Q, A79S, S90N, S94F, A138V, Q352R, V370I
Resistome Compounds with Missense Mutations: MMV006767, MMV011895, MMV024114, MMV084864, MMV665928
Resistome # Samples with Disruptive Mutations: 18 (15 missense, 12 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.127 | MFS: -3.025 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1219500)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1219500)
Modification: Mutated | RMgm-5041
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IBZ9
"Best" AlphaFill ligand hit: No AlphaFill hits
No associated EC numbersOrthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q9N623 | Chloroquine resistance transporter | Plasmodium falciparum | OrthoMCL BLAST | US10584098, Code ELQ-300US10584098, Code ELQ-336US10584098, Code ELQ-337US10584098, Code ELQ-354... |
Protein Length: 424 | Molecular Weight (kDa): 48.675
UniProt ID(s): A0A0A0VAS7, A0A5A4VYU6, A0A5A4W0H1, A0A5A4W2C7, A0A5A4W3T5, A0A5J6D0M4, A0A5J6D0T6, D5L5S1, D5L5S2, E1APF0, Q8IBZ9, Q9N623
PDB ID(s): None
Isoelectric Point: 8.66
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR013936 | Chloroquine-resistance transporter-like |
| InterPro | IPR017258 | Chloroquine resistance transporter |
| PFam | PF08627 | Chloroquine-resistance transporter-like |
| Superfamily | N/A | N/A |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 1 | 19 | 15 | 26 |
| disruptive | 36 | 13 | 14 | 43 |
| missense | 33 | 13 | 14 | 35 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 3 | 45 | 12 | 30 |
| disruptive | 39 | 54 | 41 | 102 |
| missense | 35 | 43 | 36 | 70 |
PlasmoDB Total SNPs: 279
Non-coding: 245 | Synonymous: 12 | Nonsynonymous: 22 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 11090624 | Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT andevidence for their role in chloroquine resistance. | Fidock DA, Nomura T, ..., Wellems TE | 10.1016/s1097-2765(05)00077-8 |
| 11152613 | Predicting transmembrane protein topology with a hidden Markov model: applicationto complete genomes. | Krogh A, Larsson B, von Heijne G, Sonnhammer EL | 10.1006/jmbi.2000.4315 |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 15240840 | The malaria parasite's chloroquine resistance transporter is a member of thedrug/metabolite transporter superfamily. | Martin RE, Kirk K | 10.1093/molbev/msh205 |
| 15772316 | Association of Plasmodium falciparum isolates encoding the p. Falciparumchloroquine resistance transporter gene K76T polymorphism with anemia andsplenomegaly, but not with multiple infections. | Abdel-Aziz IZ, Oster N, ..., Lanzer M | https://pubmed.ncbi.nlm.nih.gov/15772316/ |
| 16164748 | Concurrence of Plasmodium falciparum dhfr and crt mutations in northern Ghana. | Mockenhaupt FP, Bousema JT, ..., Bienzle U | 10.1186/1475-2875-4-42 |
| 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 |
| 18577328 | Association of msp-1, msp-2 and pfcrt genes with the severe complications ofPlasmodium falciparum malaria in children. | Sahu PK, Pati SS, Satpathy R | 10.1179/136485908X300814 |
| 18852275 | Chloroquine resistance-conferring mutations in pfcrt give rise to achloroquine-associated H+ leak from the malaria parasite's digestive vacuole. | Lehane AM, Kirk K | 10.1128/AAC.00666-08 |
| 19210165 | In vivo selection of Plasmodium falciparum parasites carrying thechloroquine-susceptible pfcrt K76 allele after treatment withartemether-lumefantrine in Africa. | Sisowath C, Petersen I, ..., Gil JP | 10.1086/596738 |
| 19462557 | Plasmodium falciparum: high frequency of pfcrt point mutations and emergence ofnew mutant haplotypes in Colombia. | Restrepo E, Carmona-Fonseca J, Maestre A | https://pubmed.ncbi.nlm.nih.gov/19462557/ |
| 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 |
| 19725576 | Chloroquine transport in Plasmodium falciparum. 2. Analysis of PfCRT-mediateddrug transport using proteoliposomes and a fluorescent chloroquine probe. | Paguio MF, Cabrera M, Roepe PD | 10.1021/bi901035j |
| 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 |
| 19779197 | Chloroquine transport via the malaria parasite's chloroquine resistancetransporter. | Martin RE, Marchetti RV, ..., Kirk K | 10.1126/science.1175667 |
| 20015114 | Trafficking of the phosphoprotein PfCRT to the digestive vacuolar membrane inPlasmodium falciparum. | Kuhn Y, Sanchez CP, ..., Lanzer M | 10.1111/j.1600-0854.2009.01018.x |
| 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 |
| 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 |
| 20485514 | Identification of a mutant PfCRT-mediated chloroquine tolerance phenotype inPlasmodium falciparum. | Valderramos SG, Valderramos JC, ..., Fidock DA | 10.1371/journal.ppat.1000887 |
| 20547800 | Amodiaquine resistance in Plasmodium falciparum malaria in Afghanistan isassociated with the pfcrt SVMNT allele at codons 72 to 76. | Beshir K, Sutherland CJ, ..., Hallett RL | 10.1128/AAC.00358-10 |
| 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 |
| 21124966 | On the mechanism of chloroquine resistance in Plasmodium falciparum. | Chinappi M, Via A, Marcatili P, Tramontano A | 10.1371/journal.pone.0014064 |
| 21320353 | Sequence and gene expression of chloroquine resistance transporter (pfcrt) in theassociation of in vitro drugs resistance of Plasmodium falciparum. | Chaijaroenkul W, Ward SA, ..., Na-Bangchang K | 10.1186/1475-2875-10-42 |
| 21323158 | Factors associated with regional bias of pfcrt (plasmodium falciparum chloroquineresistance transporter) haplotypes in Nepal. | Banjara MR, Imwong M, ..., Chavalitshewinkoon-Petmitr P | https://pubmed.ncbi.nlm.nih.gov/21323158/ |
| 21340360 | Sequence analysis of coding DNA fragments of pfcrt and pfmdr-1 genes inPlasmodium falciparum isolates from Odisha, India. | 10.1590/S0074-02762011000200023 | |
| 21744797 | Analysis of chloroquine resistance transporter (CRT) isoforms and orthologues inS. cerevisiae yeast. | Baro NK, Pooput C, Roepe PD | 10.1021/bi200922g |
| 22272308 | Diversity of Plasmodium falciparum chloroquine resistance transporter (pfcrt)exon 2 haplotypes in the Pacific from 1959 to 1979. | Chan CW, Spathis R, ..., Lum JK | 10.1371/journal.pone.0030213 |
| 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 |
| 22463364 | Genetic polymorphism of merozoite surface protein 2 and prevalence of K76T pfcrtmutation in Plasmodium falciparum field isolates from Congolese children withasymptomatic infections. | Koukouikila-Koussounda F, Malonga V, ..., Ntoumi F | 10.1186/1475-2875-11-105 |
| 23256874 | Glutathione transport: a new role for PfCRT in chloroquine resistance. | Patzewitz EM, Salcedo-Sora JE, ..., Muller S | 10.1089/ars.2012.4625 |
| 23688277 | Function of resistance conferring Plasmodium falciparum chloroquine resistancetransporter isoforms. | Baro NK, Callaghan PS, Roepe PD | 10.1021/bi400557x |
| 24092656 | Occurrence of multiple chloroquine-resistant Pfcrt haplotypes and emergence ofthe S(agt)VMNT type in Cameroonian Plasmodium falciparum. | Ngassa Mbenda HG, Das A | 10.1093/jac/dkt388 |
| 24402147 | Genetics of chloroquine-resistant malaria: a haplotypic view. | Awasthi G, Das A | 10.1590/0074-0276130274 |
| 24728833 | Diverse mutational pathways converge on saturable chloroquine transport via themalaria parasite's chloroquine resistance transporter. | Summers RL, Dave A, ..., Martin RE | 10.1073/pnas.1322965111 |
| 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 |
| 24916876 | Pfcrt mutant haplotypes may not correspond with chloroquine resistance. | Goswami D, Dhiman S, ..., Veer V | 10.3855/jidc.3398 |
| 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 |
| 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 |
| 25378409 | Multiple drugs compete for transport via the Plasmodium falciparum chloroquineresistance transporter at distinct but interdependent sites. | Bellanca S, Summers RL, ..., Lanzer M | 10.1074/jbc.M114.614206 |
| 25574497 | Full-length sequence analysis of chloroquine resistance transporter gene inPlasmodium falciparum isolates from Sabah, Malaysia. | Tan LL, Lau TY, Timothy W, Prabakaran D | 10.1155/2014/935846 |
| 25733858 | Plasmodium falciparum chloroquine resistance transporter is a H+-coupledpolyspecific nutrient and drug exporter. | Juge N, Moriyama S, ..., Moriyama Y | 10.1073/pnas.1417102112 |
| 25765049 | Predicting functional and regulatory divergence of a drug resistance transportergene in the human malaria parasite. | Siwo GH, Tan A, ..., Ferdig MT | 10.1186/s12864-015-1261-6 |
| 25783783 | Molecular interaction of selected phytochemicals under the charged environment ofPlasmodium falciparum chloroquine resistance transporter (PfCRT) model. | Patel SK, Khedkar VM, ..., Skelton AA | 10.1080/07391102.2015.1028449 |
| 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 |
| 26208441 | Functional Comparison of 45 Naturally Occurring Isoforms of the Plasmodiumfalciparum Chloroquine Resistance Transporter (PfCRT). | Callaghan PS, Hassett MR, Roepe PD | 10.1021/acs.biochem.5b00412 |
| 26261345 | Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquineresistance by acquisition of a mutation in pfcrt. | Pelleau S, Moss EL, ..., Musset L | 10.1073/pnas.1507142112 |
| 26296743 | Chloroquine sensitivity: diminished prevalence of chloroquine-resistant genemarker pfcrt-76 13 years after cessation of chloroquine use in Msambweni, Kenya. | Kiarie WC, Wangai L, ..., Hungu C | 10.1186/s12936-015-0850-9 |
| 26891514 | High prevalence of Plasmodium falciparum pfcrt K76T mutation in children withsickle cell disease at a tertiary hospital in north-western Tanzania. | Mongella S, Enweji N, ..., Swedberg G | 10.4314/thrb.v16i4.1 |
| 26908582 | Combinatorial Genetic Modeling of pfcrt-Mediated Drug Resistance Evolution inPlasmodium falciparum. | Gabryszewski SJ, Modchang C, ..., Fidock DA | 10.1093/molbev/msw037 |
| 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 |
| 27832198 | Evolution of Fitness Cost-Neutral Mutant PfCRT Conferring P. falciparum4-Aminoquinoline Drug Resistance Is Accompanied by Altered Parasite Metabolismand Digestive Vacuole Physiology. | Gabryszewski SJ, Dhingra SK, ..., Fidock DA | 10.1371/journal.ppat.1005976 |
| 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 |
| 28487425 | A Variant Pf CRT Isoform Can Contribute to Plasmodium falciparum Resistance to the First-Line Partner Drug Piperaquine | Dhingra SK, Redhi D, ..., Fidock DA | 10.1128/mBio.00303-17 |
| 28768767 | Iron is a substrate of the Plasmodium falciparum chloroquine resistancetransporter PfCRT in Xenopus oocytes. | Bakouh N, Bellanca S, ..., Lanzer M | 10.1074/jbc.M117.805200 |
| 28931241 | Association of a Novel Mutation in the Plasmodium falciparum ChloroquineResistance Transporter With Decreased Piperaquine Sensitivity. | Agrawal S, Moser KA, ..., Takala-Harrison S | 10.1093/infdis/jix334 |
| 30141388 | Multiple Novel Mutations in Plasmodium falciparum Chloroquine ResistanceTransporter Gene during Implementation of Artemisinin Combination Therapy inThailand. | Buppan P, Seethamchai S, ..., Jongwutiwes S | 10.4269/ajtmh.18-0401 |
| 30206341 | Evidence for Regulation of Hemoglobin Metabolism and Intracellular Ionic Flux bythe Plasmodium falciparum Chloroquine Resistance Transporter. | Lee AH, Dhingra SK, ..., Fidock DA | 10.1038/s41598-018-31715-9 |
| 31776516 | Structure and drug resistance of the Plasmodium falciparum transporter PfCRT. | Kim J, Tan YZ, ..., Mancia F | 10.1038/s41586-019-1795-x |
| 32503540 | Prevalence of mutations in the Plasmodium falciparum chloroquine resistancetransporter, PfCRT, and association with ex vivo susceptibility to commonanti-malarial drugs against African Plasmodium falciparum isolates. | Foguim FT, Bogreau H, ..., Pradines B | 10.1186/s12936-020-03281-x |
| 32764664 | The natural function of the malaria parasite's chloroquine resistancetransporter. | Shafik SH, Cobbold SA, ..., Martin RE | 10.1038/s41467-020-17781-6 |
| 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 |
| 33528566 | Distribution and Temporal Dynamics of Plasmodium falciparum ChloroquineResistance Transporter Mutations Associated With Piperaquine Resistance inNorthern Cambodia. | Shrestha B, Shah Z, ..., Takala-Harrison S | 10.1093/infdis/jiab055 |
| 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 |
| 37285379 | PfCRT mutations conferring piperaquine resistance in falciparum malaria shape thekinetics of quinoline drug binding and transport. | Gomez GM, D'Arrigo G, ..., Lanzer M | 10.1371/journal.ppat.1011436 |