Genome location: Pf3D7_14_v3:1,953,474..1,959,147(-)
Genome classification: Core
Product Description: multidrug resistance protein 2
SignalP Peptide: N/A
# Transmembrane Domains: 10
EC Numbers: 3.6.3.44 (Transferred entry: 7.6.2.2)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005773 | vacuole |
| Function | GO:0042626 | ATPase-coupled transmembrane transporter activity |
| Function | GO:0046872 | metal ion binding |
| Function | GO:0046873 | metal ion transmembrane transporter activity |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0055085 | transmembrane transport |
| Process | GO:0006855 | xenobiotic transmembrane transport |
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 | 0.20 | 0.90 |
| Trophozoite | expressed | 0.82 | 0.56 |
| Schizont | expressed | 0.27 | 0.83 |
| Gametocyte | possibly expressed | 0.30 | 0.82 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1447900
Resistome Missense Mutations: S451F, K840N
Resistome Compounds with Missense Mutations: 3-Hydroxypropanamidine 22, MMV665789, Suloctidil
Resistome # Samples with Disruptive Mutations: 11 (9 missense, 9 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.129 | MFS: -2.868 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1311700)
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PY17X_1315500)
Modification: Disrupted | RMgm-4774
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IKZ6
"Best" AlphaFill ligand hit: ADP (adenosine-5'-diphosphate, Local RMSD=0.02) with 6PAM (Global RMSD=2.63)
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 |
|---|---|---|---|---|
| Q9NP58 | ATP-binding cassette sub-family B member 6 | Homo sapiens | OrthoDB | MLS001002340MLS002701786 |
Ortholog Group (OrthoMCL): OG6_100761
Most Similar Human Ortholog: Q9NP58
TM-align score: 0.69 | RMSD: 3.39
Seq Identity: 0.32 | Length: 619 / 1024
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000115657 | ATP binding cassette subfamily B member 6 (Langereis blood group) |
Protein Length: 1024 | Molecular Weight (kDa): 119.012
UniProt ID(s): A0A060D1I9, A0A060D1V7, A0A1S6WN48, A0A1S6WN56, A0A2H4H7F1, A0A5J6C451, A0A5J6C5A4, A0A5J6C5G9, A0A5J6C6M0, A0A5J6C735, A0A5J6C8C9, I6Q0F4, I6Q0F6, I6Q0Z4, I6Q2K6, I6Q2K7, Q08667, Q25693, Q25919, Q7Z1F1, Q7Z1F2, Q8IKZ6
PDB ID(s): None
Isoelectric Point: 9.55
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 |
| InterPro | IPR039421 | Type I protein exporter |
| 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 | 7 | 45 | 20 | 59 |
| disruptive | 32 | 73 | 41 | 98 |
| missense | 29 | 66 | 40 | 82 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 11 | 92 | 39 | 62 |
| disruptive | 54 | 155 | 69 | 193 |
| missense | 40 | 128 | 56 | 134 |
PlasmoDB Total SNPs: 272
Non-coding: 193 | Synonymous: 59 | Nonsynonymous: 20 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 7914495 | Plasmodium falciparum: the pfmdr2 protein is not overexpressed inchloroquine-resistant isolates of the malaria parasite. | Rubio JP, Cowman AF | 10.1006/expr.1994.1073 |
| 8114829 | Characterization of the pfmdr2 gene for Plasmodium falciparum. | Zalis MG, Wilson CM, Zhang Y, Wirth DF | 10.1016/0166-6851(93)90180-6 |
| 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 |
| 16849328 | pfmdr2 confers heavy metal resistance to Plasmodium falciparum. | Rosenberg E, Litus I, ..., Pollack Y | 10.1074/jbc.M601686200 |
| 25267670 | Complex polymorphisms in the Plasmodium falciparum multidrug resistance protein 2gene and its contribution to antimalarial response. | Veiga MI, Osorio NS, ..., Gil JP | 10.1128/AAC.03337-14 |
| 29326268 | Mapping the malaria parasite druggable genome by using in vitro evolution andchemogenomics. | Cowell AN, Istvan ES, ..., Winzeler EA | 10.1126/science.aan4472 |