Genome location: Pf3D7_12_v3:1,192,185..1,202,986(-)
Genome classification: Core
Product Description: multidrug resistance-associated protein 2
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:0005887 | integral component of plasma membrane |
| Component | GO:0016020 | membrane |
| Component | GO:0005886 | plasma membrane |
| Function | GO:0042626 | ATPase-coupled transmembrane transporter activity |
| Process | GO:0042493 | response to drug |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0020014 | schizogony |
| 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 | expressed | N/A | N/A |
| Ring | expressed | 2.19 | 0.23 |
| Trophozoite | expressed | 0.98 | 0.52 |
| Schizont | expressed | 0.68 | 0.62 |
| Gametocyte | possibly expressed | 0.75 | 0.62 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1229100
Resistome Missense Mutations: A403P
Resistome Compounds with Missense Mutations: Atovaquone
Resistome # Samples with Disruptive Mutations: 10 (4 missense, 4 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 1 | MFS: -1.328 | #Insertions: 16
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1443800)
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PY17X_1446300)
Modification: Disrupted | RMgm-4773
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I5C7
"Best" AlphaFill ligand hit: ATP (adenosine-5'-triphosphate, Local RMSD=0.02) with 6GKD (Global RMSD=2.24)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.6.3.44 | xenobiotic-transporting ATPase | BRENDA SOAP query unsuccessful |
No evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_100026
Most Similar Human Ortholog: D6R9B3
TM-align score: 0.85 | RMSD: 2.81
Seq Identity: 0.21 | Length: 276 / 2108
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000006071 | ATP binding cassette subfamily C member 8 |
| ENSG00000023839 | ATP binding cassette subfamily C member 2 |
| ENSG00000069431 | ATP binding cassette subfamily C member 9 |
| ENSG00000091262 | ATP binding cassette subfamily C member 6 |
| ENSG00000103222 | ATP binding cassette subfamily C member 1 |
| ENSG00000108846 | ATP binding cassette subfamily C member 3 |
| ENSG00000114770 | ATP binding cassette subfamily C member 5 |
| ENSG00000121270 | ATP binding cassette subfamily C member 11 |
| ENSG00000124574 | ATP binding cassette subfamily C member 10 |
| ENSG00000125257 | ATP binding cassette subfamily C member 4 |
| ENSG00000140798 | ATP binding cassette subfamily C member 12 |
| ENSG00000275331 | ATP binding cassette subfamily C member 6 |
| ENSG00000278183 | ATP binding cassette subfamily C member 1 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 30 | 90 | 61 | 123 |
| disruptive | 107 | 191 | 100 | 256 |
| missense | 56 | 125 | 75 | 199 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 44 | 179 | 76 | 141 |
| disruptive | 166 | 373 | 206 | 418 |
| missense | 81 | 256 | 150 | 308 |
PlasmoDB Total SNPs: 749
Non-coding: 497 | Synonymous: 148 | Nonsynonymous: 104 | Stop Codon: 0
Protein Length: 2108 | Molecular Weight (kDa): 248.302
UniProt ID(s): A0A097GTS2, A0A097GTT0, A0A097GTT4, A0A097GTT5, A0A097GTT7, A0A097GTT9, A0A097GTU0, A0A097GTV2, A0A097GTV4, A0A097GTV6, A0A097GTV7, A0A097GTV9, A0A097GTW0, A0A097GTW4, A0A097GTX1, A0A097GTX6, A7XLD6, D5L5S7, D5L5S8, Q8I5C7, S5Y6H5, S5Y6I4, S5Y6J8, S5YD77, S5YJJ8, S5YJK5, S5YJQ1, S5YJR8, S5YX13
PDB ID(s): None
Isoelectric Point: 8.89
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 | IPR030244 | Oligomycin resistance ATP-dependent permease Yor1 |
| 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 |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 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 |
| 19715599 | Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2,and PfMDR5 at the Plasmodium falciparum plasma membrane. | Kavishe RA, van den Heuvel JM, ..., Koenderink JB | 10.1186/1475-2875-8-205 |
| 24372851 | Structural polymorphism in the promoter of pfmrp2 confers Plasmodium falciparumtolerance to quinoline drugs. | Mok S, Liong KY, ..., Bozdech Z | 10.1111/mmi.12505 |
| 35521513 | A Plasmodium falciparum ATP-binding cassette transporter is essential for liverstage entry into schizogony. | Goswami D, Kumar S, ..., Kappe SHI | 10.1016/j.isci.2022.104224 |