W7FI62 · CRT_PLAF8
- ProteinChloroquine resistance transporter
- GeneCRT
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids424 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Nutrient transporter (PubMed:25733858, PubMed:31776516, PubMed:32764664).
Substrate transport is pH-dependent (PubMed:25733858, PubMed:31776516).
Can transport arginine, lysine, histidine and peptides (PubMed:25733858, PubMed:31776516, PubMed:32764664).
Involved in maintaining the osmotic homeostasis of the digestive vacuole (By similarity).
Required for the normal asexual intraerythrocytic proliferation of parasites (By similarity).
Substrate transport is pH-dependent (PubMed:25733858, PubMed:31776516).
Can transport arginine, lysine, histidine and peptides (PubMed:25733858, PubMed:31776516, PubMed:32764664).
Involved in maintaining the osmotic homeostasis of the digestive vacuole (By similarity).
Required for the normal asexual intraerythrocytic proliferation of parasites (By similarity).
Miscellaneous
Can function as a drug transporter (PubMed:25733858, PubMed:31776516, PubMed:32764664).
Can transport chloroquine and verapamil (PubMed:25733858).
Active transport of chloroquine and arginine requires a membrane potential and a directed pH gradient: 5.5->7.5, corresponding to the digestive vacuole pH gradient of the parasite (PubMed:25733858, PubMed:31776516).
Binding with chloroquine and piperaquine is inhibited by verapamil, amodiaquine and excess arginine (PubMed:31776516).
Can transport chloroquine and verapamil (PubMed:25733858).
Active transport of chloroquine and arginine requires a membrane potential and a directed pH gradient: 5.5->7.5, corresponding to the digestive vacuole pH gradient of the parasite (PubMed:25733858, PubMed:31776516).
Binding with chloroquine and piperaquine is inhibited by verapamil, amodiaquine and excess arginine (PubMed:31776516).
Catalytic activity
- L-arginine(in) = L-arginine(out)This reaction proceeds in the backward direction.
- L-lysine(in) = L-lysine(out)This reaction proceeds in the backward direction.
- L-histidine(out) = L-histidine(in)This reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.8 μM | chloroquine | |||||
1.3 μM | arginine | |||||
208 μM | VDPVNF peptide |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
90 nmol/min/mg | for chloroquine | ||||
190 nmol/min/mg | for arginine |
kcat is 0.2 sec-1 with chloroquine as substrate (PubMed:31776516).
kcat is 0.4 sec-1 with arginine as substrate (PubMed:31776516).
kcat is 0.4 sec-1 with arginine as substrate (PubMed:31776516).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 207 | pH sensor, predicted to act as a hydrogen acceptor for interactions that may accelerate progression through the transport cycle. Not involved in the proton transfer pathway | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | vacuolar membrane | |
Molecular Function | xenobiotic transmembrane transporter activity | |
Biological Process | amino acid transport |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameChloroquine resistance transporter
- Short namesPfCRT
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Sar > Alveolata > Apicomplexa > Aconoidasida > Haemosporida > Plasmodiidae > Plasmodium > Plasmodium (Laverania)
Accessions
- Primary accessionW7FI62
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Multi-pass membrane protein
Vacuole membrane ; Multi-pass membrane protein
Note: Localizes to the parasite digestive vacuole, the site of chloroquine action.
Features
Showing features for topological domain, intramembrane, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-49 | Cytoplasmic | ||||
Sequence: MKFASKKNNQKNSSKNDERYRELDNLVQEGNGSRLGGGSCLGKCAHVFK | ||||||
Intramembrane | 50-58 | |||||
Sequence: LIFKEIKDN | ||||||
Transmembrane | 59-83 | Helical | ||||
Sequence: IFIYILSIIYLSVSVMNTIFAKRTL | ||||||
Topological domain | 84-89 | Vacuolar | ||||
Sequence: NKIGNY | ||||||
Transmembrane | 90-111 | Helical | ||||
Sequence: SFVTSETHNFICMIMFFIVYSL | ||||||
Topological domain | 112-126 | Cytoplasmic | ||||
Sequence: FGNKKGNSKERHRSF | ||||||
Transmembrane | 127-147 | Helical | ||||
Sequence: NLQFFAISMLDACSVILAFIG | ||||||
Topological domain | 148-152 | Vacuolar | ||||
Sequence: LTRTT | ||||||
Transmembrane | 153-173 | Helical | ||||
Sequence: GNIQSFVLQLSIPINMFFCFL | ||||||
Topological domain | 174-180 | Cytoplasmic | ||||
Sequence: ILRYRYH | ||||||
Transmembrane | 181-202 | Helical | ||||
Sequence: LYNYLGAVIIVVTIALVEMKLS | ||||||
Topological domain | 203-210 | Vacuolar | ||||
Sequence: FETQEENS | ||||||
Transmembrane | 211-236 | Helical | ||||
Sequence: IIFNLVLISSLIPVCFSNMTREIVFK | ||||||
Topological domain | 237-241 | Cytoplasmic | ||||
Sequence: KYKID | ||||||
Transmembrane | 242-263 | Helical | ||||
Sequence: ILRLNAMVSFFQLFTSCLILPV | ||||||
Topological domain | 264-279 | Vacuolar | ||||
Sequence: YTLPFLKQLHLPYNEI | ||||||
Intramembrane | 280-292 | |||||
Sequence: WTNIKNGFACLFL | ||||||
Topological domain | 293-314 | Vacuolar | ||||
Sequence: GRNTVVENCGLGMAKLCDDCDG | ||||||
Transmembrane | 315-339 | Helical | ||||
Sequence: AWKTFALFSFFDICDNLITSYIIDK | ||||||
Topological domain | 340-343 | Cytoplasmic | ||||
Sequence: FSTM | ||||||
Transmembrane | 344-361 | Helical | ||||
Sequence: TYTIVSCIQGPALAIAYY | ||||||
Topological domain | 362-374 | Vacuolar | ||||
Sequence: FKFLAGDVVREPR | ||||||
Transmembrane | 375-397 | Helical | ||||
Sequence: LLDFVTLFGYLFGSIIYRVGNII | ||||||
Topological domain | 398-424 | Cytoplasmic | ||||
Sequence: LERKKMRNEENEDSEGELTNVDSIITQ |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 145 | No effect on chloroquine and piperaquine binding at pH 7.5. Decreases piperaquine binding affinity and increases piperaquine transport rates at pH 5.5. Decreases chloroquine transport rates with no effect on chloroquine binding affinity at pH 5.5. Results in the increased survival of parasites grown in the presence of piperaquine. | ||||
Sequence: F → I | ||||||
Mutagenesis | 289 | No effect on chloroquine binding affinity and transport. | ||||
Sequence: C → A | ||||||
Mutagenesis | 301 | No effect on chloroquine binding affinity and transport. | ||||
Sequence: C → A | ||||||
Mutagenesis | 350 | No effect on chloroquine and piperaquine binding affinity at pH 7.5. Decreases piperaquine binding affinity and increases piperaquine transport rates at pH 5.5. Decreases chloroquine binding affinity and transport rates at pH 5.5. Results in the increased survival of parasites grown in the presence of piperaquine. | ||||
Sequence: C → R |
PTM/Processing
Features
Showing features for chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000459375 | 1-424 | Chloroquine resistance transporter | |||
Sequence: MKFASKKNNQKNSSKNDERYRELDNLVQEGNGSRLGGGSCLGKCAHVFKLIFKEIKDNIFIYILSIIYLSVSVMNTIFAKRTLNKIGNYSFVTSETHNFICMIMFFIVYSLFGNKKGNSKERHRSFNLQFFAISMLDACSVILAFIGLTRTTGNIQSFVLQLSIPINMFFCFLILRYRYHLYNYLGAVIIVVTIALVEMKLSFETQEENSIIFNLVLISSLIPVCFSNMTREIVFKKYKIDILRLNAMVSFFQLFTSCLILPVYTLPFLKQLHLPYNEIWTNIKNGFACLFLGRNTVVENCGLGMAKLCDDCDGAWKTFALFSFFDICDNLITSYIIDKFSTMTYTIVSCIQGPALAIAYYFKFLAGDVVREPRLLDFVTLFGYLFGSIIYRVGNIILERKKMRNEENEDSEGELTNVDSIITQ | ||||||
Disulfide bond | 289↔312 | |||||
Sequence: CLFLGRNTVVENCGLGMAKLCDDC | ||||||
Disulfide bond | 301↔309 | |||||
Sequence: CGLGMAKLC |
Keywords
- PTM
Interaction
Subunit
Monomer.
Structure
Sequence
- Sequence statusComplete
- Length424
- Mass (Da)48,649
- Last updated2014-04-16 v1
- ChecksumDA5025A7792F1EA6
Polymorphism
The 7G8 strain is chloroquine-resistant in contrast to the 3D7 strain which is chloroquine-sensitive. Compared to the 3D7 strain, the CRT protein from the 7G8 strain shows increased chloroquine transport rates and reduced capacity for the transport of natural substrates.
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
KE123602 EMBL· GenBank· DDBJ | EUR74088.1 EMBL· GenBank· DDBJ | Genomic DNA |