Q9N623 · CRT_PLAFA
- ProteinChloroquine resistance transporter
- GeneCRT
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids424 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Nutrient transporter (PubMed:25733858, PubMed:32764664, PubMed:35867395).
Substrate transport is pH-dependent (PubMed:25733858, PubMed:37454114).
Can transport arginine, lysine, histidine, peptides, histamine and spermidine (PubMed:25733858, PubMed:32764664, PubMed:35867395).
May modulate activity of endogenous transporters (PubMed:15258157).
Involved in maintaining the osmotic homeostasis of the digestive vacuole (PubMed:26351679, PubMed:26420308, PubMed:35867395).
Required for the asexual intraerythrocytic proliferation of parasites (PubMed:35867395).
Substrate transport is pH-dependent (PubMed:25733858, PubMed:37454114).
Can transport arginine, lysine, histidine, peptides, histamine and spermidine (PubMed:25733858, PubMed:32764664, PubMed:35867395).
May modulate activity of endogenous transporters (PubMed:15258157).
Involved in maintaining the osmotic homeostasis of the digestive vacuole (PubMed:26351679, PubMed:26420308, PubMed:35867395).
Required for the asexual intraerythrocytic proliferation of parasites (PubMed:35867395).
Miscellaneous
Can function as a drug transporter (PubMed:25733858, PubMed:32764664, PubMed:37454114).
Can transport chloroquine, quinidine and verapamil (PubMed:25733858, PubMed:32764664, PubMed:37454114).
Drug-resistance-conferring mutations reduce capacities for the transport of the natural substrates (PubMed:25733858, PubMed:32764664).
Active transport requires a directed pH gradient and a membrane potential (PubMed:25733858).
Can transport chloroquine, quinidine and verapamil (PubMed:25733858, PubMed:32764664, PubMed:37454114).
Drug-resistance-conferring mutations reduce capacities for the transport of the natural substrates (PubMed:25733858, PubMed:32764664).
Active transport requires a directed pH gradient and a membrane potential (PubMed:25733858).
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.
- histamine(out) = histamine(in)This reaction proceeds in the forward direction.
- spermidine(in) = spermidine(out)This reaction proceeds in the backward direction.
Activity regulation
Transporter activity is trans-stimulated by host-derived peptides containing 4-11 amino acids (PubMed:32764664).
Trans-stimulation by hemoglobin-derived peptide VDPVNF is pH-dependent and sodium-independent (PubMed:32764664).
Saquinavir trans-stimulates transport of hemoglobin-derived peptide VDPVNF (PubMed:32764664).
Protons are non-competitive inhibitors of chloroquine transport (PubMed:37454114).
Trans-stimulation by hemoglobin-derived peptide VDPVNF is pH-dependent and sodium-independent (PubMed:32764664).
Saquinavir trans-stimulates transport of hemoglobin-derived peptide VDPVNF (PubMed:32764664).
Protons are non-competitive inhibitors of chloroquine transport (PubMed:37454114).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.13 μM | chloroquine | |||||
0.57 mM | arginine | |||||
0.43 mM | lysine | |||||
0.085 mM | histidine |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
0.52 nmol/min/mg | for chloroquine | ||||
44.7 nmol/min/mg | for arginine | ||||
105 nmol/min/mg | for lysine | ||||
26 nmol/min/mg | for histidine |
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
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameChloroquine resistance transporter
- Short namesPfCRT
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Sar > Alveolata > Apicomplexa > Aconoidasida > Haemosporida > Plasmodiidae > Plasmodium > Plasmodium (Laverania)
Accessions
- Primary accessionQ9N623
- Secondary accessions
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Vacuole membrane ; Multi-pass membrane protein
Note: Localizes to the parasite digestive vacuole, the site of chloroquine action.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-58 | Cytoplasmic | ||||
Sequence: MKFASKKNNQKNSSKNDERYRELDNLVQEGNGSRLGGGSCLGKCAHVFKLIFKEIKDN | ||||||
Transmembrane | 59-79 | Helical | ||||
Sequence: IFIYILSIIYLSVCVMNKIFA | ||||||
Topological domain | 80-90 | Vacuolar | ||||
Sequence: KRTLNKIGNYS | ||||||
Transmembrane | 91-111 | Helical | ||||
Sequence: FVTSETHNFICMIMFFIVYSL | ||||||
Topological domain | 112-127 | Cytoplasmic | ||||
Sequence: FGNKKGNSKERHRSFN | ||||||
Transmembrane | 128-148 | Helical | ||||
Sequence: LQFFAISMLDACSVILAFIGL | ||||||
Topological domain | 149-154 | Vacuolar | ||||
Sequence: TRTTGN | ||||||
Transmembrane | 155-175 | Helical | ||||
Sequence: IQSFVLQLSIPINMFFCFLIL | ||||||
Topological domain | 176-178 | Cytoplasmic | ||||
Sequence: RYR | ||||||
Transmembrane | 179-199 | Helical | ||||
Sequence: YHLYNYLGAVIIVVTIALVEM | ||||||
Topological domain | 200-209 | Vacuolar | ||||
Sequence: KLSFETQEEN | ||||||
Transmembrane | 210-230 | Helical | ||||
Sequence: SIIFNLVLISALIPVCFSNMT | ||||||
Topological domain | 231-248 | Cytoplasmic | ||||
Sequence: REIVFKKYKIDILRLNAM | ||||||
Transmembrane | 249-269 | Helical | ||||
Sequence: VSFFQLFTSCLILPVYTLPFL | ||||||
Topological domain | 270-317 | Vacuolar | ||||
Sequence: KQLHLPYNEIWTNIKNGFACLFLGRNTVVENCGLGMAKLCDDCDGAWK | ||||||
Transmembrane | 318-338 | Helical | ||||
Sequence: TFALFSFFNICDNLITSYIID | ||||||
Topological domain | 339-346 | Cytoplasmic | ||||
Sequence: KFSTMTYT | ||||||
Transmembrane | 347-367 | Helical | ||||
Sequence: IVSCIQGPAIAIAYYFKFLAG | ||||||
Topological domain | 368-377 | Vacuolar | ||||
Sequence: DVVREPRLLD | ||||||
Transmembrane | 378-398 | Helical | ||||
Sequence: FVTLFGYLFGSIIYRVGNIIL | ||||||
Topological domain | 399-424 | Cytoplasmic | ||||
Sequence: ERKKMRNEENEDSEGELTNVDSIITQ |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 72 | reduced sensitivity to quinine | ||||
Sequence: C → R | ||||||
Natural variant | 72 | |||||
Sequence: C → S | ||||||
Natural variant | 74 | |||||
Sequence: M → I | ||||||
Natural variant | 75 | |||||
Sequence: N → E | ||||||
Natural variant | 75 | |||||
Sequence: N → K | ||||||
Natural variant | 76 | reduced sensitivity to quinine | ||||
Sequence: K → I | ||||||
Natural variant | 76 | reduced sensitivity to quinine | ||||
Sequence: K → N | ||||||
Natural variant | 76 | in chloroquine resistance type 1; when associated with S-220 and in chloroquine resistance type 2; when associated with T-144; Y-160 and D-326; reduced sensitivity to drugs | ||||
Sequence: K → T | ||||||
Mutagenesis | 80 | Decreases pH sensitivity of chloroquine transport. | ||||
Sequence: K → A | ||||||
Mutagenesis | 80 | No significant effects on pH sensitivity of chloroquine transport; when associated with K-207. | ||||
Sequence: K → E | ||||||
Mutagenesis | 84 | Modestly decreases pH sensitivity of chloroquine transport. | ||||
Sequence: N → A | ||||||
Natural variant | 97 | |||||
Sequence: H → Q | ||||||
Mutagenesis | 97 | Increases transport activity for chloroquine at pH 6.0 with no significant effects on pH-sensitivity of chloroquine transport. | ||||
Sequence: H → A | ||||||
Natural variant | 123 | |||||
Sequence: H → R | ||||||
Mutagenesis | 137 | Decreases transport activity for chloroquine at pH 6.0. | ||||
Sequence: D → N | ||||||
Natural variant | 144 | in chloroquine resistance type 2; when associated with T-76; Y-160 and D-326 | ||||
Sequence: A → T | ||||||
Natural variant | 152 | |||||
Sequence: T → A | ||||||
Natural variant | 160 | in chloroquine resistance type 2; when associated with T-76; T-144 and D-326 | ||||
Sequence: L → Y | ||||||
Natural variant | 163 | may repel chloroquine from moving through the channel, leading to higher chloroquine accumulation at its site of action | ||||
Sequence: S → R | ||||||
Natural variant | 205 | |||||
Sequence: T → A | ||||||
Mutagenesis | 207 | Abrogates pH sensitivity of chloroquine transport. | ||||
Sequence: E → A | ||||||
Mutagenesis | 207 | No significant effects on pH sensitivity of chloroquine transport; when associated with E-80. | ||||
Sequence: E → K | ||||||
Mutagenesis | 207 | No significant effects on pH sensitivity of chloroquine transport. | ||||
Sequence: E → N or H | ||||||
Mutagenesis | 208 | No significant effects on pH sensitivity of chloroquine transport. | ||||
Sequence: E → A | ||||||
Natural variant | 220 | in chloroquine resistance type 1; when associated with T-76 | ||||
Sequence: A → S | ||||||
Natural variant | 271 | |||||
Sequence: Q → E | ||||||
Natural variant | 272 | causes the development of enlarged digestive vacuole in the asexual blood stages of the parasites, decreases peptide transport, increases sensitivity of parasites to chloroquine and quinine, decreases sensitivity to blasticidin, has no effect on sensitivity to mefloquine, amodiaquine, monodesethyl amodiaquine, piperaquine and artemisinin | ||||
Sequence: L → F | ||||||
Mutagenesis | 273 | Increases pH sensitivity of chloroquine transport. | ||||
Sequence: H → A | ||||||
Natural variant | 275 | |||||
Sequence: P → L | ||||||
Natural variant | 326 | in chloroquine resistance type 2; when associated with T-76; T-144 and Y-160 | ||||
Sequence: N → D | ||||||
Natural variant | 326 | |||||
Sequence: N → S | ||||||
Mutagenesis | 329 | Decreases transport activity for chloroquine at pH 6.0. | ||||
Sequence: D → N | ||||||
Natural variant | 333 | |||||
Sequence: T → S | ||||||
Natural variant | 334 | |||||
Sequence: S → N | ||||||
Natural variant | 352 | reduced sensitivity to quinine | ||||
Sequence: Q → K | ||||||
Natural variant | 352 | reduced sensitivity to quinine | ||||
Sequence: Q → R | ||||||
Natural variant | 356 | |||||
Sequence: I → L | ||||||
Natural variant | 356 | |||||
Sequence: I → T | ||||||
Natural variant | 356 | |||||
Sequence: I → V | ||||||
Natural variant | 371 | |||||
Sequence: R → I | ||||||
Natural variant | 371 | |||||
Sequence: R → T | ||||||
Mutagenesis | 372 | Modestly decreases pH sensitivity of chloroquine transport. | ||||
Sequence: E → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 30 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000385355 | 1-424 | Chloroquine resistance transporter | |||
Sequence: MKFASKKNNQKNSSKNDERYRELDNLVQEGNGSRLGGGSCLGKCAHVFKLIFKEIKDNIFIYILSIIYLSVCVMNKIFAKRTLNKIGNYSFVTSETHNFICMIMFFIVYSLFGNKKGNSKERHRSFNLQFFAISMLDACSVILAFIGLTRTTGNIQSFVLQLSIPINMFFCFLILRYRYHLYNYLGAVIIVVTIALVEMKLSFETQEENSIIFNLVLISALIPVCFSNMTREIVFKKYKIDILRLNAMVSFFQLFTSCLILPVYTLPFLKQLHLPYNEIWTNIKNGFACLFLGRNTVVENCGLGMAKLCDDCDGAWKTFALFSFFNICDNLITSYIIDKFSTMTYTIVSCIQGPAIAIAYYFKFLAGDVVREPRLLDFVTLFGYLFGSIIYRVGNIILERKKMRNEENEDSEGELTNVDSIITQ | ||||||
Glycosylation | 88 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 289↔312 | |||||
Sequence: CLFLGRNTVVENCGLGMAKLCDDC | ||||||
Disulfide bond | 301↔309 | |||||
Sequence: CGLGMAKLC |
Keywords
- PTM
PTM databases
Interaction
Structure
Sequence
- Sequence statusComplete
- Length424
- Mass (Da)48,675
- Last updated2000-10-01 v1
- ChecksumEC642763C5C73732
Polymorphism
The Dd2 strain is chloroquine-resistant in contrast to the 3D7 strain which is chloroquine-sensitive. Compared to the 3D7 strain, the CRT protein from the Dd2 strain shows increased chloroquine transport rates and reduced capacity for the transport of natural substrates, and determines increased sensitivity of the parasites to saquinavir.
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF030694 EMBL· GenBank· DDBJ | AAF26926.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF233064 EMBL· GenBank· DDBJ | AAF60271.1 EMBL· GenBank· DDBJ | mRNA | ||
AF233065 EMBL· GenBank· DDBJ | AAF60272.1 EMBL· GenBank· DDBJ | mRNA | ||
AF233066 EMBL· GenBank· DDBJ | AAF60273.1 EMBL· GenBank· DDBJ | mRNA | ||
AF233067 EMBL· GenBank· DDBJ | AAF60274.1 EMBL· GenBank· DDBJ | mRNA | ||
AF233068 EMBL· GenBank· DDBJ | AAF60275.1 EMBL· GenBank· DDBJ | mRNA | ||
AF495376 EMBL· GenBank· DDBJ | AAO85506.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF495377 EMBL· GenBank· DDBJ | AAO85507.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF495378 EMBL· GenBank· DDBJ | AAO85508.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY651315 EMBL· GenBank· DDBJ | AAU00067.1 EMBL· GenBank· DDBJ | mRNA | ||
AF468006 EMBL· GenBank· DDBJ | AAL75580.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ156107 EMBL· GenBank· DDBJ | AAZ81606.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ156108 EMBL· GenBank· DDBJ | AAZ81607.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ156109 EMBL· GenBank· DDBJ | AAZ81608.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ533840 EMBL· GenBank· DDBJ | ABF82363.1 EMBL· GenBank· DDBJ | mRNA | ||
AY254700 EMBL· GenBank· DDBJ | AAP79044.1 EMBL· GenBank· DDBJ | mRNA |