W7FI62 · CRT_PLAF8

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).

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).

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 μMchloroquine
1.3 μMarginine
208 μMVDPVNF peptide
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
90 nmol/min/mgfor chloroquine
190 nmol/min/mgfor 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).

Features

Showing features for site.

TypeIDPosition(s)Description
Site207pH 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

GO annotations

AspectTerm
Cellular Componentvacuolar membrane
Molecular Functionxenobiotic transmembrane transporter activity
Biological Processamino acid transport

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Chloroquine resistance transporter
  • Short names
    PfCRT

Gene names

    • Name
      CRT
    • Synonyms
      CG10
    • ORF names
      PFBG_01689

Organism names

  • Taxonomic identifier
  • Strain
    • 7G8
  • Taxonomic lineage
    Eukaryota > Sar > Alveolata > Apicomplexa > Aconoidasida > Haemosporida > Plasmodiidae > Plasmodium > Plasmodium (Laverania)

Accessions

  • Primary accession
    W7FI62

Proteomes

Organism-specific databases

Subcellular Location

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.

TypeIDPosition(s)Description
Topological domain1-49Cytoplasmic
Intramembrane50-58
Transmembrane59-83Helical
Topological domain84-89Vacuolar
Transmembrane90-111Helical
Topological domain112-126Cytoplasmic
Transmembrane127-147Helical
Topological domain148-152Vacuolar
Transmembrane153-173Helical
Topological domain174-180Cytoplasmic
Transmembrane181-202Helical
Topological domain203-210Vacuolar
Transmembrane211-236Helical
Topological domain237-241Cytoplasmic
Transmembrane242-263Helical
Topological domain264-279Vacuolar
Intramembrane280-292
Topological domain293-314Vacuolar
Transmembrane315-339Helical
Topological domain340-343Cytoplasmic
Transmembrane344-361Helical
Topological domain362-374Vacuolar
Transmembrane375-397Helical
Topological domain398-424Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis145No 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.
Mutagenesis289No effect on chloroquine binding affinity and transport.
Mutagenesis301No effect on chloroquine binding affinity and transport.
Mutagenesis350No 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.

PTM/Processing

Features

Showing features for chain, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00004593751-424Chloroquine resistance transporter
Disulfide bond289↔312
Disulfide bond301↔309

Keywords

Interaction

Subunit

Monomer.

Family & Domains

Sequence similarities

Belongs to the CRT-like transporter family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    424
  • Mass (Da)
    48,649
  • Last updated
    2014-04-16 v1
  • Checksum
    DA5025A7792F1EA6
MKFASKKNNQKNSSKNDERYRELDNLVQEGNGSRLGGGSCLGKCAHVFKLIFKEIKDNIFIYILSIIYLSVSVMNTIFAKRTLNKIGNYSFVTSETHNFICMIMFFIVYSLFGNKKGNSKERHRSFNLQFFAISMLDACSVILAFIGLTRTTGNIQSFVLQLSIPINMFFCFLILRYRYHLYNYLGAVIIVVTIALVEMKLSFETQEENSIIFNLVLISSLIPVCFSNMTREIVFKKYKIDILRLNAMVSFFQLFTSCLILPVYTLPFLKQLHLPYNEIWTNIKNGFACLFLGRNTVVENCGLGMAKLCDDCDGAWKTFALFSFFDICDNLITSYIIDKFSTMTYTIVSCIQGPALAIAYYFKFLAGDVVREPRLLDFVTLFGYLFGSIIYRVGNIILERKKMRNEENEDSEGELTNVDSIITQ

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

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
KE123602
EMBL· GenBank· DDBJ
EUR74088.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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