Q9N623 · CRT_PLAFA

  • Protein
    Chloroquine resistance transporter
  • Gene
    CRT
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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).

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).

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
0.13 μMchloroquine
0.57 mMarginine
0.43 mMlysine
0.085 mMhistidine
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
0.52 nmol/min/mgfor chloroquine
44.7 nmol/min/mgfor arginine
105 nmol/min/mgfor lysine
26 nmol/min/mgfor histidine

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

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Chloroquine resistance transporter
  • Short names
    PfCRT

Gene names

    • Name
      CRT
    • Synonyms
      CG10

Organism names

  • Taxonomic identifier
  • Strains
    • Dd2
    • TM6
    • TA6182
    • TA7519
    • TU741
    • FVO
  • Taxonomic lineage
    Eukaryota > Sar > Alveolata > Apicomplexa > Aconoidasida > Haemosporida > Plasmodiidae > Plasmodium > Plasmodium (Laverania)

Accessions

  • Primary accession
    Q9N623
  • Secondary accessions
    • Q19AE2
    • Q3Y5Z4
    • Q3Y5Z5
    • Q3Y5Z6
    • Q68PG1

Organism-specific databases

Subcellular Location

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.

TypeIDPosition(s)Description
Topological domain1-58Cytoplasmic
Transmembrane59-79Helical
Topological domain80-90Vacuolar
Transmembrane91-111Helical
Topological domain112-127Cytoplasmic
Transmembrane128-148Helical
Topological domain149-154Vacuolar
Transmembrane155-175Helical
Topological domain176-178Cytoplasmic
Transmembrane179-199Helical
Topological domain200-209Vacuolar
Transmembrane210-230Helical
Topological domain231-248Cytoplasmic
Transmembrane249-269Helical
Topological domain270-317Vacuolar
Transmembrane318-338Helical
Topological domain339-346Cytoplasmic
Transmembrane347-367Helical
Topological domain368-377Vacuolar
Transmembrane378-398Helical
Topological domain399-424Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variant72reduced sensitivity to quinine
Natural variant72
Natural variant74
Natural variant75
Natural variant75
Natural variant76reduced sensitivity to quinine
Natural variant76reduced sensitivity to quinine
Natural variant76in 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
Mutagenesis80Decreases pH sensitivity of chloroquine transport.
Mutagenesis80No significant effects on pH sensitivity of chloroquine transport; when associated with K-207.
Mutagenesis84Modestly decreases pH sensitivity of chloroquine transport.
Natural variant97
Mutagenesis97Increases transport activity for chloroquine at pH 6.0 with no significant effects on pH-sensitivity of chloroquine transport.
Natural variant123
Mutagenesis137Decreases transport activity for chloroquine at pH 6.0.
Natural variant144in chloroquine resistance type 2; when associated with T-76; Y-160 and D-326
Natural variant152
Natural variant160in chloroquine resistance type 2; when associated with T-76; T-144 and D-326
Natural variant163may repel chloroquine from moving through the channel, leading to higher chloroquine accumulation at its site of action
Natural variant205
Mutagenesis207Abrogates pH sensitivity of chloroquine transport.
Mutagenesis207No significant effects on pH sensitivity of chloroquine transport; when associated with E-80.
Mutagenesis207No significant effects on pH sensitivity of chloroquine transport.
Mutagenesis208No significant effects on pH sensitivity of chloroquine transport.
Natural variant220in chloroquine resistance type 1; when associated with T-76
Natural variant271
Natural variant272causes 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
Mutagenesis273Increases pH sensitivity of chloroquine transport.
Natural variant275
Natural variant326in chloroquine resistance type 2; when associated with T-76; T-144 and Y-160
Natural variant326
Mutagenesis329Decreases transport activity for chloroquine at pH 6.0.
Natural variant333
Natural variant334
Natural variant352reduced sensitivity to quinine
Natural variant352reduced sensitivity to quinine
Natural variant356
Natural variant356
Natural variant356
Natural variant371
Natural variant371
Mutagenesis372Modestly decreases pH sensitivity of chloroquine transport.

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.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, glycosylation, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00003853551-424Chloroquine resistance transporter
Glycosylation88N-linked (GlcNAc...) asparagine
Disulfide bond289↔312
Disulfide bond301↔309

Keywords

PTM databases

Interaction

Subunit

Monomer.

Chemistry

Structure

Family & Domains

Sequence similarities

Belongs to the CRT-like transporter family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    424
  • Mass (Da)
    48,675
  • Last updated
    2000-10-01 v1
  • Checksum
    EC642763C5C73732
MKFASKKNNQKNSSKNDERYRELDNLVQEGNGSRLGGGSCLGKCAHVFKLIFKEIKDNIFIYILSIIYLSVCVMNKIFAKRTLNKIGNYSFVTSETHNFICMIMFFIVYSLFGNKKGNSKERHRSFNLQFFAISMLDACSVILAFIGLTRTTGNIQSFVLQLSIPINMFFCFLILRYRYHLYNYLGAVIIVVTIALVEMKLSFETQEENSIIFNLVLISALIPVCFSNMTREIVFKKYKIDILRLNAMVSFFQLFTSCLILPVYTLPFLKQLHLPYNEIWTNIKNGFACLFLGRNTVVENCGLGMAKLCDDCDGAWKTFALFSFFNICDNLITSYIIDKFSTMTYTIVSCIQGPAIAIAYYFKFLAGDVVREPRLLDFVTLFGYLFGSIIYRVGNIILERKKMRNEENEDSEGELTNVDSIITQ

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 SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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