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2.A.7.20.1
Chloroquine resistance transporter, PfCRT. Martin et al. (2009) have demonstrated Chloroquine transport via the malaria parasite's chloroquine resistance transporter. PfCRT cotransports chloroquine and Hout of the digestive vacuole (and hence away from its site of action) via a mutant form of the parasite's chloroquine resistance transporter (Lehane and Kirk, 2010).  Many mutations give rise to resistance (Tan et al. 2014). The orthologue in P. vivax is 73% identical to the P. faciparum protein and has the same function (et al. 2006). It is inhibited by verapamil, quinine, saquinavir and dibemethin 6a (Meier et al. 2018). Many mutations give rise to artemisinin resistance (Buppan et al. 2018). TMS1 is involved in substrate selectivity and catalyzes chroroquine efflux (Antony et al. 2018).

Accession Number:Q9N623
Protein Name:Chloroquine resistance transporter
Length:424
Molecular Weight:48675.00
Species: [5833]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Vacuole membrane1 / Multi-pass membrane protein2
Substrate chloroquine, H+

Cross database links:

Pfam: PF00892   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005774 C:vacuolar membrane

References (7)

[1] “Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance.”  Fidock D.A.et.al.   11090624
[2] “Evidence for a central role for PfCRT in conferring Plasmodium falciparum resistance to diverse antimalarial agents.”  Johnson D.J.et.al.   15383277
[3] “Polymorphisms in the pfcrt and pfmdr1 Genes of Plasmodium falciparum and in Vitro Susceptibility to Amodiaquine and Desethylamodiaquine.”  Echeverry D.F.et.al.   18165517
[4] “pfcrt Allelic types with two novel amino acid mutations in chloroquine-resistant Plasmodium falciparum isolates from the Philippines.”  Chen N.et.al.   14576108
[5] “Evidence for activation of endogenous transporters in Xenopus laevis oocytes expressing the Plasmodium falciparum chloroquine resistance transporter, PfCRT.”  Nessler S.et.al.   15258157
[6] “Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum.”  Cooper R.A.et.al.   11752204
[7] “Mutations in transmembrane domains 1, 4 and 9 of the Plasmodium falciparum chloroquine resistance transporter alter susceptibility to chloroquine, quinine and quinidine.”  Cooper R.A.et.al.   17163969

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FASTA formatted sequence
1:	MKFASKKNNQ KNSSKNDERY RELDNLVQEG NGSRLGGGSC LGKCAHVFKL IFKEIKDNIF 
61:	IYILSIIYLS VCVMNKIFAK RTLNKIGNYS FVTSETHNFI CMIMFFIVYS LFGNKKGNSK 
121:	ERHRSFNLQF FAISMLDACS VILAFIGLTR TTGNIQSFVL QLSIPINMFF CFLILRYRYH 
181:	LYNYLGAVII VVTIALVEMK LSFETQEENS IIFNLVLISA LIPVCFSNMT REIVFKKYKI 
241:	DILRLNAMVS FFQLFTSCLI LPVYTLPFLK QLHLPYNEIW TNIKNGFACL FLGRNTVVEN 
301:	CGLGMAKLCD DCDGAWKTFA LFSFFNICDN LITSYIIDKF STMTYTIVSC IQGPAIAIAY 
361:	YFKFLAGDVV REPRLLDFVT LFGYLFGSII YRVGNIILER KKMRNEENED SEGELTNVDS 
421:	IITQ