CRT_PLAFA
ID CRT_PLAFA Reviewed; 424 AA.
AC Q9N623; Q19AE2; Q3Y5Z4; Q3Y5Z5; Q3Y5Z6; Q68PG1; Q6X529; Q7KQ06; Q86M68;
AC Q86M69; Q86M70; Q8T9R7; Q9N653; Q9NH61;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 63.
DE RecName: Full=Chloroquine resistance transporter;
DE Short=PfCRT;
GN Name=CRT;
OS Plasmodium falciparum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5833;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, VARIANTS
RP CHLOROQUINE RESISTANCE TYPE 1 THR-76 AND SER-220, AND VARIANTS SER-72;
RP ILE-74; GLU-75; ILE-76; THR-76; SER-220; GLU-271; ASP-326; SER-326;
RP LEU-356; THR-356 AND ILE-371.
RX PubMed=11090624; DOI=10.1016/s1097-2765(05)00077-8;
RA Fidock D.A., Nomura T., Talley A.K., Cooper R.A., Dzekunov S.M.,
RA Ferdig M.T., Ursos L.M.B., bir Singh Sidhu A., Naude B., Deitsch K.W.,
RA Su X.-Z., Wootton J.C., Roepe P.D., Wellems T.E.;
RT "Mutations in the P. falciparum digestive vacuole transmembrane protein
RT PfCRT and evidence for their role in chloroquine resistance.";
RL Mol. Cell 6:861-871(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CHLOROQUINE RESISTANCE TYPE 1
RP THR-76 AND SER-220, AND VARIANTS ILE-74; GLU-75; LYS-75; THR-76; ALA-152;
RP ARG-163; SER-220; GLU-271; LEU-275; SER-326; VAL-356 AND ILE-371.
RX PubMed=15383277; DOI=10.1016/j.molcel.2004.09.012;
RA Johnson D.J., Fidock D.A., Mungthin M., Lakshmanan V., bir Singh Sidhu A.,
RA Bray P.G., Ward S.A.;
RT "Evidence for a central role for PfCRT in conferring Plasmodium falciparum
RT resistance to diverse antimalarial agents.";
RL Mol. Cell 15:867-877(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ILE-74; GLU-75; THR-76; ARG-123;
RP ALA-205; SER-220; GLU-271; SER-326 AND ILE-371.
RC STRAIN=TM6;
RA Li G.-D., Ward S.A.;
RT "Plasmodium falciparum TM6 putative chloroquine resistance transporter
RT (crt) mRNA.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-416, AND VARIANTS GLU-75; THR-76; GLN-97;
RP SER-220; ASP-326; SER-333; ASN-334; LEU-356; ILE-371 AND THR-371.
RC STRAIN=TA6182, TA7519, and TU741;
RX PubMed=18165517; DOI=10.4269/ajtmh.2007.77.1034;
RA Echeverry D.F., Holmgren G., Murillo C., Higuita J.C., Bjoerkman A.,
RA Gil J.P., Osorio L.;
RT "Polymorphisms in the pfcrt and pfmdr1 Genes of Plasmodium falciparum and
RT in Vitro Susceptibility to Amodiaquine and Desethylamodiaquine.";
RL Am. J. Trop. Med. Hyg. 77:1034-1038(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-395, AND VARIANTS ILE-74; GLU-75; THR-76;
RP SER-220; GLU-271; SER-326 AND ILE-371.
RC STRAIN=FVO;
RA Kumar A., Zheng H., Chizhikov V.;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 44-380, VARIANTS CHLOROQUINE RESISTANCE TYPE
RP 2 THR-76; THR-144; TYR-160 AND ASP-326, AND VARIANTS THR-76; THR-144;
RP TYR-160 AND ASP-326.
RX PubMed=14576108; DOI=10.1128/aac.47.11.3500-3505.2003;
RA Chen N., Kyle D.E., Pasay C., Fowler E.V., Baker J., Peters J.M., Cheng Q.;
RT "pfcrt Allelic types with two novel amino acid mutations in chloroquine-
RT resistant Plasmodium falciparum isolates from the Philippines.";
RL Antimicrob. Agents Chemother. 47:3500-3505(2003).
RN [7]
RP FUNCTION.
RX PubMed=15258157; DOI=10.1074/jbc.m404671200;
RA Nessler S., Friedrich O., Bakouh N., Fink R.H.A., Sanchez C.P.,
RA Planelles G., Lanzer M.;
RT "Evidence for activation of endogenous transporters in Xenopus laevis
RT oocytes expressing the Plasmodium falciparum chloroquine resistance
RT transporter, PfCRT.";
RL J. Biol. Chem. 279:39438-39446(2004).
RN [8]
RP CHARACTERIZATION OF VARIANTS ASN-76 AND ILE-76, AND SUBCELLULAR LOCATION.
RX PubMed=11752204; DOI=10.1124/mol.61.1.35;
RA Cooper R.A., Ferdig M.T., Su X.-Z., Ursos L.M.B., Mu J., Nomura T.,
RA Fujioka H., Fidock D.A., Roepe P.D., Wellems T.E.;
RT "Alternative mutations at position 76 of the vacuolar transmembrane protein
RT PfCRT are associated with chloroquine resistance and unique stereospecific
RT quinine and quinidine responses in Plasmodium falciparum.";
RL Mol. Pharmacol. 61:35-42(2002).
RN [9]
RP CHARACTERIZATION OF VARIANTS ARG-72; ASN-76; ILE-76; THR-76; LYS-352 AND
RP ARG-352.
RX PubMed=17163969; DOI=10.1111/j.1365-2958.2006.05511.x;
RA Cooper R.A., Lane K.D., Deng B., Mu J., Patel J.J., Wellems T.E., Su X.,
RA Ferdig M.T.;
RT "Mutations in transmembrane domains 1, 4 and 9 of the Plasmodium falciparum
RT chloroquine resistance transporter alter susceptibility to chloroquine,
RT quinine and quinidine.";
RL Mol. Microbiol. 63:270-282(2007).
RN [10]
RP ERRATUM OF PUBMED:17163969.
RA Cooper R.A., Lane K.D., Deng B., Mu J., Patel J.J., Wellems T.E., Su X.,
RA Ferdig M.T.;
RL Mol. Microbiol. 643:1139-1139(2007).
CC -!- FUNCTION: May regulate endogenous transporter.
CC {ECO:0000269|PubMed:15258157}.
CC -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:11090624,
CC ECO:0000269|PubMed:11752204}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11090624, ECO:0000269|PubMed:11752204}.
CC Note=Localizes to the parasite digestive vacuole, the site of
CC chloroquine action.
CC -!- SIMILARITY: Belongs to the CRT-like transporter family. {ECO:0000305}.
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DR EMBL; AF030694; AAF26926.1; -; Genomic_DNA.
DR EMBL; AF233064; AAF60271.1; -; mRNA.
DR EMBL; AF233065; AAF60272.1; -; mRNA.
DR EMBL; AF233066; AAF60273.1; -; mRNA.
DR EMBL; AF233067; AAF60274.1; -; mRNA.
DR EMBL; AF233068; AAF60275.1; -; mRNA.
DR EMBL; AF495376; AAO85506.1; -; Genomic_DNA.
DR EMBL; AF495377; AAO85507.1; -; Genomic_DNA.
DR EMBL; AF495378; AAO85508.1; -; Genomic_DNA.
DR EMBL; AY651315; AAU00067.1; -; mRNA.
DR EMBL; AF468006; AAL75580.1; -; mRNA.
DR EMBL; DQ156107; AAZ81606.1; -; mRNA.
DR EMBL; DQ156108; AAZ81607.1; -; mRNA.
DR EMBL; DQ156109; AAZ81608.1; -; mRNA.
DR EMBL; DQ533840; ABF82363.1; -; mRNA.
DR EMBL; AY254700; AAP79044.1; -; mRNA.
DR AlphaFoldDB; Q9N623; -.
DR SMR; Q9N623; -.
DR BindingDB; Q9N623; -.
DR ChEMBL; CHEMBL1795182; -.
DR DrugBank; DB11638; Artenimol.
DR DrugCentral; Q9N623; -.
DR TCDB; 2.A.7.20.1; the drug/metabolite transporter (dmt) superfamily.
DR EnsemblProtists; CAD50842; CAD50842; PF3D7_0709000.
DR VEuPathDB; PlasmoDB:PF3D7_0709000; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000193300; -.
DR VEuPathDB; PlasmoDB:Pf7G8_070014400; -.
DR VEuPathDB; PlasmoDB:PfCD01_070012900; -.
DR VEuPathDB; PlasmoDB:PfDd2_070013200; -.
DR VEuPathDB; PlasmoDB:PfGA01_070012400; -.
DR VEuPathDB; PlasmoDB:PfGB4_070014200; -.
DR VEuPathDB; PlasmoDB:PfGN01_070014100; -.
DR VEuPathDB; PlasmoDB:PfHB3_070013000; -.
DR VEuPathDB; PlasmoDB:PfIT_070013900; -.
DR VEuPathDB; PlasmoDB:PfKE01_070012600; -.
DR VEuPathDB; PlasmoDB:PfKH01_070013000; -.
DR VEuPathDB; PlasmoDB:PfKH02_070012300; -.
DR VEuPathDB; PlasmoDB:PfML01_070013400; -.
DR VEuPathDB; PlasmoDB:PfNF166_070013500; -.
DR VEuPathDB; PlasmoDB:PfNF54_070013900; -.
DR VEuPathDB; PlasmoDB:PfSD01_070012900; -.
DR VEuPathDB; PlasmoDB:PfSN01_070013800; -.
DR VEuPathDB; PlasmoDB:PfTG01_070014000; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IEA:InterPro.
DR InterPro; IPR013936; CRT-like.
DR InterPro; IPR017258; Transprt_Chloroquine.
DR PANTHER; PTHR31326; PTHR31326; 1.
DR Pfam; PF08627; CRT-like; 1.
DR PIRSF; PIRSF037671; Transprt_Chloroquine_res; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; Transmembrane; Transmembrane helix; Vacuole.
FT CHAIN 1..424
FT /note="Chloroquine resistance transporter"
FT /id="PRO_0000385355"
FT TOPO_DOM 1..58
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 59..79
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 80..90
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 91..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..127
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 128..148
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 149..154
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..178
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..209
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 210..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..248
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..269
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..317
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 339..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 368..377
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..424
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 72
FT /note="C -> R (reduced sensitivity to quinine)"
FT /evidence="ECO:0000269|PubMed:17163969"
FT VARIANT 72
FT /note="C -> S"
FT /evidence="ECO:0000269|PubMed:11090624"
FT VARIANT 74
FT /note="M -> I"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:15383277, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.5"
FT VARIANT 75
FT /note="N -> E"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:15383277, ECO:0000269|PubMed:18165517,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5"
FT VARIANT 75
FT /note="N -> K"
FT /evidence="ECO:0000269|PubMed:15383277"
FT VARIANT 76
FT /note="K -> I (reduced sensitivity to quinine)"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:11752204, ECO:0000269|PubMed:17163969"
FT VARIANT 76
FT /note="K -> N (reduced sensitivity to quinine)"
FT /evidence="ECO:0000269|PubMed:11752204,
FT ECO:0000269|PubMed:17163969"
FT VARIANT 76
FT /note="K -> T (in chloroquine resistance type 1; associated
FT with S-220 and in chloroquine resistance type 2; associated
FT with T-144, Y-160 and D-326; reduced sensitivity to drugs)"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:14576108, ECO:0000269|PubMed:15383277,
FT ECO:0000269|PubMed:17163969, ECO:0000269|PubMed:18165517,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5"
FT VARIANT 97
FT /note="H -> Q"
FT /evidence="ECO:0000269|PubMed:18165517"
FT VARIANT 123
FT /note="H -> R"
FT /evidence="ECO:0000269|Ref.3"
FT VARIANT 144
FT /note="A -> T (in chloroquine resistance type 2; associated
FT with T-76, Y-160 and D-326)"
FT /evidence="ECO:0000269|PubMed:14576108"
FT VARIANT 152
FT /note="T -> A"
FT /evidence="ECO:0000269|PubMed:15383277"
FT VARIANT 160
FT /note="L -> Y (in chloroquine resistance type 2; associated
FT with T-76, T-144 and D-326)"
FT /evidence="ECO:0000269|PubMed:14576108"
FT VARIANT 163
FT /note="S -> R (may repel chloroquine from moving through
FT the channel, leading to higher chloroquine accumulation at
FT its site of action)"
FT /evidence="ECO:0000269|PubMed:15383277"
FT VARIANT 205
FT /note="T -> A"
FT /evidence="ECO:0000269|Ref.3"
FT VARIANT 220
FT /note="A -> S (in chloroquine resistance type 1; associated
FT with T-76)"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:15383277, ECO:0000269|PubMed:18165517,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5"
FT VARIANT 271
FT /note="Q -> E"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:15383277, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.5"
FT VARIANT 275
FT /note="P -> L"
FT /evidence="ECO:0000269|PubMed:15383277"
FT VARIANT 326
FT /note="N -> D (in chloroquine resistance type 2; associated
FT with T-76, T-144 and Y-160)"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:14576108, ECO:0000269|PubMed:18165517"
FT VARIANT 326
FT /note="N -> S"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:15383277, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.5"
FT VARIANT 333
FT /note="T -> S"
FT /evidence="ECO:0000269|PubMed:18165517"
FT VARIANT 334
FT /note="S -> N"
FT /evidence="ECO:0000269|PubMed:18165517"
FT VARIANT 352
FT /note="Q -> K (reduced sensitivity to quinine)"
FT /evidence="ECO:0000269|PubMed:17163969"
FT VARIANT 352
FT /note="Q -> R (reduced sensitivity to quinine)"
FT /evidence="ECO:0000269|PubMed:17163969"
FT VARIANT 356
FT /note="I -> L"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:18165517"
FT VARIANT 356
FT /note="I -> T"
FT /evidence="ECO:0000269|PubMed:11090624"
FT VARIANT 356
FT /note="I -> V"
FT /evidence="ECO:0000269|PubMed:15383277"
FT VARIANT 371
FT /note="R -> I"
FT /evidence="ECO:0000269|PubMed:11090624,
FT ECO:0000269|PubMed:15383277, ECO:0000269|PubMed:18165517,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5"
FT VARIANT 371
FT /note="R -> T"
FT /evidence="ECO:0000269|PubMed:18165517"
SQ SEQUENCE 424 AA; 48675 MW; EC642763C5C73732 CRC64;
MKFASKKNNQ KNSSKNDERY RELDNLVQEG NGSRLGGGSC LGKCAHVFKL IFKEIKDNIF
IYILSIIYLS VCVMNKIFAK RTLNKIGNYS FVTSETHNFI CMIMFFIVYS LFGNKKGNSK
ERHRSFNLQF FAISMLDACS VILAFIGLTR TTGNIQSFVL QLSIPINMFF CFLILRYRYH
LYNYLGAVII VVTIALVEMK LSFETQEENS IIFNLVLISA LIPVCFSNMT REIVFKKYKI
DILRLNAMVS FFQLFTSCLI LPVYTLPFLK QLHLPYNEIW TNIKNGFACL FLGRNTVVEN
CGLGMAKLCD DCDGAWKTFA LFSFFNICDN LITSYIIDKF STMTYTIVSC IQGPAIAIAY
YFKFLAGDVV REPRLLDFVT LFGYLFGSII YRVGNIILER KKMRNEENED SEGELTNVDS
IITQ
