Plasmodium falciparum cyclic amine resistance locus | Antimalarial targets | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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Plasmodium falciparum cyclic amine resistance locus

Target id: 3074

Nomenclature: Plasmodium falciparum cyclic amine resistance locus

Abbreviated Name: PfCARL

Family: Antimalarial targets

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 1283 CARL cyclic amine resistance locus protein
Database Links
UniProtKB
Malaria Pharmacology Comments
The P. falciparum cyclic amine resistance locus (PfCARL) encodes a conserved protein of unknown function that localizes to the cis-Golgi apparatus of the parasite in both asexual and sexual blood stages [1]. Homology analysis provides an insight into possible function: the S. cerevisiae homolog, Emp65, is a part of a molecular chaperone complex in the endoplasmic reticulum and the mouse homolog, Tapt1, is involved in embryonic skeletal formation, signal transduction, and hormone trafficking [1,3].
Mutations in PfCARL are associated with parasite resistance to two distinct compound classes: the imidazolopiperazines, a novel class of antimalarial compounds that includes the clinical candidate ganaplacide, and the benzimidazolyl piperidines, with the suggestion that PfCARL is a multidrug-resistance gene rather than the common target [1-2].

References

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1. LaMonte G, Lim MY, Wree M, Reimer C, Nachon M, Corey V, Gedeck P, Plouffe D, Du A, Figueroa N et al.. (2016) Mutations in the Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL) Confer Multidrug Resistance. MBio, 7 (4). [PMID:27381290]

2. Magistrado PA, Corey VC, Lukens AK, LaMonte G, Sasaki E, Meister S, Wree M, Winzeler E, Wirth DF. (2016) Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL), a Resistance Mechanism for Two Distinct Compound Classes. ACS Infect Dis, 2 (11): 816-826. [PMID:27933786]

3. Zhang S, Xu C, Larrimore KE, Ng DTW. (2017) Slp1-Emp65: A Guardian Factor that Protects Folding Polypeptides from Promiscuous Degradation. Cell, 171 (2): 346-357.e12. [PMID:28919078]

How to cite this page

Antimalarial targets: Plasmodium falciparum cyclic amine resistance locus. Last modified on 18/03/2019. Accessed on 18/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3074.