Disease relevance of CAN1

• This protein is highly homologous with the AroP (general aromatic transport) system of E. coli (59.6% identity) and to a lesser extent with the yeast permeases CAN1 (arginine), PUT4 (proline), and HIP1 (histidine) of Saccharomyces cerevisiae [1].

High impact information on CAN1

• The mutation rate in the CAN1 gene increased 10- to 100-fold in est1Delta strains as telomeres became dysfunctional [2].
• The fidelity of yeast RNA polymerase II (Pol II) was assessed in vivo with an assay in which errors in transcription of can1-100, a nonsense allele of CAN1, result in enhanced sensitivity to the toxic arginine analog canavanine [3].
• A genomewide screen of a collection of 4,847 yeast gene deletion mutants was carried out to identify the genes required for suppressing mutations in the CAN1 forward-mutation assay [4].
• Finally, we present evidence that Slm proteins are also required for the trafficking of the raft-associated arginine permease Can1 to the plasma membrane, a process that requires sphingolipid synthesis and actin polymerization [5].
• In chromosome stability assays, rad27-G67S strains displayed a higher frequency of repeat tract instabilities relative to CAN1 duplication events; in contrast, the rad27-G240D strains displayed the opposite phenotype [6].

Biological context of CAN1

• Structural analysis of the recombinant plasmids obtained from the resistant cells showed that the plasmids had deletions at various sites of the CAN1-CYH2 region and there were only short regions of homology (1-5 bp) at the recombination junctions [7].
• In contrast, RAD5 and RAD18 play alternative roles in mutagenic repair: mutations in each of these genes elevate spontaneous forward mutation at the CAN1 locus, but when both genes are deleted, a low level of spontaneous mutagenesis is seen [8].
• L-[(14)C]citrulline uptake measurements confirmed that suppressor mutations in CAN1 conferred uptake of this amino acid, while none of the mutant permeases had lost the ability to transport L-[(14)C]arginine [9].
• Using the CAN1 gene in haploid cells or heterozygous diploid cells, we characterized the effects of mutations in the RAD52 and REV3 genes of Saccharomyces cerevisiae in spontaneous mutagenesis [10].
• In diploid rev3 cells, frequencies of can1Delta::LEU2/can1Delta::LEU2 from CAN1/can1Delta::LEU2 due to recombination were increased over the wild-type level [10].

Anatomical context of CAN1

• Ribosomes encountering premature UAA or UGA codons in the CAN1 mRNA fail to release and, instead, migrate to upstream AUGs [11].
• Unidirectional arginine transport in reconstituted plasma-membrane vesicles from yeast overexpressing CAN1 [12].
• Double labeling experiments with Can1p-GFP- and Pma1p-RFP-containing cells demonstrate that these proteins occupy two different nonoverlapping membrane microdomains [13].
• Transport in isolated yeast vacuoles: characterization of arginine permease [14].
• The depletion of this phospholipid results in an accumulation of a typical raft-resident, the arginine transporter Can1p, in the membranes of Golgi, while the trafficking of another plasma membrane transporter, Pma1p, is interrupted at the level of the ER [15].

Associations of CAN1 with chemical compounds

• Upon formation of a deletion over the active CAN1-CYH2 genes, a cell becomes resistant to both canavanine and cycloheximide [16].
• Selection for suppressor mutants that restored growth on L-citrulline led to isolation of 21 mutations in the arginine permease gene CAN1 [9].
• Fluctuation tests failed to detect any significant effect of mobile phone fields on forward mutation rates at CAN1, on the frequency of petite formation, on rates of intrachromosomal deletion formation, or on rates of intragenic recombination in the absence or presence of the genotoxic agent methyl methansulfonate [17].
• The activities of arginine (Can1p), proline (Put4p) and general amino acid permease (Gap1p) are decreased more than 20-fold [18].
• Those genes susceptible to giving rise to formamide-sensitive alleles include the structural gene for DNA ligase, CDC9, and the structural gene for arginine permease, CAN1 [19].

Other interactions of CAN1

• Here we show that mutations in rad6 increase the frequency of transposition of the retrotransposon Ty into the CAN1 and URA3 loci [20].
• In the aligned sequences HIP1 and CAN1, the postulated membrane-spanning alpha-helices often start at corresponding sites, even though the overall sequence similarity of the two proteins is only 30% [21].
• These data, together with previous studies of Ty1 integration positions at CAN1 and SUP4, indicate that the rad6 effect on Ty1 target-site selection is not gene specific [22].
• A Saccharomyces cerevisiae gene (1722 bp), encoding a protein (574 aa) highly homologous to the basic-amino-acid permeases LYP1 and CAN1, was sequenced [23].
• Helix III was affected in both CAN1 (Y173H, Y173D) and GNP1 (W239C) mutants and has previously been found to be important for substrate preference in other members of the family [9].

Analytical, diagnostic and therapeutic context of CAN1

• We have for the first time purified arginine permease from a pathogenic yeast, Candida albicans, to homogeneity by affinity chromatography using L-arginine-linked agarose matrix as affinity column [24].

References