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Gene Review

CAN1  -  Can1p

Saccharomyces cerevisiae S288c

Synonyms: Arginine permease, YEL063C
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Disease relevance of CAN1


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


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


  1. Cloning and sequencing of the pheP gene, which encodes the phenylalanine-specific transport system of Escherichia coli. Pi, J., Wookey, P.J., Pittard, A.J. J. Bacteriol. (1991) [Pubmed]
  2. Telomere dysfunction increases mutation rate and genomic instability. Hackett, J.A., Feldser, D.M., Greider, C.W. Cell (2001) [Pubmed]
  3. RNA polymerase II subunit Rpb9 is important for transcriptional fidelity in vivo. Nesser, N.K., Peterson, D.O., Hawley, D.K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. A genomewide screen in Saccharomyces cerevisiae for genes that suppress the accumulation of mutations. Huang, M.E., Rio, A.G., Nicolas, A., Kolodner, R.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. The Yeast PH Domain Proteins Slm1 and Slm2 Are Targets of Sphingolipid Signaling during the Response to Heat Stress. Daquinag, A., Fadri, M., Jung, S.Y., Qin, J., Kunz, J. Mol. Cell. Biol. (2007) [Pubmed]
  6. Identification of rad27 mutations that confer differential defects in mutation avoidance, repeat tract instability, and flap cleavage. Xie, Y., Liu, Y., Argueso, J.L., Henricksen, L.A., Kao, H.I., Bambara, R.A., Alani, E. Mol. Cell. Biol. (2001) [Pubmed]
  7. Effects of mutations of RAD50, RAD51, RAD52, and related genes on illegitimate recombination in Saccharomyces cerevisiae. Tsukamoto, Y., Kato, J., Ikeda, H. Genetics (1996) [Pubmed]
  8. Genetic interactions between mutants of the 'error-prone' repair group of Saccharomyces cerevisiae and their effect on recombination and mutagenesis. Liefshitz, B., Steinlauf, R., Friedl, A., Eckardt-Schupp, F., Kupiec, M. Mutat. Res. (1998) [Pubmed]
  9. Amino acid residues important for substrate specificity of the amino acid permeases Can1p and Gnp1p in Saccharomyces cerevisiae. Regenberg, B., Kielland-Brandt, M.C. Yeast (2001) [Pubmed]
  10. Error-free RAD52 pathway and error-prone REV3 pathway determines spontaneous mutagenesis in Saccharomyces cerevisiae. Endo, K., Tago, Y., Daigaku, Y., Yamamoto, K. Genes Genet. Syst. (2007) [Pubmed]
  11. A faux 3'-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay. Amrani, N., Ganesan, R., Kervestin, S., Mangus, D.A., Ghosh, S., Jacobson, A. Nature (2004) [Pubmed]
  12. Unidirectional arginine transport in reconstituted plasma-membrane vesicles from yeast overexpressing CAN1. Opekarová, M., Caspari, T., Tanner, W. Eur. J. Biochem. (1993) [Pubmed]
  13. Visualization of protein compartmentation within the plasma membrane of living yeast cells. Malínská, K., Malínský, J., Opekarová, M., Tanner, W. Mol. Biol. Cell (2003) [Pubmed]
  14. Transport in isolated yeast vacuoles: characterization of arginine permease. Boller, T., Dürr, M., Wiemken, A. Meth. Enzymol. (1989) [Pubmed]
  15. Differential effect of phosphatidylethanolamine depletion on raft proteins: further evidence for diversity of rafts in Saccharomyces cerevisiae. Opekarová, M., Malínská, K., Nováková, L., Tanner, W. Biochim. Biophys. Acta (2005) [Pubmed]
  16. Effect of the DNA topoisomerase II inhibitor VP-16 on illegitimate recombination in yeast chromosomes. Asami, Y., Jia, D.W., Tatebayashi, K., Yamagata, K., Tanokura, M., Ikeda, H. Gene (2002) [Pubmed]
  17. No mutagenic or recombinogenic effects of mobile phone fields at 900 MHz detected in the yeast Saccharomyces cerevisiae. Gos, P., Eicher, B., Kohli, J., Heyer, W.D. Bioelectromagnetics. (2000) [Pubmed]
  18. Construction of phosphatidylethanolamine-less strain of Saccharomyces cerevisiae. Effect on amino acid transport. Robl, I., Grassl, R., Tanner, W., Opekarová, M. Yeast (2001) [Pubmed]
  19. Formamide sensitivity: a novel conditional phenotype in yeast. Aguilera, A. Genetics (1994) [Pubmed]
  20. Mutations in RAD6, a yeast gene encoding a ubiquitin-conjugating enzyme, stimulate retrotransposition. Picologlou, S., Brown, N., Liebman, S.W. Mol. Cell. Biol. (1990) [Pubmed]
  21. Evolutionary relationship and secondary structure predictions in four transport proteins of Saccharomyces cerevisiae. Weber, E., Chevallier, M.R., Jund, R. J. Mol. Evol. (1988) [Pubmed]
  22. Host genes that affect the target-site distribution of the yeast retrotransposon Ty1. Huang, H., Hong, J.Y., Burck, C.L., Liebman, S.W. Genetics (1999) [Pubmed]
  23. APL1, a yeast gene encoding a putative permease for basic amino acids. Sychrova, H., Chevallier, M.R. Yeast (1994) [Pubmed]
  24. Purified arginine permease of Candida albicans is functionally active in a reconstituted system. Mukherjee, P.K., Prasad, R. Yeast (1998) [Pubmed]
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