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Gene Review

KEX1  -  Kex1p

Saccharomyces cerevisiae S288c

Synonyms: Carboxypeptidase D, Killer expression defective protein 1, Pheromone-processing carboxypeptidase KEX1, YGL203C
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Disease relevance of KEX1

  • A vaccinia virus vector was used to express the yeast KEX1 gene, which encodes a prohormone carboxypeptidase specific for the removal of basic amino acids from prohormone processing intermediates, in mammalian cells [1].
  • The resulting truncated KEX1 gene (KEX1 delta) has been expressed in the baculovirus/insect cell system [2].

High impact information on KEX1

  • The predicted amino acid sequence of the "protective protein" bears homology to yeast carboxypeptidase Y and the KEX1 gene product [3].
  • A mutant replacing serine at the putative active site of the KEX1 protein abolished activity in vivo [4].
  • Kex2 and Kex1 may promote cell fusion by proteolytically processing substrates that act in parallel to Prm1 as an alternative fusion machine, as cell wall components, or both [5].
  • Kre2p/Mnt1p is localized in a Golgi compartment that overlaps with that containing the medial-Golgi mannosyltransferase Mnn1p, and distinct from that including the late Golgi protein Kex1p [6].
  • Glycosylation studies of Kex1p were consistent with a Golgi location, as Kex1p was progressively N-glycosylated in an MNN1-dependent manner [7].

Biological context of KEX1


Anatomical context of KEX1

  • To address the basis of Kex1p targeting to the Golgi apparatus, we examined the cellular location of a series of carboxy-terminal truncations of the protein [7].
  • The method gives a high yield of sealed organelles that are essentially free of contamination from other secretory pathway organelles while being significantly enriched for two other late Golgi enzymes, dipeptidylaminopeptidase A and the Kex1 carboxypeptidase [11].
  • The mature C terminus of the beta subunit is trimmed by Kex1p, which removes the terminal Arg(345) residue, thus uncovering the toxin's endoplasmic reticulum targeting signal (HDEL) which--in a sensitive target cell--is essential for retrograde toxin transport [12].

Associations of KEX1 with chemical compounds

  • Our results provide biochemical evidence consistent with earlier genetic work, that KEX1 encodes a serine carboxypeptidase involved in the processing of precursors to secreted mature proteins [13].
  • Kex2 is located on chromosome XIV, but it does not show meiotic linkage to any gene previously located on this chromosome.--When the killer plasmid of kex1 or kex2 strains is eliminated by curing with heat or cycloheximide, the strains become sensitive to killing [9].
  • We hypothesized that the KEX1 homologue in P. pastoris is responsible for the loss of the C-terminal lysine of endostatin [14].
  • Kex1p was found to be a membrane-associated glycoprotein with N-linked carbohydrate [13].
  • We demonstrate that Kex1 contributes also to the active cell death program induced by acetic acid stress or during chronological aging, suggesting that Kex1 plays a more general role in cellular suicide of yeast [15].

Other interactions of KEX1

  • Maturation of the alpha-factor precursor involves three proteolytic activities which are encoded by the KEX1, KEX2, and STE13 genes, respectively [16].
  • Direct involvement of yscY and ysc alpha was confirmed by sequential disruption of their structural genes PRC1 and KEX1, respectively [17].
  • The clathrin heavy chain gene was mapped 1-2 cM distal to KEX1 on the left arm of chromosome VII by making use of integrated 2 mu plasmid sequences to destabilize distal chromosome segments and allow ordering of the genes [18].
  • Combination of mutations and disruptions of the host genes encoding proteinase A, B, carboxypeptidase Y, and Kex1p or Mkc7p did not influence the C-terminal deletions [19].

Analytical, diagnostic and therapeutic context of KEX1

  • Site-directed mutagenesis further indicated that the toxin's beta-HDEL motif ensures retrograde transport, although in a toxin-secreting yeast the beta-C-terminus is initially masked by an R residue (beta-HDELR) until Kex1p cleavage uncovers the toxin's targeting signal in a late Golgi compartment [20].
  • Southern blotting of restriction enzyme digests of genomic DNA from P. carinii-infected mouse lung demonstrated that kex1 is a single copy gene [21].
  • Crystallization of a soluble form of the Kex1p serine carboxypeptidase from Saccharomyces cerevisiae [22].


  1. Yeast KEX1 protease cleaves a prohormone processing intermediate in mammalian cells. Thomas, L., Cooper, A., Bussey, H., Thomas, G. J. Biol. Chem. (1990) [Pubmed]
  2. Secretion, purification and characterization of a soluble form of the yeast KEX1-encoded protein from insect-cell cultures. Latchinian-Sadek, L., Thomas, D.Y. Eur. J. Biochem. (1994) [Pubmed]
  3. Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases. Galjart, N.J., Gillemans, N., Harris, A., van der Horst, G.T., Verheijen, F.W., Galjaard, H., d'Azzo, A. Cell (1988) [Pubmed]
  4. Yeast KEX1 gene encodes a putative protease with a carboxypeptidase B-like function involved in killer toxin and alpha-factor precursor processing. Dmochowska, A., Dignard, D., Henning, D., Thomas, D.Y., Bussey, H. Cell (1987) [Pubmed]
  5. The Golgi-resident protease Kex2 acts in conjunction with Prm1 to facilitate cell fusion during yeast mating. Heiman, M.G., Engel, A., Walter, P. J. Cell Biol. (2007) [Pubmed]
  6. Localization and targeting of the Saccharomyces cerevisiae Kre2p/Mnt1p alpha 1,2-mannosyltransferase to a medial-Golgi compartment. Lussier, M., Sdicu, A.M., Ketela, T., Bussey, H. J. Cell Biol. (1995) [Pubmed]
  7. Yeast Kex1p is a Golgi-associated membrane protein: deletions in a cytoplasmic targeting domain result in mislocalization to the vacuolar membrane. Cooper, A., Bussey, H. J. Cell Biol. (1992) [Pubmed]
  8. A nuclear gene required for the expression of the linear DNA-associated killer system in the yeast Kluyveromyces lactis. Wesolowski-Louvel, M., Tanguy-Rougeau, C., Fukuhara, H. Yeast (1988) [Pubmed]
  9. Two chromosomal genes required for killing expression in killer strains of Saccharomyces cerevisiae. Wickner, R.B., Leibowitz, M.J. Genetics (1976) [Pubmed]
  10. Prohormone processing by yeast proteases. Bourbonnais, Y., Germain, D., Latchinian-Sadek, L., Boileau, G., Thomas, D.Y. Enzyme (1991) [Pubmed]
  11. Immunoisolation of Kex2p-containing organelles from yeast demonstrates colocalisation of three processing proteinases to a single Golgi compartment. Bryant, N.J., Boyd, A. J. Cell. Sci. (1993) [Pubmed]
  12. Mutational analysis of K28 preprotoxin processing in the yeast Saccharomyces cerevisiae. Riffer, F., Eisfeld, K., Breinig, F., Schmitt, M.J. Microbiology (Reading, Engl.) (2002) [Pubmed]
  13. Characterization of the yeast KEX1 gene product: a carboxypeptidase involved in processing secreted precursor proteins. Cooper, A., Bussey, H. Mol. Cell. Biol. (1989) [Pubmed]
  14. Disruption of the KEX1 gene in Pichia pastoris allows expression of full-length murine and human endostatin. Boehm, T., Pirie-Shepherd, S., Trinh, L.B., Shiloach, J., Folkman, J. Yeast (1999) [Pubmed]
  15. Kex1 protease is involved in yeast cell death induced by defective N-glycosylation, acetic acid, and chronological aging. Hauptmann, P., Lehle, L. J. Biol. Chem. (2008) [Pubmed]
  16. Regulation of alpha-factor production in Saccharomyces cerevisiae: a-factor pheromone-induced expression of the MF alpha 1 and STE13 genes. Achstetter, T. Mol. Cell. Biol. (1989) [Pubmed]
  17. C-terminal proteolytic degradation of recombinant desulfato-hirudin and its mutants in the yeast Saccharomyces cerevisiae. Heim, J., Takabayashi, K., Meyhack, B., Märki, W., Pohlig, G. Eur. J. Biochem. (1994) [Pubmed]
  18. Genetic instability of clathrin-deficient strains of Saccharomyces cerevisiae. Lemmon, S.K., Freund, C., Conley, K., Jones, E.W. Genetics (1990) [Pubmed]
  19. High-level production of human parathyroid hormone (hPTH) by induced expression in Saccharomyces cerevisiae. Vad, R., Moe, E., Saga, K., Kvinnsland, A.M., Oyen, T.B. Protein Expr. Purif. (1998) [Pubmed]
  20. Endocytotic uptake and retrograde transport of a virally encoded killer toxin in yeast. Eisfeld, K., Riffer, F., Mentges, J., Schmitt, M.J. Mol. Microbiol. (2000) [Pubmed]
  21. Molecular characterization of KEX1, a kexin-like protease in mouse Pneumocystis carinii. Lee, L.H., Gigliotti, F., Wright, T.W., Simpson-Haidaris, P.J., Weinberg, G.A., Haidaris, C.G. Gene (2000) [Pubmed]
  22. Crystallization of a soluble form of the Kex1p serine carboxypeptidase from Saccharomyces cerevisiae. Shilton, B.H., Li, Y., Tessier, D., Thomas, D.Y., Cygler, M. Protein Sci. (1996) [Pubmed]
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