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Gene Review

APE1  -  Ape1p

Saccharomyces cerevisiae S288c

Synonyms: API, Aminopeptidase yscI, LAP4, LAPIV, Leucine aminopeptidase IV, ...
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Disease relevance of LAP4

  • We evaluated the API 20C AUX yeast identification system as well as several biochemical tests and Kirby-Bauer susceptibility patterns for the identification of 75 isolates encompassing the 8 medically relevant Nocardia species [1].
  • The gram-positive coccus was identified as Enterococcus faecium by the API 20 Strepsystem, conventional biochemical tests, and it had 99% 16S rDNA sequence identity (GenBank Accession Number AJ276355) to E. faecium (GenBank Accession Number AF529204) [2].

High impact information on LAP4

  • The cytoplasm to vacuole targeting (Cvt) pathway transports the vacuolar hydrolase, aminopeptidase I (API), whereas pexophagy mediates the delivery of excess peroxisomes for degradation [3].
  • In nutrient-rich, vegetative conditions, the yeast Saccharomyces cerevisiae transports a resident protease, aminopeptidase I (API), to the vacuole by the cytoplasm to vacuole targeting (Cvt) pathway, thus contributing to the degradative capacity of this organelle [4].
  • Fractionation and protease protection experiments indicate that Tlg2p is required prior to or at the step of API segregation into the Cvt vesicle [5].
  • Aminopeptidase I (API) is imported into the yeast vacuole/lysosome by a constitutive non-classical vesicular transport mechanism, the cytoplasm to vacuole targeting (Cvt) pathway [5].
  • This overlap coupled with both in vitro and in vivo analysis of API import suggested that, like autophagy, API transport is vesicular [6].

Biological context of LAP4

  • Further, the aminopeptidase I gene, localized previously by genetic mapping to yeast chromosome XI and called the LAP4 gene (Trumbly, R. J., and Bradley, G. (1983) J. Bacteriol. 156, 36-48), was determined by DNA blot analyses to be a single copy gene located on chromosome XI [7].
  • In addition to genes encoding subunits of the 20S proteasome, genes related to vacuolar proteolysis (PEP4 and LAP4), protein sorting into the vacuole, and vacuolar fusion were found to be induced [8].
  • The DNA sequence analysis of the HAP4-LAP4 region on chromosome XI of Saccharomyces cerevisiae suggests the presence of a second aspartate aminotransferase gene in yeast [9].
  • By deletion analysis of the fusion gene APE1-lacZ we have identified a number of strong regulatory regions in the APE1 promoter [10].
  • Aminopeptidase I (API) is delivered to the yeast vacuole by one of two alternative pathways, cytoplasm to vacuole targeting (Cvt) or autophagy, depending on nutrient conditions [11].

Anatomical context of LAP4

  • In the yeast Saccharomyces cerevisiae, for example, double-membrane vesicles are used to transport the Ape1 protease into the vacuole, or for the elimination of superfluous peroxisomes [12].
  • Before targeting, the precursor form of API is localized mostly in restricted regions of the cytosol as a complex with spherical particles (termed Cvt complex) [13].
  • Our findings indicate that API is maintained as a dodecamer throughout its import and will be useful to study the posttranslational movement of folded proteins across biological membranes [14].
  • Their identification was based on sugar assimilation reactions using API 20 C Aux. A total of seven (9%) isolates recovered from sputum, bronchial lavage and nasopharyngeal aspirate were identified as C. dubliniensis [15].
  • Putative C. albicans colony-forming units on selective bismuth sulfite glucose glycine yeast agar plates were identified with the API 20C system [16].

Associations of LAP4 with chemical compounds

  • When added to induced cells, glucose leads to the disappearance of hybridizable aminopeptidase yscI RNA sequences within 30 min [10].
  • In particular, we show that precursor Ape1 is not correctly recruited to the PAS, the putative site of double-membrane vesicle biogenesis, and superfluous peroxisomes are not degraded in a conditional actin mutant [12].
  • Atg19p is ubiquitinated on two lysine residues, Lys(213) and Lys(216), which, when mutated, reduce the interaction of Atg19p with Ape1p [17].
  • Aminopeptidase I (API) is a soluble leucine aminopeptidase resident in the yeast vacuole (Frey, J., and K.H. Rohm. 1978. Biochim. Biophys. Acta. 527:31-41) [18].
  • ATP gamma S inhibits this reaction, indicating that API transport is ATP driven [19].

Physical interactions of LAP4

  • We show that the Cvt13 and Cvt20 proteins are required for transport of precursor Ape1 through the Cvt pathway [20].

Regulatory relationships of LAP4

  • These data suggest that Aut7p is induced during autophagy and delivered to the vacuole together with precursor API by Cvt/autophagic vesicles [11].

Other interactions of LAP4

  • The deletion of APE1 or ATG19 compromised the organization of the pre-autophagosomal structure (PAS), a site that is thought to play a critical role in Cvt vesicle/autophagosome formation [21].
  • Accordingly, the deletion of APE1, ATG19, or ATG11 affected the formation of Cvt vesicles [21].
  • Deletion of UBP3 also leads to decreased targeting of Ape1p to the vacuole [17].
  • The cytoplasm to vacuole (Cvt) trafficking pathway in S. cerevisiae is a constitutive biosynthetic pathway required for the transport of two vacuolar enzymes, aminopeptidase I (Ape1p) and alpha-mannosidase (Ams1p), to the vacuole [17].
  • Finally, the aut7/cvt5 mutant accumulates precursor API at a stage prior to vesicle completion [11].

Analytical, diagnostic and therapeutic context of LAP4

  • PCR fingerprinting was more discriminatory when compared with routinely used biochemical tests (Vitek YBC and API ID 32C) [22].
  • The Auxacolor system provided more rapid, accurate results and displayed less interobserver variability than the API 20C Aux [23].
  • A newly developed commercial serological test (Iatron Laboratories, Inc., Tokyo, Japan) for the rapid identification of medically important species of Candida was evaluated against the API 20C (Analytab Products, Plainview, N.Y.) and the standard Wickerham assimilation and fermentation procedures [24].


  1. Identification of medically relevant Nocardia species with an abbreviated battery of tests. Kiska, D.L., Hicks, K., Pettit, D.J. J. Clin. Microbiol. (2002) [Pubmed]
  2. Metschnikowia bicuspidata and Enterococcus faecium co-infection in the giant freshwater prawn Macrobrachium rosenbergii. Chen, S.C., Chen, T.H., Wang, P.C., Chen, Y.C., Huang, J.P., Lin, Y.D., Chaung, H.C., Liaw, L.L. Dis. Aquat. Org. (2003) [Pubmed]
  3. Cvt9/Gsa9 functions in sequestering selective cytosolic cargo destined for the vacuole. Kim, J., Kamada, Y., Stromhaug, P.E., Guan, J., Hefner-Gravink, A., Baba, M., Scott, S.V., Ohsumi, Y., Dunn, W.A., Klionsky, D.J. J. Cell Biol. (2001) [Pubmed]
  4. Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways. Noda, T., Kim, J., Huang, W.P., Baba, M., Tokunaga, C., Ohsumi, Y., Klionsky, D.J. J. Cell Biol. (2000) [Pubmed]
  5. Cytoplasm to vacuole trafficking of aminopeptidase I requires a t-SNARE-Sec1p complex composed of Tlg2p and Vps45p. Abeliovich, H., Darsow, T., Emr, S.D. EMBO J. (1999) [Pubmed]
  6. Aminopeptidase I is targeted to the vacuole by a nonclassical vesicular mechanism. Scott, S.V., Baba, M., Ohsumi, Y., Klionsky, D.J. J. Cell Biol. (1997) [Pubmed]
  7. Molecular cloning and sequencing of genomic DNA encoding aminopeptidase I from Saccharomyces cerevisiae. Chang, Y.H., Smith, J.A. J. Biol. Chem. (1989) [Pubmed]
  8. The Pep4p vacuolar proteinase contributes to the turnover of oxidized proteins but PEP4 overexpression is not sufficient to increase chronological lifespan in Saccharomyces cerevisiae. Marques, M., Mojzita, D., Amorim, M.A., Almeida, T., Hohmann, S., Moradas-Ferreira, P., Costa, V. Microbiology (Reading, Engl.) (2006) [Pubmed]
  9. The DNA sequence analysis of the HAP4-LAP4 region on chromosome XI of Saccharomyces cerevisiae suggests the presence of a second aspartate aminotransferase gene in yeast. Chéret, G., Pallier, C., Valens, M., Diagnan-Fornier, B., Fukuhara, H., Bolotin-Fukuhara, M., Sor, F. Yeast (1993) [Pubmed]
  10. Transcriptional regulation of the yeast vacuolar aminopeptidase yscI encoding gene (APE1) by carbon sources. Bordallo, J., Cueva, R., Suárez-Rendueles, P. FEBS Lett. (1995) [Pubmed]
  11. The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. Huang, W.P., Scott, S.V., Kim, J., Klionsky, D.J. J. Biol. Chem. (2000) [Pubmed]
  12. The actin cytoskeleton is required for selective types of autophagy, but not nonspecific autophagy, in the yeast Saccharomyces cerevisiae. Reggiori, F., Monastyrska, I., Shintani, T., Klionsky, D.J. Mol. Biol. Cell (2005) [Pubmed]
  13. Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome. Baba, M., Osumi, M., Scott, S.V., Klionsky, D.J., Ohsumi, Y. J. Cell Biol. (1997) [Pubmed]
  14. Transport of a large oligomeric protein by the cytoplasm to vacuole protein targeting pathway. Kim, J., Scott, S.V., Oda, M.N., Klionsky, D.J. J. Cell Biol. (1997) [Pubmed]
  15. Prevalence of Candida dubliniensis among germ tube-positive yeasts recovered from the respiratory specimens in HIV-negative patients. Fotedar, R., Al Hedaithy, S.S. Mycoses (2004) [Pubmed]
  16. Oral Candida albicans in bone marrow transplant patients given chlorhexidine rinses: occurrence and susceptibilities to the agent. Thurmond, J.M., Brown, A.T., Sims, R.E., Ferretti, G.A., Raybould, T.P., Lillich, T.T., Henslee, P.J. Oral Surg. Oral Med. Oral Pathol. (1991) [Pubmed]
  17. Atg19p ubiquitination and the cytoplasm to vacuole trafficking pathway in yeast. Baxter, B.K., Abeliovich, H., Zhang, X., Stirling, A.G., Burlingame, A.L., Goldfarb, D.S. J. Biol. Chem. (2005) [Pubmed]
  18. Identification of a cytoplasm to vacuole targeting determinant in aminopeptidase I. Oda, M.N., Scott, S.V., Hefner-Gravink, A., Caffarelli, A.D., Klionsky, D.J. J. Cell Biol. (1996) [Pubmed]
  19. In vitro reconstitution of cytoplasm to vacuole protein targeting in yeast. Scott, S.V., Klionsky, D.J. J. Cell Biol. (1995) [Pubmed]
  20. Cooperative binding of the cytoplasm to vacuole targeting pathway proteins, Cvt13 and Cvt20, to phosphatidylinositol 3-phosphate at the pre-autophagosomal structure is required for selective autophagy. Nice, D.C., Sato, T.K., Stromhaug, P.E., Emr, S.D., Klionsky, D.J. J. Biol. Chem. (2002) [Pubmed]
  21. Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vacuole targeting pathway. Shintani, T., Klionsky, D.J. J. Biol. Chem. (2004) [Pubmed]
  22. Identification of pathogenic yeasts of the imperfect genus Candida by polymerase chain reaction fingerprinting. Meyer, W., Latouche, G.N., Daniel, H.M., Thanos, M., Mitchell, T.G., Yarrow, D., Schönian, G., Sorrell, T.C. Electrophoresis (1997) [Pubmed]
  23. Evaluation of the auxacolor system for biochemical identification of medically important yeasts. Sheppard, D.C., deSouza, E., Hashmi, Z., Robson, H.G., René, P. J. Clin. Microbiol. (1998) [Pubmed]
  24. Comparative evaluation of the Iatron serological Candida check kit and the API 20C kit for identification of medically important Candida species. Shinoda, T., Kaufman, L., Padhye, A.A. J. Clin. Microbiol. (1981) [Pubmed]
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