NPl1, an essential yeast gene involved in induced degradation of Gap1 and Fur4 permeases, encodes the Rsp5 ubiquitin-protein ligase

Mol Microbiol. 1995 Oct;18(1):77-87. doi: 10.1111/j.1365-2958.1995.mmi_18010077.x.


When yeast cells growing on a poor nitrogen source are supplied with NH4+ ions, several nitrogen permeases including the general amino acid permease (Gap1p) are rapidly and completely inactivated. This report shows that inactivation by NH4+ of the Gap1 permease is accompanied by its degradation. A functional NPl1 gene product is required for both inactivation and degradation of Gap1p. Molecular analysis of the NPl1 gene showed that it is identical to RSP5. The RSP5 product is a ubiquitin-protein ligase (E3 enzyme) whose physiological function was, however, unknown. Its C-terminal region is very similar to that of other members of the E6-AP-like family of ubiquitin-protein ligases. Its N-terminal region contains a single C2 domain that may be a Ca(2+)-dependent phospholipid interaction motif, followed by several copies of a recently identified domain called WW(P). The Npi1/Rsp5 protein has a homologue both in humans and in mice, the latter being involved in brain development. Stress-induced degradation of the uracil permease (Fur4p), a process in which ubiquitin is probably involved, was also found to require a functional NPl1/RSP5 product. Chromosomal deletion of NPl1/RSP5 showed that this gene is essential for cell viability. In the viable npi1/rsp5 strain, expression of NPl1/RSP5 is reduced as a result of insertion of a Ty1 element in its 5' region. Our results show that the Npi1/Rsp5 ubiquitin-protein ligase participates in induced degradation of at least two permeases, Gap1p and Fur4p, and probably also other proteins.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Transport Systems
  • Cloning, Molecular
  • Endosomal Sorting Complexes Required for Transport
  • Fungal Proteins / genetics*
  • Genes, Fungal*
  • Genes, Lethal
  • Immunoblotting
  • Ligases / genetics*
  • Membrane Transport Proteins / metabolism*
  • Molecular Sequence Data
  • Nucleotide Transport Proteins*
  • Quaternary Ammonium Compounds / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Ubiquitin-Protein Ligase Complexes*
  • Ubiquitin-Protein Ligases


  • Amino Acid Transport Systems
  • Endosomal Sorting Complexes Required for Transport
  • FUR4 protein, S cerevisiae
  • Fungal Proteins
  • Membrane Transport Proteins
  • Nucleotide Transport Proteins
  • Quaternary Ammonium Compounds
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Ubiquitin-Protein Ligases
  • Ligases
  • RSP5 protein, S cerevisiae

Associated data

  • GENBANK/D10714
  • GENBANK/D24373
  • GENBANK/D42055
  • GENBANK/L07557
  • GENBANK/L11119
  • GENBANK/U18916
  • GENBANK/Z17560