The recognition component of the N-end rule pathway.
The N-end rule-based degradation signal, which targets a protein for ubiquitin-dependent proteolysis, comprises a destabilizing amino-terminal residue and a specific internal lysine residue. We report the isolation and functional analysis of a gene (UBR1) for the N-end recognizing protein of the yeast Saccharomyces cerevisiae. UBR1 encodes a approximately 225 kd protein with no significant sequence similarities to other known proteins. Null ubr1 mutants are viable but are unable to degrade the substrates of the N-end rule pathway. These mutants are partially defective in sporulation and grow slightly more slowly than their wild-type counterparts. The UBR1 protein specifically binds in vitro to proteins bearing amino-terminal residues that are destabilizing according to the N-end rule, but does not bind to otherwise identical proteins bearing stabilizing amino-terminal residues.
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
B
B
Bartel
I
I
Wünning
A
A
Varshavsky
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004271:DNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005800:Genes, Fungal; D005838:Genotype; D008025:Ligases; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D010641:Phenotype; D010957:Plasmids; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases
D004271:DNA, Fungal; D005656:Fungal Proteins; D015345:Oligonucleotide Probes; D029701:Saccharomyces cerevisiae Proteins; C066066:UBR1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D008025:Ligases