In a forward genetic screen for interaction with mitochondrial iron carrier proteins in Saccharomyces cerevisiae, a hypomorphic mutation of the essential DRE2 gene was found to confer lethality when combined with Delta mrs3 and Delta mrs4. The dre2 mutant or Dre2-depleted cells were deficient in cytosolic Fe/S cluster protein activities while maintaining mitochondrial Fe/S clusters. The Dre2 amino acid sequence was evolutionarily conserved, and cysteine motifs (CX(2)CXC and twin CX(2)C) in human and yeast proteins were perfectly aligned. The human Dre2 homolog (implicated in blocking apoptosis and called CIAPIN1 or anamorsin) was able to complement the nonviability of a Deltadre2 deletion strain. The Dre2 protein with triple hemagglutinin tag was located in the cytoplasm and in the mitochondrial intermembrane space. Yeast Dre2 overexpressed and purified from bacteria was brown and exhibited signature absorption and electron paramagnetic resonance spectra, indicating the presence of both [2Fe-2S] and [4Fe-4S] clusters. Thus, Dre2 is an essential conserved Fe/S cluster protein implicated in extramitochondrial Fe/S cluster assembly, similar to other components of the so-called CIA (cytoplasmic Fe/S cluster assembly) pathway although partially localized to the mitochondrial intermembrane space.
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Gene | Phenotype | Experiment Type | Mutant Information | Strain Background | Chemical | Details |
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DRE2 | protein activity: decreased Reporter: IRP1 human cytosolic aconitase | classical genetics | repressible Allele: Gal-Dre2 DRE2 under Gal-inducible promoter | S288C | Media: media lacking galactose | |
DRE2 | protein activity: decreased Reporter: Leu1p pRS426-Leu1-His6 | classical genetics | repressible Allele: Gal-Dre2 DRE2 under Gal-inducible promoter | S288C | Media: media lacking galactose | |
DRE2 | protein/peptide distribution: abnormal Reporter: Rpl25p-eGFP 60S ribosomal subunit reporter | classical genetics | repressible Allele: Gal-Dre2 DRE2 under Gal-inducible promoter | S288C | Details: nuclear retention of ribosomal protein Rpl25p | |
DRE2 | utilization of iron source: decreased | classical genetics | reduction of function Allele: dre2-137 K26stop | Other | ||
DRE2 | vegetative growth: decreased | classical genetics | reduction of function Allele: dre2-137 K26stop | Other | Details: very slow growth rate |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.