ArticleMolecular biology of the cell2001
Topological and mutational analysis of Saccharomyces cerevisiae Ste14p, founding member of the isoprenylcysteine carboxyl methyltransferase family.
Article in Molecular biology of the cell, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Snowball: a novel gene family required for developmental patterning of fruiting bodies of mushroom-forming fungi (Agaricomycetes).mSystems · 2024Article
- Lessons on fruiting body morphogenesis from genomes and transcriptomes ofStudies in mycology · 2023Article
- Methyltransferases: Functions and Applications.Chembiochem : a European journal of chemical biology · 2022Review
- Transcriptional regulation by methyltransferases and their role in the heart: highlighting novel emerging functionality.American journal of physiology. Heart and circulatory physiology · 2020Review
- The topology of the ER-resident phospholipid methyltransferase Opi3 ofThe Journal of biological chemistry · 2020Article
- Article
- Host Methyltransferases and Demethylases: Potential New Epigenetic Targets for HIV Cure Strategies and Beyond.AIDS research and human retroviruses · 2017Review
- A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes.eLife · 2016Article
- The Role of Protein Arginine Methyltransferases in Inflammatory Responses.Mediators of inflammation · 2016Review
- A novel pathway producing dimethylsulphide in bacteria is widespread in soil environments.Nature communications · 2015Article
- Control of Ras-mediated signaling in Aspergillus fumigatus.Mycopathologia · 2014Review
- Mutational analysis of the integral membrane methyltransferase isoprenylcysteine carboxyl methyltransferase (ICMT) reveals potential substrate binding sites.The Journal of biological chemistry · 2014Article
- Topology of the yeast Ras converting enzyme as inferred from cysteine accessibility studies.Biochemistry · 2013Article
- Structural and functional studies of S-adenosyl-L-methionine binding proteins: a ligand-centric approach.BMC structural biology · 2013Article
- Biogenesis of the Saccharomyces cerevisiae pheromone a-factor, from yeast mating to human disease.Microbiology and molecular biology reviews : MMBR · 2012Review
- Evaluation of substrate and inhibitor binding to yeast and human isoprenylcysteine carboxyl methyltransferases (Icmts) using biotinylated benzophenone-containing photoaffinity probes.Biochemical and biophysical research communications · 2012Article
- Photoaffinity labeling of Ras converting enzyme using peptide substrates that incorporate benzoylphenylalanine (Bpa) residues: improved labeling and structural implications.Bioorganic & medicinal chemistry · 2011Article
- Asparagine peptide lyases: a seventh catalytic type of proteolytic enzymes.The Journal of biological chemistry · 2011Article
- Uncovering the human methyltransferasome.Molecular & cellular proteomics : MCP · 2011Article
- Functional oligomerization of the Saccharomyces cerevisiae isoprenylcysteine carboxyl methyltransferase, Ste14p.The Journal of biological chemistry · 2010Article
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2 authors.
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Abstract
Eukaryotic proteins that terminate in a CaaX motif undergo three processing events: isoprenylation, C-terminal proteolytic cleavage, and carboxyl methylation. In Saccharomyces cerevisiae, the latter step is mediated by Ste14p, an integral endoplasmic reticulum membrane protein. Ste14p is the founding member of the isoprenylcysteine carboxyl methyltransferase (ICMT) family, whose members share significant sequence homology. Because the physiological substrates of Ste14p, such as Ras and the yeast a-factor precursor, are isoprenylated and reside on the cytosolic side of membranes, the Ste14p residues involved in enzymatic activity are predicted to be cytosolically disposed. In this study, we have investigated the topology of Ste14p by analyzing the protease protection of epitope-tagged versions of Ste14p and the glycosylation status of Ste14p-Suc2p fusions. Our data lead to a topology model in which Ste14p contains six membrane spans, two of which form a helical hairpin. According to this model most of the Ste14p hydrophilic regions are located in the cytosol. We have also generated ste14 mutants by random and site-directed mutagenesis to identify residues of Ste14p that are important for activity. Notably, four of the five loss-of-function mutations arising from random mutagenesis alter residues that are highly conserved among the ICMT family. Finally, we have identified a novel tripartite consensus motif in the C-terminal region of Ste14p. This region is similar among all ICMT family members, two phospholipid methyltransferases, several ergosterol biosynthetic enzymes, and a group of bacterial open reading frames of unknown function. Site-directed and random mutations demonstrate that residues in this region play a critical role in the function of Ste14p.
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