Protein abundance is controlled at the transcriptional, translational and post-translational levels, and its regulatory principles are starting to emerge. Investigating these principles requires large-scale proteomics data and cannot just be done with transcriptional outcomes that are commonly used as a proxy for protein abundance. Here, we determine proteome changes resulting from the individual knockout of 3308 nonessential genes in the yeast Schizosaccharomyces pombe. We use similarity clustering of global proteome changes to infer gene functionality that can be extended to other species, such as humans or baker's yeast. Furthermore, we analyze a selected set of deletion mutants by paired transcriptome and proteome measurements and show that upregulation of proteins under stable transcript expression utilizes optimal codons.