In this paper, we present the Functional Catalogue (FunCat), a hierarchically structured, organism-independent, flexible and scalable controlled classification system enabling the functional description of proteins from any organism. FunCat has been applied for the manual annotation of prokaryotes, fungi, plants and animals. We describe how FunCat is implemented as a highly efficient and robust tool for the manual and automatic annotation of genomic sequences. Owing to its hierarchical architecture, FunCat has also proved to be useful for many subsequent downstream bioinformatic applications. This is illustrated by the analysis of large-scale experiments from various investigations in transcriptomics and proteomics, where FunCat was used to project experimental data into functional units, as 'gold standard' for functional classification methods, and also served to compare the significance of different experimental methods. Over the last decade, the FunCat has been established as a robust and stable annotation scheme that offers both, meaningful and manageable functional classification as well as ease of perception.

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In a genetic screen aimed at the identification of trans-acting factors involved in mRNA 3-end processing of budding yeast, we have previously isolated two temperature-sensitive mutants with an apparent defect in the 3-end formation of a plasmid-derived pre-mRNA. Surprisingly, both mutants were rescued by the essential gene ESS1/PTF1 that encoded a putative peptidylprolyl-cis/trans-isomerase (PPIase) (Hani, J., Stumpf, G., and Domdey, H. (1995) FEBS Lett. 365, 198 -202). Such enzymes, which catalyze the cis/trans-interconversion of peptide bonds N-terminal of prolines, are suggested to play a role in protein folding or trafficking. Here we report that Ptf1p shows PPIase activity in vitro, displaying an unusual substrate specificity for peptides with phosphorylated serine and threonine residues preceding proline. Both mutations were found to result in amino acid substitutions of highly conserved residues within the PPIase domain, causing a marked decrease in PPIase activity of the mutant enzymes. Our results are suggestive of a so far unknown involvement of a PPIase in mRNA 3-end formation in Saccharomyces cerevisiae.Despite intensive efforts to unravel the complex process of mRNA 3Ј-end formation in Saccharomyces cerevisiae, the list of participating factors still awaits its completion.We have recently isolated a gene complementing the phenotype of two temperature-sensitive yeast mutants that were impaired in mRNA 3Ј-end formation. This gene, designated PTF1 (processing/termination factor 1; identical with the previously described ESS1 (1)), encodes a protein that, by virtue of sequence similarity, was identified as a peptidylprolyl-cis/ trans-isomerase (PPIase) 1 (2). PPIases are ubiquitous enzymes that catalyze the interconversion from cis to trans of peptide bonds preceding a proline and are thought to accelerate this often rate-limiting step in the folding of a number of proteins in vivo (3-6).PPIases are divided in three families, based on their sensitivities toward two clinically relevant immunosuppressants: the cyclosporin A-binding proteins (cyclophilins), the FK506-binding proteins, and a third family, named after the Escherichia coli protein parvulin, which is not inhibited by either of the two drugs (for review see Refs. 3-6). In addition, the members of each family are characterized by conserved but distinct amino acid domains. By this criterion, PTF1 was predicted to belong to the parvulin family of PPIases (2).Although disruption of PPIase genes did not generally impair cell growth (7-8), PTF1 was the first PPIase gene shown to be essential for cell viability (1). In fact, PTF1 is the only essential PPIase gene in S. cerevisiae as demonstrated more recently by the viability of a yeast mutant lacking the remaining 12 PPIases, members of the other two immunosuppressant binding families. (8). So far, the only other example of an essential PPIase is the recently discovered PIN1, a human protein, that is structurally and functionally related to Ptf1p (9 -10).In this paper we describe the genetic screen ...

The collaboration of more than 600 scientists from over 100 laboratories to sequence the Saccharomyces cerevisiae genome was the largest decentralised experiment in modern molecular biology and resulted in a unique data resource representing the first complete set of genes from a eukaryotic organism. 12 million bases were sequenced in a truly international effort involving European, US, Canadian and Japanese laboratories. While the yeast genome represents only a small fraction of the information in today's public sequence databases, the complete, ordered and non-redundant sequence provides an invaluable resource for the detailed analysis of cellular gene function and genome architecture. In terms of throughput, completeness and information content, yeast has always been the lead eukaryotic organism in genomics; it is still the largest genome to be completely sequenced.

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