Search

Motivation The number of protein records in the UniProt Knowledgebase (UniProtKB: https://www.uniprot.org) continues to grow rapidly as a result of genome sequencing and the prediction of protein-coding genes. Providing functional annotation for these proteins presents a significant and continuing challenge. Results In response to this challenge, UniProt has developed a method of annotation, known as UniRule, based on expertly curated rules, which integrates related systems (RuleBase, HAMAP, PIRSR, PIRNR) developed by the members of the UniProt consortium. UniRule uses protein family signatures from InterPro, combined with taxonomic and other constraints, to select sets of reviewed proteins which have common functional properties supported by experimental evidence. This annotation is propagated to unreviewed records in UniProtKB that meet the same selection criteria, most of which do not have (and are never likely to have) experimentally verified functional annotation. Release 2020_01 of UniProtKB contains 6496 UniRule rules which provide annotation for 53 million proteins, accounting for 30% of the 178 million records in UniProtKB. UniRule provides scalable enrichment of annotation in UniProtKB. Availability and implementation UniRule rules are integrated into UniProtKB and can be viewed at https://www.uniprot.org/unirule/. UniRule rules and the code required to run the rules, are publicly available for researchers who wish to annotate their own sequences. The implementation used to run the rules is known as UniFIRE and is available at https://gitlab.ebi.ac.uk/uniprot-public/unifire.

SwissBioPics (www.swissbiopics.org) is a freely available resource of interactive, high-resolution cell images designed for the visualization of subcellular location data. SwissBioPics provides images describing cell types from all kingdoms of life—from the specialized muscle, neuronal and epithelial cells of animals, to the rods, cocci, clubs and spirals of prokaryotes. All cell images in SwissBioPics are drawn in Scalable Vector Graphics (SVG), with each subcellular location tagged with a unique identifier from the controlled vocabulary of subcellular locations and organelles of UniProt (https://www.uniprot.org/locations/). Users can search and explore SwissBioPics cell images through our website, which provides a platform for users to learn more about how cells are organized. A web component allows developers to embed SwissBioPics images in their own websites, using the associated JavaScript and a styling template, and to highlight subcellular locations and organelles by simply providing the web component with the appropriate identifier(s) from the UniProt-controlled vocabulary or the ‘Cellular Component’ branch of the Gene Ontology (www.geneontology.org), as well as an organism identifier from the National Center for Biotechnology Information taxonomy (https://www.ncbi.nlm.nih.gov/taxonomy). The UniProt website now uses SwissBioPics to visualize the subcellular locations and organelles where proteins function. SwissBioPics is freely available for anyone to use under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. Database URL www.swissbiopics.org

BackgroundGenome and proteome annotation pipelines are generally custom built and not easily reusable by other groups. This leads to duplication of effort, increased costs, and suboptimal annotation quality. One way to address these issues is to encourage the adoption of annotation standards and technological solutions that enable the sharing of biological knowledge and tools for genome and proteome annotation.ResultsHere we demonstrate one approach to generate portable genome and proteome annotation pipelines that users can run without recourse to custom software. This proof of concept uses our own rule-based annotation pipeline HAMAP, which provides functional annotation for protein sequences to the same depth and quality as UniProtKB/Swiss-Prot, and the World Wide Web Consortium (W3C) standards Resource Description Framework (RDF) and SPARQL (a recursive acronym for the SPARQL Protocol and RDF Query Language). We translate complex HAMAP rules into the W3C standard SPARQL 1.1 syntax, and then apply them to protein sequences in RDF format using freely available SPARQL engines. This approach supports the generation of annotation that is identical to that generated by our own in-house pipeline, using standard, off-the-shelf solutions, and is applicable to any genome or proteome annotation pipeline.ConclusionsHAMAP SPARQL rules are freely available for download from the HAMAP FTP site, ftp://ftp.expasy.org/databases/hamap/sparql/, under the CC-BY-ND 4.0 license. The annotations generated by the rules are under the CC-BY 4.0 license. A tutorial and supplementary code to use HAMAP as SPARQL are available on GitHub at https://github.com/sib-swiss/HAMAP-SPARQL, and general documentation about HAMAP can be found on the HAMAP website at https://hamap.expasy.org.

The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.

The UniProt Knowledgebase is a collection of sequences and annotations for over 120 million proteins across all branches of life. Detailed annotations extracted from the literature by expert curators have been collected for over half a million of these proteins. These annotations are supplemented by annotations provided by rule based automated systems, and those imported from other resources. In this article we describe significant updates that we have made over the last 2 years to the resource. We have greatly expanded the number of Reference Proteomes that we provide and in particular we have focussed on improving the number of viral Reference Proteomes. The UniProt website has been augmented with new data visualizations for the subcellular localization of proteins as well as their structure and interactions. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.

UniProt continues to support the ongoing process of making scientific data FAIR. Here we contribute to this process with a FAIRness assessment of our UniProtKB dataset followed by a critical reflection on the challenges and future directions of the adoption and validation of the FAIR principles and metrics.

The Gene Ontology (GO) is a comprehensive resource of computable knowledge regarding the functions of genes and gene products. As such, it is extensively used by the biomedical research community for the analysis of -omics and related data. Our continued focus is on improving the quality and utility of the GO resources, and we welcome and encourage input from researchers in all areas of biology. In this update, we summarize the current contents of the GO knowledgebase, and present several new features and improvements that have been made to the ontology, the annotations and the tools. Among the highlights are 1) developments that facilitate access to, and application of, the GO knowledgebase, and 2) extensions to the resource as well as increasing support for descriptions of causal models of biological systems and network biology. To learn more, visit http://geneontology.org/.

The GO annotation dataset provided by the UniProt Consortium (GOA: http://www.ebi.ac.uk/GOA) is a comprehensive set of evidenced-based associations between terms from the Gene Ontology resource and UniProtKB proteins. Currently supplying over 100 million annotations to 11 million proteins in more than 360,000 taxa, this resource has increased 2-fold over the last 2 years and has benefited from a wealth of checks to improve annotation correctness and consistency as well as now supplying a greater information content enabled by GO Consortium annotation format developments. Detailed, manual GO annotations obtained from the curation of peer-reviewed papers are directly contributed by all UniProt curators and supplemented with manual and electronic annotations from 36 model organism and domain-focused scientific resources. The inclusion of high-quality, automatic annotation predictions ensures the UniProt GO annotation dataset supplies functional information to a wide range of proteins, including those from poorly characterized, non-model organism species. UniProt GO annotations are freely available in a range of formats accessible by both file downloads and web-based views. In addition, the introduction of a new, normalized file format in 2010 has made for easier handling of the complete UniProt-GOA data set.

The mission of the Universal Protein Resource (UniProt) (http://www.uniprot.org) is to provide the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequences and functional annotation. It integrates, interprets and standardizes data from literature and numerous resources to achieve the most comprehensive catalog possible of protein information. The central activities are the biocuration of the UniProt Knowledgebase and the dissemination of these data through our Web site and web services. UniProt is produced by the UniProt Consortium, which consists of groups from the European Bioinformatics Institute (EBI), the SIB Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is updated and distributed every 4 weeks and can be accessed online for searches or downloads.

HAMAP (High-quality Automated and Manual Annotation of Proteins-available at http://hamap.expasy.org/) is a system for the classification and annotation of protein sequences. It consists of a collection of manually curated family profiles for protein classification, and associated annotation rules that specify annotations that apply to family members. HAMAP was originally developed to support the manual curation of UniProtKB/Swiss-Prot records describing microbial proteins. Here we describe new developments in HAMAP, including the extension of HAMAP to eukaryotic proteins, the use of HAMAP in the automated annotation of UniProtKB/TrEMBL, providing high-quality annotation for millions of protein sequences, and the future integration of HAMAP into a unified system for UniProtKB annotation, UniRule. HAMAP is continuously updated by expert curators with new family profiles and annotation rules as new protein families are characterized. The collection of HAMAP family classification profiles and annotation rules can be browsed and viewed on the HAMAP website, which also provides an interface to scan user sequences against HAMAP profiles.

IntAct is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. Two levels of curation are now available within the database, with both IMEx-level annotation and less detailed MIMIx-compatible entries currently supported. As from September 2011, IntAct contains approximately 275,000 curated binary interaction evidences from over 5000 publications. The IntAct website has been improved to enhance the search process and in particular the graphical display of the results. New data download formats are also available, which will facilitate the inclusion of IntAct's data in the Semantic Web. IntAct is an active contributor to the IMEx consortium (http://www.imexconsortium.org). IntAct source code and data are freely available at http://www.ebi.ac.uk/intact.

The mission of UniProt is to support biological research by providing a freely accessible, stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces. UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. A key development at UniProt is the provision of complete, reference and representative proteomes. UniProt is updated and distributed every 4 weeks and can be accessed online for searches or download at http://www.uniprot.org.

The Gene Ontology (GO) (http://www.geneontology.org) is a community bioinformatics resource that represents gene product function through the use of structured, controlled vocabularies. The number of GO annotations of gene products has increased due to curation efforts among GO Consortium (GOC) groups, including focused literature-based annotation and ortholog-based functional inference. The GO ontologies continue to expand and improve as a result of targeted ontology development, including the introduction of computable logical definitions and development of new tools for the streamlined addition of terms to the ontology. The GOC continues to support its user community through the use of e-mail lists, social media and web-based resources.

The primary mission of UniProt is to support biological research by maintaining a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces freely accessible to the scientific community. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is updated and distributed every 3 weeks and can be accessed online for searches or download at http://www.uniprot.org.

The mission of UniProt is to provide the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequence and functional information that is essential for modern biological research. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute, the Protein Information Resource and the Swiss Institute of Bioinformatics. The core activities include manual curation of protein sequences assisted by computational analysis, sequence archiving, a user-friendly UniProt website and the provision of additional value-added information through cross-references to other databases. UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. One of the key achievements of the UniProt consortium in 2008 is the completion of the first draft of the complete human proteome in UniProtKB/Swiss-Prot. This manually annotated representation of all currently known human protein-coding genes was made available in UniProt release 14.0 with 20 325 entries. UniProt is updated and distributed every three weeks and can be accessed online for searches or downloaded at www.uniprot.org.

The Gene Ontology (GO; http://www.geneontology.org) is a community-based bioinformatics resource that supplies information about gene product function using ontologies to represent biological knowledge. Here we describe improvements and expansions to several branches of the ontology, as well as updates that have allowed us to more efficiently disseminate the GO and capture feedback from the research community. The Gene Ontology Consortium (GOC) has expanded areas of the ontology such as cilia-related terms, cell-cycle terms and multicellular organism processes. We have also implemented new tools for generating ontology terms based on a set of logical rules making use of templates, and we have made efforts to increase our use of logical definitions. The GOC has a new and improved web site summarizing new developments and documentation, serving as a portal to GO data. Users can perform GO enrichment analysis, and search the GO for terms, annotations to gene products, and associated metadata across multiple species using the all-new AmiGO 2 browser. We encourage and welcome the input of the research community in all biological areas in our continued effort to improve the Gene Ontology.

Eukaryotic cell proliferation is controlled by growth factors and essential nutrients. In their absence, cells may enter into a quiescent state (G0). In Saccharomyces cerevisiae, the conserved protein kinase A (PKA) and rapamycin-sensitive TOR (TORC1) pathways antagonize G0 entry in response to carbon and/or nitrogen availability primarily by inhibiting the PAS kinase Rim15 function. Here, we show that the phosphate-sensing Pho80–Pho85 cyclin–cyclin-dependent kinase (CDK) complex also participates in Rim15 inhibition through direct phosphorylation, thereby effectively sequestering Rim15 in the cytoplasm via its association with 14-3-3 proteins. Inactivation of either Pho80–Pho85 or TORC1 causes dephosphorylation of the 14-3-3-binding site in Rim15, thus enabling nuclear import of Rim15 and induction of the Rim15-controlled G0 program. Importantly, we also show that Pho80–Pho85 and TORC1 converge on a single amino acid in Rim15. Thus, Rim15 plays a key role in G0 entry through its ability to integrate signaling from the PKA, TORC1, and Pho80–Pho85 pathways.

International audience; The Ccr4-Not complex is a conserved global regulator of gene expression, which serves as a regulatory platform that senses and/or transmits nutrient and stress signals to various downstream effectors. Presumed effectors of this complex in yeast are TFIID, a general transcription factor that associates with the core promoter, and Msn2, a key transcription factor that regulates expression of stress-responsive element (STRE)-controlled genes. Here we show that the constitutively high level of STRE-driven expression in ccr4-not mutants results from two independent effects. Accordingly, loss of Ccr4-Not function causes a dramatic Msn2-independent redistribution of TFIID on promoters with a particular bias for STRE-controlled over ribosomal protein gene promoters. In parallel, loss of Ccr4-Not complex function results in an alteration of the post-translational modification status of Msn2, which depends on the type 1 protein phosphatase Glc7 and its newly identified subunit Bud14. Tests of epistasis as well as transcriptional analyses of Bud14-dependent transcription support a model in which the Ccr4-Not complex prevents activation of Msn2 via inhibition of the Bud14/Glc7 module in exponentially growing cells. Thus, increased activity of STRE genes in ccr4-not mutants may result from both altered general distribution of TFIID and unscheduled activation of Msn2.

The highly conserved Tor kinases (TOR) and the protein kinase A (PKA) pathway regulate cell proliferation in response to growth factors and/or nutrients. In Saccharomyces cerevisiae , loss of either TOR or PKA causes cells to arrest growth early in G 1 and to enter G 0 by mechanisms that are poorly understood. Here we demonstrate that the protein kinase Rim15 is required for entry into G 0 following inactivation of TOR and/or PKA. Induction of Rim15-dependent G 0 traits requires two discrete processes, i.e., nuclear accumulation of Rim15, which is negatively regulated both by a Sit4-independent TOR effector branch and the protein kinase B (PKB/Akt) homolog Sch9, and release from PKA-mediated inhibition of its protein kinase activity. Thus, Rim15 integrates signals from at least three nutrient-sensory kinases (TOR, PKA, and Sch9) to properly control entry into G 0 , a key developmental process in eukaryotic cells.

UniProt is an important collection of protein sequences and their annotations, which has doubled in size to 80 million sequences during the past year. This growth in sequences has prompted an extension of UniProt accession number space from 6 to 10 characters. An increasing fraction of new sequences are identical to a sequence that already exists in the database with the majority of sequences coming from genome sequencing projects. We have created a new proteome identifier that uniquely identifies a particular assembly of a species and strain or subspecies to help users track the provenance of sequences. We present a new website that has been designed using a user-experience design process. We have introduced an annotation score for all entries in UniProt to represent the relative amount of knowledge known about each protein. These scores will be helpful in identifying which proteins are the best characterized and most informative for comparative analysis. All UniProt data is provided freely and is available on the web at http://www.uniprot.org/.

UniProtKB/Swiss-Prot provides expert curation with information extracted from literature and curator-evaluated computational analysis. As knowledgebases continue to play an increasingly important role in scientific research, a number of studies have evaluated their accuracy and revealed various errors. While some are curation errors, others are the result of incorrect information published in the scientific literature. By taking the example of sirtuin-5, a complex annotation case, we will describe the curation procedure of UniProtKB/Swiss-Prot and detail how we report conflicting information in the database. We will demonstrate the importance of collaboration between resources to ensure curation consistency and the value of contributions from the user community in helping maintain error-free resources. Database URL: www.uniprot.org

The Saccharomyces cerevisiae protein kinase Rim15 was identified previously as a component of the Ras/cAMP pathway acting immediately downstream of cAMP-dependent protein kinase (cAPK) to control a broad range of adaptations in response to nutrient limitation. Here, we show that the zinc finger protein Gis1 acts as a dosage-dependent suppressor of the rim15Delta defect in nutrient limitation-induced transcriptional derepression of SSA3. Loss of Gis1 results in a defect in transcriptional derepression upon nutrient limitation of various genes that are negatively regulated by the Ras/cAMP pathway (e.g. SSA3, HSP12 and HSP26). Tests of epistasis as well as transcriptional analyses of Gis1-dependent expression indicate that Gis1 acts in this pathway downstream of Rim15 to mediate transcription from the previously identified post-diauxic shift (PDS) element. Accordingly, deletion of GIS1 partially suppresses, and overexpression of GIS1 exacerbates the growth defect of mutant cells that are compromised for cAPK activity. Moreover, PDS element-driven expression, which is negatively regulated by the Ras/cAMP pathway and which is induced upon nutrient limitation, is almost entirely dependent on the presence of Gis1.

International audience; The primary mission of Universal Protein Resource (UniProt) is to support biological research by maintaining a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces freely accessible to the scientific community. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is updated and distributed every 4 weeks and can be accessed online for searches or download at http://www.uniprot.org.

BACKGROUND: Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum, both of which induce highly inflammatory infections in humans. RESULTS: 97% of the 22.5 megabase genome sequences of A. benhamiae and T. verrucosum are unambiguously alignable and collinear. To unravel dermatophyte-specific virulence-associated traits, we compared sets of potentially pathogenicity-associated proteins, such as secreted proteases and enzymes involved in secondary metabolite production, with those of closely related onygenales (Coccidioides species) and the mould Aspergillus fumigatus. The comparisons revealed expansion of several gene families in dermatophytes and disclosed the peculiarities of the dermatophyte secondary metabolite gene sets. Secretion of proteases and other hydrolytic enzymes by A. benhamiae was proven experimentally by a global secretome analysis during keratin degradation. Molecular insights into the interaction of A. benhamiae with human keratinocytes were obtained for the first time by global transcriptome profiling. Given that A. benhamiae is able to undergo mating, a detailed comparison of the genomes further unraveled the genetic basis of sexual reproduction in this species. CONCLUSIONS: Our results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens.

With the dramatic increase in the volume of experimental results in every domain of life sciences, assembling pertinent data and combining information from different fields has become a challenge. Information is dispersed over numerous specialized databases and is presented in many different formats. Rapid access to experiment-based information about well-characterized proteins helps predict the function of uncharacterized proteins identified by large-scale sequencing. In this context, universal knowledgebases play essential roles in providing access to data from complementary types of experiments and serving as hubs with cross-references to many specialized databases. This review outlines how the value of experimental data is optimized by combining high-quality protein sequences with complementary experimental results, including information derived from protein 3D-structures, using as an example the UniProt knowledgebase (UniProtKB) and the tools and links provided on its website ( http://www.uniprot.org/ ). It also evokes precautions that are necessary for successful predictions and extrapolations.

Regulated interactions between microtubules (MTs) and the cell cortex control MT dynamics and position the mitotic spindle. In eukaryotic cells, the adenomatous polyposis coli/Kar9p and dynein/dynactin pathways are involved in guiding MT plus ends and MT sliding along the cortex, respectively. Here we identify Bud14p as a novel cortical activator of the dynein/dynactin complex in budding yeast. Bud14p accumulates at sites of polarized growth and the mother-bud neck during cytokinesis. The localization to bud and shmoo tips requires an intact actin cytoskeleton and the kelch-domain-containing proteins Kel1p and Kel2p. While cells lacking Bud14p function fail to stabilize the pre-anaphase spindle at the mother-bud neck, overexpression of Bud14p is toxic and leads to elongated astral MTs and increased dynein-dependent sliding along the cell cortex. Bud14p physically interacts with the type-I phosphatase Glc7p, and localizes Glc7p to the bud cortex. Importantly, the formation of Bud14p–Glc7p complexes is necessary to regulate MT dynamics at the cortex. Taken together, our results suggest that Bud14p functions as a regulatory subunit of the Glc7p type-I phosphatase to stabilize MT interactions specifically at sites of polarized growth.

Bacteriophage T5-encoded lipoprotein, synthesized by infected Escherichia coli cells, prevents superinfection of the host cell by this virus. The molecular basis of its ability to inactivate the receptor of phage T5, the FhuA protein, was investigated in vitro. Fully competent T5 lipoprotein, with a His tag attached to the C-terminus, was purified in detergent solution. Coreconstitution with homogeneous FhuA protein into liposomes revealed that the lipoprotein inhibited the irreversible inactivation of phage T5 by FhuA protein. This phenomenon correlated with the inhibition of phage DNA ejection determined by fluorescence monitoring. Addition of detergent abolished the interaction between T5 lipoprotein and FhuA protein. When the signal sequence and N-terminal cysteinyl residue of the lipoprotein were removed by genetic truncation, the soluble polypeptide could be refolded and purified from inclusion bodies. The truncated lipoprotein interfered with infection of E. coli by phage T5, but only at very high concentrations. Circular dichroism spectra of both forms of T5 lipoprotein exhibited predominantly beta-structure. T5 lipoprotein is sufficient for inactivation of the FhuA protein, presumably by inserting the N-terminal acyl chains into the membrane, thus increasing its local concentration. An in vitro stoichiometry of 10:1 has been calculated for the phage-encoded T5 lipoprotein to FhuA protein complex.

The major constraint in attaining high resolution structures of membrane proteins by X-ray crystallography is the growth of well-ordered three-dimensional crystals. To enable such crystallizations, we have used lipidic cubic phases consisting of monoglycerides and water. Bacteriorhodopsin and lysozyme, as paradigms of membrane and soluble proteins, nucleate and grow to well-ordered crystals that diffract X-rays isotropically in all three dimensions to 2.0 A. We envisage bacteriorhodopsin to partition into, and diffuse within, the bilayer of a lipidic cubic matrix, while the polar lysozyme resides in the aqueous compartment thereof. The phenomenology of bicontinuous cubic phases, consisting of curved bilayers whose structures follow infinitely periodic minimal surfaces (IPMS), is presented. Detailed prescriptions of the preparation of lipidic cubic phase matrices are given and their potential for the crystallization of other biological macromolecules is discussed. Copyright 1998 Academic Press.

The UniProt Knowledgebase (UniProtKB) acts as a central hub of protein knowledge by providing a unified view of protein sequence and functional information. Manual and automatic annotation procedures are used to add data directly to the database while extensive cross-referencing to more than 120 external databases provides access to additional relevant information in more specialized data collections. UniProtKB also integrates a range of data from other resources. All information is attributed to its original source, allowing users to trace the provenance of all data. The UniProt Consortium is committed to using and promoting common data exchange formats and technologies, and UniProtKB data is made freely available in a range of formats to facilitate integration with other databases. Database URL: http://www.uniprot.org/

UniProtKB/Swiss-Prot, a curated protein database, and dictyBase, the Model Organism Database for Dictyostelium discoideum, have established a collaboration to improve data sharing. One of the major steps in this effort was the 'Dicty annotation marathon', a week-long exercise with 30 annotators aimed at achieving a major increase in the number of D. discoideum proteins represented in UniProtKB/Swiss-Prot. The marathon led to the annotation of over 1000 D. discoideum proteins in UniProtKB/Swiss-Prot. Concomitantly, there were a large number of updates in dictyBase concerning gene symbols, protein names and gene models. This exercise demonstrates how UniProtKB/Swiss-Prot can work in very close cooperation with model organism databases and how the annotation of proteins can be accelerated through those collaborations.

In recent years, the general understanding of nutrient sensing and signalling, as well as the knowledge about responses triggered by altered nutrient availability have greatly advanced. While initial studies were directed to top-down elucidation of single nutrient-induced pathways, recent investigations place the individual signalling pathways into signalling networks and pursue the identification of converging effector branches that orchestrate the dynamical responses to nutritional cues. In this review, we focus on Rim15, a protein kinase required in yeast for the proper entry into stationary phase (G0). Recent studies revealed that the activity of Rim15 is regulated by the interplay of at least four intercepting nutrient-responsive pathways.