The Gene Ontology knowledgebase in 2023.

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms.

SwissBioPics-an interactive library of cell images for the visualization of subcellular location data.

Unlabelled: SwissBioPics (www.swissbiopics.org) is a freely available resource of interactive, high-resolution cell images designed for the visualization of subcellular location data.

An enhanced workflow for variant interpretation in UniProtKB/Swiss-Prot improves consistency and reuse in ClinVar.

Personalized genomic medicine depends on integrated analyses that combine genetic and phenotypic data from individual patients with reference knowledge of the functional and clinical significance of sequence variants. Sources of this reference knowledge include the ClinVar repository of human genetic variants, a community resource that accepts submissions from external groups, and UniProtKB/Swiss-Prot, an expert-curated resource of protein sequences and functional annotation. UniProtKB/Swiss-Prot provides knowledge on the functional impact and clinical significance of over 30 000 human protein-coding sequence variants, curated from peer-reviewed literature reports.

Expert curation for building network-based dynamical models: a case study on atherosclerotic plaque formation.

http://biomodels.caltech.edu.

The UniProtKB guide to the human proteome.

Advances in high-throughput and advanced technologies allow researchers to routinely perform whole genome and proteome analysis. For this purpose, they need high-quality resources providing comprehensive gene and protein sets for their organisms of interest. Using the example of the human proteome, we will describe the content of a complete proteome in the UniProt Knowledgebase (UniProtKB).

Genetic variations and diseases in UniProtKB/Swiss-Prot: the ins and outs of expert manual curation.

During the last few years, next-generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease-associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease.

Gene Ontology annotations and resources.

The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies.

Mug20, a novel protein associated with linear elements in fission yeast meiosis.

In the fission yeast, Schizosaccharomyces pombe, homologous chromosomes efficiently pair and recombine during meiotic prophase without forming a canonical synaptonemal complex (SC). Instead, it features simpler filamentous structures, the so-called linear elements (LinEs), which bear some resemblance to the axial/lateral element subunits of the SC. LinEs are required for wild-type recombination frequency.

The UniProt-GO Annotation database in 2011.

The GO annotation dataset provided by the UniProt Consortium (GOA: http://www.ebi.ac.

Animal Toxins: How is Complexity Represented in Databases?

Peptide toxins synthesized by venomous animals have been extensively studied in the last decades. To be useful to the scientific community, this knowledge has been stored, annotated and made easy to retrieve by several databases. The aim of this article is to present what type of information users can access from each database.

SUMOylation is required for normal development of linear elements and wild-type meiotic recombination in Schizosaccharomyces pombe.

In the fission yeast, Schizosaccharomyces pombe, synaptonemal complexes (SCs) are not formed during meiotic prophase. However, structures resembling the axial elements of SCs, the so-called linear elements (LinEs) appear. By in situ immunostaining, we found Pmt3 (S.

The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts.

Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts.

Linear element-independent meiotic recombination in Schizosaccharomyces pombe.

Most organisms form protein-rich, linear, ladder-like structures associated with chromosomes during early meiosis, the synaptonemal complex. In Schizosaccharomyces pombe, linear elements (LinEs) are thread-like, proteinacious chromosome-associated structures that form during early meiosis. LinEs are related to axial elements, the synaptonemal complex precursors of other organisms.

Meiotic recombination proteins localize to linear elements in Schizosaccharomyces pombe.

In fission yeast, meiotic prophase nuclei develop structures known as linear elements (LinEs), instead of a canonical synaptonemal complex. LinEs contain Rec10 protein. While Rec10 is essential for meiotic recombination, the precise role of LinEs in this process is unknown.

Pax2 mutant mice display increased number and size of islets of Langerhans but no change in insulin and glucagon content.

Pax2 is a paired box transcription factor expressed in a spatially and temporally restricted manner and its absence results in major developmental defects of the central nervous system, eyes, ears and urogenital system. We recently reported that Pax2 is expressed in pancreatic endocrine cell lines and adult islets of Langerhans and activates glucagon gene expression. We have shown here that the Pax2 gene is expressed during pancreas development as early as embryonic day 10.

Ectopic expression of the beta-cell specific transcription factor Pdx1 inhibits glucagon gene transcription.

Aims/hypothesis: The transcription factor Pdx1 is required for the development and differentiation of all pancreatic cells. Beta-cell specific inactivation of Pdx1 in developing or adult mice leads to an increase in glucagon-expressing cells, suggesting that absence of Pdx1could favour glucagon gene expression by a default mechanism.

Method: We investigated the inhibitory role of Pdx1 on glucagon gene expression in vitro.

The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003.

The SWISS-PROT protein knowledgebase (http://www.expasy.org/sprot/ and http://www.

The pancreatic beta-cell-specific transcription factor Pax-4 inhibits glucagon gene expression through Pax-6.

Aims/hypothesis: The paired-homeobox genes pax-4 and pax-6 are crucial for islet development; whereas the null mutation of pax-6 results in the nearly absence of glucagon-producing alpha cells, pax-4 homozygous mutant mice lack insulin and somatostatin-producing beta and delta cells but contain an increased number of alpha cells suggesting that alpha cells could develop by a default mechanism.

Methods: To investigate whether beta-cell specific factors act negatively on glucagon gene transcription, we ectopically expressed pax-4 in glucagon producing InR1G9 cells; Pax-4 inhibited basal transcription of the glucagon gene promoter by 60%. To assess the mechanism of this inhibition, we cotransfected the non-islet cell line BHK-21 with Pax-4 and various transcription factors present in alpha cells.

The paired homeodomain transcription factor Pax-2 is expressed in the endocrine pancreas and transactivates the glucagon gene promoter.

Glucagon gene expression is controlled by at least four DNA elements within the promoter; G2, G3, and G4 confer islet-specific expression, while G1 restricts glucagon transcription to alpha cells. Two islet-specific complexes are formed on G3, the insulin-responsive element of the glucagon gene; one of these corresponds to the paired homeodomain protein Pax-6, a major glucagon gene transactivator that plays a crucial role in alpha cell development. We describe here the identification of the second complex as Pax-2, another member of the paired box family.

Prognostic significance of p53 mutation in breast cancer: frequent detection of non-missense mutations by yeast functional assay.

p53 status was tested in 180 patients with primary breast cancer using a yeast functional assay. Mutations were identified in 32% of cases. Only half were point missense mutations; the remainder were nonsense, insertion, deletion and splice site mutations.

Increased apoptosis induction by 121F mutant p53.

p53 mutants in tumours have a reduced affinity for DNA and a reduced ability to induce apoptosis. We describe a mutant with the opposite phenotype, an increased affinity for some p53-binding sites and an increased ability to induce apoptosis. The apoptotic function requires transcription activation by p53.

Pax-6 and Cdx-2/3 interact to activate glucagon gene expression on the G1 control element.

The promoter element G1, critical for alpha-cell-specific expression of the glucagon gene, contains two AT-rich sequences important for transcriptional activity. Pax-6, a paired homeodomain protein previously shown to be required for normal alpha-cell development and to interact with the enhancer element G3 of the glucagon gene, binds as a monomer to the distal AT-rich site of G1. However, although the paired domain of Pax-6 is sufficient for interaction with the G3 element, the paired domain and the homeodomain are required for high affinity binding to G1.

Use of transcription reporters with novel p53 binding sites to target tumour cells expressing endogenous or virally transduced p53 mutants with altered sequence-specificity.

p53 triple mutants (120N/121G/277H, 120H/121G/ 277H, 120S/121G/277H and 120H/121G/277Y) have altered sequence specificity in bandshift assays in vitro and transcription assays in vivo. These mutants activate transcription from the site TTT CATG AAA but not from wild type sites. The triple mutants activate more strongly than p53 with a single 277Y mutation.