OWL--a non-redundant composite protein sequence database.

A comprehensive, non-redundant composite protein sequence database is described. The database, OWL, is an amalgam of data from six publicly-available primary sources, and is generated using strict redundancy criteria. The database is updated monthly and its size has increased almost eight-fold in the last six years: the current version contains > 76,000 entries. For added flexibility, OWL is distributed with a tailor-made query language, together with a number of programs for database exploration, information retrieval and sequence analysis, which together form an integrated database and software resource for protein sequences.     

PRINTS--a database of protein motif fingerprints.

PRINTS is a compendium of protein motif 'fingerprints'. A fingerprint is defined as a group of motifs excised from conserved regions of a sequence alignment, whose diagnostic power or potency is refined by iterative databasescanning (in this case the OWL composite sequence database). Generally, the motifs do not overlap, but are separated along a sequence, though they may be contiguous in 3D-space. The use of groups of independent, linearly- or spatially-distinct motifs allows protein folds and functionalities to be characterised more flexibly and powerfully than conventional single-component patterns or regular expressions. The current version of the database contains 200 entries (encoding 950 motifs), covering a wide range of globular and membrane proteins, modular polypeptides, and so on. The growth of the databaseis influenced by a number of factors; e.g. the use of multiple motifs; the maximisation of sequence information through iterative database scanning; and the fact that the database searched is a large composite. The information contained within PRINTS is distinct from, but complementary to the consensus expressions stored in the widely-used PROSITE dictionary of patterns.     

UniRef: comprehensive and non-redundant UniProt reference clusters

MOTIVATION: Redundant protein sequences in biological databases hinder sequence similarity searches and make interpretation of search results difficult. Clustering of protein sequence space based on sequence similarity helps organize all sequences into manageable datasets and reduces sampling bias and overrepresentation of sequences. RESULTS: The UniRef (UniProt Reference Clusters) provide clustered sets of sequences from the UniProt Knowledgebase (UniProtKB) and selected UniProt Archive records to obtain complete coverage of sequence space at several resolutions while hiding redundant sequences. Currently covering >4 million source sequences, the UniRef100 database combines identical sequences and subfragments from any source organism into a single UniRef entry. UniRef90 and UniRef50 are built by clustering UniRef100 sequences at the 90 or 50% sequence identity levels. UniRef100, UniRef90 and UniRef50 yield a database size reduction of approximately 10, 40 and 70%, respectively, from the source sequence set. The reduced redundancy increases the speed of similarity searches and improves detection of distant relationships. UniRef entries contain summary cluster and membership information, including the sequence of a representative protein, member count and common taxonomy of the cluster, the accession numbers of all the merged entries and links to rich functional annotation in UniProtKB to facilitate biological discovery. UniRef has already been applied to broad research areas ranging from genome annotation to proteomics data analysis. AVAILABILITY: UniRef is updated biweekly and is available for online search and retrieval at http://www.uniprot.org, as well as for download at ftp://ftp.uniprot.org/pub/databases/uniprot/uniref. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

UniProt archive

UniProt Archive (UniParc) is the most comprehensive, non-redundant protein sequence database available. Its protein sequences are retrieved from predominant, publicly accessible resources. All new and updated protein sequences are collected and loaded daily into UniParc for full coverage. To avoid redundancy, each unique sequence is stored only once with a stable protein identifier, which can be used later in UniParc to identify the same protein in all source databases. When proteins are loaded into the database, database cross-references are created to link them to the origins of the sequences. As a result, performing a sequence search against UniParc is equivalent to performing the same search against all databases cross-referenced by UniParc. UniParc contains only protein sequences and database cross-references; all other information must be retrieved from the source databases.     

The MetaFam Server: a comprehensive protein family resource

MetaFam is a comprehensive relational database of protein family information. This web-accessible resource integrates data from several primary sequence and secondary protein family databases. By pooling together the information from these disparate sources, MetaFam is able to provide the most complete protein family sets available. Users are able to explore the interrelationships among these primary and secondary databases using a powerful graphical visualization tool, MetaFamView. Additionally, users can identify corresponding sequence entries among the sequence databases, obtain a quick summary of corresponding families (and their sequence members) among the family databases, and even attempt to classify their own unassigned sequences. Hypertext links to the appropriate source databases are provided at every level of navigation. Global family database statistics and information are also provided. Public access to the data is available at http://metafam.ahc.umn.edu/.     

UniProt蛋白质数据库简介

UniProt(https://www.uniprot.org/)是国际知名蛋白质数据库,主要包括UniProtKB知识库、UniParc归档库和UniRef参考序列集三部分。UniProtKB知识库是UniProt的核心,除蛋白质序列数据外,还包括大量注释信息。UniProtKB知识库分Swiss-Prot和TrEMBL两个子库。Swiss-Prot子库中50多万条序列均由人工审阅和注释,而TrEMBL子库中1.4亿多条序列是由核酸序列数据库EMBL中的蛋白质编码序列翻译所得,并由计算机根据一定规则进行注释。UniParc归档库将存放于不同数据库中的同一个蛋白质归并到一个记录中以避免冗余,并赋予序列唯一性特定标识符。UniRef参考序列集按相似性程度将UniProtKB和UniParc中的序列分为UniRef100、UniRef90和UniRef50三个数据集。UniProt网站为用户提供了高效实用的高级检索系统和大量帮助文档。UniProt数据库每4周发布新版的同时也发布统计报表,用户可通过统计报表了解该数据库的数据量及更新情况、数据类别和物种分布等基本信息,查看常规注释信息、序列特征注释信息和数据库交叉链接等统计数据。UniProt是目前国际上序列数据最完整、注释信息最丰富的非冗余蛋白质序列数据库,自本世纪初创建以来,为生命科学领域提供了宝贵资源。     

Progress with the PRINTS protein fingerprint database.

PRINTS is a compendium of protein motif 'fingerprints' derived from the OWL composite sequence database. Fingerprints are groups of motifs within sequence alignments whose conserved nature allows them to be used as signatures of family membership. To date, 400 fingerprints have been constructed and stored in Prints, the size of which has doubled in the last year. The current version, 9.0, encodes approximately 2000 motifs, covering a range of globular and membrane proteins, modular polypeptides, and so on. Fingerprints inherently offer improved diagnostic reliability over single motif methods by virtue of the mutual context provided by motif neighbours. PRINTS thus provides a useful adjunct to the widely used PROSITE dictionary of patterns. The database is now accessible via the Database Browser on the UCL Bioinformatics server at http://www.biochem.ucl.ac.uk/bsm/dbbrowser .     

Histone and histone fold sequences and structures: a database.

A database of aligned histone protein sequences has been constructed based on the results of homology searches of the major public sequence databases. In addition, sequences of proteins identified as containing the histone fold motif and structures of all known histone and histone fold proteins have been included in the current release. Database resources include information on conflicts between similar sequence entries in different source databases, multiple sequence alignments, and links to the Entrez integrated information retrieval system at the National Center for Biotechnology Information (NCBI). The database currently contains over 1000 protein sequences. All sequences and alignments in this database are available through the World Wide Web at: http: //www.ncbi.nlm.nih.gov/Baxevani/HISTONES/ .     

The role SWISS-PROT and TrEMBL play in the genome research environment

SWISS-PROT, a curated protein sequence data bank, contains not only sequence data but also annotation relevant to a particular sequence. The annotation added to each entry is done by a team of biologists and comes, primarily, from articles in journals reporting the actual sequencing and sometimes characterisation. Review articles and collaboration with external experts also play a role along with the use of secondary databases like PROSITE and Pfam in addition to a variety of feature prediction methods. Annotation added by these methods is checked for relevance and likelihood to a particular sequence. The onset of genome sequencing has led to a dramatic increase in sequence data to be included in SWISS-PROT. This has led to the production of TrEMBL (Translation of the EMBL database). TrEMBL consists of entries in a SWISS-PROT format that are derived from the translation of all coding sequences in the EMBL nucleotide sequence database, that are not in SWISS-PROT. Unlike SWISS-PROT entries those in TrEMBL are awaiting manual annotation. However, rather than just representing basic sequence and source information, steps have been taken to add features and annotation automatically. In taking these steps it is hoped that TrEMBL entries are enhanced with some indication as to what a protein is, could or may be.     

UTRdb: a specialized database of 5' and 3' untranslated regions of eukaryotic mRNAs.

The 5' and 3' untranslated regions of eukaryotic mRNAs may play a crucial role in the regulation of gene expression controlling mRNA localization, stability and translational efficiency. For this reason we developed UTRdb (http://bigarea.area.ba.cnr.it:8000/BioWWW/#U TRdb), a specialized database of 5' and 3' untranslated sequences of eukaryotic mRNAs cleaned from redundancy. UTRdb entries are enriched with specialized information not present in the primary databases including the presence of nucleotide sequence patterns already demonstrated by experimental analysis to have some functional role. All these patterns have been collected in the UTRsite database so that it is possible to search any input sequence for the presence of annotated functional motifs. Furthermore, UTRdb entries have been annotated for the presence of repetitive elements.     

UTRdb and UTRsite: specialized databases of sequences and functional elements of 5' and 3' untranslated regions of eukaryotic mRNAs

The 5' and 3' untranslated regions of eukaryotic mRNAs may play a crucial role in the regulation of gene expression controlling mRNA localization, stability and translational efficiency. For this reason we developed UTRdb, a specialized database of 5' and 3' untranslated sequences of eukaryotic mRNAs cleaned from redundancy. UTRdb entries are enriched with specialized information not present in the primary databases including the presence of nucleotide sequence patterns already demonstrated by experimental analysis to have some functional role. All these patterns have been collected in the UTRsite database so that it is possible to search any input sequence for the presence of annotated functional motifs. Furthermore, UTRdb entries have been annotated for the presence of repetitive elements. All internet resources implemented for retrieval and functional analysis of 5' and 3' untranslated regions of eukaryotic mRNAs are accessible at http://bigarea.area.ba.cnr.it:8000/EmbIT/UTRH ome/     

EpoDB: a prototype database for the analysis of genes expressed during vertebrate erythropoiesis.

EpoDB is a database of genes expressed in vertebrate red blood cells. It is also a prototype for the creation of cell and tissue-specific databases from multiple external sources. The information in EpoDB obtained from GenBank, SWISS-PROT, Transfac, TRRD and GERD is curated to provide high quality data for sequence analysis aimed at understanding gene regulation during erythropoiesis. New protocols have been developed for data integration and updating entries. Using a BLAST-based algorithm, we have grouped GenBank entries representing the same gene together. This sequence similarity protocol was also used to identify new entries to be included in EpoDB. We have recently implemented our database in Sybase (relational tables) in addition to SICStus Prolog to provide us with greater flexibility in asking complex queries that utilize information from multiple sources. New additions to the public web site (http://www.cbil.upenn.edu/epodb) for accessing EpoDB are the ability to retrieve groups of entries representing different variants of the same gene and to retrieve gene expression data. The BLAST query has been enhanced by incorporating BLASTView, an interactive and graphical display of BLAST results. We have also enhanced the queries for retrieving sequence from specified genes by the addition of MEME, a motif discovery tool, to the integrated analysis tools which include CLUSTALW and TESS.     

O-GLYCBASE version 4.0: a revised database of O-glycosylated proteins.

O-GLYCBASE is a database of glycoproteins with O-linked glycosylation sites. Entries with at least one experimentally verified O-glycosylation site have been compiled from protein sequence databases and literature. Each entry contains information about the glycan involved, the species, sequence, a literature reference and http-linked cross-references to other databases. Version 4.0 contains 179 protein entries, an approximate 15% increase over the last version. Sequence logos representing the acceptor specificity patterns for GalNAc, GlcNAc, mannosyl and xylosyl transferases are shown. The O-GLYCBASE database is available through the WWW at http://www.cbs.dtu.dk/databases/OGLYCBASE/     

GenBank.

The GenBank sequence database has undergone an expansion in data coverage, annotation content and the development of new services for the scientific community. In addition to nucleotide sequences, data from the major protein sequence and structural databases, and from U.S. and European patents is now included in an integrated system. MEDLINE abstracts from published articles describing the sequences provide an important new source of biological annotation for sequence entries. In addition to the continued support of existing services, new CD-ROM and network-based systems have been implemented for literature retrieval and sequence similarity searching. Major releases of GenBank are now more frequent and the data are distributed in several new forms for both end users and software developers.     

A database of unique protein sequence identifiers for proteome studies

In proteome studies, identification of proteins requires searching protein sequence databases. The public protein sequence databases (e.g., NCBInr, UniProt) each contain millions of entries, and private databases add thousands more. Although much of the sequence information in these databases is redundant, each database uses distinct identifiers for the identical protein sequence and often contains unique annotation information. Users of one database obtain a database-specific sequence identifier that is often difficult to reconcile with the identifiers from a different database. When multiple databases are used for searches or the databases being searched are updated frequently, interpreting the protein identifications and associated annotations can be problematic. We have developed a database of unique protein sequence identifiers called Sequence Globally Unique Identifiers (SEGUID) derived from primary protein sequences. These identifiers serve as a common link between multiple sequence databases and are resilient to annotation changes in either public or private databases throughout the lifetime of a given protein sequence. The SEGUID Database can be downloaded (http://bioinformatics.anl.gov/SEGUID/) or easily generated at any site with access to primary protein sequence databases. Since SEGUIDs are stable, predictions based on the primary sequence information (e.g., pI, Mr) can be calculated just once; we have generated approximately 500 different calculations for more than 2.5 million sequences. SEGUIDs are used to integrate MS and 2-DE data with bioinformatics information and provide the opportunity to search multiple protein sequence databases, thereby providing a higher probability of finding the most valid protein identifications.     

The 1999 SWISS-2DPAGE database update

SWISS-2DPAGE (http://www.expasy.ch/ch2d/ ) is an annotated two-dimensional polyacrylamide gel electro-phoresis (2-DE) database established in 1993. The current release contains 24 reference maps from human and mouse biological samples, as well as from Saccharomyces cerevisiae, Escherichia coli and Dictyostelium discoideum origin. These reference maps have now 2824 identified spots, corresponding to 614 separate protein entries in the database, in addition to virtual entries for each SWISS-PROT sequence or any user-entered amino acids sequence. Last year improvements in the SWISS-2DPAGE database are as follows: three new maps have been created and several others have been updated; cross-references to newly built federated 2-DE databases have been added; new functions to access the data have been provided through the ExPASy proteomics server.     

PhosphoBase: a database of phosphorylation sites.

PhosphoBase is a database of experimentally verified phosphorylation sites. Version 1.0 contains 156 entries and 398 experimentally determined phosphorylation sites. Entries are compiled and revised from the literature and from major protein sequence databases such as SwissProt and PIR. The entries provide information about the phosphoprotein and the exact position of its phosphorylation sites. Furthermore, part of the entries contain information about kinetic data obtained from enzyme assays on specific peptides. To illustrate the use of data extracted from PhosphoBase we present a sequence logo displaying the overall conservation of positions around serines phosphorylated by protein kinase A (PKA). PhosphoBase is available on the WWW at http://www.cbs.dtu.dk/databases/PhosphoBase/     

ProClass protein family database

ProClass is a protein family database that organizes non-redundant sequence entries into families defined collectively by PIR superfamilies and PROSITE patterns. By combining global similarities and functional motifs into a single classification scheme, ProClass helps to reveal domain and family relationships and classify multi-domain proteins. The database currently consists of >155 000 sequence entries retrieved from both PIR-International and SWISS-PROT databases. Approximately 92 000 or 60% of the ProClass entries are classified into approximately 6000 families, including a large number of new members detected by our GeneFIND family identification system. The ProClass motif collection contains approximately 72 000 motif sequences and >1300 multiple alignments for all PROSITE patterns, including >21 000 matches not listed in PROSITE and mostly detected from unique PIR sequences. To maximize family information retrieval, the database provides links to various protein family, domain, alignment and structural class databases. With its high classification rate and comprehensive family relationships, ProClass can be used to support full-scale genomic annotation. The database, now being implemented in an object-relational database management system, is available for online sequence search and record retrieval from our WWW server at http://pir.georgetown.edu/gfserver/proclass.html     

GenBank.

The GenBank sequence database continues to expand its data coverage, quality control, annotation content and retrieval services for the scientific community. Besides handling direct submissions of sequence data from authors, GenBank also incorporates DNA sequences from all available public sources; an integrated retrieval system, known as Entrez, also makes available data from the major protein sequence and structural databases, and from U.S. and European patents. MIDLINE abstracts from published articles describing the sequences are also included as an additional source of biological annotation for sequence entries. GenBank supports distribution of the data via FTP, CD-ROM, and E-mail servers. Network server-client programs provide access to an integrated database for literature retrieval and sequence similarity searching.