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M Kanehisa

Publications and source records attributed to M Kanehisa.

At least 37 records · Page 2Linked to original sources
PubMed2000

LIGAND: chemical database of enzyme reactions.

LIGAND is a composite database comprising three sections: ENZYME for the information of enzyme molecules and enzymatic reactions, COMPOUND for the information of metabolites and other chemical compounds, and REACTION for the collection of substrate-product relations. The current release includes 3390 enzymes, 5645 compounds and 5207 reactions. The database is indispensable for the reconstruction of metabolic pathways in the completely sequenced organisms. The LIGAND database can be accessed through the WWW (http://www.genome.ad.jp/dbget/ligand.html ) or may be downloaded by anonymous FTP (ftp://kegg.genome.ad.jp/molecules/ligand/ ).

Databases, Factual↗
PubMed2000

Tandem clusters of membrane proteins in complete genome sequences.

The distribution of genes coding for membrane proteins was investigated in 16 complete genomes: 4 archaea, 11 bacteria, and 1 eukaryote. Membrane proteins were identified by our new method of predicting transmembrane segments () after the removal of amino-terminal signal peptides. Interestingly, about half of the membrane protein genes in each genome were found to be located next to another, forming tandem clusters. Roughly 10%-30% of the tandem clusters were conserved among organisms, and most of the conserved tandem clusters belonged to one of the three functional groups, namely, transporters, the electron transport system, and cell motility. A tandem cluster sometimes contained paralogous membrane proteins, in which case the cluster size and the number of transmembrane segments could be related to a functional category, especially to transporters. In addition to the clustering of membrane proteins, the clustering of membrane proteins and ATP-binding proteins in the complete genomes was also analyzed. Although this clustering was not statistically significant, it was useful to identify candidate membrane protein partners of isolated ATP-binding protein components in the ABC transporters. Possible implications of tandem cluster organization of membrane protein genes are discussed including the complex formation and other functional coupling of protein products and the mechanism of protein translocation to the cell membrane.

ATP-Binding Cassette Transporters↗
PubMed1999

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Kyoto Encyclopedia of Genes and Genomes (KEGG) is a knowledge base for systematic analysis of gene functions in terms of the networks of genes and molecules. The major component of KEGG is the PATHWAY database that consists of graphical diagrams of biochemical pathways including most of the known metabolic pathways and some of the known regulatory pathways. The pathway information is also represented by the ortholog group tables summarizing orthologous and paralogous gene groups among different organisms. KEGG maintains the GENES database for the gene catalogs of all organisms with complete genomes and selected organisms with partial genomes, which are continuously re-annotated, as well as the LIGAND database for chemical compounds and enzymes. Each gene catalog is associated with the graphical genome map for chromosomal locations that is represented by Java applet. In addition to the data collection efforts, KEGG develops and provides various computational tools, such as for reconstructing biochemical pathways from the complete genome sequence and for predicting gene regulatory networks from the gene expression profiles. The KEGG databases are daily updated and made freely available (http://www.genome.ad.jp/kegg/).

Animals↗
PubMed1999

AAindex: Amino Acid Index Database.

AAindex is a database of numerical indices representing various physicochemical and biochemical properties of amino acids and pairs of amino acids. It consists of two sections: AAindex1 for the amino acid index of 20 numerical values and AAindex2 for the amino acid mutation matrix of 210 numerical values. Each entry of either AAindex1 or AAindex2 consists of the definition, the reference information, a list of related entries in terms of the correlation coefficient, and the actual data. The database may be accessed through the DBGET/LinkDB system at GenomeNet (http://www.genome.ad. jp/dbget/) or may be downloaded by anonymous FTP (ftp://ftp.genome. ad.jp/db/genomenet/aaindex/).

Amino Acids↗
PubMed1999

LIGAND database for enzymes, compounds and reactions.

LIGAND is a composite database consisting of three sections and containing the information of chemical substances, chemical reactions and enzymes that catalyze reactions. The COMPOUND section is a collection of metabolic compounds, as well as macromolecules, chemical elements and other chemical substances in a living cell. The ENZYME section is a collection of all known enzymatic reactions, together with the information of enzyme molecules, classified according to the EC (Enzyme Commission) numbers. The REACTION section is a new addition to the database containing metabolic reactions that appear in the pathway diagrams of the KEGG/PATHWAY database and/or in the ENZYME section. The LIGAND database can be accessed through the WWW (http://www.genome.ad.jp/dbget/ligand.html) or may be downloaded by anonymous FTP (ftp://kegg.genome.ad. jp/molecules/ligand).

Catalysis↗
PubMed1999

Genome-scale Gene Expression Analysis and Pathway Reconstruction in KEGG.

The massively parallel hybridization technologies by DNA chips and microarrays make it possible to monitor expression patterns of the whole set of genes in a genome under various conditions. The vast amount of data generated by such technologies necessitates the development of a new database management system that integrates expression data with other molecular biology databases and various analysis tools. We report here an extension of our KEGG (Kyoto Encyclopedia of Genes and Genomes) and DBGET/LinkDB systems for analyzing gene expression data in conjunction with pathway information and genomic information. It is now possible to make use of expression data for the reconstruction of pathways from the complete genome sequences.

Journal Article↗
PubMed1998

Folding of the human protein FKBP. Lattice Monte-Carlo simulations.

Monte-Carlo simulations of folding of the human protein FKBP are presented. The protein is confined in a simple cubic lattice and only nearest-neighbour interactions are considered. The evolution of protein structure, energy and diameter is followed over time. Starting from different extended conformations, compact globular forms with a hydrophobic core are reached above a critical temperature Tc, while below Tc the protein 'freezes' into high-energy, non-compact states. In the temperature range of folding, all the recorded intermediate states belong to two structural groups, where the process spends most of its time, separated by relatively fast transitions. During folding, the protein is successively composed of three and two compact fragments, whose separation occurs at loop positions. From comparisons performed on a domain of the family sharing 24% identity with FKBP, it appears that the number of fragments, and therefore their location, are sequence dependent.

Amino Acid Sequence↗
PubMed1998

LIGAND: chemical database for enzyme reactions.

MOTIVATION: The existing molecular biology databases focus on the sequence and structural aspects of biological macromolecules, i.e. DNAs, RNAs and proteins. However, in order to understand the functional aspects, it is essential to computerize the interaction of these molecules. Furthermore, living cells contain additional molecules, such as metabolic compounds and metal ions, that may also be considered as parts of the basic building blocks of life, but are not well organized in public databases. LIGAND chemical database is our attempt to solve these problems, at least for enzymatic reactions. RESULTS: LIGAND consists of two sections: ENZYME and COMPOUND. The ENZYME section is an extension of previous studies (Suyama et al. , Comput. Applic. Biosci., 9, 9-15, 1993), and it is a flat-file representation of 3303 enzymes and 2976 enzymatic reactions in the chemical equation format that can be parsed by machine. The COMPOUND section has been newly constructed for information on the nomenclature and chemical structures of compounds. It contains 5383 chemical compounds. Both ENZYME and COMPOUND entries contain rich cross-reference information, most of which is automatically generated by the DBGET/LinkDB system, thus providing the linkage between chemical and biological databases. LIGAND is updated daily, tightly coupled with the KEGG metabolic pathway database, and forms the basis for reconstruction and computation of pathways. AVAILABILITY: LIGAND can be accessed through the DBGET/LinkDB and KEGG systems in the Japanese GenomeNet database service via http://www.genome.ad.jp/. The flat-file format of the LIGAND database can be downloaded by anonymous FTP via ftp://kegg. genome.adjp/molecules/ligand/. CONTACT: goto@kuicr.kyoto-u.ac.jp; nishioka@scl.kyoto-u.ac.jp; kanehisa@kuicr.kyoto-u.ac.jp

Computational Biology↗
PubMed1998

Prediction of membrane proteins based on classification of transmembrane segments.

The number of transmembrane segments often corresponds to a structural or functional class of membrane proteins such as to seven-transmembrane receptors and six-transmembrane ion channels. We have developed a new prediction method to detect the membrane protein class that is defined by the number of transmembrane segments, as well as to locate the transmembrane segments in the amino acid sequence. Each membrane protein class is represented by a model of ordering different types of transmembrane segments. Specifically, we have classified the transmembrane segments in known membrane proteins into five groups (types) using the Mahalanobis distance with the average hydrophobicity and the periodicity of hydrophobicity as a measure of similarity. The discriminant functions derived for these groups were then used to detect transmembrane segments and to match with the models for one- to fourteen-spanning membrane proteins and for globular proteins. Using the test data set of 89 membrane proteins whose transmembrane positions are known by experimental evidence, 61.8% of the proteins and 85.1% of the transmembrane segments were correctly predicted. Because of the new feature to predict membrane protein classes, the method should be useful in the functional assignment of genomic sequences.

Animals↗
PubMed1998

A comparative analysis of ABC transporters in complete microbial genomes.

The ABC transporter is a major class of cellular translocation machinery in all bacterial species encoded in the largest set of paralogous genes. The operon structure is frequently found for the genes of three molecular components: the ATP-binding protein, the membrane protein, and the substrate-binding protein. Here, we developed an "ortholog group table" by comparison and classification of known and putative ABC transporters in the complete genomes of seven microorganisms. Our procedure was to first search and classify the most conserved ATP-binding protein components by the sequence similarity and then to classify the entire transporter units by examining the similarity of the other components and the conservation of the operon structure. The resulting 25 ortholog groups of ABC transporters were well correlated with known functions. Through the analysis, we could assign substrate specificity to hypothetical transporters, predict additional transporter operons, and identify novel types of putative transporters. The ortholog group table was also used as a reference data set for functional assignment in four additional genomes. In general, the ABC transporter operons were strongly conserved despite the extensive shuffling of gene locations in bacterial evolution. In Synechocystis, however, the tendency of forming operons was clearly diminished. Our result suggests that the ancestral ABC transporter operons may have arisen early in evolution before the speciation of bacteria and archaea.

ATP-Binding Cassette Transporters↗
PubMed1998

Reconstruction of amino acid biosynthesis pathways from the complete genome sequence.

The complete genome sequence of an organism contains information that has not been fully utilized in the current prediction methods of gene functions, which are based on piece-by-piece similarity searches of individual genes. We present here a method that utilizes a higher level information of molecular pathways to reconstruct a complete functional unit from a set of genes. Specifically, a genome-by-genome comparison is first made for identifying enzyme genes and assigning EC numbers, which is followed by the reconstruction of selected portions of the metabolic pathways by use of the reference biochemical knowledge. The completeness of the reconstructed pathway is an indicator of the correctness of the initial gene function assignment. This feature has become possible because of our efforts to computerize the current knowledge of metabolic pathways under the KEGG project. We found that the biosynthesis pathways of all 20 amino acids were completely reconstructed in Escherichia coli, Haemophilus influenzae, and Bacillus subtilis, and probably in Synechocystis and Saccharomyces cerevisiae as well, although it was necessary to assume wider substrate specificity for aspartate aminotransferases.

Amino Acids↗
PubMed1998

Systematic Prediction of Orthologous Units of Genes in the Complete Genomes.

In order to fully make use of the vast amount of information in the complete genome sequences, we are developing a genome-scale system for predicting gene functions and cellular functions. The system makes use of the information of sequence similarity, the information of positional correlations in the genome, and the reference knowledge stored as the ortholog group tables in KEGG (Kyoto Encyclopedia of Genes and Genomes). The ortholog group table summarizes orthologous and paralogous relations among different organisms for a set of genes that are considered to form a functional unit, such as a conserved portion of the metabolic pathway or a molecular machinery for the membrane transport. At the moment, the ortholog group table is constructed for the cases where the genes are clustered in physically close positions in the genome for at least one organism. In this paper, we describe the system and the actual analysis of the complete genome of Pyrococcus horikoshii to identify ABC transporters.

Journal Article↗
PubMed1998

DBGET/LinkDB: an integrated database retrieval system.

The integrated database retrieval system DBGET/LinkDB is the backbone of the Japanese GenomeNet service. DBGET is used to search and extract entries from a wide range of molecular biology databases, while LinkDB is used to search and compute links between entries in different databases. DBGET/LinkDB is designed to be a network distributed database system with an open architecture, which is suitable for incorporating local databases or establishing a specialized server environment. It also has an advantage of simple architecture allowing rapid daily updates of all the major databases. The WWW version of DBGET/LinkDB at GenomeNet is integrated with other search tools, such as BLAST, FASTA and MOTIF, and with local helper applications, such as RasMol. In addition to factual links between database entries, LinkDB is being extended to included similarity links and biological links toward computerization of logical reasoning processes.

Databases, Factual↗
PubMed1997

Prediction of gene expression specificity by promoter sequence patterns.

We present here a heuristic method toward predicting the expression specificity in the transcriptional process, which is known to be regulated in large part by promoter sequences, by observing the appearance of conserved sequence patterns in a group of known promoters, such as for housekeeping or tissue-specific genes. Statistically conserved patterns were automatically extracted from a set of unaligned sequences up to 200 bp upstream of the transcription initiation site, by a standard procedure using the Markov chain and binomial distribution models. Furthermore, to obtain signal sequences of optimal lengths we devised a method that combines the multiple alignment and the analysis of the information content (or relative entropy). Groups of related promoters were compiled from the EPD eukaryotic promoter database and the EMBL nucleic acid sequence database. Each promoter was examined for its specificity by linear discriminant analysis to test the validity of the extracted patterns. Our method could correctly discriminate 77.6% of the housekeeping gene promoters and 62.9% of the liver promoters.

Algorithms↗