The pathway maps - 'wiring diagrams' of molecular interconversions - are hand-drawn, and form the core of KEGG
. They integrate many molecular types, including proteins, RNA, primary and secondary metabolites, and chemical reactions. The maps are classified in a number of ways (metabolism, disease, and so on), each of which can be considered a conceptual 'view' onto the pathway data.
KEGG
can be queried in a number of ways, including:
KEGG
website [http://www.genome.jp/kegg/pathway.html) in your web browserKEGG
website, using a programming languageKEGG
websiteKEGG
webpage. The landing page offers a menu of choices: PATHWAY
, BRITE
, MODULE
and so on (the main page shown is the PATHWAY
page) , which each link to different databases within KEGG
. For example:
BRITE
: Functional hierarchies and binary relationships of biological entitiesMODULE
: Functional units for annotating and interpreting genomesKO
: Linking genomes to pathways by ortholog annotationA full account of all the databases at KEGG
is beyond the scope of this lesson.
KEGG
GENOMEKEGG
GENOME: Organisms and ecosystems with genome sequence informationKEGG
GENOME database landing page.The landing page presents you with a search field.
The KEGG
entry for a genome typically links out to the GenBank record used for the KEGG
entry, and also links internally to related genes and pathways in the other KEGG
databases.
KEGG
GENESKEGG
GENES: Molecular building blocks of life in the genomic spaceWhen genes are imported into the KEGG
system, several analyses are applied, including assignment to KO
(KEGG Orthology) groups that attempt to cluster genes that have similar function, on the basis of sequence similarity. These KO
groups have their own KEGG
KO database:
KEGG
KO: KO Database of Molecular Functions
Click on the menu link to the GENES database.
Keeping the Kitasatospora genome with code ksk
as our example from above, we will search for genes whose annotation includes the phrase xylulose
:
Organism
to ksk
and enter xylulose
in the search field, then click Go
.We will select one of the returned genes to focus on: KSE_17560
.
KSE_17560
.The gene record describes links to KEGG
resources such as pathways, functional modules, and predicted orthologues, paralogues and gene clusters.
The record also shows the amino acid and coding sequences (with optional upstream and downstream sequence) for the gene. Links to these sequences can be followed via the AA seq
or NT seq
buttons.
KEGG
PATHWAYKEGG
PATHWAY: Wiring diagrams of molecular interactions, reactions, and relationsThe PATHWAY landing page gives a single search field, allowing a free-text search of the complete PATHWAY database. Note that the "Organism" selected by default is map
, which is the generic reference map.
The search result lists pathways that match the free text search, and gives a short account of each.
map00900
.The map shown is a reference map, and is interactive:
KEGG
ORTHOLOGY (KO) databaseKEGG
COMPOUND databaseKEGG
PATHWAY databaseKEGG
PATHWAY search page.ksk
in the "Organism" field, and search again for "terpenoid".Note that the search result pathways now have the prefix ksk
. This is how KEGG
allows us to index pathway maps directly: the three-letter code identifies the organism, and the five digit number identifies the pathway. Combining the two as <organism><pathway>
means we can directly construct the pathway map ID for any combination of organism and pathway.
ksk00900
map. This will open the terpenoid backbone biosynthesis map for Kitasatospora setae.The ksk
map is identical in structure to the map
map, except that some of the rectangular boxes representing chemical interconversions have now been shaded green. This indicates that there is a gene annotated in the organism whose product is expected to be able to perform the biochemical interconversion indicated on the map.
2.2.1.7
.map01100
: Metabolic pathways overviewmap01110
: Biosynthesis of secondary metabolitesmap01120
: Microbial metabolism in diverse environmentsmap01130
: Biosynthesis of antibioticsFollowing the links above, these are interactive. The individual pathways can be highlighted by selecting the checkboxes on the left hand side, and clicking on the circles will link out to compounds, while clicking on the graph edges will link out to reactions.
KEGG
PATHWAYS database page.M00774
Erythromycin biosynthesis on the left-hand side. Note that the erythromycin pathway is highlighted.After a short delay, you should see that many of the edges and nodes in the image are greyed out. These pathways are not annotated in K. setae. The pathways that remain coloured are, however, annotated as present in that organism.
To download a copy of the image you have generated with your selections, click on the Image (png) file
link at the top of the page.
The UniProt
record Q05655
describes a human protein kinase. Using KEGG
, can you discover: