A Database of human biological pathways Bijay Jassal. Rationale – Journal information. Nature 407(6805):770-6.The Biochemistry of Apoptosis.
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Nature 407(6805):770-6.The Biochemistry of Apoptosis.
“Caspase-8 is the key initiator caspase in the death-receptor pathway. Upon ligand binding, death receptors such as CD95 (Apo-1/Fas) aggregate and form membrane-bound signalling complexes (Box 3). These complexes then recruit, through adapter proteins, several molecules of procaspase-8, resulting in a high local concentration of zymogen. The induced proximity model posits that under these crowded conditions, the low intrinsic protease activity of procaspase-8 (ref. 20) is sufficient to allow the various proenzyme molecules to mutually cleave and activate each other (Box 2). A similar mechanism of action has been proposed to mediate the activation of several other caspases, including caspase-2 and the nematode caspase CED-3 (ref. 21).”
How can I access the pathway described here and maybe reuse it?
A picture paints a thousand words…
Nature. 2000 Oct 12;407(6805):770-6.
The biochemistry of apoptosis.
Free, online, open-source curated
database of pathways and reactions in human biology
Authored by expert biologists, maintained by
Reactome editorial staff (curators)
Mapped to cellular compartment
Tools for data analysis – Pathway Analysis, Expression Overlay, Species Comparison, Biomart…
Used to infer orthologous events in 20 non-human species
Transport of Ca++ from platelet dense tubular system to cytoplasm
KEGG, ChEBI – small molecules
UniProt – proteins
Sequence dbs – Ensembl, OMIM, Entrez Gene, RefSeq, HapMap, UCSC, KEGG Gene
PubMed references – literature evidence for events
No orthologue - Protein not inferred
Inferred from complexes and reactions
Interactions between proteins in the same complex, reaction, or adjoining reaction
Lists available from Downloads
See Readme document for more details
And many more...
Interactive Pathway Browser
Pathway Mapping and Over-representation
Expression overlay onto pathways
Molecular Interaction overlay
From the homepage, search for ‘Notch signaling’.
Click on the top pathway hit. This will open it in the Pathway Browser.
Ignoring the diagram for now, look at the Pathways tab on the left.
How many sub-pathways does this pathway have?
How many reactions are in the first of these sub-pathways?
What reaction follows Notch 2 precursor transport to Golgi?
Hint: If it’s not visible, open the Details pane at the bottom of the page by clicking on the blue triangle.
Boxes are proteins, sets or complexes.
Ovals are small molecules.
Green boxes are proteins or sets, blue are complexes.
Transition Binding Dissociation Omitted Uncertain
From the Homepage, search for the pathway ‘Effects of PIP2 hydrolysis’ and open it in the Pathway Browser.
What symbol represents the reaction for ‘Binding of IP3 to the IP3 receptor’?
2. What symbol represents the reaction ‘Transport of Ca++ from platelet dense tubular system to cytoplasm’? What subtype of reaction is this?
3. What is the catalyst (descriptive name) for ‘2-AG hydrolysis to arachidonate by MAGL’? Can you find its UniProt ID and name the two outputs of this reaction?
Home and Analyze buttons
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What is the most significantly over-represented top-level pathway for this dataset?
How many genes are in this pathway, and how many were represented in the dataset?
Why is the top-level pathway Chromosome Maintenance higher in the list than Signalling by Wnt when the latter has a more significant probability score? (Hint – use the Open All button)
Can you interpret these results in terms of the underlying biology? (Hint: good luck, there are many correct answers!)
Yellow = human/rat
Blue = human only
Grey = not relevant
Black = Complex
Open the pathway diagram for Netrin-1 Signaling.
Find the protein FADK1 (top centre of the cytosol). Right click on it and select Display Interactors. How many are there?
How many times has the interaction between FADK1 and Tumor endothelial marker 6 been documented? Hint: This detail is not in Reactome.
Find the protein SRC (to the left of FADK1). Display interactors for this protein. How many are there? Can you get a list of them?
Display interactors for UNC5B (bottom left of the cytosol). What happens and why?
What is the easiest way to remove interactors?
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