Chondroitin sulfate biosynthesis (R-HSA-2022870)

[ukemi]

• [x] Create a mouse model based on the Reactome pathway
• [x] Is R-HSA-2018682 missing R-HSA-9632033 as a preceding event? Yes - DONE
• [x] We need to remember to update the relationships for transporters/transport. Moved into new ticket #174 in this project.
• [x] We need to review the inference of transporters. In some cases we are actually referring to the process of transport, R-HSA-2022911. Moved into new ticket #174 in this project.
• [x] Can we fill in missing ChEBI entities with CHEBI:26349 proteochondroitin sulfate in the Reactome pathway? This is a preliminary ChEBI term - the closest fully edited and released one may be ChEBI:37397 chondroitin sulfate. TO DO: investigate structure of these glycoproteins: can they be handled as proteins with modified (i.e., chondroitin-ligated) residues? If so then the same strategy that works for R-HSA-163125 GPI-modified proteins and for their biosynthesis would work here. Do we really want to use preliminary ChEBI entities or should we work with ChEBI to have them ‘promoted’? PD comment: ChEBI:37397 chondroitin sulfate is a grouping term that has children differing from one another in the carbon of the N-acetylgalactosamine (GalNAc) sugar that is sulfated. Those children show the polymeric structure of chondroitin sulfate explicitly. Not clear whether it's known which child or children are found in human and mouse chondroitin sulfate glycoproteins. Further PD comment - Despite the missing details of oligosaccharide structure and incomplete description of its asembly, do we want to declare that since all relevant gene products and f=their molecular functions in connection with this pathway are covered by the annotations that we do have, this is sufficient for now and declare the work done? @ukemi
• [x] Do sequential reactions that can be catalyzed by the same gene product always feed into each other, or do they ever switch catalysts? Eg. R-HSA-1971491 and R-HSA-1971487. Answer-NO in vitro work shows that you require 2 different transferases to elongate chondroitin chains. It’s thought that they work as heterodimeric complexes. Referenced in PMID:22952769.
• [x] Challenges representing the processive nature of polymerization. The model makes it look like the chains are only three sugars long after the initiation step.
• [x] Release the mouse model to production

[ukemi]

Challenges representing the processive nature of polymerization. The model makes it look like the chains are only three sugars long after the initiation step.

These kinds polymers are complex in that they are actually chains of disaccharides, some of which get modified after the or during their extension. We decided that there is no need to represent the cyclical nature of the additions in Reactome or in the GO-CAM models.