What are protein interaction networks?
Within organisms, protein-protein interactions occur, which impacts signaling within cells. In turn, cell signaling influences response to genetic information and the environment [1]. A database, known as the STRING database, can provide information and make predictions about these types of interactions. Additionally, STRING can describe protein interactions that occur in a indirect or direct manner [2].
What does the human protein interaction network look like for GBA1?
GBA1, which is shown in red in the center, can also be referred to as GBA [3]. The following images shows the protein interaction network of GBA1 as seen in the STRING database [2]. The image on the left depicts a network of proteins that physically interact with GBA1. The image on the right also includes indirect GBA1 protein interactions, which are more functional in nature [2]. A legend is also provided to allow for proper interpretation of this data.
How can we organize the protein interaction network of GBA1?
We can sort protein interaction networks by gene ontology terms. These terms were color-coded accordingly: sphingolipid metabolic growth (humans) and glycosphingolipid metabolic growth (zebrafish), glucosylceramidase activity, and lysosome.
![Picture](/uploads/1/4/4/5/144563580/screenshot-2023-04-29-at-5-29-34-pm_orig.png)
Discussion
It is important to note that zebrafish have the biological process, glycosphingolipid metabolic process, while the human term is sphingolipid metabolic process. Glycosphingolipids are a type of sphingolipid, therefore, the biological process is still closely related between humans and zebrafish [4]. Additionally, both zebrafish and humans are associated with lysosomal function. However, in zebrafish, the lysosomes are associated with the proteins shown in red via KEGG pathways. KEGG pathways are part of a database that provide information about relation networks and molecular interactions [5]. Therefore, there are many similarities in the protein interaction networks when comparing humans to zebrafish, as seen in the image above. This serves as another justification as to why zebrafish is a good model organism for studying Gaucher disease.
References
1. Silverbush, D., Sharan, R. A systematic approach to orient the human protein–protein interaction network. Nat Commun 10, 3015 (2019). https://doi.org/10.1038/s41467-019-10887-6
2. Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, Annika GL, Fang T, Doncheva NT, Pyysalo S, Bork P‡, Jensen LJ‡, von Mering C‡.
The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest.
Nucleic Acids Res. 2023 Jan 6;51(D1):D638-646.PubMed
3. National Library of Medicine. (n.d.). Gba1 glucosylceramidase beta 1 [homo sapiens (human)]. National Center for Biotechnology Information. Retrieved April 14, 2023, from https://www.ncbi.nlm.nih.gov/gene/2629
4. Hannun, Y. A., & Obeid, L. M. (2017, November 22). Sphingolipids and their metabolism in physiology and disease. Nature. Retrieved April 14, 2023, from https://www.nature.com/articles/nrm.2017.107
5. Kegg pathway database. (n.d.). Retrieved May 7, 2023, from https://www.genome.jp/kegg/pathway.html
2. Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, Annika GL, Fang T, Doncheva NT, Pyysalo S, Bork P‡, Jensen LJ‡, von Mering C‡.
The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest.
Nucleic Acids Res. 2023 Jan 6;51(D1):D638-646.PubMed
3. National Library of Medicine. (n.d.). Gba1 glucosylceramidase beta 1 [homo sapiens (human)]. National Center for Biotechnology Information. Retrieved April 14, 2023, from https://www.ncbi.nlm.nih.gov/gene/2629
4. Hannun, Y. A., & Obeid, L. M. (2017, November 22). Sphingolipids and their metabolism in physiology and disease. Nature. Retrieved April 14, 2023, from https://www.nature.com/articles/nrm.2017.107
5. Kegg pathway database. (n.d.). Retrieved May 7, 2023, from https://www.genome.jp/kegg/pathway.html
Links to Images
Cover Image: https://www.phenoswitchbioscience.com/en/identification-of-protein-protein-interactions/
GBA Protein Interaction Networks (in human and zebrafish): https://string-db.org/
GBA Protein Interaction Networks (in human and zebrafish): https://string-db.org/