Introduction: What are protein interaction networks?
Protein-protein interactions (PPIs) / Protein-protein interaction networks (PPIN) are mathematical representations of the physical contacts (including electrostatic forces, hydrogen bonding and the hydrophobic effect) between proteins in the cell. These contacts are specific and bear a particular biological meaning.[1] Those interactions can be both transient and stable. [1] The study of PPIs is useful to identify novel pathways in certain disease and provides insightful information for drug discovery. [2] The data of PPIs can be found on String Database, IntAct and BioGrid. PPIs data are collected by both experimental and computational methods.
Human & zebrafish HTRA1 protein interactions from STRING
There is limited protein interaction of HTRA1 based on STRING analysis. The human HTRA1 protein interactions are based on experimental data. In zebrafish, there is no available experimental HTRA1 protein interactions on STRING. The HTRA1 protein interactions of zebrafish is based on all data available including textmining, co-expression, neighborhood, gene fusion and co-occurence. After I expanded the protein interaction network, I found that both human and zebrafish HTRA1 protein interactions are involved in a common biological process: serine-type endopeptidase activity. This is consistent with HTRA1's GO term. Interestingly, although not found in human and zebrafish protein interactions, the Drosophila interaction analysis shows that HtrA2 interacts with proteins involved in the positive regulation of compound eye pigmentation (red) and positive regulation of autophagy of mitochondria (purple). These two processes are potentially associated with age-related eye diseases, as autophagy is an important pathway involved in aging. Therefore, the interactions of HTRA1 in different model organisms with proteins involved in those pathways provide great insights into AMD research.
Other human HTRA1 protein interactions
Discussion
The human protein-protein interactions for HTRA1 data abstracted from String Database, IntAct and BioGrid show different gene interaction profiles. However, some genes such as TAF1, which is a transcription initiation factor is identified in all three sites. In the PPI data obtained from BioGRID, APOE gene which is associated with many age-related disease such as Alzheimer's disease is identified to interact with HTRA1, which provides insights into a common pathway in the human aging process that contributes to the age-related diseases. In addition, APOE is also a lipid transport gene that is found in drusen in retinal pigment epithelium (RPE). The early stage of AMD is characterized by the appearance of drusen in RPE, indicating an important role of lipid metabolism in the progression of AMD. [6] The experimental PPI data for zebrafish is very limited, suggesting further proteomics investigation into zebrafish HTRA1 protein interactions.
Reference:
Header: https://www.mbi.nus.edu.sg/wp-content/uploads/2018/06/2018-predicting-DNA-protein-interactions_800by600.png
[1]EMBL-EBI. (2024). Protein-protein interaction networks | Network analysis of protein interaction data. Retrieved March 29, 2024, from Ebi.ac.uk website: https://www.ebi.ac.uk/training/online/courses/network-analysis-of-protein-interaction-data-an-introduction/protein-protein-interaction-networks/
[2]Safari-Alighiarloo, N., Taghizadeh, M., Rezaei-Tavirani, M., Goliaei, B., & Peyvandi, A. A. (2014). Protein-protein interaction networks (PPI) and complex diseases. Gastroenterology and Hepatology from Bed to Bench, 7(1), 17–31. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017556/
[3]STRING protein-protein interaction networks. (2015). Retrieved March 29, 2024, from String-db.org website: https://string-db.org/cgi/input?sessionId=bZTkXrVsPMRt&input_page_show_search=on
[4]STRING protein-protein interaction networks. (2015). Retrieved March 29, 2024, from String-db.org website: https://string-db.org/cgi/input?sessionId=bZTkXrVsPMRt&input_page_show_search=on
[5]
Mike Tyers Lab. (2023). BioGRID. Retrieved March 29, 2024, from Thebiogrid.org website: https://thebiogrid.org/
[6]Borchert, G. A., Hoda Shamsnajafabadi, Hu, M. L., De, S. R., Downes, S. M., MacLaren, R. E., … Jasmina Cehajic-Kapetanovic. (2023). The Role of Inflammation in Age-Related Macular Degeneration—Therapeutic Landscapes in Geographic Atrophy. Cells, 12(16), 2092–2092. https://doi.org/10.3390/cells12162092
Header: https://www.mbi.nus.edu.sg/wp-content/uploads/2018/06/2018-predicting-DNA-protein-interactions_800by600.png
[1]EMBL-EBI. (2024). Protein-protein interaction networks | Network analysis of protein interaction data. Retrieved March 29, 2024, from Ebi.ac.uk website: https://www.ebi.ac.uk/training/online/courses/network-analysis-of-protein-interaction-data-an-introduction/protein-protein-interaction-networks/
[2]Safari-Alighiarloo, N., Taghizadeh, M., Rezaei-Tavirani, M., Goliaei, B., & Peyvandi, A. A. (2014). Protein-protein interaction networks (PPI) and complex diseases. Gastroenterology and Hepatology from Bed to Bench, 7(1), 17–31. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017556/
[3]STRING protein-protein interaction networks. (2015). Retrieved March 29, 2024, from String-db.org website: https://string-db.org/cgi/input?sessionId=bZTkXrVsPMRt&input_page_show_search=on
[4]STRING protein-protein interaction networks. (2015). Retrieved March 29, 2024, from String-db.org website: https://string-db.org/cgi/input?sessionId=bZTkXrVsPMRt&input_page_show_search=on
[5]
Mike Tyers Lab. (2023). BioGRID. Retrieved March 29, 2024, from Thebiogrid.org website: https://thebiogrid.org/
[6]Borchert, G. A., Hoda Shamsnajafabadi, Hu, M. L., De, S. R., Downes, S. M., MacLaren, R. E., … Jasmina Cehajic-Kapetanovic. (2023). The Role of Inflammation in Age-Related Macular Degeneration—Therapeutic Landscapes in Geographic Atrophy. Cells, 12(16), 2092–2092. https://doi.org/10.3390/cells12162092