Using the European Bioinformatics Institute's Database to Determine Pirin Pathology

        Two weeks ago I used the National Center for Biotechnology Information’s protein and 

nucleotide databases to investigate the amino sequences in pirin as well as the nucleotide 

sequences that allowed the gene PIR to express pirin. This week we will be using a similar 

database provided by the European Bioinformatics Institute to investigate what pathological 

process pirin is involved in (EBI) (Madeira, Park, Lee, et al., 2019).

A search for pirin using EBI’s search tool provides information identical to what I retrieved from the UnitProt and NCBI  databases in past weeks. However, EBI’s database goes much further in depth about pirin’s protein structure and expression than UniProt, compiling information such a R-values and an extensive list of experiments detailing pirin’s baseline and differential expression levels in various conditions. While NCBI’s databases do contain this information it was, at least for pirin, spread out across multiple files within multiple databases, EBI’s database compiles all of this information into a single directory.

EBI’s database also contains a wealth of information on gene-disease associations that I will be using to explore some of the pathologies that PIR, the gene that encodes pirin, might play a part in. The first of these gene-disease associations I found was contained in an article that correlates the delocalization of pirin with the advancement of melanoma (Licciulli, Luise, Zanardi, et al., 2010); a study that I also briefly cited during the first week of this blog when summarizing pirin. The study states that pirin is almost always clustered within a cell’s nucleus, but that when pirin begins to delocalize out of a melanocyte cell’s nucleus and into the cell’s cytoplasm there is a correlation between cytoplasmic pirin concentration and melanoma progression. This conclusion suggests that melanoma may be possible to detect if high concentrations of cytoplasmic pirin is found when conducting immunohistochemical analysis of melanocytes. Immunohistochemical analysis is a process in which proteins are located in the body by inducing catabolic reactions that break a given substrate down into a colored product, with a higher absorbance of a corresponding wavelength of light indicating a higher concentration of the colored product and by extension the substrate that was catabolized to make it (Abendroth & Dabbs, 1995). 

Pirin has also been associated with neoplasm, a condition in which the body cannot regulate cell division, resulting in rapid cell and tissue growths that have the potential to become cancerous (Madeira, Park, Lee, et al., 2019). During the first week of this blog I mentioned that some studies have suggested that pirin’s role as an oxidative-stress sensor may inhibit ferroptosis in certain tissues when pirin concentration is too high, resulting in unmitigated cell growth (Hu, Bai, Dai, et al., 2020). Pirin’s role in the inhibition of programmed cell death may readily be linked to the association between neoplasm and pirin that the aforementioned study suggested. 

Pirin has also been shown to be associated with Miyoshi myopathy, a disease in which muscle tissue in the extremities begins to deteriorate over time (Ma, Wang, Tian, et al., 2020). The study I pulled this information from suggests a correlation between pirin overexpression in myeloid cells (Bone marrow) and the progression of Miyoshi myopathy. Furthermore, the study hypothesizes that pirin induced Miyoshi myopathy is part of the prognosis of the previously mentioned pirin-associated neoplasm.

References

Abendroth CS, Dabbs DJ. Immunocytochemical staining of unstained versus previously 

stained cytologic preparations. Acta Cytol. 1995 May-Jun;39(3):379-86. PMID: 

7539200.

Hu N, Bai L, Dai E, Han L, Kang R, Li H, Tang D. Pirin is a nuclear redox-sensitive
modulator of autophagy-dependent ferroptosis. Biochem Biophys Res Commun.
2021 Jan 15;536:100-106. doi: 10.1016/j.bbrc.2020.12.066. Epub 2020 Dec 26.
PMID: 33373853.

Licciulli S, Luise C, Zanardi A, et al. Pirin delocalization in melanoma progression 

identified by high content immuno-detection based approaches. BMC Cell 

Biology. 2010 Jan; 11:5. DOI: 10.1186/1471-2121-11-5. PMID: 20089166; 

PMCID: PMC2823719.

Ma H, Wang H, Tian F, et al. PIWI-Interacting RNA-004800 Is Regulated by S1P 

Receptor Signaling Pathway to Keep Myeloma Cell Survival. Frontiers in 

Oncology. 2020 ;10:438. DOI: 10.3389/fonc.2020.00438. PMID: 32351883; 

PMCID: PMC7175921.

Madeira F., Park Y.M., Lee J., Buso N., Gur T., Madhusoodanan N., Basutkar P., Tivey 

ARN., Potter SC., Finn RD., Lopez R. (2019). The EMBL-EBI search and 

sequence analysis tools APIs in 2019 Nucleic Acids Research, April 12, 2019; 

doi: 10.1093/nar/gkz268