 Schizosaccharomyces pombe  Grx4, Fep1, and Php4:  In silico  analysis and expression response to different iron concentrations.
Due to iron's essential role in cellular metabolism, most organisms must maintain their homeostasis. In this regard, the fission yeast  Schizosaccharomyces pombe  (sp) uses two transcription factors to regulate intracellular iron levels: spFep1 under iron-rich conditions and spPhp4 under iron-deficient conditions, which are controlled by spGrx4. However, bioinformatics analysis to understand the role of the spGrx4/spFep1/spPhp4 axis in maintaining iron homeostasis in  S. pombe  is still lacking. Our study aimed to perform bioinformatics analysis on  S. pombe  proteins and their sequence homologs in  Aspergillus flavus  (af),  Saccharomyces cerevisiae  (sc), and  Homo sapiens  (hs) to understand the role of spGrx4, spFep1, and spPhp4 in maintaining iron homeostasis. The three genes' expression patterns were also examined at various iron concentrations. A multiple sequence alignment analysis of spGrx4 and its sequence homologs revealed a conserved cysteine residue in each PF00085 domain. Blast results showed that hsGLRX3 is most similar to spGrx4. In addition, spFep1 is most closely related in sequence to scDal80, whereas scHap4 is most similar to spFep1. We also found two highly conserved motifs in spFep1 and its sequence homologs that are significant for iron transport systems because they contain residues involved in iron homeostasis. The scHap4 is most similar to spPhp4. Using STRING to analyze protein-protein interactions, we found that spGrx4 interacts strongly with spPhp4 and spFep1. Furthermore, spGrx4, spPhp4, and spFep1 interact with spPhp2, spPhp3, and spPhp5, indicating that the three proteins play cooperative roles in iron homeostasis. At the highest level of Fe,  spgrx4  had the highest expression, followed by  spfep1 , while  spphp4  had the lowest expression; a contrast occurred at the lowest level of Fe, where  spgrx4  expression remained constant. Our findings support the notion that organisms develop diverse strategies to maintain iron homeostasis.
Ebrahim A, Alfwuaires MA, Abukhalil MH, Alasmari F, Ahmad F, Yao R, Luo Y, Huang Y