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Human phytanoyl-CoA dioxygenase domain-containing 1 (PHYHD1) is a putative oxygen sensor associated with RNA and carbohydrate metabolism

Human phytanoyl-CoA dioxygenase domain-containing 1 (PHYHD1) is a 2-oxoglutarate (2OG)-dependent dioxygenase implicated in Alzheimer's disease, some cancers, and immune cell functions. The substrate, kinetic and inhibitory properties, function and subcellular localization of PHYHD1 are unknown. We used recombinant expression and enzymatic, biochemical, biophysical, cellular and microscopic assays for their determination. The apparent Km values of PHYHD1 for 2OG, Fe2+ and O2 were 27, 6 and > 200 μm, respectively. PHYHD1 activity was tested in the presence of 2OG analogues, and it was found to be inhibited by succinate and fumarate but not R-2-hydroxyglutarate, whereas citrate acted as an allosteric activator. PHYHD1 bound mRNA, but its catalytic activity was inhibited upon interaction. PHYHD1 was found both in the nucleus and cytoplasm. Interactome analyses linked PHYHD1 to cell division and RNA metabolism, while phenotype analyses linked it to carbohydrate metabolism. Thus, PHYHD1 is a potential novel oxygen sensor regulated by mRNA and citrate.

 

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The information you provided describes the research findings related to Human phytanoyl-CoA dioxygenase domain-containing 1 (PHYHD1). Here's a summary of the key points from the text you provided:

**1. Enzymatic Properties:**
   - PHYHD1 is a 2-oxoglutarate (2OG)-dependent dioxygenase.
   - The apparent Km values for PHYHD1 are 27 μm for 2OG, 6 μm for Fe2+, and > 200 μm for O2.

**2. Inhibition and Activation:**
   - PHYHD1 activity is inhibited by succinate and fumarate but not R-2-hydroxyglutarate.
   - Citrate acts as an allosteric activator of PHYHD1.

**3. Substrate and Inhibitor Interactions:**
   - The enzyme binds mRNA, but this interaction inhibits its catalytic activity.

**4. Subcellular Localization:**
   - PHYHD1 is found in both the nucleus and cytoplasm of cells.

**5. Functional Insights:**
   - Interactome analyses suggest that PHYHD1 is linked to cell division and RNA metabolism.
   - Phenotype analyses indicate a connection to carbohydrate metabolism.

**6. Implications:**
   - PHYHD1 is implicated in various diseases such as Alzheimer's disease, certain cancers, and immune cell functions.
   - The enzyme might function as an oxygen sensor, regulated by mRNA and citrate interactions.

This research provides valuable insights into the biochemical and functional properties of PHYHD1, shedding light on its potential roles in diseases and cellular processes.

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