Disease relevance of PHO84

• The manganese taken in via Pho84p is indeed biologically active and can not only cause toxicity but can also be incorporated into manganese-requiring enzymes [1].
• The proton-coupled Pho84 phosphate permease of Saccharomyces cerevisiae, overexpressed as a histidine-tagged chimera in Escherichia coli, was detergent-solubilized, purified, and reconstituted into proteoliposomes [2].

High impact information on PHO84

• This differential kinetic behavior is largely eliminated in cells that lack the ability to store phosphate internally in the form of polyphosphate, but the threshold of external phosphate required for induction of PHO5 and PHO84 is unaffected [3].
• In the budding yeast Saccharomyces cerevisiae, PHO84 and PHO86 are among the genes that are most highly induced in response to phosphate starvation [4].
• Here, we show that the subcellular localization of Pho84p is regulated in response to extracellular phosphate levels; it is localized to the plasma membrane in low-phosphate medium but quickly endocytosed and transported to the vacuole upon addition of phosphate to the medium [4].
• Upon expression, both AtPT1 and AtPT2 were able to complement the pho84 mutant phenotype of yeast strain NS219 lacking the high-affinity phosphate transport activity [5].
• For this study, using a formaldehyde-based in vivo cross-linking and chromatin immunoprecipitation (ChIP) assay, we have analyzed the role of Ubp8p in the regulation of H3-K4 methylation at three other SAGA-dependent yeast genes, namely, PHO84, ADH1, and CUP1 [6].

Biological context of PHO84

• We have found an open reading frame which is 1.1 kb upstream of PHO84 (which encodes a Pi transporter) and is transcribed from the opposite strand [7].
• By comparison of nucleotide sequences and by tetrad analysis with GAL80 as a standard, the PHO84 locus was mapped at a site beside the TUB3 locus on the left arm of chromosome XIII [8].
• The PHO84 gene in Saccharomyces cerevisiae encodes a Pi transporter, mutation of which confers constitutive synthesis of repressible acid phosphatase (rAPase), in medium containing repressible amounts of Pi, and an arsenate-resistant phenotype [9].
• The triple disruptants showed high levels of constitutive rAPase synthesis and arsenate resistance similar to the pho84 mutant, but showed slower cell growth than the pho84 mutant [10].
• Disruption of PHO86 did not affect cell viability even in combination with the pho84 and/or pho87 disruptions [10].

Anatomical context of PHO84

• Pho86p, an endoplasmic reticulum (ER) resident protein in Saccharomyces cerevisiae, is required for ER exit of the high-affinity phosphate transporter Pho84p [4].
• Proteoliposomes containing the Pho84 protein were fused with proteoliposomes containing purified cytochrome c oxidase from beef heart mitochondria [2].

Associations of PHO84 with chemical compounds

• In a search for other genes involved in manganese homeostasis, PHO84 was identified [1].
• In this study, we have compared the phosphate-responsive mechanism of cells expressing PHO84 with a Deltapho84 strain by use of a phosphate analogue, methylphosphonate, which was judged to be suitable for assessment of phosphate homeostasis in the cells [11].
• These results demonstrate that phosphate acts as a nutrient signal for activation of the protein kinase A pathway in yeast in a glucose-dependent way and they indicate that the Pho84 and Pho87 carriers act as specific phosphate sensors for rapid phosphate signalling [12].
• Intriguingly, in this study we found a tight correlation between selenite resistance and expression of the high affinity orthophosphate carrier Pho84p [13].
• The predicted Git1p has similarity to a variety of S. cerevisiae transporters, including a phosphate transporter (Pho84p), and both inositol transporters (Itr1p and Itr2p) [14].

Regulatory relationships of PHO84

• The constitutive rAPase+ phenotype of the pho86 pho87 mutant was partially suppressed by an increased dosage of the PHO84 gene [9].

Other interactions of PHO84

• The high-affinity system consists of Pho84p and Pho89p [15].
• The latter phenotypes were shown to be due to a defect in Pi uptake, and the Gtr1 protein was found to be functionally associated with the Pho84 Pi transporter [7].
• In Saccharomyces cerevisiae, the phosphate signal transduction pathway (PHO pathway) is known to regulate the expression of several phosphate-responsive genes, such as PHO5 and PHO84 [16].
• Deletion of MOT2 also caused increased transcription of unrelated genes such as GAL7 and PHO84 [17].
• Under these conditions, cells lacking both Pho84p and the high affinity Smf1p transporter accumulated low levels of manganese, although there was no major effect on activity of manganese-requiring enzymes [1].

References