Disease relevance of FET4

• First, FET4 repression by Rox1p under oxygenated conditions helps minimize metal toxicity [1].

High impact information on FET4

• In contrast, a screen of high-copy number plasmid libraries for clones able to increase tolerance to alkaline pH revealed only two genes: FET4 (encoding a low affinity transporter for copper, iron, and zinc) and CTR1 (encoding a high affinity copper transporter) [2].
• Second, FET4 is regulated by zinc status via the Zap1 transcription factor [3].
• Finally, FET4 expression is regulated in response to oxygen by the Rox1 repressor [3].
• First, we found that FET4 expression is induced in iron-limited cells by the Aft1 iron-responsive transcriptional activator [3].
• Combinatorial control of yeast FET4 gene expression by iron, zinc, and oxygen [3].

Chemical compound and disease context of FET4

• Sensitivity towards cadmium was high in either anaerobically grown wild-type yeast or in oxygenated rox1Delta strains, and in both cases cadmium toxicity was reversed by FET4 mutations [1].

Biological context of FET4

• This BSD2 control of ion transport occurs independently of the CTR1 and FET4 metal transport systems [4].
• The region surrounding approximately -960 to -490 contains two consensus Rox1p binding sites and mediates Rox1p, but not iron control of FET4 [1].

Anatomical context of FET4

• Consistent with its role as an Fe2+ transporter, FET4 is an integral membrane protein present in the plasma membrane [5].

Associations of FET4 with chemical compounds

• The FET4 gene encodes an Fe(II) transporter required for low-affinity uptake [6].

Other interactions of FET4

• Fet4p is not the only metal transporter that is negatively regulated by oxygen; we find that Rox1p also represses S. cerevisiae SMF3, proposed to function in vacuolar iron transport [1].
• The high affinity transporters, Ftr1p and Fet3p, are primarily expressed in oxygenated cultures, whereas anaerobic conditions induce the low affinity iron transporter, Fet4p [1].
• For these experiments, we utilized yeast lacking the major iron uptake pathways (FET3 and FET4) and yeast deficient in SIT1, encoding the major up-regulated iron siderophore transporter [7].
• An sod1/fet3 double mutant showed increased sensitivity to oxygen and increased transcription of FET4, an alternative, low affinity, iron transporter [8].
• We present evidence that FET4 is a physiologically relevant zinc transporter and this provides a rationale for its regulation by Zap1 [3].

References