Protein products of metalloregulated genes involved in metal homeostasis in S. cerevisiae. Products of genes that are activated under metal-limiting conditions (A) and metal-replete conditions (B) by Aft1 (green), Mac1 (blue), Zap1 (red), and Ace1 (purple) are shown. Iron that is bound to siderophores has been circled, and stars indicate proteins that undergo iron-dependent cellular trafficking. The metal ion specificities of proteins required for metal uptake are indicated. See the text for further details of the functional roles of each protein.

Schematic representation of the fungal iron-responsive GATA factors (A) and copper-responsive transcription factors (B). Shown are Mac1, Ace1, and Haa1 from S. cerevisiae, Fep1 and Cuf1 from S. pombe, SREA from A. nidulans, SRE from N. crassa, SreP from P. chrysogenum, Urbs1 from U. maydis, GRISEA from P. anserina, Amt1 from C. glabrata, and Crf1 from Y. lipolytica. In panel A, the conserved zinc finger motifs (green rectangles), the cysteine-rich region (blue rectangle), and the RXXE motif of the iron-responsive GATA factors are indicated. In panel B, the following motifs are shown: conserved zinc modules (white ovals), conserved (R/K)GRP motifs (black triangles), positions of N-terminal Cys-X-Cys or Cys-X₂-Cys motifs outside the zinc motif (black rectangles), and positions of the C1 and C2 motifs (red rectangles). Proteins that are active under copper-limiting or copper-replete conditions are shown in grey and blue, respectively. Proteins that are not copper-responsive are shown in yellow.

(A) Schematic diagram of S. cerevisiae Zap1 and mouse MTF-1. The following are shown: zinc finger domains (numbered black ovals), position of the cysteine-to-serine mutation in Zap1-1^up (grey triangle), MTF-1 nuclear localization signal (gold star), MTF-1 NES (black star), and MTF-1 acid-, proline-, and serine/threonine-rich activation domains (red, green, and blue boxes labeled A, P, and S/T, respectively). (B) The multiple levels of Zap1 regulation: 1, autoregulation; 2, AD2 repression; 3, AD1 repression; 4, DNA-binding control. (C) The multiple levels of MTF-1 regulation: 1, nuclear translocation; 2, nucleocytoplasmic shuttling; 3, DNA-binding control; 4, posttranslational modification by phosphorylation; 5, interactions and binding inhibition by other factors. The absence of zinc in a metalloregulatory finger is indicated by a white numbered oval. Possible phosphorylation events (yellow circle labeled P), a putative repressor (purple square), and target genes (hatched boxes) are shown.