2.A.89 The Vacuolar Iron Transporter (VIT) Family
Members of the VIT family (DUF125) have been characterized in yeast (Ccc1; TC #2.A.89.1.1) and plants (Vit1; TC #2.A.89.1.2) (Kim et al., 2006). The former transports Fe2+ and Mn2+ into the vacuole where Fe2+ is stored, while the latter has been shown to transport Fe2+. Mutants accumulate excess Fe2+ in the cytoplasm which can be toxic. Excess Fe2+ is taken up into the vacuole. Vacuolar iron storage is critical for seedling development, and so is Vit1. Vit2 and Ccc1 have 5 putative TMSs in a 2 + 2 + 1 arrangement. Homologues are found in eukaryotes, bacteria and archaea where they may have a 1 + 2 + 2 arrangement (e.g., TC #2.A.89.2.1 from Pyrococcus abyssi) or a 1 + 2 + 3 arrangement (e.g., TC #2.A.89.3.1 from Burkholderia phytofirmans). Other bacterial and archaeal homologues are about 250 aas in length. A 270 aa homologue EAN12646 from Frankia sp. has 5 TMSs in a 2 + 3 arrangement. A 399 residue homologue from Ustilago maydis (EAK82927) has 5 putative TMSs in a 2 + 3 arrangement with two less hydrophobic peaks between the 2 and 3 strongly hydrophobic peaks. Of the two pairs of 2 TMSs, the first peak is smaller than the second peak in both cases, suggesting that these proteins arose by an intragenic duplication followed by addition of other domains. The separation between the 2 pairs is variable (>100 aas to <20 aas). These proteins always have an extended hydrophilic N-terminus.
Distant homologues include nodulin-22 of Phaseolus vulgaris (common beans) which may be involved in stress responses in plants (Mohammad et al., 2004), and rubrerythrin of Porphyremona gingivalis which is a non-heme, iron protein that protects air-sensitive bacteria against oxidative stress (Mydel et al., 2006). VIT family proteins probably function by a H+ antiport carrier-type mechanism accounting for vacuolar uptake.