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 may have an extended hydrophilic N-terminus. Eukaryotic VIT family proteins probably function by an H+ antiport carrier-type mechanism accounting for vacuolar uptake.
The vacuolar Fe2+ uptake transporter, VIT1 of 250 aas and 5 putative TMSs (Gollhofer et al. 2011). The crystal structure of the orthogous VIT1 from rose gum, Eucalyptus grandis, which probably functions as a H+-dependent antiporter for Fe2+ and other transition metal ions, has been solved. VIT1 adopts a novel protein fold forming a dimer of five membrane-spanning domains, with an ion-translocating pathway constituted by the conserved methionine and carboxylate residues at the dimer interface. The second transmembrane helix protrudes from the lipid membrane by about 40 Å, and connects to a three-helical bundle, triangular, cytoplasmic domain, which binds to the substrate metal ions in preparation for their transport (Kato et al. 2019).
VIT1 of Arabidopsis thaliana (Q9ZUA5)
Uncharacterized protein of 242 aas and 5 TMSs
Uncharacterized protein of Marivirga tractuosa
Uncharacterized protein of 252 aas with 5 TMSs
Uncharacterized protein of Parachlamydia acanthamoebae
CCC1 (VIT) family protein of 248 aas
VIT family protein of Chlamydia trachomatis
Uncharacterized protein of 173 aas and 5 TMSs.
UP of Candidatus Sungbacteria bacterium
Member of rubrerythrin family of electron transporters; of 327 aas and 5 TMSs.
VIT family member of Rhizobium leguminosarum
Membrane-bound ferritin-like ferrous iron (Fe2+) exporter, MbfA, of the erythrin-vacuolar iron transport-1 (Er-VIT1) family of 327 aas. The protein has an N-terminal ferritin domain and a C-terminal VIT domain of 5 established TMSs (Bhubhanil et al. 2014).
MbfA of Agrobacterium tumefaciens
VIT family member of 2690 aas and 5 TMSs.
VIT of Bartonella clarridgeiae
The bacterial VIT family homologue
VIT homologue of Burkholderia phytofirmans (376 aas; B2TCH9)
VIT family member, Spr0814 (Becker et al., 2009).
Spr0814, VIT family member of Streptococcus pneumoniae (E1H0W3)
Vacuolar Nodulin-like1 (At1g21140) Iron regulated (Gollhofer et al., 2011).
VIT homolog1 of Arabidopsis thaliana (Q9LPU9)
Nodulin-like2 (At1g76800) Iron regulated (Gollhofer et al., 2011).
VIT homolog2 of Arabidopsis thaliana (Q9SR03)
Nodulin-like2.1 (At3g25190) Iron regulated; involved in Fe homeostasis (Gollhofer et al., 2011).
VIT homolog2.1 of Arabidopsis thaliana (Q9LSF6)
Nodulin-like3 (At3g43630) Not iron regulated; involved in Fe homeostasis (Gollhofer et al., 2011).
VIT3 of Arabidopsis thaliana (Q9M2C3)
Nodulin-like4 (At3g43660) Not iron regulated (Gollhofer et al., 2011).
VIT4 of Arabidopsis thaliana (Q9M2C0)
Fe2+/Mn2+ transporter Pcl1 (Pombe ccc1-like protein 1)
Pcl1 of Schizosaccharomyces pombe
VIT family protein of 413 aas with an N-terminal rubrerythrin-like (ferritin-like) domain and a C-terminal DUF125 (5 TMS) domain.
VIT family protein of Methylacidiphilum infernorum (Methylokorus infernorum)