Nickel/cobalt transporters (NiCoTs), a family of secondary metal transporters in prokaryotes and fungi, are characterized by an eight-transmembrane-domain (TMD) architecture and mediate high-affinity uptake of cobalt and/or nickel ions into the cells. One of the strongly conserved regions within the NiCoTs is the signature sequence RHA(V/F)DADHI within TMD II. This stretch of amino acid residues plays an important role in the affinity, velocity and specificity of metal transport. Some relatives of the NiCoTs, named HupE, UreJ and UreH, contain a similar signature sequence and are encoded within or adjacent to [NiFe] hydrogenase or urease operons, or elsewhere in the genome of many prokaryotes. HupE and UreH from Rhodopseudomonas palustris CGA009 and UreJ from Cupriavidus necator H16 were shown to mediate Ni(2+) transport upon heterologous production in E. coli. Other variants of NiCoTs are found in many marine cyanobacteria and in plants. The cyanobacterial proteins are encoded by a segment adjacent to the genes for [Ni] superoxide dismutase and a corresponding putative maturation peptidase. The plant proteins contain N-terminal sequences resembling bipartite transit peptides of thylakoid lumenal and thylakoid integral membrane precursor proteins; expression of a YFP-fusion protein in transfected leaf cells is consistent with targeting of this protein to the plastid, but the function of the plant gene product has yet to be demonstrated.