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2.A.52 The Ni2+-Co2+ Transporter (NiCoT) Family

Currently sequenced proteins of the NiCoT family are found in Gram-negative and Gram-positive bacteria as well as archaea and eukaryotes. The functionally best characterized members of the family catalyze uptake of Ni2+ and/or Co2+ in a proton motive force-dependent process. These proteins vary in size from 301 to 381 amino acyl residues and possess 7 or 8 TMSs. Topological analyses with the HoxN Ni2+ transporter of Ralstonia eutropha (Alcaligenes eutrophus) suggest that it possesses 8 TMSs with its N- and C-termini in the cytoplasm. The Co2+ (Ni2+) transporter of Rhodococcus rhodochrous, NhlF, exhibits eight putative TMSs, and eight apparent TMSs are revealed by a hydropathy analysis of the multiple alignment of the NiCoT family protein sequences. An HX4DH sequence in helix 2 of the HoxN protein has been implicated in Ni2+ binding, and both helix 1 and helix 2 which interact spatially, form the selectivity filter (Degan and Eitinger, 2002). In the H. pylori NixA homologue, several conserved motifs have been shown to be important for Ni2+ binding and transport (Wolfram and Bauerfeind, 2002).


The overall reaction catalyzed by the proteins of the NiCoT family is:

[Ni2+ or Co2+] (out) [Ni2+ or Co2+] (in).



References associated with 2.A.52 family:

Degen, O. and T. Eitinger. (2002). Substrate specificity of nickel/cobalt permeases: insights from mutants altered in transmembrane domains I and II. J. Bacteriol. 184: 3569-3577. 12057951
Degen, O., M. Kobayashi, S. Shimizu, and T. Eitinger. (1999). Selective transport of divalent cations by transition metal permeases: the Alcaligenes eutrophus HoxN and the Rhodococcus rhodochrous NhlF. Arch. Microbiol. 171: 139-145. 10201093
Deng, X., J. He, and N. He. (2013). Comparative study on Ni2+-affinity transport of nickel/cobalt permeases (NiCoTs) and the potential of recombinant Escherichia coli for Ni2+ bioaccumulation. Bioresour Technol 130: 69-74. 23306112
Eitinger, T. and B. Friedrich. (1991). Cloning, nucleotide sequence, and heterologous expression of a high-affinity nickel transport gene from Alcaligenes eutrophus. J. Biol. Chem. 266: 3222-3227. 1847142
Eitinger, T. and B. Friedrich. (1994). A topological model for the high affinity nickel transporter of Alcaligenes eutrophus. Mol. Microbiol. 12: 1025-1032. 7934894
Eitinger, T. and M.-A. Mandrand-Berthelot. (2000). Nickel transport systems in microorganisms. Arch. Microbiol. 173: 1-9. 10648098
Eitinger, T., L. Wolfram, O. Degen, and C. Anthon. (1997). A Ni2+ binding motif is the basis of high affinity transport of the Alcaligenes eutrophus nickel permease. J. Biol. Chem. 272: 17139-17144. 9202033
Eitinger, T., O. Degen, U. Böhnke, and M. Müller. (2000). Nic1p, a relative of bacterial transition metal permeases in Schizosaccharomyces pombe, provides nickel ion for urease biosynthesis. J. Biol. Chem. 275: 18029-18033. 10748059
Eitinger, T., O. Degen, U. Bohnke, and M. Muller. (2000). Nic1p, a relative of bacterial transition metal permeases in schizosaccharomyces pombe, provides nickel ion for urease biosynthesis. J. Biol. Chem. 275: 33184. 11032848
Fu, C., S. Javedan, F. Moshiri, and R.J. Maier. (1994). Bacterial genes involved in incorporation of nickel into hydrogenase enzyme. Proc. Natl. Acad. Sci. USA 91: 5099-5103. 8197192
Fulkerson, J.F., Jr. and H.L.T. Mobley. (2000). Membrane topology of the NixA nickel transporter of Helicobacter pylori: two nickel transport-specific motifs within transmembrane helices II and III. J. Bacteriol. 182: 1722-1730. 10692379
Hebbeln, P. and T. Eitinger. (2004). Heterologous production and characterization of bacterial nickel/cobalt permeases. FEMS Microbiol. Lett. 230: 129-135. 14734175
Iwig, J.S., J.L. Rowe, and P.T. Chivers. (2006). Nickel homeostasis in Escherichia coli - the rcnR-rcnA efflux pathway and its linkage to NikR function. Mol. Microbiol. 62: 252-262. 16956381
Komeda, H., M. Kobayashi, and S. Shimizu. (1997). A novel transporter involved in cobalt uptake. Proc. Natl. Acad. Sci. USA 94: 36-41. 8990157
Rodrigue, A., G. Effantin, and M.A. Mandrand-Berthelot. (2005). Identification of rcnA (yohM), a nickel and cobalt resistance gene in Escherichia coli. J. Bacteriol. 187: 2912-2916. 15805538
Saier, M.H., Jr., B.H. Eng, S. Fard, J. Garg, D.A. Haggerty, W.J. Hutchinson, D.L. Jack, E.C. Lai, H.J. Liu, D.P. Nusinew, A.M. Omar, S.S. Pao, I.T. Paulsen, J.A. Quan, M. Sliwinski, T.-T. Tseng, S. Wachi, and G.B. Young. (1999). Phylogenetic characterization of novel transport protein families revealed by genome analyses. Biochim. Biophys. Acta 1422: 1-56. 10082980
Wolfram, L. and P. Bauerfeind. (2002). Conserved low-affinity nickel-binding amino acids are essential for the function of the nickel permease NixA of Helicobacter pylori. J. Bacteriol. 184: 1438-1443. 11844775
Wolfram, L., B. Friedrich, and T. Eitinger. (1995). The Alcaligenes eutrophus protein HoxN mediates nickel transport in Escherichia coli. J. Bacteriol. 177: 1840-1843. 7896709
Wolfram, L., E. Haas, and P. Bauerfeind. (2006). Nickel represses the synthesis of the nickel permease NixA of Helicobacter pylori. J. Bacteriol. 188: 1245-1250. 16452405