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View Proteins belonging to: The Ni²⁺-Co²⁺ Transporter (NiCoT) Family

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).

Distant homologues of the NiCoT family (subfamily 2) have differing predicted topologies: 4, 5, 6, 7 and 8 TMSs. One such homologue, RcnA (YohM) of E. coli (274 aas) has 6 putative TMSs in a 3+3 arrangement with a large hydrophilic loop between putative TMSs 3 and 4. This protein is believed to catalyze Ca²⁺ and Ni²⁺ efflux (Rodrique et al., 2005). A close homologue of RcnA, NirC of Klebsiella oxytoca (307 aas) has 4 putative TMSs (1+3). Several homologues of RcnA (e.g., from Ralstonia solanacearum; CAD17703) have 7 putative TMSs (4+3). Still another homologue, UreH of Methanocaldococcus janaschii has 6 putative TMSs in a 1+2+2+1 arrangement. This apparent topological variation is not understood.

The overall reaction catalyzed by the proteins of subclass 1 of the NiCoT family is:

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

The overall reaction catalyzed by proteins of subclass 2 of the NiCoT family is probably:

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

View Proteins belonging to: The Ni²⁺-Co²⁺ Transporter (NiCoT) Family

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

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

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

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