2.A.11. The Citrate-Mg²⁺:H⁺ (CitM) Citrate-Ca²⁺:H⁺ (CitH) Symporter (CitMHS) Family The two characterized members of the CitMHS family are both citrate uptake permeases from Bacillus subtilis. CitM is believed to transport a citrate^2--Mg²⁺ complex in symport with one H⁺ per Mg²⁺-citrate while CitH apparently transports a citrate^2--Ca²⁺ complex in symport with protons (Boorsma et al., 1996; Krom et al., 2000). The cation specificity of CitM is: Mg²⁺, Mn²⁺, Ba²⁺, Ni²⁺, Co²⁺, Ca²⁺ and Zn²⁺ with an order of preference in this order. CitM is highly specific for citrate and D-isocitrate and does not transport other di- and tri-carboxylates including succinate, L-isocitrate, cis-aconitate and tricarballylate (Li and Pajor, 2002; Warner and Lolkema, 2002). For CitH, the cation specificity (in order of preference) is: Ca²⁺, Ba²⁺ and Sr²⁺ (Krom et al., 2000). The two proteins are 60% identical, contain about 400 amino acyl residues and possess twelve putative transmembrane spanners. A CitM homologue in S. mutans transports citrate conjugated to Fe²⁺ or Mn²⁺ but not Ca²⁺, Mg²⁺ or Ni²⁺ (Korithoski et al., 2005). The CitMHS family belongs within the IT superfamily (Prakash et al., 2003; Rabus et al., 1999). Members of this family are found in Gram-positive and Gram-negative bacteria, archaea and possibly in eukaryotes. These proteins all probably arose by an internal gene duplication event. The transport reactions catalyzed by (1) CitM and (2) CitH, respectively, are: (1) Citrate &149; Mg (out) + nH⁺ (out) → Citrate &149; Mg (in) + nH⁺ (in) (2) Citrate (out) + nH⁺ (out) → Citrate (in) + nH⁺ (3) Citrate &149; Ca²⁺ (out) + nH⁺ (out) → Citrate &149; Ca²⁺ (in) + nH⁺ (in)
This family belongs to the IT Superfamily.
References:
Boorsma, A., M.E. van der Rest, J.S. Lolkema, and W.N. Konings. (1996). Secondary transporters for citrate and the Mg²⁺-citrate complex in Bacillus subtilis are homologous proteins. J. Bacteriol. 178: 6216-6222.
Korithoski, B., K. Krastel, and D.G. Cvitkovitch. (2005). Transport and metabolism of citrate by Streptococcus mutans. J. Bacteriol. 187: 4451-4456.
Krom, B.P., J.B. Warner, W.N. Konings, and J.S. Lolkema. (2000). Complementary metal ion specificity of the metal-citrate transporters CitM and CitH of Bacillus subtilis. J. Bacteriol. 182: 6374-6381.
Lensbouer, J.J., A. Patel, J.P. Sirianni, and R.P. Doyle. (2008). Functional characterization and metal ion specificity of the metal-citrate complex transporter from Streptomyces coelicolor. J. Bacteriol. 190: 5616-5623.
Li, H. and A.M. Pajor. (2002). Functional characterization of CitM, the Mg²⁺-citrate transporter. J. Membr. Biol. 185: 9-16.
Prakash, S., G. Cooper, S. Singhi, and M.H. Saier, Jr. (2003). The ion transporter superfamily. Biochim. Biophys. Acta 1618: 79-92.
Rabus, R., D.L. Jack, D.J. Kelly, and M.H. Saier Jr. (1999). TRAP transporters: an ancient family of extracytoplasmic solute-receptor-dependent secondary active transporters. Microbiology 145: 3431-3445.
Warner, J.B. and J.S. Lolkema. (2002). Growth of Bacillus subtilis on citrate and isocitrate is supported by the Mg²⁺-citrate transporter CitM. Microbiology 148: 3405-3412.
Examples:
TC#	Name	Organismal Type	Example
2.A.11.1.1	[Citrate or D-isocitrate]•M²⁺ (Mg²⁺ preferring):H⁺ symporter, CitM (transports Mg²⁺, Mn²⁺, Ni²⁺, Co²⁺ & Zn²⁺).	Bacteria	CitM of Bacillus subtilis

2.A.11.1.2	[Citrate]•M²⁺ (Ca²⁺ preferring):H⁺ symporter, CitH (transports Ca²⁺, Ba²⁺ & Sr²⁺).	Bacteria	CitH of Bacillus subtilis

2.A.11.1.3	Citrate•Me²⁺ (Fe²⁺/Mn²⁺ preferring):H⁺ symporter, CitM	Bacteria	*CitM of Streptococcus mutans* (AAN58714)**

2.A.11.1.4	*Citrate-M²⁺ (Fe³⁺ preferring): H⁺ symporter, Cit (transports Fe³⁺, Ca²⁺, Pb²⁺, Ba²⁺ and Mn²⁺, but not Mg²⁺, Ni²⁺ or Co²⁺) (Lensbouer et al.,* 2008).**	Bacteria	*Cit of Streptomyces coelicolor* (Q9S242)**