This subfamily belongs to the Thermotoga maritima CorA (TmCorA)-family of the MIT superfamily of essential membrane proteins involved in transporting divalent cations (uptake or efflux) across membranes. Members of this subfamily are found in all three kingdoms of life. It is functionally diverse subfamily, in addition to the CorA Co2+ transporter from the hyperthermophilic Thermotoga maritima, it includes Methanosarcina mazei CorA which may be involved in transport of copper and/or other divalent metal ions. Thermotoga maritima CorA forms funnel-shaped homopentamers, the tip of the funnel is formed from two C-terminal transmembrane (TM) helices from each monomer, and the large opening of the funnel from the N-terminal cytoplasmic domains. The GMN signature motif of the MIT superfamily occurs just after TM1, mutation within this motif is known to abolish Mg2+ transport by a related protein, Saccharomyces cerevisiae Alr1p. Natural variants in this signature sequence may be associated with the transport of different divalent cations. The functional diversity of the MIT superfamily may also be due to minor structural differences regulating gating, substrate selection, and transport.
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