The human SLC41A1 protein contains two MgtE domains with 52% and 46% respective similarity to the PF01769 consensus sequence and is predicted to contain ten TM domains, five in each MgtE domain (see figure), which suggests that the MgtE protein of bacteria may work as a dimer. Adapted from Wabakken et al. (2003) and the pFAM database, the figure shows the computer predicted membrane topology of MgtE in H. sapiens. The TM domains are shown in light blue, the orientation in the membrane and the positions of the N- and C-termini are indicated, and the figure is not drawn to scale. Wabakken et al. (2003) found that the transcript of the SLC41A1 gene was expressed in all human tissues tested, but at varying levels, with the heart and testis having the highest expression of the gene. No explanation of the expression pattern has been suggested with regard to Mg2+-related physiology. It has not been shown whether the SLC41 proteins transport Mg2+ or complement a Mg2+ transport mutation in any experimental system. However, it has been suggested that as MgtE proteins have no other known function, they are likely to be Mg2+ transporters in the metazoa as they are in the bacteria. This will need to be verified using one of the now standard experiment systems for examining Mg2+ transport. TRPM6/ TRPM7 The investigation of the TRPM genes and proteins in human cells is an area of intense recent study and, at times, debate. Montell et al. (2002) have reviewed the research into the TRP genes, and a second review by Montell (2003) has reviewed the research into the TRPM genes. The TRPM family of ion channels has members throughout the metazoa. The TRPM6 and TRPM7 proteins are highly unusual, containing both an ion channel domain and a kinase domain (Figure 1.7), the role of which brings about the most heated debate. The activity of these two proteins has been very difficult to quantify. TRPM7 by itself appears to be a Ca2+ channel but in the presence of TRPM6 the affinity series of transported cations places Mg2+ above Ca2+. The differences in reported conductance were caused by the expression patterns of these genes. TRPM7 is expressed in all cell types tested so far, while TRPM6 shows a more restricted pattern of expression. An unfortunate choice of experimental system by Voets et al., (2004) led to the conclusion that TRPM6 is a