Solute carrier family 6, member 20 also known as SLC6A20 is a protein which in humans is encoded by the SLC6A20 gene cite journal Function Transport of small hydrophilic substances across cell membranes is mediated by substrate-specific transporter proteins which have been cla...
Sodium translocation by the iminoglycinuria associated imino transporter (SLC6A20).
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Molecular membrane biology, ISSN: 1464-5203, Vol: 26, Issue: 5, Page: 333-46
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- Biochemistry, Genetics and Molecular Biology; imino; associated; sodium; iminoglycinuria; transporter; translocation; slc6a20; CMMB; Life Sciences; Physical Sciences and Mathematics; Social and Behavioral Sciences
The system IMINO transporter plays an essential role in the transport of proline and hydroxyproline in the intestine and kidney. Its molecular correlate has been identified and named SIT1 or IMINO (SLC6A20). Initial characterization of the transporter showed it to be Na(+) and Cl(-)-dependent, but the stoichiometry remained unresolved. Using homology modeling along the structure of the bacterial leucine transporter LeuT, we identified two highly conserved Na(+)-binding sites and a putative Cl(-)-binding site. Mutation of all residues in the two proposed Na(+)-binding sites revealed that most of them were essential for uptake and completely inactivated the transporter. However, mutants A22V (Na(+)-binding site 1) and mutants S20A, S20G, S20G/G405S (Na(+)-binding site 2) were partially active and characterized further. Flux studies suggested that mutations of Na(+)-binding site 1 caused a decrease of the Na(+)-K(0.5), whereas mutations of site 2 increased the K(0.5). Mutation of Na(+)-binding site 1 also changed the ion selectivity of the IMINO transporter. IMINO actively translocates (36)Cl(-) demonstrating that the proposed chloride binding site is used in the transporter. Accumulation experiments and flux measurements at different holding potentials showed that the transporter can work as a 2Na(+)/1Cl(-)-proline cotransporter. The proposed homology model allows to study mutations in IMINO associated with iminoglycinuria.