The Nucleobase:Cation Symporter-1 (NCS1) Family (TC# 2.A.39) consists of over 1000 currently sequenced proteins derived from Gram-negative and Gram-positive bacteria, archaea, fungi and plants.
These proteins exhibit limited sequence similarity with the xanthine permease, PbuX (TC# 2.A.39.4.1), of Bacillus subtilis which is a member of the NCS2 family.
[3] Proteins of the NCS1 family are 419-635 amino acyl residues long and possess twelve putative transmembrane α-helical spanners (TMSs).
The two families probably arose by an early gene duplication event that occurred long before divergence of the three major kingdoms of life.
The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.
Their evolutionary and structure-function analyses led to the concept that selective channel-like gates may contribute to substrate specificity.