Family 1.A.14 - The Non-selective Cation Channel-1 Family        

Family ID: 52602

The NSCC1 family consists of a single functionally characterized protein, the non-selective cation channel found in insulin-secreting b-cells of the mouse (mNSC1). The protein is 423 amino acyl residues long and exhibits four putative transmembrane spanners (TMSs), one near the N-terminus of the protein (residues 52-70) and three near the C-terminus. The mNSC1 protein conducts monovalent cations (Na+, K+, Li+) nondiscriminantly, but transport of divalent cations was not detected. mNSC1 exhibits a selectivity ratio of cations to anions (PK/PCl) of 10. The mRNA of this protein was found to be abundant in brain, heart and lung tissues.

mNSC1 has no homologues in the databases. A cluster of charged residues (RX2RXRX2R), similar to the voltage sensor in the Shaker K+ channel, precedes TMS 2. Additionally, a 24-residue segment (residues 24-48) shows 68% identity to rat ubiquitin ligase (pirS70642). The conserved residues are: EPPCGWELNX3LEEX5TAES. This region corresponds to the N-terminal hydrophilic region preceding TMS 1. Residues 97-181 of mNSC1 exhibit 28% identity with several proteoglycan (condroitin sulfate) core proteins. This region corresponds to the large hydrophilic loop between TMSs 1 and 2. Although the functional significance of these observations is not clear, the latter observation suggests that the N- and C-termini are intracellular, and the large loop between TMSs 1 and 2 is extracellular.