2.A.135.  The Inorganic Cation (Na⁺(Li⁺, K⁺)/H⁺) Antiporter (ICA) Family 

Genomic DNA was screened for novel Na⁺/H⁺ antiporter genes from Halomonas zhaodongensis by selection in Escherichia coli KNabc lacking three major Na⁺/H⁺ antiporters (Meng et al. 2017). Co-expression of two genes designated umpAB, encoding paired homologous unknown membrane proteins belonging to DUF1538 family (Pfam # PF07556), were found to confer E. coli KNabc tolerance to 0.4 M NaCl and 30 mM LiCl, and an alkaline pH resistance at 8.0. UmpAB localize as a hetero-dimer in the cytoplasmic membrane and exhibits pH-dependent Na⁺(Li⁺, K⁺)/H⁺ antiport activity at a wide pH range of 6.5 to 9.5 with an optimal pH at 9.0. Neither UmpA nor UmpB showed homology with previously known single-gene or multi-gene Na⁺/H⁺ antiporters, and thus, UmpAB represents a novel two-component Na⁺(Li⁺, K⁺)/H⁺ antiporter (Meng et al. 2017).

Many other proteins proved to be members of this family. Those in subfamily 1 have 7 or (duplicated) 14 TMSs, while those in subfamily 2 have fewer TMSs, usually 4 or 5 TMSs.  They may be of smaller sizes (as suggested by the large number of homologues of about this size) or may be fragments of the larger proteins.  This family was previously assigned to TC# 9.A.336.