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.
References:
Heterodimeric inorganic cation antiporter, UmpAB, both subunits belonging to the DUF1538 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, 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 localizes 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 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).
UmpAB of Halomonas zhaodongensis
Uncharacterized DUF1538 proteins of (1) 230 aas and (2) 250 aas, both with 7 TMSs in a 3 + 4 TMS arrangement.
DUF1538 proteins of Evansella cellulosilytica (Bacillus cellulosilyticus)
Uncharacterized protein of 570 aas and 14 TMSs in a 3 + 4 + 3 + 4 TMS arrangement (GB# OUT43428). This protein (GB# OUT43428) is encoded by a gene that is one gene down from two genes encoding proteins of the MFP family (8.A.1, OUT43436 and OUT43425), clearlly indicating that this system is a solute efflux system, possibly of the ABC superfamily.
UP of Pelagibacteraceae bacterium TMED13 (marine metagenome)
DUF1538 domain-containing protein of 255 aas and 7 TMSs in a 3 + 4 TMS arrangement.
DUF1538 domain protein of Rhodobacteraceae bacterium
DUF1538 domain protein of 255 aas and 7 TMSs. This protein brings up 2.A.63.1.3 (residues 10 - 251 (TMSs 1 - 7) aligning with residues 157 - 391 aas (TMSs 4 - 9) in 2.A.63.1.3 which has 14 TMSs. It is possible that these two families are part of a superfamily, but this possibility has not yet been tested rigorously. However, if homologous, this suggests that there was a rearrangement between the two families so that TMSs 1 - 7 in this protein corresponds to TMS 4 - 10 in MnhD (P60686) in the multisubunit Mnh cation exchanger (2.A.63.1.3). The fact that both systems catalyze the same reaction also suggests that these two families are part of a superfamily.
DUF1538 protein of Halomonas nanhaiensis
DUF1538 domain-containing protein of 497 aas and 14 TMSs.
DUF1538 domain protein of Firmicutes bacterium
DUF1538 domain-containing protein of 230 aas and 7 TMSs.
DUF1538 protein of Methanosarcina sp. MSH10X1
DUF1538 domain-containing protein of 250 aas and 7 TMSs.
DUF538 protein of Acholeplasmataceae bacterium