Family 2.A.36 - The Monovalent Cation:Proton Antiporter-1 Family
Family ID: 52631
The CPA1 family is a large family of proteins derived from Gram-positive
and Gram-negative bacteria, blue green bacteria, yeast, plants
and animals. Transporters from eukaryotes have been functionally
characterized, and all of these catalyze Na+:H+ exchange. Their
primary physiological functions may be in (1) cytoplasmic pH regulation,
extruding the H+ generated during metabolism, and (2) salt tolerance
(in plants), due to Na+ uptake into vacuoles.
The phylogenetic
tree for the CPA1 family shows three principal clusters. The first
cluster includes proteins derived exclusively from animals, and
all of the functionally characterized members of the family belong
to this cluster. Of the two remaining clusters, one includes all
bacterial homologues while the other includes one from Arabidopsis
thaliana, one from Homo sapiens and two from yeast (S. cerevisiae
and S. pombe). Several organisms possess multiple paralogues;
for example seven paralogues are found in C. elegans, and five
are known for humans. Most of these paralogues are very similar
in sequence, and they belong to the animal specific cluster.
Numerous members
of the CPA1 family have been sequenced, and these proteins vary
substantially in size. The bacterial proteins have 527-549 amino
acyl residues while eukaryotic proteins are generally larger,
varying in size from 541-894 residues. They exhibit 10-12 putative
transmembrane a-helical spanners (TMSs). A recently proposed topological
model (Wakabayashi; et al, 2000) suggests that in addition to
12 TMSs, a region between TMSs 9 and 10 dips into the membrane
to line the pore. However, one homologue, Nhx1 of S. cerevisiae
has an extracellular glycosylated C-terminus (Wells and Rao, 2001).
Some members show limited sequence similarity with members of
the CPA2 family although this similarity is insufficient to establish
homology. PSI-BLAST results with a single iteration provide further
evidence that these two large families comprise part of a single
superfamily.
