| Literature References | 1. ORLOWSKI, J. AND GRINSTEIN, S.
Na+/H+ exchangers of mammalian cells.
J.BIOL.CHEM. 272 22373-22376 (1997).
2. NUMATA, M., PETRECCA, K., LAKE, N. AND ORLOWSKI, J.
Identification of a mitochondrial Na+/H+ exchanger.
J.BIOL.CHEM. 273 6951-6959 (1998).
3. DIBROV, P. AND FLIEGEL, L.
Comparative molecular analysis of Na+/H+ exchangers: a unified model for
Na+/H+ antiport.
FEBS LETT. 424 1-5 (1998).
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| Documentation | Na+/H+ exchange proteins eject protons from cells, effectively eliminating
excess acid from actively metabolising cells. Na+/H+ exchange activity is
also crucial for the regulation of cell volume, and for the reabsorption of
NaCl across renal, intestinal, and other epithelia. These antiports exchange
Na+ for H+ in an electroneutral manner, and this activity is carried out by
a family of Na+/H+ exchangers, or NHEs, which are known to be present in
both prokaryotic and eukaryotic cells. In mammalian cells, Na+/H+ exchange
activity is found in both the plasma membrane and inner mitochondrial
membrane. To date, six mammalian isoforms have been identified (designated
NHE1-NHE6) [1,2]. These exchangers are highly-regulated (glyco)phospho-
proteins, which, based on their primary structure, appear to contain 10-12
membrane-spanning regions at the N-terminus and a large cytoplasmic region
at the C-terminus. There is some evidence that they may exist in the cell
membrane as homodimers, but little is currently known about the mechanism
of their antiport [3].
NHE2, which shares around 50% amino acid identity with NHE1, has a limited
expression pattern, being found preferentially in the gastrointestinal tract
and the kidney. It is also much less sensitive to the inhibitory diuretic
amiloride than the more ubiquitous NHE1. The targeting of NHE2 in polarised
epithelial cells is controversial, some studies reporting basolateral, and
others reporting apical localisation. When transfected into mutagenised
cells devoid of endogenous NHE activity, NHE2 is capable of regulating pH,
cellular volume, and proliferation, in a manner similar to NHE1.
NAHEXCHNGR2 is a 9-element fingerprint that provides a signature for the
Na+/H+ exchanger isoform 2 (NHE2). The fingerprint was derived from an
initial alignment of 4 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise NHE2 but distinguish it from other NHE isoforms -
motif 1 encodes the first putative extracellular domain; and motifs 2-9 span
the C-terminal putative cytoplasmic domain. A single iteration on OWL31.1
was required to reach convergence, no further sequences being identified
beyond the starting set. Two partial matches were found, S83549 and AF012894,
which are NHE2 protein fragments, from human and prairie dog, respectively.
An update on SPTR37_9f identified a true set of 3 sequences.
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