| Literature References | 1. KOPITO, R.R.
Molecular biology of the anion exchanger gene family.
INT.REV.CYTOL. 123 177-199 (1990).
2. BORON, W.F., FONG, P., HEDIGER, M.A., BOULPAEP, E.L. AND ROMERO, M.F.
The electrogenic Na/HCO3 cotransporter.
WIEN.KLIN.WOCHENSCHR. 109 445-456 (1997).
3. BURNHAM, C.E., HASSANE, A., WANG, Z., SHULL, G.E. AND SOLEIMANI, M.
Cloning and functional expression of a human kidney Na+:HCO3-
cotransporter.
J.BIOL.CHEM. 272 19111-19114 (1997).
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| Documentation | Bicarbonate (HCO3-) transport mechanisms are the principal regulators of pH
in animal cells. Such transport also plays a vital role in acid-base
movements in the stomach, pancreas, intestine, kidney, reproductive organs
and the central nervous system. Functional studies have suggested four
different HCO3- transport modes. Anion exchanger proteins exchange HCO3-
for Cl- in a reversible, electroneutral manner [1]. Na+/HCO3- co-transport
proteins mediate the coupled movement of Na+ and HCO3- across plasma
membranes, often in an electrogenic manner [2]. Na- driven Cl-/HCO3-
exchange and K+/HCO3- exchange activities have also been detected in
certain cell types, although the molecular identities of the proteins
responsible remain to be determined.
Sequence analysis of the two families of HCO3- transporters that have been
cloned to date (the anion exchangers and Na+/HCO3- co-transporters) reveals
that they are homologous. This is not entirely unexpected, given that they
both transport HCO3- and are inhibited by a class of pharmacological agents
called disulphonic stilbenes [3]. They share around ~25-30% sequence
identity, which is distributed along their entire sequence length, and have
similar predicted membrane topologies, suggesting they have ~10
transmembrane (TM) domains.
HCO3TRNSPORT is an 8-element fingerprint that provides a signature for the
HCO3- transporter superfamily. The fingerprint was derived from an initial
alignment of 18 sequences: the motifs were drawn from conserved regions
from the central portion of the alignment - motif 1 lies near the end of
the long presumed-cytoplasmic N-terminus; motifs 2-3 encode most of the
first TM domain; motif 4 spans the end of fourth TM domain and the start
of the following cytoplasmic loop; motif 5 encodes ~2/3 of the fifth TM
domain; motif 6 lies on the sixth TM domain; motif 7 encodes a portion of
the seventh TM domain; and motif 8 lies on the putative extracellular loop,
between TM domains 7 and 8. Two iterations on SPTR37_10f were required to
reach convergence, at which point a true set comprising 28 sequences was
identified.
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