| Literature References | 1. 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).
2. ROMERO, M.F., HEDIGER, M.A., BOULPAEP, E.L. AND BORON W.F.
Expression cloning and characterization of a renal eletrogenic Na+/HCO3-
cotransporter.
NATURE 387 409-413 (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).
4. ABULADZE, N., LEE, I., NEWMAN, D., HWANG, J., BOORER, K., PUSHKIN, A.
AND KURTZ, I.
Molecular cloning, chromosomal localization, tissue distribution, and
functional expression of the human pancreatic sodium bicarbonate
cotransporter.
J.BIOL.CHEM. 273 17689-17695 (1998).
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| Documentation | Na+/HCO3- co-transport proteins are involved in cellular HCO3- absorption
and secretion, and also with intracellular pH regulation. They mediate the
coupled movement of Na+ and HCO3- across plasma membranes in most of the
cell types so far investigated. A single HCO3- is transported together with
one to three Na+; this transport mode is therefore often electrogenic. In
the kidney, an electrogenic Na+/HCO3- co-transporter is the principal HCO3-
transporter of the renal proximal tubule, and is responsible for
reabsorption of more than 85% of the filtered load of HCO3- [1]. Until
recently, the molecular nature of these Na+/HCO3- co-transporters had
remained undiscovered, as initial attempts to clone them based on presumed
homology to Cl-/HCO3- (anion) exchangers had proved unsuccessful. Instead,
an expression cloning strategy was successfully utilised to identify the
Na+/HCO3- co-transporter from salamander kidney, an organ previously found
to possess electrogenic Na+/HCO3- co-transport activity [2]. The cloned co-
transporter consists of 1035 amino acids, and shows ~25-30% sequence
identity to anion exchanger proteins, which is distributed along the entire
sequence length. They also share very similar hydropathy plots, suggesting
they have ~10 transmembrane (TM) domains.
At least 3 mammalian Na+/HCO3- co-transporters have since been cloned, with
similar primary sequence lengths and putative membrance topologies. One of
these has been found to be a kidney-specific isoform [3], which is near-
identical (except for a varying N-terminal region) to a more widely-
distributed co-transporter cloned from pancreatic tissue [4].
NAHCO3TRSPRT is a 7-element fingerprint that provides a signature for
Na+/HCO3- co-transporters. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from conserved regions
spanning the N-terminal half of the alignment; motifs 1-5 lie in the
putative cytoplasmic N-terminus; motif 6 spans the end of the second
putative TM domain, through the start of the third TM domain; and motif
7 lies at the end of the fourth TM domain. Two iterations on SPTR37_10f
were required to reach convergence, at which point a true set comprising
10 sequences was identified.
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