| Literature References | 1. KOPITO, R.R.
Molecular biology of the anion exchanger gene family.
INT.REV.CYTOL. 123 177-199 (1990).
2. ALPER, S.L.
The band 3-related anion exchanger (AE) gene family.
ANNU.REV.PHYSIOL. 53 549-564 (1991).
3. TANNER, M.J.
The structure and function of band 3 (AE1): recent developments (review).
MOL.MEMBR.BIOL. 14 155-165 (1997).
4. BRUCE, L.J., UNWIN, R.J., WRONG, O. AND TANNER, M.J.
The association between familial distal renal tubular acidosis and
mutations in the red cell anion exchanger (band 3, AE1) gene.
BIOCHEM.CELL BIOL. 76 723-728 (1998).
|
| Documentation | Anion exchange proteins are thought to participate in pH and cell volume
regulation. They are glycosylated, plasma-membrane transport proteins that
exchange hydrogen carbonate (HCO3-) for chloride (Cl-) in a reversible,
electroneutral manner [1,2]. To date three anion exchanger isoforms have
been identified (AE1-3), AE1 being the previously-characterised erythrocyte
band 3 protein. They share a predicted topology of 12-14 transmembrane (TM)
domains, but have differing distribution patterns and cellular localisation.
The best characterised isoform, AE1, is known to be the most abundant
membrane protein in mature erythrocytes. It has a molecular mass of ~95 kDa
and consists of two major domains. The N-terminal 390 residues form a water-
soluble, highly elongated domain that serves as an attachment site for the
binding of the membrane skeleton and other cytoplasmic proteins. The
remainder of the protein is a 55kDa hydrophobic domain that is responsible
for catalysing anion exchange. The function of the analogous domains of AE2
and AE3 remains to be determined [3].
Naturally-occuring mutations have been characterised in the AE1 gene, which
give rise to forms of several inherited human diseases. Around 20% of
hereditary spherocytosis cases arise from heterozygosity for AE1 mutations,
and result in the absence or decrease of the mutant protein in the red cell
membrane. Similarly, familial distal renal tubular acidosis, a condition
associated with kidney stones, has been shown to be associated with
mutations of AE1 of the renal collecting duct alpha-intercalated cell, and
it has been postulated that such mutations may affect the targeting of the
AE1 protein, which is usually directed to the basolateral membrane of
these cells [4].
ANIONEXHNGR1 is a 4-element fingerprint that provides a signature for the
anion exchanger isoform 1. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length, focusing on those sections
that characterise the anion exchanger isoform 1 but distinguish it from
others - motif 1 resides within the putative cytoplasmic N-terminus; motif
2 lies on the exoplasmic loop connecting putative TM domains 7 and 8; motif
3 encodes a small portion of the intracellular loop between TM domains 8
and 9; and motif 4 is located on the putative extracellular loop connecting
TM domains 11 and 12. Two iterations on SPTR37_9f were required to reach
convergence, at which point a true set comprising 7 sequences was identified.
|