Cloning and structural characterization of a human non-erythroid band 3-like protein

Polypeptides which are immunologically related to the erythrocyte anion transport protein have been identified in a variety of non-erythroid cells. We describe two cDNA clones encoding a human non-erythroid band 3 protein (HKB3) and the mouse erythrocyte band 3 (MEB3) and show that these proteins are structurally similar. Comparison of the predicted amino acid sequences from HKB3 and MEB3 reveals a high degree of sequence homology (71%) and conservation of the overall topography of the transmembrane domain. Similar levels of homology are also observed in comparisons with published amino acid sequence from the human erythrocyte band 3. In addition, specific residues which have been demonstrated to be involved in erythroid anion transport are conserved in HKB3, suggesting that this non-erythroid band 3 protein functions in this respect. Although protein sequence homology within the cytoplasmic domain is considerably lower (35%), three specific regions in HKB3 are conserved, one of which may represent an ankyrin binding site. Northern blot analysis reveals transcripts that cross-hybridize with the HKB3 cDNA in a variety of non-erythroid cell lines but not in cells of erythroid lineage.