Characterization of a histidine rich cluster of amino acids in the cytoplasmic domain of the Na+/H+ exchanger

We examined the function of a highly conserved Histidine rich sequence of a mino acids found in the carboxyl-terminal of the Na+/H+ exchanger (NHE1). A fusion protein containing the sequence HYGHHH (540-545) and the balance of the carboxyl terminal of the protein did not bind calcium but bound to an immobilized metal affinity column and could be used to partially purify the exchanger protein. Mutation of the sequence to either HYGAAA or HYGRRR did not affect activity of the intact protein. Mutation to HHHHHH did not affe ct proton activation of the Na+/H+ exchanger or localization but caused a d ecreased maximal velocity suggesting that this conserved sequence is import ant in maximal activity of the Na+/H+ exchanger.