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Particularly with increasing knowledge on contribution of acidosis to all key steps of cancer progression, it is becoming apparent that even those attributes of CA IX that were previously thought to be unrelated to its catalytic activity, such as disruption of E-cadherin-related cell-cell contacts, formation of focal adhesion contacts, endocytosis, and possibly others, are linked to low pericellular pH

3 Specifically, it reacts with cysteine, tyrosine, tryptophan, methionine, proline, hydroxyproline, and histidine, with most of its biologic activity coming from the reactions with cysteine, methionine, tyrosine, and tryptophan