CA12

CA12, or carbonic anhydrase XII, is a member of the alpha carbonic anhydrase family. It is a transmembrane zinc metalloenzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate and protons on the cell surface, contributing to extracellular pH regulation and CO2 transport. The enzyme is encoded by the CA12 gene in humans and is expressed in several epithelial tissues, including the breast, kidney, and colon, with varying levels among normal and diseased states.

Structurally, CA12 is a transmembrane protein with an extracellular catalytic domain in which a zinc ion is coordinated at the active site. This arrangement enables catalytic activity at the cell surface, influencing the local microenvironment around cells. The extracellular orientation facilitates interaction with components of the tumor microenvironment and other extracellular processes.

In cancer, CA12 is frequently overexpressed in certain tumor types, and its expression has been associated with tumor hypoxia and progressive disease in some contexts. It is studied as a potential diagnostic or prognostic biomarker and a contributor to the adaptation of cancer cells to acidic environments.

Therapeutically, CA12 inhibitors, including sulfonamide derivatives, are being investigated to selectively target this enzyme while minimizing effects on other carbonic anhydrases. The aim is to reduce extracellular acidity and potentially limit tumor progression, with many inhibitors in preclinical or early clinical development.

Disambiguation note: the acronym CA12 can denote other designations in different contexts, but in scientific literature it most commonly refers to carbonic anhydrase XII.