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Calcium-activated chloride channel protein regulator 1
- Molecular classification
- CLCA family, Calcium-dependent chloride channel accessory/regulator, Zinc metalloprotease
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Overview
Calcium-activated chloride channel regulator 1 (CLCA1) is a secreted protein involved in the regulation of calcium-dependent chloride channels (CaCCs). It modulates TMEM16A/ANO1 channels on cell surfaces, affecting electrolyte and fluid secretion, mucus production, and cellular signaling. CLCA1 contains a von Willebrand factor type A (VWA) domain and a zinc metalloprotease domain. It undergoes self-cleavage in the endoplasmic reticulum to produce an N-terminal fragment that is essential for activating CaCCs.
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Mechanism of action
Paracrine activation; secreted soluble CLCA1 interacts with neighboring cell membranes where TMEM16A resides; cleaved N-terminal VWA domain binds TMEM16A directly to potentiate Ca2+-dependent Cl− conductance
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Biological functions
Electrolyte and fluid secretionModulation of TMEM16A/ANO1 channelsMucus productionRegulation of calcium-dependent chloride currentsCellular signaling (proliferation, apoptosis, migration, angiogenesis)
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Disease associations
Mucus overproduction disordersCancerTumor suppressionDiseases characterized by abnormal ion transport or mucus secretion
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Safety considerations
Potential roles in cancer development and progressionAberrant mucus secretion
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