SERPINA3 Human

Alpha-1 Antichymotrypsin (AACT), also known as SERPINA3, is a glycoprotein and a member of the serpin (serine protease inhibitor) superfamily. It is encoded by the SERPINA3 gene located on chromosome 14 in humans . AACT plays a crucial role in inhibiting the activity of certain proteases, such as cathepsin G and chymases, which are involved in various physiological and pathological processes .

AACT is composed of 423 amino acids and has a molecular weight of approximately 47.651 kDa . The protein structure includes an α-helix, β-folded sheets, and a reaction center loop (RCL) . It is primarily synthesized in the liver and then secreted into the bloodstream . Additionally, AACT is expressed in other organs, including the brain and aorta, and is secreted by astrocytes .

As a serine protease inhibitor, AACT’s primary function is to inhibit proteases like neutrophil cathepsin G and mast cell chymase . This inhibition is essential for protecting cells and tissues from damage caused by proteolysis during inflammation . AACT is also involved in maintaining intracellular homeostasis and extracellular matrix reconstruction .

AACT is an acute-phase protein, meaning its levels increase in response to inflammation . It is associated with several clinical conditions, including liver disease, Parkinson’s disease, chronic obstructive pulmonary disease (COPD), and Alzheimer’s disease . In Alzheimer’s disease, AACT is tightly associated with amyloid plaques and enhances the formation of amyloid-fibrils .

Recent studies have highlighted the potential of AACT as a biomarker for cancer diagnosis, prognosis, and therapy prediction . Dysregulation of AACT and its glycosylation levels are linked to tumor progression and recurrence . AACT expression levels have been associated with overall survival in patients with various cancers, including liver, pancreatic, and lung cancers .