Antisecretory factor (AF) (AF)

Antisecretory factor (AF) is a 41 kDa endogenous protein, also known as the S5a (or Rpn10) subunit of the 19S regulatory particle of the 26S proteasome (UniProt P55036). It is found in most tissues and body fluids and is characterized by its potent antisecretory and anti-inflammatory properties. AF regulates fluid and ion transport across cell membranes, particularly in the intestinal epithelium, by inhibiting chloride secretion and stabilizing tight junction proteins like ZO-1 and occludin. Its production can be induced by specific dietary triggers, such as specially processed cereals (SPC), or it can be administered exogenously via AF-enriched egg yolk (Salovum) or synthetic peptide fragments like AF-16. Clinically, the AF system is targeted for the treatment of secretory diarrhea, inflammatory bowel disease, and conditions involving abnormal fluid pressure, such as Meniere's disease and glaucoma. Additionally, in oncology, its role as a proteasome subunit (PSMD4) makes it a target for inhibition in diseases like multiple myeloma and chemoresistant colorectal cancer, where its blockade leads to the accumulation of polyubiquitinated proteins and apoptosis.

Other names

S5aRpn10Proteasome 26S subunit non-ATPase 4PSMD4Antisecretory factor 1AF-1ASFMCB1

Inhibition of chloride ion secretion and stimulation of water absorption in the intestinal epithelium; stabilization of tight junction proteins like ZO-1 and occludin; inhibition of GABAergic signaling in the enteric nervous system; as a proteasome subunit, it facilitates the degradation of ubiquitinated proteins by acting as a ubiquitin receptor.