Sialate O-acetylesterase (SIAE)

Sialate O-acetylesterase (SIAE) is an enzyme (EC 3.1.1.53) that specifically removes acetyl groups from the 9-O and 4-O positions of sialic acids on glycoproteins, thereby negatively regulating B cell receptor (BCR) signaling and playing a vital role in the maintenance of immunological tolerance[1][2][3][4][5]. SIAE acts as a key negative regulator of B cell activation through a pathway involving CD22/Siglec proteins, Lyn tyrosine kinase, and SHP-1 phosphatase, setting signaling thresholds essential to prevent autoreactive immune responses[1][4][5]. Mutations or deficiencies of SIAE increase the risk of developing various autoimmune diseases, likely due to impaired inhibitory signaling and increased B cell activity[1][4][5]. Structurally, SIAE is a member of the SGNH hydrolase superfamily, active at alkaline pH, glycosylated, and expressed both in the cytosol and secretory pathways[2][3]. While SIAE is recognized as an optimal target class for small-molecule drug discovery in the theoretical context of modulating immune tolerance, effective therapies targeting SIAE have not yet been established[1].

Other names

Sialic acid acetylesteraseSialic acid-specific 9-O-acetylesteraseSialic acid-specific acetylesterase IISialate O-acetylesteraseYSG2CSE-CMGC87009LSEH-LseAIS6CSECCytosolic sialic acid 9-O-acetylesterase homolog

Small molecule inhibition (theoretically proposed for modulating immune tolerance in autoimmunity)[1]