EC number 3.1.1.53 IntEnz IntEnz view ExPASy NiceZyme view | CAS number 89400-31-7 BRENDA BRENDA entry KEGG KEGG entry | |
Sialate O-acetylesterase (SIAE) is a protein that in human is encoded by the SIAE gene located on chromosome 11. The SIAE protein functions in carbohydrate metabolism and catalyzes the removal of O-acetyl ester groups from position 9 of the parent sialic acid.
Contents
Structure
The SIAE gene contains 15 exons and expresses a protein that is approximately 56 kDa in size. It is known to be expressed in the adult testis.
Function
SIAE activity negatively regulates B lymphocyte antigen receptor signalling and is required for the maintenance of immunological tolerance.
In enzymology, a sialate O-acetylesterase (EC 3.1.1.53) is an enzyme that catalyzes the chemical reaction
N-acetyl-O-acetylneuraminate + H2OThus, the two substrates of this enzyme are N-acetyl-O-acetylneuraminate and H2O, whereas its two products are N-acetylneuraminate and acetate.
This enzyme belongs to the family of hydrolases, specifically those acting on carboxylic ester bonds. The systematic name of this enzyme class is N-acyl-O-acetylneuraminate O-acetylhydrolase. Other names in common use include N-acetylneuraminate acetyltransferase, sialate 9(4)-O-acetylesterase, and sialidase.
Clinical Significance
Genetic defects in SIAE have been associated with multiple autoimmune diseases.
Genetic variants and polymorphisms associated with the SIAE gene have been implicated in susceptibility to Autoimmune Disease 6 (AIS6). Individuals susceptible to AIS6 may suffer from rheumatoid arthritis, multiple sclerosis, lupus erythematosus, type 1 diabetes, and other autoimmune diseases. Individuals harboring rare heterozygous loss-of-function variants or homozygous defective polymorphic variants commonly produced enzymes that functioned in a dominant negative manner, leading to lack of SIAE enzymatic activities.
Missense single-nucleotide polymorphism in the SIAE gene has also been associated with the anti-PIT-1 antibody syndrome, a novel clinical entity related to autoimmune polyglandular syndrome (APS). Individuals with defective SIAE are characterized by the presence of circulating autoimmune antibodies against the pituitary-specific transcriptional factor-1 (PIT-1).
Rare variants for SIAE have also been implicated in autoimmune Addison's disease, but their pathogenic roles are inconclusive.