The enzyme sialate O-acetylesterase (EC 3.1.1.53) catalyzes the reaction
N -acetyl-O -acetylneuraminate + H2 O = N -acetylneuraminate + acetateIn human it is encoded by the SIAE gene located on chromosome 11 .
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 -acetylhydrolaseN -acetylneuraminate acetyltransferasesialate 9(4)-O -acetylesterase , and sialidase .
Function
SIAE activity negatively regulates B lymphocyte antigen receptor signalling and is required for the maintenance of immunological tolerance.[ 1] CD22 ), and is required for immunological tolerance e.g. in mice.[ 2]
Structure
The SIAE gene contains 15 exons [ 3] testis .[ 4]
Clinical Significance
Genetic defects in SIAE have been associated with multiple autoimmune diseases . Loss of function mutations in SIAE are much more frequently found in humans with autoimmune diseases especially rheumatoid arthritis and type 1 diabetes .[ 2]
Genetic variants and polymorphisms associated with the SIAE gene have been implicated in susceptibility to Autoimmune Disease 6 (AIS6).[ 2] rheumatoid arthritis , multiple sclerosis , lupus erythematosus , type 1 diabetes , and other autoimmune diseases .[ 5] 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.[ 2]
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).[ 6]
Rare variants for SIAE have also been implicated in autoimmune Addison's disease , but their pathogenic roles are inconclusive.[ 7]
References
^ Cariappa A, Takematsu H, Liu H, Diaz S, Haider K, Boboila C, Kalloo G, Connole M, Shi HN, Varki N, Varki A, Pillai S (2009). "B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O -acetyl sialic acid esterase" . J. Exp. Med . 206 (1): 125– 38. doi :10.1084/jem.20081399 . PMC 2626685 PMID 19103880 . ^ a b c d Ira Surolia; et al. (8 July 2010). "Functionally defective germline variants of sialic acid acetylesterase in autoimmunity" . Nature 466 (7303): 243– 247. Bibcode :2010Natur.466..243S . doi :10.1038/nature09115 . PMC 2900412 PMID 20555325 . ^ "SIAE sialic acid acetylesterase [Homo sapiens (Human)] - Gene - NCBI" .^ Zhu H, Chan HC, Zhou Z, Li J, Zhu H, Yin L, Xu M, Cheng L, Sha J (2004). "A gene encoding sialic-acid-specific 9-O -acetylesterase found in human adult testis" . J. Biomed. Biotechnol . 2004 (3): 130– 136. doi :10.1155/S1110724304307084 PMC 551583 PMID 15292578 . ^ "OMIM Entry - # 613551 - AUTOIMMUNE DISEASE, SUSCEPTIBILITY TO, 6; AIS6" .^ Yamamoto M, Iguchi G, Bando H, Fukuoka H, Suda K, Takahashi M, Nishizawa H, Matsumoto R, Tojo K, Mokubo A, Ogata T, Takahashi Y (2014). "A missense single-nucleotide polymorphism in the sialic acid acetylesterase (SIAE) gene is associated with anti-PIT-1 antibody syndrome" . Endocr. J . 61 (6): 641– 4. doi :10.1507/endocrj.ej13-0539 PMID 24748456 . ^ Gan EH, MacArthur K, Mitchell AL, Pearce SH (2012). "The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease" . Eur. J. Endocrinol . 167 (6): 825– 8. doi :10.1530/EJE-12-0579 . PMC 3494867 PMID 23011869 .
Activity Regulation Classification Kinetics Types
