Sialate O-acetylesterase

{{infobox enzyme

| Name = sialate O-acetylesterase

| EC_number = 3.1.1.53

| CAS_number = 89400-31-7

| GO_code = 0001681

| image =

| width =

| caption =

}}

The enzyme sialate O-acetylesterase (EC 3.1.1.53) catalyzes the reaction

:N-acetyl-O-acetylneuraminate + H₂O = N-acetylneuraminate + acetate

In 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-acetylhydrolase. Other names in common use include N-acetylneuraminate acetyltransferase, sialate 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.{{cite journal |vauthors=Cariappa A, Takematsu H, Liu H, Diaz S, Haider K, Boboila C, Kalloo G, Connole M, Shi HN, Varki N, Varki A, Pillai S |title=B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase |journal=J. Exp. Med. |volume=206 |issue=1 |pages=125–38 |year=2009 |pmid=19103880 |pmc=2626685 |doi=10.1084/jem.20081399 }} It down-regulates B lymphocyte antigen receptor signaling (involving CD22), and is required for immunological tolerance e.g. in mice.{{Cite journal| author = Ira Surolia | title = Functionally defective germline variants of sialic acid acetylesterase in autoimmunity | journal = Nature | volume = 466| pages = 243–247 | date = 8 July 2010 | doi = 10.1038/nature09115 | pmid=20555325 | issue=7303| pmc = 2900412| bibcode = 2010Natur.466..243S |display-authors=etal}}

Structure

The SIAE gene contains 15 exons {{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/54414|title=SIAE sialic acid acetylesterase [Homo sapiens (Human)] - Gene - NCBI}} and expresses a protein that is approximately 56 kDa in size. It is known to be expressed in the adult testis.{{cite journal |vauthors=Zhu H, Chan HC, Zhou Z, Li J, Zhu H, Yin L, Xu M, Cheng L, Sha J |title=A gene encoding sialic-acid-specific 9-O-acetylesterase found in human adult testis |journal=J. Biomed. Biotechnol. |volume=2004 |issue=3 |pages=130–136 |year=2004 |pmid=15292578 |pmc=551583 |doi=10.1155/S1110724304307084 |doi-access=free }}

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.

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.{{Cite web|url=http://www.omim.org/entry/613551|title = OMIM Entry - # 613551 - AUTOIMMUNE DISEASE, SUSCEPTIBILITY TO, 6; AIS6}} 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).{{cite journal |vauthors=Yamamoto M, Iguchi G, Bando H, Fukuoka H, Suda K, Takahashi M, Nishizawa H, Matsumoto R, Tojo K, Mokubo A, Ogata T, Takahashi Y |title=A missense single-nucleotide polymorphism in the sialic acid acetylesterase (SIAE) gene is associated with anti-PIT-1 antibody syndrome |journal=Endocr. J. |volume=61 |issue=6 |pages=641–4 |year=2014 |pmid=24748456 |doi= 10.1507/endocrj.ej13-0539|doi-access=free }}

Rare variants for SIAE have also been implicated in autoimmune Addison's disease, but their pathogenic roles are inconclusive.{{cite journal |vauthors=Gan EH, MacArthur K, Mitchell AL, Pearce SH |title=The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease |journal=Eur. J. Endocrinol. |volume=167 |issue=6 |pages=825–8 |year=2012 |pmid=23011869 |pmc=3494867 |doi=10.1530/EJE-12-0579 }}

References

{{cite journal |vauthors=Garcia-Sastre A, Villar E, Manuguerra JC, Hannoun C, Cabezas JA | date = January 1991| title = Activity of influenza C virus O-acetylesterase with O-acetyl-containing compounds | journal = Biochem. J. | volume = 273 | issue = 2| pages = 435–41 | pmid = 1991039 | pmc = 1149864 | doi = 10.1042/bj2730435}}
{{cite journal |vauthors=Shukla AK, Schauer R| date = 1982 | title = High performance liquid chromatography of enzymes of sialic acid metabolism | journal = Hoppe-Seyler's Z. Physiol. Chem. | volume = 363 | pages = 1039–1040 }}

Category:EC 3.1.1

Category:Enzymes of unknown structure