sialate O-acetylesterase
Identifiers
EC no.3.1.1.53
CAS no.89400-31-7
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

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.[1] It down-regulates B lymphocyte antigen receptor signaling (involving CD22), and is required for immunological tolerance e.g. in mice.[2]

Structure

The SIAE gene contains 15 exons [3] and expresses a protein that is approximately 56 kDa in size. It is known to be expressed in the adult 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] Individuals susceptible to AIS6 may suffer from rheumatoid arthritis, multiple sclerosis, lupus erythematosus, type 1 diabetes, and other autoimmune diseases.[5] 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.[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

  1. ↑ 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.
  2. 1 2 3 4 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.
  3. ↑ "SIAE sialic acid acetylesterase [Homo sapiens (Human)] - Gene - NCBI".
  4. ↑ 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.
  5. ↑ "OMIM Entry - # 613551 - AUTOIMMUNE DISEASE, SUSCEPTIBILITY TO, 6; AIS6".
  6. ↑ 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.
  7. ↑ 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.


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.