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Ormdl sphingolipid biosynthesis regulator 3
Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia
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ORMDL sphingolipid biosynthesis regulator 3 is a protein that in humans is encoded by the ORMDL3 gene.[5] Variants affecting the expression of this gene are associated with asthma in childhood.[6] Transgenic mice which overexpress human ORMDL3 have increased levels of IgE. This correlated with increased numbers of macrophages, neutrophils, eosinophils, CD4+ and enhanced Th2 cytokine levels in the lung tissue.[7]
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Localisation
The ORMDL family, whose name stands for ORM1 (Saccharomyces cerevisiae)–like genes,[8] consists of three members (ORMDL1-3) which are localised in the membrane of the endoplasmic reticulum (ER).[9] All three human ORMDL genes encode 153 amino acid products.[9] The genes ORMDL1, ORMDL2 and ORMDL3 are located on human chromosomes 2q32, 12q13.2 and 17q21, respectively.[8]
Function
ORMDL3 negatively regulates de novo sphingolipid synthesis through interaction with serine palmitoyltransferase (SPT),[9][10] but it may be present in relative excess of SPT physiologically, as ORMDL3 overexpression does not significantly reduce cellular sphingolipid biosynthesis.[11] ORMDL3 also has a role in regulating Ca2+ levels in the endoplasmic reticulum.[12] The ER is very important for generation, signaling function and storage of intracellular Ca2+. There are channels, which control the exit of Ca2+ from the ER into the cytoplasm and also pumps (sarco-endoplasmic reticulum Ca2+ ATPase or SERCA) which return Ca2+ back to the ER.[13] Dysregulation of Ca2+ has the key role in several pathological conditions like dysfunction of SERCA, asthma,[14] and Alzheimer's.[15]
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Clinical significance
Mutations in ORMDL3 are associated with inflammatory diseases like Crohn's disease, type 1 diabetes,[16] and rheumatoid arthritis.[17]
References
Further reading
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