Biology:Ormdl sphingolipid biosynthesis regulator 3
 Generic protein structure example |
ORMDL sphingolipid biosynthesis regulator 3 is a protein that in humans is encoded by the ORMDL3 gene.[1] This gene is associated with asthma in childhood.[2] 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.[3]
Localisation
Mouse and human ORMDL3 gene encode 153 aa. ORMDL family consists of three members (ORMDL1-3) which are localised in the membrane of endoplasmic reticulum (ER).[4] Human ORMDL1, ORMDL2 and ORMDL3 are localised in chromosomes 2q32, 12q13.2 a 17q21.[5]
Function
ORMDL3 plays role in sphingolipid synthesis like negative regulators.[4][6] It also has a role in regulation of Ca2+ levels in the endoplasmic reticulum. ER is very important for generation, signalisation, functioning and store 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 (SERCA)) which return Ca2+ back to the ER.[7] Dysregulation of Ca2+ has the key role in several pathological conditions like dysfunction of SERCA, asthma,[8] and Alzheimer's.[9]
Clinical significance
Mutations in ORMDL3 are associated with inflammatory disease like Crohn's disease, type 1 diabetes,[10] and rheumatoid arthritis.[11]
References
- ↑ "Entrez Gene: ORMDL sphingolipid biosynthesis regulator 3". https://www.ncbi.nlm.nih.gov/gene/94103.
- ↑ "Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma". Nature 448 (7152): 470–3. July 2007. doi:10.1038/nature06014. PMID 17611496. Bibcode: 2007Natur.448..470M. https://deepblue.lib.umich.edu/bitstream/2027.42/62682/1/nature06014.pdf.
- ↑ "ORMDL3 transgenic mice have increased airway remodeling and airway responsiveness characteristic of asthma". Journal of Immunology 192 (8): 3475–87. April 2014. doi:10.4049/jimmunol.1303047. PMID 24623133.
- ↑ 4.0 4.1 "Orm/ORMDL proteins: Gate guardians and master regulators". Advances in Biological Regulation. Sphingolipid Signaling in Chronic Disease 70: 3–18. December 2018. doi:10.1016/j.jbior.2018.08.002. PMID 30193828.
- ↑ "ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins". Genome Biology 3 (6): RESEARCH0027. 2002. doi:10.1186/gb-2002-3-6-research0027. PMID 12093374.
- ↑ "Orm family proteins mediate sphingolipid homeostasis". Nature 463 (7284): 1048–53. February 2010. doi:10.1038/nature08787. PMID 20182505. Bibcode: 2010Natur.463.1048B.
- ↑ "The versatility and universality of calcium signalling". Nature Reviews. Molecular Cell Biology 1 (1): 11–21. October 2000. doi:10.1038/35036035. PMID 11413485.
- ↑ "Diminished sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma". Proceedings of the National Academy of Sciences of the United States of America 106 (26): 10775–80. June 2009. doi:10.1073/pnas.0902295106. PMID 19541629. Bibcode: 2009PNAS..10610775M.
- ↑ "Linking calcium to Abeta and Alzheimer's disease". Neuron 59 (2): 190–4. July 2008. doi:10.1016/j.neuron.2008.07.013. PMID 18667147.
- ↑ "Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease". American Journal of Human Genetics 85 (3): 377–93. September 2009. doi:10.1016/j.ajhg.2009.08.007. PMID 19732864.
- ↑ "Use of a multiethnic approach to identify rheumatoid- arthritis-susceptibility loci, 1p36 and 17q12". American Journal of Human Genetics 90 (3): 524–32. March 2012. doi:10.1016/j.ajhg.2012.01.010. PMID 22365150.
Further reading
- "Genetic polymorphism regulating ORM1-like 3 (Saccharomyces cerevisiae) expression is associated with childhood atopic asthma in a Japanese population". The Journal of Allergy and Clinical Immunology 121 (3): 769–70. March 2008. doi:10.1016/j.jaci.2007.09.038. PMID 18155279.
- "ORMDL3 gene is associated with asthma in three ethnically diverse populations". American Journal of Respiratory and Critical Care Medicine 177 (11): 1194–200. June 2008. doi:10.1164/rccm.200711-1644OC. PMID 18310477.
- "A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications". The Journal of Allergy and Clinical Immunology 121 (4): 860–3. April 2008. doi:10.1016/j.jaci.2008.01.015. PMID 18395550.
- "ORMDL3 variants associated with asthma susceptibility in North Americans of European ancestry". The Journal of Allergy and Clinical Immunology 122 (6): 1225–7. December 2008. doi:10.1016/j.jaci.2008.06.041. PMID 18760456.
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