ORM1 Like Protein 3 (ORMDL3)

The deduced 153-amino acid protein contains 4 putative transmembrane domains and shares 84%, 80%, and 96% amino acid identity with ORMDL1, ORMDL2, and mouse Ormdl3, respectively. It also shares significant homology with its yeast orthologs, Orm1 and Orm2. RT-PCR detected ORMDL3 expression in all adult and fetal tissues examined. Fluorescence-tagged ORMDL3 localized with an endoplasmic reticulum marker following transfection into COS-7 cells.Overexpression of ORMDL3 decreased both the basal and endoplasmic reticulum (ER)-stress-induced unfolded protein response (UPR). Knockdown of ORMDL3 expression induced a higher UPR after tunicamycin or thapsigargin stimulation, indicating that ORMDL3 expression levels can regulate UPR and that ORMDL3 might be an important factor in ensuring ER homeostasis.