Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes . Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments . The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (, ). With VAPA, may regulate ER morphology . Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion . Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 . Also binds 25-hydroxycholesterol and cholesterol .
Subcellular locations: Endoplasmic reticulum membrane, Cytoplasm, Cytosol, Cell membrane, Cell projection, Filopodium tip, Nucleus membrane
Co-localizes with OSBPL6 at contact sites between the plasma membrane and the endoplasmic reticulum.
Expressed in a subset of small lymphocytes (at protein level). Expressed at high concentration in kidney, lymph node and thymus. Expressed at moderate concentration in stomach, jejunum, ileum, appendix, spleen, leukocytes, trachea, lung and thyroid gland. Expressed at low concentration in whole brain, esophagus, duodenum, ileocecum, colon, skeletal muscle, bone marrow, placenta and mammary gland . Isoform 1a, isoform 1b, isoform 1c and isoform 1d are highly expressed in brain, bone marrow, colon, kidney, lung, skeletal muscle, spleen, thymus and thyroid. Not expressed in heart and liver. Isoform 2a, isoform 2b, isoform 2c and isoform 2d are expressed in brain, bone marrow, kidney, skeletal muscle, spleen, thymus and thyroid. Not expressed in heart, liver and lung .