Sortilin (human) (rec.) (His)

Human sortilin (aa 78-755) is fused at the C-terminus to a His-tag. Endotoxin Content: <0.01EU/µg purified protein (LAL test). Concentration: 1mg/ml after reconstitution. Reconstitution: Reconstitute with 50µl endotoxin-free water. Sortilin is a type I transmembrane multiligand receptor that is a member of the Vacuolar protein sorting 10 protein (Vps10p) domain receptor family. It is a 95 kDa protein, ubiquitously expressed, although most abundantly expressed in neurons, hepatocytes, adipocytes and white blood cells including macrophages. Sortilin is synthesized as a propeptide in the endoplasmic reticulum (ER) and processed to its mature form by furin-mediated cleavage in the trans-Golgi network. The primary function of sortilin is trafficking proteins from the Golgi to secretory vesicles and endolysosomal compartments. The majority of trafficking is from the Golgi to the endosomal compartment where sortilin deposits cargo targeted for catabolism in the lysosome and then is trafficked back to the Golgi via a retromer complex. At the cell surface, sortilin can remain intact and act as a receptor for extracellular ligands that can initiate signaling cascades or be internalized as a method of receptor-mediated endocytosis. Additionally, cell surface sortilin protein can undergo an additional cleavage that results in the release of the soluble form of the protein into the extracellular space. The sortilin receptor binds the nerve growth factor precursor (proNGF), neurotensin and Progranulin (PGRN), a secreted growth factor implicated in a multitude of processes ranging from regulation of inflammation to wound healing, tumorigenesis and neurological diseases. Sortilin controls PGRN trafficking (endocytosis) and is indirectly involved in lysosomal degradation of PGRN. Sortilin down-regulation via blocking antibodies is a key mechanism in increasing extracellular PGRN levels suggesting that sortilin is a potential target to correct PGRN reduction, such as that in patients with frontotemporal dementia (FTD) caused by GRN mutations. Protein function: Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Lysosomal proteins bind specifically to the receptor in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex. The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer. Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi. [The UniProt Consortium]