SORT1
Description
The SORT1 (sortilin 1) is a protein-coding gene located on chromosome 1.
Sortilin (SORT1) is a protein encoded by the SORT1 gene located on chromosome 1 in humans. It is a type I membrane glycoprotein belonging to the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors. While expressed in many tissues, sortilin is most abundant in the central nervous system. It functions in protein transport between the Golgi apparatus, endosome, lysosome, and plasma membrane, playing a role in glucose and lipid metabolism, neural development, and cell death. Additionally, sortilin is linked to various human diseases, including hypertension, atherosclerosis, coronary artery disease, Alzheimer's disease, and cancer. The SORT1 gene is associated with an increased risk of coronary artery disease. The SORT1 gene resides on chromosome 1 at the band 1p13.3 and contains 23 exons, encoding 2 isoforms through alternative splicing. Sortilin, a member of the Vps10p sorting receptor family, forms a ten-bladed beta-propeller structure with an inner tunnel containing multiple ligand binding sites when complexed with neurotensin.
SORT1, also known as sortilin, acts as a sorting receptor in the Golgi apparatus, directing proteins to lysosomes and endosomes. It facilitates protein transport from the Golgi to lysosomes independent of the mannose-6-phosphate receptor (M6PR) pathway. In the Golgi, lysosomal proteins bind to SORT1, and the complex is transported to prelysosomal compartments, where low pH releases the proteins. SORT1 is recycled back to the Golgi through interactions with the retromer. It also plays a role in transporting proteins from the Golgi to endosomes. SORT1 promotes neuronal apoptosis by mediating endocytosis of proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Additionally, it acts as a receptor for neurotensin and may contribute to extracellular matrix mineralization during osteogenic differentiation by scavenging extracellular LPL. In adipocytes, SORT1 is likely involved in forming specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4, which helps regulate insulin responsiveness. SORT1 may also mediate transport from the endoplasmic reticulum to the Golgi.
SORT1 is also known as Gp95, LDLCQ6, NT3, NTR3.
