Recombinant Rat Sortilin (Sort1), partial

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 (By similarity). May also mediate transport from the endoplasmic reticulum to the Golgi (PubMed:12771154)

Subcellular Location

Golgi apparatus, Golgi stack membrane (Single-pass type I membrane protein); Endosome membrane (Single-pass type I membrane protein); Endoplasmic reticulum membrane (Single-pass type I membrane protein); Nucleus membrane (Single-pass type I membrane protein); Cell membrane (Single-pass type I membrane protein); Lysosome membrane (Single-pass type I membrane protein)

Tissue Specificity

Highly expressed in fat, brain, and lung. Expressed in neuronal bodies and dendrites of the piriform cortex and hippocampus. Also expressed in the islands of Calleja, medial and lateral septal nuclei, amygdaloid nuclei, thalamic nuclei, the supraoptic nucleus, the substantia nigra, the Purkinje layer of the cerebellar cortex and the cranial motor nerve nuclei of the brainstem

Subunit

Interacts with LPL and SLC2A4 (By similarity). Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP, GM2A and NTS. Forms a complex with NGFR which binds specifically to the precursor forms of NGFB (proNGFB) and BDNF (proBDNF) (PubMed:15987945). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; may regulate their anterograde axonal transport and signaling. Interacts with CLN5. Interacts with PSAP. Interacts with GRN; this interaction mediates endocytosis and lysosome delivery of progranulin; interaction occurs at the neuronal cell surface in a stressed nervous system (By similarity). Interacts with the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35; which is involved in retrograde trafficking of the receptor from endosomes to the Golgi apparatus (By similarity). Interacts with SMPD1; the interaction is required for SMPD1 targeting to lysosomes (By similarity)

• Gibbs R.A. et al. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. — Nature (2004)
• Morris N.J. et al. Sortilin is the major 110-kDa protein in GLUT4 vesicles from adipocytes. — J. Biol. Chem. (1998)
• Lin B.-Z. et al. Sortilin is a major protein component of Glut4-containing vesicles. — J. Biol. Chem. (1997)
• Conticello S.G. et al. The prodomain of a secreted hydrophobic mini-protein facilitates its export from the endoplasmic reticulum by hitchhiking on sorting receptors. — J. Biol. Chem. (2003)
• Sarret P. et al. Distribution of NTS3 receptor/sortilin mRNA and protein in the rat central nervous system. — J. Comp. Neurol. (2003)
• Chen Z.-Y. et al. Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway. — J. Neurosci. (2005)
• Lundby A. et al. Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. — Nat. Commun. (2012)
• Parker B.L. et al. Site-specific glycan-peptide analysis for determination of N-glycoproteome heterogeneity. — J. Proteome Res. (2013)