Sortilin

The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding.

The extracellular domain may be shed following protease cleavage in some cell types.

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 (PubMed:16787399). 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.

A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.

The N-terminal propeptide is cleaved by furin and possibly other homologous proteases.

Palmitoylated (PubMed:18817523). Undergoes cysteine S-palmitoylation which promotes the partitioning of the receptor into an endosomal membrane subdomain where it can interact with the retromer cargo-selective complex which mediates its retrograde trafficking to the Golgi apparatus (PubMed:18817523).

Phosphorylation at Ser-825 facilitates the interaction with GGA1.

Belongs to the VPS10-related sortilin family. SORT1 subfamily.

Expressed in brain and prostate (at protein level). Expressed at high levels in brain, spinal cord, heart, skeletal muscle, thyroid, placenta and testis. Expressed at lower levels in lymphoid organs, kidney, colon and liver.

• 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
• Extracellular side
• Lysosome membrane
• Single-pass type I membrane protein
• Localized to membranes of the endoplasmic reticulum, endosomes, Golgi stack, lysosomes and nucleus. A small fraction of the protein is also localized to the plasma membrane. May also be found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes. Localization to the plasma membrane in adipocytes may be enhanced by insulin.

Sortilin, 100 kDa NT receptor, Glycoprotein 95, Neurotensin receptor 3, Gp95, NT3, NTR3, SORT1

• entrezGene:6272
• omim:602458
• swissprot:Q99523

Proteins

Metabolism

92068Da