Sortilin
GeneName
SORT1
Summary
SORT1, also known as sortilin, NT-3, or NT3, is a 92kDa type I transmembrane protein that is predominantly expressed in the nervous system and various tissues. It is localised to multiple cellular compartments including the plasma membrane, endosomes, lysosomes, and the Golgi apparatus. SORT1 functions as a receptor for neurotrophins and plays a role in the endocytosis and intracellular transport of proteins. It is involved in processes such as D-glucose import, maintenance of synapse structure, and the regulation of gene expression, contributing to neuropeptide and neurotrophin signalling pathways.
Importance
SORT1 is relevant to: - Neurodegenerative diseases, as it is implicated in the transport and processing of neurotrophic factors that support neuronal health. - Metabolic disorders due to its role in the regulation of glucose transport and insulin response. - Cancer research, as it may influence cell differentiation and apoptosis through its involvement in extrinsic apoptotic signalling pathways. - The understanding of synaptic function and plasticity, given its contribution to synapse structure maintenance and vesicle organisation.
Top Products
For researchers investigating SORT1, we recommend two excellent primary antibodies that cater to various experimental needs. The first is the well-cited polyclonal antibody, Anti-Sortilin/NT3 antibody (ab16640), which has garnered 103 citations, reflecting its reliability in the field. This antibody is validated in knockout models and is particularly effective for Western blotting (WB) and immunohistochemistry (IHC).In addition, we offer the recombinant antibody, Anti-Sortilin/NT3 antibody [EPR23093-58] (ab263864). This product is suitable for a broader range of applications, including WB, IHC, immunocytochemistry (ICC), and flow cytometry (FC). With 4 citations, it is gaining traction among researchers. The recombinant nature of this antibody ensures batch-to-batch consistency, making it a dependable choice for SORT1 studies. The Anti-Sortilin/NT3 antibody ELISA Kit (ab263864), supported by 4 citations, is an excellent option for researchers looking to accurately measure SORT1 levels in their samples.
Abcam Product Citation Summary
The data indicates that the SORT1 antibody (ab16640) has been extensively used in Western blotting across various human cell lines, particularly HEK293 cells, to study sortilin dimerization and its implications in cancer. Additionally, it has been applied in studies involving anxiety-like and depression-like phenotypes in rats, as well as in the context of ovarian and endometrial cancer.
Abcam Product Citation Table
Domain
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.
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 (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.
Involvement in disease
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.
Post-translational modifications
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.
Sequence Similarities
Belongs to the VPS10-related sortilin family. SORT1 subfamily.
Tissue Specificity
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.
Cellular localization
- 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.
Alternative names
Sortilin, 100 kDa NT receptor, Glycoprotein 95, Neurotensin receptor 3, Gp95, NT3, NTR3, SORT1