SORCS2
Description
The SORCS2 (sortilin related VPS10 domain containing receptor 2) is a protein-coding gene located on chromosome 4.
The SorCS2 (sortilin-related Vps10p domain containing receptor 2) gene is located on chromosome 4 (4p16.1) and is composed of 28 exons. The N-terminal exons encoding the Vps10p domain are spaced by large introns. The functional receptor protein is primarily found in the brain. It is 1109 amino acids long, largely neutral, and has a single transmembrane pass. SorCS2 belongs to the mammalian Vps10p (vacuolar protein sorting 10 protein) domain family, which consists of five transmembrane proteins with structural similarities: SorCS1, SorCS2, SorCS3, SorLA (sorting protein-related receptor with A-type repeats), and sortilin. SorCS2 plays critical roles in neuronal viability and function. Single nucleotide polymorphisms (SNPs) in the protein have been associated with a range of diseases, including attention-deficit hyperactivity disorder (ADHD), bipolar disorders, and schizophrenia. The receptor family has also been associated with Alzheimer's disease and type 2 diabetes. The Vps10p domain receptor family was discovered based on the identification of SorLA in 1996 and sortilin in 1997. The SorCS subfamily, including SorCS2, was described in 2001. SorCS2 was first identified from isolated cDNA in murine floor plate samples of the central nervous system (CNS) as well as in regions of the brain. The cDNA contained the characteristic Vps10p domain, enabling its classification as a SorCS protein. Soon after, a corresponding partial cDNA was found in human samples, and it was possible to determine the missing N-terminal by homology to murine SorCS2.
The heterodimer formed by NGFR and SORCS2 functions as a receptor for the precursor forms of NGF (proNGF) and BDNF (proBDNF). ProNGF and proBDNF binding promote axon growth cone collapse. SORCS2 plays a role in regulating dendritic spine density in hippocampus neurons. It is required for normal neurite branching and extension in response to BDNF. SORCS2 plays a role in BDNF-dependent hippocampal synaptic plasticity. Together with NGFR and NTRK2, SORCS2 is required for both BDNF-mediated synaptic long-term depression and long-term potentiation. ProNGF binding promotes dissociation of TRIO from the heterodimer, leading to inactivation of RAC1 and/or RAC2 and reorganization of the actin cytoskeleton. SORCS2, together with the retromer complex subunit VPS35, is required for normal expression of GRIN2A at synapses and dendritic cell membranes. SORCS2 is required for normal expression of the amino acid transporter SLC1A1 at the cell membrane, contributing to protecting cells against oxidative stress.
SORCS2 is also known as -.
