SORCS2

This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. [provided by RefSeq]

Full Name

sortilin-related VPS10 domain containing receptor 2

Function

The heterodimer formed by NGFR and SORCS2 functions as receptor for the precursor forms of NGF (proNGF) and BDNF (proBDNF) (PubMed:22155786, PubMed:24908487).
ProNGF and proBDNF binding both promote axon growth cone collapse (in vitro) (PubMed:22155786, PubMed:24908487).
Plays a role in the regulation of dendritic spine density in hippocampus neurons (By similarity).
Required for normal neurite branching and extension in response to BDNF (PubMed:27457814).
Plays a role in BDNF-dependent hippocampal synaptic plasticity. Together with NGFR and NTRK2, is required both for BDNF-mediated synaptic long-term depression and long-term potentiation (PubMed:27457814).
ProNGF binding promotes dissociation of TRIO from the heterodimer, which leads to inactivation of RAC1 and/or RAC2 and subsequent reorganization of the actin cytoskeleton (PubMed:22155786).
Together with the retromer complex subunit VPS35, required for normal expression of GRIN2A at synapses and dendritic cell membranes. Required for normal expression of the amino acid transporter SLC1A1 at the cell membrane, and thereby contributes to protect cells against oxidative stress (By similarity).
SorCS2 122 kDa chain
Does not promote Schwann cell apoptosis in response to proBDNF.
SorCS2 104 kDa chain and SorCS2 18 kDa chain together promote Schwann cell apoptosis in response to proBDNF.

Biological Process

Biological Process intracellular protein transportIEA:Ensembl
Biological Process long-term synaptic depressionIEA:Ensembl
Biological Process neuropeptide signaling pathway1 PublicationNAS:UniProtKB

Cellular Location

Cell membrane
Cell projection
Cytoplasmic vesicle membrane
Early endosome membrane
Recycling endosome membrane
Synapse, synaptosome
Perikaryon
Cell projection, dendrite
Cell projection, dendritic spine
Postsynaptic density membrane

Topology

Extracellular: 51-1078
Helical: 1079-1099
Cytoplasmic: 1100-1159

PTM

Proteolytic cleavage removes a propeptide, giving rise to a 122 kDa chain that includes a cytoplasmic tail. Further cleavage gives rise to a 104 kDa chain that lacks the cytoplasmic tail, and a membrane-bound 18 kDa chain. The 104 kDa chain remains bound to the 18 kDa chain.
N-glycosylated.