Protein: VPS10 domain-containing receptor SorCS2 [Cleaved into: SorCS2 122 kDa chain; SorCS2 104 kDa chain; SorCS2 18 kDa chain] (Q9EPR5)
Organism: Mus musculus (Mouse)
Function: The heterodimer formed by NGFR and SORCS2 functions as receptor for the precursor forms of NGF (proNGF) and BDNF (proBDNF). ProNGF and proBDNF binding both promote axon growth cone collapse (in vitro). Plays a role in the regulation of dendritic spine density in hippocampus neurons. Required for normal neurite branching and extension in response to BDNF. 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. 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 (By similarity). 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.
Subcellular location: Cell membrane {ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:27457814, ECO:0000269|PubMed:30840898, ECO:0000305|PubMed:30061605}; Single-pass type I membrane protein {ECO:0000305|PubMed:30061605}. Cell projection {ECO:0000269|PubMed:24908487}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:28469074, ECO:0000269|PubMed:30840898}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q96PQ0}. Early endosome membrane {ECO:0000269|PubMed:30840898}. Recycling endosome membrane {ECO:0000269|PubMed:30840898}. Synapse, synaptosome {ECO:0000269|PubMed:30840898}. Perikaryon {ECO:0000269|PubMed:28469074}. Cell projection, dendrite {ECO:0000269|PubMed:27457814}. Cell projection, dendritic spine {ECO:0000269|PubMed:29909994}. Synapse {ECO:0000269|PubMed:27457814}. Postsynaptic density membrane {ECO:0000269|PubMed:27457814}.
Interaction partners:
- Tumor necrosis factor receptor superfamily member 16
- Beta-nerve growth factor
- Sortilin
- Neurotrophic factor BDNF precursor form
- Vacuolar protein sorting-associated protein 35
Sequence:
MAHRGPPSAPKRPGPTAPDRSFQALLPPCWPRSWPLLLLLLVLVAACGAMGRSPQPGRQGPGVQITRLLPAGRTESGDRKDPQARESEPSVPGLGPGSASGPSTDGAPAPGKGRRARAVPVAGAASASRAQVSLISTSFVLKGDATHNQAMVHWTGENSSVILILTKYYHADMGKVLESSLWRSSDFGTTYTKLTLQPGVTTVIDNFYICPANKRKIILVSSSLGDREQSLFLSTDEGATFQKYPVPFLVEMLLFHPKEEDKVLAYTKDSKLYVSSDLGKKWTLLQERVTKDHVFWAVSGVDDDPNLVHVEAQDLSGGYRYYTCLIYNCSAQPHIAPFSGPIDRGSLTVQDEYIFLKATSTNRTKYYVSYRRSDFVLMKLPKYALPKDLQIISTDEQQVFVAVQEWNQVDTYNLYQSDLRGVRYSLVLENVRSSRQAEENVVIDILEVRGVKGVFLANQKVDGKVTTVITYNKGRDWDYLRPPSTDMNGKPTNCQPPDCYLHLHLRWADNPYVSGTVHTKDTAPGLIMGAGNLGSQLVEYKEEMYITSDCGHTWRQVFEEEHHVLYLDHGGVIAAIKDTSIPLKILKFSVDEGHTWSTHNFTSTSVFVDGLLSEPGDETLVMTVFGHISFRSDWELVKVDFRPSFPRQCGEDDYSSWDLTDLQGDHCIMGQQRSYRKRKSTSWCVKGRSFTSALTSRVCKCRDSDFLCDYGFERSSSSESTANKCSANFWFNPLSPPEDCVLGQTYTSSLGYRKVVSNVCEGGVDLQQSPVQLQCPLQAPRGLQVSIRGEAVAVRPREDVLFVVRQEQGDVLTTKYQVDLGDGFKAMYVNLTLTGEPIRHHYESPGIYRVSVRAENMAGHDEAVLFVQVNSPLQALYLEVVPVIGVNQEVNLTAVLLPLNPNLTVFYWWIGHSLQPLLSLDNSVTTKFTDAGDVRVTVQAACGNSVLQDSRLVRVLDQFQVVPLRFSRELDTFNPNTPEWREDVGLVVTRLLSKETSIPEELLVTVVKPGLPTIADLYVLLPLPRPTRKRSLTSDKRLAAVQQALNSHRISFILRGGLRILVELRDTDTGPQRPGGSGGYWAVVVLFVIGLFAVGAFILYKFKRKRPGRTVYAQMHNEKEQEMTSPVSHSEDAQSTMQGNHSGVVLSINSREMHSYLVG