Protein: VPS10 domain-containing receptor SorCS2 [Cleaved into: SorCS2 122 kDa chain; SorCS2 104 kDa chain; SorCS2 18 kDa chain] (Q96PQ0)
Organism: Homo sapiens (Human)
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 (By similarity). 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. 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).
Subcellular location: Cell membrane {ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:24908487}; Single-pass type I membrane protein {ECO:0000269|PubMed:24908487}. Cell projection {ECO:0000250|UniProtKB:Q9EPR5}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:24908487}; Single-pass type I membrane protein {ECO:0000269|PubMed:24908487}. Early endosome membrane {ECO:0000250|UniProtKB:Q9EPR5}. Recycling endosome membrane {ECO:0000250|UniProtKB:Q9EPR5}. Synapse, synaptosome {ECO:0000250|UniProtKB:Q9EPR5}. Perikaryon {ECO:0000269|PubMed:28469074}. Cell projection, dendrite {ECO:0000269|PubMed:28469074}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q9EPR5}. Postsynaptic density membrane {ECO:0000250|UniProtKB:Q9EPR5}.
Sequence: MAHRGPSRASKGPGPTARAPSPGAPPPPRSPRSRPLLLLLLLLGACGAAGRSPEPGRLGPHAQLTRVPRSPPAGRAEPGGGEDRQARGTEPGAPGPSPGPAPGPGEDGAPAAGYRRWERAAPLAGVASRAQVSLISTSFVLKGDATHNQAMVHWTGENSSVILILTKYYHADMGKVLESSLWRSSDFGTSYTKLTLQPGVTTVIDNFYICPTNKRKVILVSSSLSDRDQSLFLSADEGATFQKQPIPFFVETLIFHPKEEDKVLAYTKESKLYVSSDLGKKWTLLQERVTKDHVFWSVSGVDADPDLVHVEAQDLGGDFRYVTCAIHNCSEKMLTAPFAGPIDHGSLTVQDDYIFFKATSANQTKYYVSYRRNEFVLMKLPKYALPKDLQIISTDESQVFVAVQEWYQMDTYNLYQSDPRGVRYALVLQDVRSSRQAEESVLIDILEVRGVKGVFLANQKIDGKVMTLITYNKGRDWDYLRPPSMDMNGKPTNCKPPDCHLHLHLRWADNPYVSGTVHTKDTAPGLIMGAGNLGSQLVEYKEEMYITSDCGHTWRQVFEEEHHILYLDHGGVIVAIKDTSIPLKILKFSVDEGLTWSTHNFTSTSVFVDGLLSEPGDETLVMTVFGHISFRSDWELVKVDFRPSFSRQCGEEDYSSWELSNLQGDRCIMGQQRSFRKRKSTSWCIKGRSFTSALTSRVCECRDSDFLCDYGFERSSSSESSTNKCSANFWFNPLSPPDDCALGQTYTSSLGYRKVVSNVCEGGVDMQQSQVQLQCPLTPPRGLQVSIQGEAVAVRPGEDVLFVVRQEQGDVLTTKYQVDLGDGFKAMYVNLTLTGEPIRHRYESPGIYRVSVRAENTAGHDEAVLFVQVNSPLQALYLEVVPVIGLNQEVNLTAVLLPLNPNLTVFYWWIGHSLQPLLSLDNSVTTRFSDTGDVRVTVQAACGNSVLQDSRVLRVLDQFQVMPLQFSKELDAYNPNTPEWREDVGLVVTRLLSKETSVPQELLVTVVKPGLPTLADLYVLLPPPRPTRKRSLSSDKRLAAIQQVLNAQKISFLLRGGVRVLVALRDTGTGAEQLGGGGGYWAVVVLFVIGLFAAGAFILYKFKRKRPGRTVYAQMHNEKEQEMTSPVSHSEDVQGAVQGNHSGVVLSINSREMHSYLVS
InterPro domains: - IPR031778: Sortilin, N-terminal (domain) [180-611]
- IPR050310: VPS10-related sortilin family receptors (family) [73-1134]
- IPR022409: PKD/Chitinase domain (domain) [782-872]
- IPR015943: WD40/YVTN repeat-like-containing domain superfamily (homologous_superfamily) [128-315]
- IPR000601: PKD domain (domain) [786-876]
- IPR013783: Immunoglobulin-like fold (homologous_superfamily) [778-874]
- IPR006581: VPS10 (domain) [170-780]
- IPR031777: Sortilin, C-terminal (domain) [614-775]
- IPR035986: PKD domain superfamily (homologous_superfamily) [753-873]
Interaction partners: - Tumor necrosis factor receptor superfamily member 16
- Beta-nerve growth factor
- Neurotrophic factor BDNF precursor form
- Vacuolar protein sorting-associated protein 35
- Sortilin
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0051641 (cellular localization), GO:0050793 (regulation of developmental process), GO:0065008 (regulation of biological quality), GO:0050794 (regulation of cellular process), GO:0051234 (establishment of localization), GO:0023051 (regulation of signaling), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0033036 (macromolecule localization), GO:0051129 (negative regulation of cellular component organization), GO:0046907 (intracellular transport), GO:0010646 (regulation of cell communication), GO:0045596 (negative regulation of cell differentiation), GO:0006810 (transport), GO:0070727 (cellular macromolecule localization), GO:0051649 (establishment of localization in cell), GO:0045595 (regulation of cell differentiation), GO:0099177 (regulation of trans-synaptic signaling), GO:0051128 (regulation of cellular component organization), GO:0045184 (establishment of protein localization), GO:0044087 (regulation of cellular component biogenesis), GO:0031333 (negative regulation of protein-containing complex assembly), GO:0006886 (intracellular protein transport), GO:0043254 (regulation of protein-containing complex assembly), GO:0071705 (nitrogen compound transport), GO:0015031 (protein transport), GO:0050804 (modulation of chemical synaptic transmission), GO:0071702 (organic substance transport), GO:0008104 (protein localization), GO:0045665 (negative regulation of neuron differentiation), GO:0006811 (monoatomic ion transport), GO:1902531 (regulation of intracellular signal transduction), GO:0051963 (regulation of synapse assembly), GO:0006812 (monoatomic cation transport), GO:0006816 (calcium ion transport), GO:0030001 (metal ion transport), GO:0000041 (transition metal ion transport), GO:0006826 (iron ion transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0071944 (cell periphery), GO:0030054 (cell junction), GO:0005615 (extracellular space), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005576 (extracellular region), GO:0031090 (organelle membrane), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0045202 (synapse), GO:0043230 (extracellular organelle), GO:0005794 (Golgi apparatus), GO:0070161 (anchoring junction), GO:0070062 (extracellular exosome), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0055037 (recycling endosome), GO:0030055 (cell-substrate junction), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0012506 (vesicle membrane), GO:0005770 (late endosome), GO:0065010 (extracellular membrane-bounded organelle), GO:0005769 (early endosome), GO:0010008 (endosome membrane), GO:0031982 (vesicle), GO:0030659 (cytoplasmic vesicle membrane), GO:0005925 (focal adhesion), GO:1903561 (extracellular vesicle), GO:0097708 (intracellular vesicle), GO:0031901 (early endosome membrane), GO:0031902 (late endosome membrane), GO:0055038 (recycling endosome membrane)