General Information of Target

Target ID LDTP10693
Target Name VPS10 domain-containing receptor SorCS2 (SORCS2)
Gene Name SORCS2
Gene ID 57537
Synonyms
KIAA1329; VPS10 domain-containing receptor SorCS2 [Cleaved into: SorCS2 122 kDa chain; SorCS2 104 kDa chain; SorCS2 18 kDa chain]
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGERTLHAAVPTPGYPESESIMMAPICLVENQEEQLTVNSKALEILDKISQPVVVVAIVG
LYRTGKSYLMNRLAGKRNGFPLGSTVQSETKGIWMWCVPHLSKPNHTLVLLDTEGLGDVE
KSNPKNDSWIFALAVLLSSSFVYNSVSTINHQALEQLHYVTELAELIRAKSCPRPDEAED
SSEFASFFPDFIWTVRDFTLELKLDGNPITEDEYLENALKLIPGKNPKIQNSNMPRECIR
HFFRKRKCFVFDRPTNDKQYLNHMDEVPEENLERHFLMQSDNFCSYIFTHAKTKTLREGI
IVTGKRLGTLVVTYVDAINSGAVPCLENAVTALAQLENPAAVQRAADHYSQQMAQQLRLP
TDTLQELLDVHAACEREAIAVFMEHSFKDENHEFQKKLVDTIEKKKGDFVLQNEEASAKY
CQAELKRLSEHLTESILRGIFSVPGGHNLYLEEKKQVEWDYKLVPRKGVKANEVLQNFLQ
SQVVVEESILQSDKALTAGEKAIAAERAMKEAAEKEQELLREKQKEQQQMMEAQERSFQE
YMAQMEKKLEEERENLLREHERLLKHKLKVQEEMLKEEFQKKSEQLNKEINQLKEKIEST
KNEQLRLLKILDMASNIMIVTLPGASKLLGVGTKYLGSRI
Target Bioclass
Other
Family
VPS10-related sortilin family, SORCS subfamily
Subcellular location
Cell membrane
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. 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.; [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.
Uniprot ID
Q96PQ0
Ensemble ID
ENST00000507866.6
HGNC ID
HGNC:16698

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C210(2.03)  LDD3487  [1]
BTD
 Probe Info 
C46(1.02)  LDD2136  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 8305C C210(2.20)  LDD2248  [1]
 LDCM0023  KB03 8305C C210(3.32)  LDD2665  [1]
 LDCM0024  KB05 VMRC-RCW C210(2.03)  LDD3487  [1]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C46(1.02)  LDD2136  [2]

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761