General Information of Target

Target ID LDTP01218
Target Name Vacuolar protein sorting-associated protein 26A (VPS26A)
Gene Name VPS26A
Gene ID 9559
Synonyms
VPS26; Vacuolar protein sorting-associated protein 26A; Vesicle protein sorting 26A; hVPS26
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSFLGGFFGPICEIDIVLNDGETRKMAEMKTEDGKVEKHYLFYDGESVSGKVNLAFKQPG
KRLEHQGIRIEFVGQIELFNDKSNTHEFVNLVKELALPGELTQSRSYDFEFMQVEKPYES
YIGANVRLRYFLKVTIVRRLTDLVKEYDLIVHQLATYPDVNNSIKMEVGIEDCLHIEFEY
NKSKYHLKDVIVGKIYFLLVRIKIQHMELQLIKKEITGIGPSTTTETETIAKYEIMDGAP
VKGESIPIRLFLAGYDPTPTMRDVNKKFSVRYFLNLVLVDEEDRRYFKQQEIILWRKAPE
KLRKQRTNFHQRFESPESQASAEQPEM
Target Bioclass
Transporter and channel
Family
VPS26 family
Subcellular location
Cytoplasm
Function
Acts as a component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins (Probable). The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Required for the endosomal localization of WASHC2A (indicative for the WASH complex). Required for the endosomal localization of TBC1D5. Mediates retromer cargo recognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP. Involved in retromer-independent lysosomal sorting of F2R. Involved in recycling of ADRB2. Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins.
Uniprot ID
O75436
Ensemble ID
ENST00000263559.11
HGNC ID
HGNC:12711

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HT115 SNV: p.L278F .
KMS11 SNV: p.V17G .
MFE319 Deletion: p.M26WfsTer4 .
NCIH1048 SNV: p.A155V .
YSCCC SNV: p.S245Ter .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 13 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info 
9.79  LDD0402  [1]
YN-1
 Probe Info 
100.00  LDD0444  [2]
HHS-475
 Probe Info 
Y157(0.92)  LDD0264  [3]
ATP probe
 Probe Info 
K242(0.00); K38(0.00)  LDD0199  [4]
IA-alkyne
 Probe Info 
N.A.  LDD0165  [5]
NHS
 Probe Info 
N.A.  LDD0010  [6]
SF
 Probe Info 
N.A.  LDD0028  [7]
STPyne
 Probe Info 
N.A.  LDD0009  [6]
Acrolein
 Probe Info 
N.A.  LDD0217  [8]
AOyne
 Probe Info 
7.00  LDD0443  [9]
NAIA_5
 Probe Info 
N.A.  LDD2223  [10]
HHS-465
 Probe Info 
N.A.  LDD2240  [11]
HHS-482
 Probe Info 
Y157(1.59)  LDD2239  [12]
PAL-AfBPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STS-1
 Probe Info 
N.A.  LDD0137  [13]
STS-2
 Probe Info 
N.A.  LDD0138  [13]
VE-P
 Probe Info 
N.A.  LDD0396  [14]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0156  Aniline NCI-H1299 10.55  LDD0403  [1]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [8]
 LDCM0116  HHS-0101 DM93 Y157(0.92)  LDD0264  [3]
 LDCM0117  HHS-0201 DM93 Y157(0.70)  LDD0265  [3]
 LDCM0118  HHS-0301 DM93 Y157(0.82)  LDD0266  [3]
 LDCM0119  HHS-0401 DM93 Y157(0.90)  LDD0267  [3]
 LDCM0120  HHS-0701 DM93 Y157(0.97)  LDD0268  [3]
 LDCM0107  IAA HeLa N.A.  LDD0221  [8]
 LDCM0109  NEM HeLa N.A.  LDD0223  [8]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
NADH dehydrogenase flavoprotein 2, mitochondrial (NDUFV2) Complex I 24 kDa subunit family P19404
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Vacuolar protein sorting-associated protein 29 (VPS29) VPS29 family Q9UBQ0
Vacuolar protein sorting-associated protein 35 (VPS35) VPS35 family Q96QK1
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Zinc finger and SCAN domain-containing protein 12 (ZSCAN12) Krueppel C2H2-type zinc-finger protein family O43309

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors. J Med Chem. 2022 Aug 11;65(15):10408-10418. doi: 10.1021/acs.jmedchem.2c00272. Epub 2022 Jul 26.
3 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
4 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
5 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
6 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
7 Solid Phase Synthesis of Fluorosulfate Containing Macrocycles for Chemoproteomic Workflows. bioRxiv [Preprint]. 2023 Feb 18:2023.02.17.529022. doi: 10.1101/2023.02.17.529022.
Mass spectrometry data entry: PXD039931
8 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
9 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
10 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
11 Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation. Cell Chem Biol. 2022 Dec 15;29(12):1709-1720.e7. doi: 10.1016/j.chembiol.2022.11.008. Epub 2022 Dec 6.
Mass spectrometry data entry: PXD038010
12 Global targeting of functional tyrosines using sulfur-triazole exchange chemistry. Nat Chem Biol. 2020 Feb;16(2):150-159. doi: 10.1038/s41589-019-0404-5. Epub 2019 Nov 25.
13 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
14 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.