Details of the Target

General Information of Target

Target ID LDTP03418
Target Name Proteasome subunit beta type-6 (PSMB6)
Gene Name PSMB6
Gene ID 5694
Synonyms
LMPY; Y; Proteasome subunit beta type-6; EC 3.4.25.1; Macropain delta chain; Multicatalytic endopeptidase complex delta chain; Proteasome delta chain; Proteasome subunit Y
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAATLLAARGAGPAPAWGPEAFTPDWESREVSTGTTIMAVQFDGGVVLGADSRTTTGSYI
ANRVTDKLTPIHDRIFCCRSGSAADTQAVADAVTYQLGFHSIELNEPPLVHTAASLFKEM
CYRYREDLMAGIIIAGWDPQEGGQVYSVPMGGMMVRQSFAIGGSGSSYIYGYVDATYREG
MTKEECLQFTANALALAMERDGSSGGVIRLAAIAESGVERQVLLGDQIPKFAVATLPPA
Target Type
Patented-recorded
Target Bioclass
Enzyme
Family
Peptidase T1B family
Subcellular location
Cytoplasm
Function
Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB6 displays a peptidylglutamyl-hydrolizing activity also termed postacidic or caspase-like activity, meaning that the peptides bond hydrolysis occurs directly after acidic residues.
TTD ID
T54973
Uniprot ID
P28072
DrugMap ID
TT8EPLT
Ensemble ID
ENST00000270586.8
HGNC ID
HGNC:9543
ChEMBL ID
CHEMBL1944496

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 22 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C-Sul
 Probe Info  		2.76  LDD0066  [1]
TH211
 Probe Info  		Y95(8.52); Y124(5.73)  LDD0257  [2]
TH214
 Probe Info  		Y95(8.58)  LDD0258  [2]
YN-1
 Probe Info  		100.00  LDD0444  [3]
STPyne
 Probe Info  		K67(10.00)  LDD0277  [4]
AZ-9
 Probe Info  		E215(10.00)  LDD2209  [5]
DBIA
 Probe Info  		C186(1.53)  LDD3312  [6]
HHS-482
 Probe Info  		Y59(1.04); Y95(0.58)  LDD0285  [7]
HHS-475
 Probe Info  		Y59(0.92); Y95(0.94); Y124(1.15)  LDD0264  [8]
HHS-465
 Probe Info  		Y124(2.35)  LDD2237  [9]
5E-2FA
 Probe Info  		N.A.  LDD2235  [10]
m-APA
 Probe Info  		H72(0.00); H100(0.00)  LDD2231  [10]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [11]
IA-alkyne
 Probe Info  		N.A.  LDD0036  [11]
IPIAA_H
 Probe Info  		N.A.  LDD0030  [12]
IPIAA_L
 Probe Info  		N.A.  LDD0031  [12]
Lodoacetamide azide
 Probe Info  		N.A.  LDD0037  [11]
ATP probe
 Probe Info  		N.A.  LDD0035  [13]
SF
 Probe Info  		N.A.  LDD0028  [14]
MPP-AC
 Probe Info  		N.A.  LDD0428  [15]
NAIA_5
 Probe Info  		N.A.  LDD2223  [16]
TPP-AC
 Probe Info  		N.A.  LDD0427  [15]
PAL-AfBPP Probe
Click To Hide/Show 79 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
ILS-1 PP
 Probe Info  		2.09  LDD0417  [17]
C004
 Probe Info  		6.59  LDD1714  [18]
C017
 Probe Info  		9.92  LDD1725  [18]
C022
 Probe Info  		7.26  LDD1728  [18]
C041
 Probe Info  		7.57  LDD1741  [18]
C044
 Probe Info  		5.13  LDD1743  [18]
C055
 Probe Info  		26.91  LDD1752  [18]
C059
 Probe Info  		5.62  LDD1756  [18]
C064
 Probe Info  		6.92  LDD1761  [18]
C085
 Probe Info  		6.19  LDD1777  [18]
C087
 Probe Info  		14.83  LDD1779  [18]
C106
 Probe Info  		43.41  LDD1793  [18]
C107
 Probe Info  		6.36  LDD1794  [18]
C108
 Probe Info  		17.88  LDD1795  [18]
C112
 Probe Info  		18.38  LDD1799  [18]
C130
 Probe Info  		8.28  LDD1812  [18]
C139
 Probe Info  		11.31  LDD1821  [18]
C140
 Probe Info  		10.85  LDD1822  [18]
C141
 Probe Info  		11.88  LDD1823  [18]
C147
 Probe Info  		8.75  LDD1829  [18]
C153
 Probe Info  		20.68  LDD1834  [18]
C159
 Probe Info  		9.58  LDD1839  [18]
C160
 Probe Info  		11.00  LDD1840  [18]
C161
 Probe Info  		17.03  LDD1841  [18]
C163
 Probe Info  		9.65  LDD1843  [18]
C178
 Probe Info  		35.26  LDD1857  [18]
C194
 Probe Info  		11.24  LDD1870  [18]
C201
 Probe Info  		32.22  LDD1877  [18]
C206
 Probe Info  		21.11  LDD1881  [18]
C208
 Probe Info  		6.50  LDD1883  [18]
C211
 Probe Info  		13.18  LDD1885  [18]
C216
 Probe Info  		8.57  LDD1890  [18]
C220
 Probe Info  		13.45  LDD1894  [18]
C225
 Probe Info  		5.24  LDD1898  [18]
C228
 Probe Info  		19.56  LDD1901  [18]
C231
 Probe Info  		27.10  LDD1904  [18]
C234
 Probe Info  		6.11  LDD1907  [18]
C240
 Probe Info  		13.36  LDD1913  [18]
C249
 Probe Info  		14.03  LDD1922  [18]
C270
 Probe Info  		6.02  LDD1940  [18]
C277
 Probe Info  		11.55  LDD1947  [18]
C278
 Probe Info  		51.27  LDD1948  [18]
C280
 Probe Info  		9.13  LDD1950  [18]
C282
 Probe Info  		19.16  LDD1952  [18]
C284
 Probe Info  		25.28  LDD1954  [18]
C307
 Probe Info  		6.36  LDD1975  [18]
C314
 Probe Info  		13.55  LDD1981  [18]
C326
 Probe Info  		11.39  LDD1990  [18]
C333
 Probe Info  		13.74  LDD1996  [18]
C342
 Probe Info  		5.78  LDD2004  [18]
C344
 Probe Info  		5.86  LDD2006  [18]
C348
 Probe Info  		14.22  LDD2009  [18]
C350
 Probe Info  		22.16  LDD2011  [18]
C353
 Probe Info  		10.06  LDD2014  [18]
C354
 Probe Info  		11.55  LDD2015  [18]
C357
 Probe Info  		5.70  LDD2018  [18]
C364
 Probe Info  		17.75  LDD2025  [18]
C376
 Probe Info  		16.91  LDD2036  [18]
C383
 Probe Info  		11.71  LDD2042  [18]
C386
 Probe Info  		18.00  LDD2045  [18]
C387
 Probe Info  		8.57  LDD2046  [18]
C399
 Probe Info  		7.67  LDD2058  [18]
C407
 Probe Info  		12.04  LDD2064  [18]
C419
 Probe Info  		9.45  LDD2074  [18]
C420
 Probe Info  		14.22  LDD2075  [18]
C428
 Probe Info  		5.78  LDD2083  [18]
C429
 Probe Info  		15.03  LDD2084  [18]
C431
 Probe Info  		57.28  LDD2086  [18]
FFF probe11
 Probe Info  		6.49  LDD0471  [19]
FFF probe13
 Probe Info  		20.00  LDD0475  [19]
FFF probe14
 Probe Info  		20.00  LDD0477  [19]
FFF probe15
 Probe Info  		10.55  LDD0478  [19]
FFF probe2
 Probe Info  		12.52  LDD0463  [19]
FFF probe3
 Probe Info  		10.39  LDD0465  [19]
FFF probe4
 Probe Info  		13.31  LDD0466  [19]
FFF probe6
 Probe Info  		13.02  LDD0468  [19]
BD-F
 Probe Info  		V89(0.00); D91(0.00); Y95(0.00); Q96(0.00)  LDD0024  [20]
LD-F
 Probe Info  		G98(0.00); Y95(0.00)  LDD0015  [20]
OEA-DA
 Probe Info  		18.09  LDD0046  [21]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0572  Fragment10 Ramos C186(0.64)  LDD2189  [22]
 LDCM0573  Fragment11 Ramos C186(0.80)  LDD2190  [22]
 LDCM0576  Fragment14 Ramos C186(1.70)  LDD2193  [22]
 LDCM0579  Fragment20 Ramos C186(0.37)  LDD2194  [22]
 LDCM0580  Fragment21 Ramos C186(0.48)  LDD2195  [22]
 LDCM0582  Fragment23 Ramos C186(1.53)  LDD2196  [22]
 LDCM0578  Fragment27 Ramos C186(0.61)  LDD2197  [22]
 LDCM0586  Fragment28 Ramos C186(0.55)  LDD2198  [22]
 LDCM0588  Fragment30 Ramos C186(0.73)  LDD2199  [22]
 LDCM0468  Fragment33 Ramos C186(1.01)  LDD2202  [22]
 LDCM0566  Fragment4 Ramos C186(1.45)  LDD2184  [22]
 LDCM0610  Fragment52 Ramos C186(0.77)  LDD2204  [22]
 LDCM0614  Fragment56 Ramos C186(0.37)  LDD2205  [22]
 LDCM0569  Fragment7 Ramos C186(1.49)  LDD2186  [22]
 LDCM0116  HHS-0101 DM93 Y59(0.92); Y95(0.94); Y124(1.15)  LDD0264  [8]
 LDCM0117  HHS-0201 DM93 Y59(0.83); Y124(1.15); Y95(1.16)  LDD0265  [8]
 LDCM0118  HHS-0301 DM93 Y124(0.87); Y59(0.89); Y95(2.04)  LDD0266  [8]
 LDCM0119  HHS-0401 DM93 Y59(0.81); Y95(1.37); Y124(2.26)  LDD0267  [8]
 LDCM0120  HHS-0701 DM93 Y59(1.24); Y95(2.53); Y124(3.60)  LDD0268  [8]
 LDCM0123  JWB131 DM93 Y59(1.04); Y95(0.58)  LDD0285  [7]
 LDCM0124  JWB142 DM93 Y59(0.75); Y95(0.57)  LDD0286  [7]
 LDCM0125  JWB146 DM93 Y59(1.19); Y95(0.98)  LDD0287  [7]
 LDCM0126  JWB150 DM93 Y59(2.66); Y95(3.64)  LDD0288  [7]
 LDCM0127  JWB152 DM93 Y59(1.70); Y95(1.16)  LDD0289  [7]
 LDCM0128  JWB198 DM93 Y59(0.96); Y95(1.24)  LDD0290  [7]
 LDCM0129  JWB202 DM93 Y59(0.68); Y95(0.38)  LDD0291  [7]
 LDCM0130  JWB211 DM93 Y59(1.03); Y95(0.77)  LDD0292  [7]
 LDCM0022  KB02 Ramos C186(1.09)  LDD2182  [22]
 LDCM0023  KB03 Ramos C186(1.26)  LDD2183  [22]
 LDCM0024  KB05 HMCB C186(1.53)  LDD3312  [6]
 LDCM0131  RA190 MM1.R C186(0.85)  LDD0304  [23]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
NADPH-dependent diflavin oxidoreductase 1 (NDOR1) NADPH-dependent diflavin oxidoreductase NDOR1 family; Flavodoxin family; Flavoprotein pyridine nucleotide cytochrome reductase family Q9UHB4
Proteasome subunit beta type-7 (PSMB7) Peptidase T1B family Q99436
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Huntingtin (HTT) Huntingtin family P42858

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
(3ar6r6as)-6-((S)-((S)-cyclohex-2-enyl)(Hydroxy)Methyl)-6a-methyl-4-oxo-hexahydro-2h-furo[32-c]Pyrrole-6-carbaldehyde . DB08515
Patented
Click To Hide/Show 10 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Peptide Analog 21 Small molecular drug D02PJI
Peptide Analog 23 Small molecular drug D0T1YB
Peptide Analog 39 Small molecular drug D02CQG
Peptide Analog 41 Small molecular drug D01OOO
Pmid29865878-compound-46 Small molecular drug D0C2MH
Pmid29865878-compound-48 Small molecular drug D0K0GJ
Pmid29865878-compound-49 Small molecular drug D0TU5R
Pmid29865878-compound-51 Small molecular drug D0NE8M
Pmid29865878-compound-53 Small molecular drug D01VMN
Pmid29865878-compound-55 Small molecular drug D03CMD

References

1 Low-Toxicity Sulfonium-Based Probes for Cysteine-Specific Profiling in Live Cells. Anal Chem. 2022 Mar 15;94(10):4366-4372. doi: 10.1021/acs.analchem.1c05129. Epub 2022 Mar 4.
2 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
3 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.
4 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
5 2H-Azirine-Based Reagents for Chemoselective Bioconjugation at Carboxyl Residues Inside Live Cells. J Am Chem Soc. 2020 Apr 1;142(13):6051-6059. doi: 10.1021/jacs.9b12116. Epub 2020 Mar 23.
6 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
7 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
8 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.
9 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.
10 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
11 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
12 SP3-Enabled Rapid and High Coverage Chemoproteomic Identification of Cell-State-Dependent Redox-Sensitive Cysteines. Mol Cell Proteomics. 2022 Apr;21(4):100218. doi: 10.1016/j.mcpro.2022.100218. Epub 2022 Feb 25.
Mass spectrometry data entry: PXD029500 , PXD031647
13 Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer. J Proteome Res. 2018 Jan 5;17(1):63-75. doi: 10.1021/acs.jproteome.7b00329. Epub 2017 Nov 22.
Mass spectrometry data entry: PXD006095 , PXD006096
14 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
15 Differently Tagged Probes for Protein Profiling of Mitochondria. Chembiochem. 2019 May 2;20(9):1155-1160. doi: 10.1002/cbic.201800735. Epub 2019 Mar 26.
16 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
17 A Chemical Proteomic Analysis of Illudin-Interacting Proteins. Chemistry. 2019 Sep 25;25(54):12644-12651. doi: 10.1002/chem.201902919. Epub 2019 Sep 3.
Mass spectrometry data entry: PXD014175
18 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
19 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
20 Evaluation of fully-functionalized diazirine tags for chemical proteomic applications. Chem Sci. 2021 May 7;12(22):7839-7847. doi: 10.1039/d1sc01360b.
Mass spectrometry data entry: PXD025652
21 Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics. ACS Chem Biol. 2017 Oct 20;12(10):2671-2681. doi: 10.1021/acschembio.7b00581. Epub 2017 Sep 20.
Mass spectrometry data entry: PXD007570
22 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
23 Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190. Cell Chem Biol. 2020 Nov 19;27(11):1371-1382.e6. doi: 10.1016/j.chembiol.2020.08.007. Epub 2020 Aug 27.