Details of the Target

General Information of Target

Target ID LDTP05277
Target Name Protein SET (SET)
Gene Name SET
Gene ID 6418
Synonyms
Protein SET; HLA-DR-associated protein II; Inhibitor of granzyme A-activated DNase; IGAAD; PHAPII; Phosphatase 2A inhibitor I2PP2A; I-2PP2A; Template-activating factor I; TAF-I
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKGEKEQQEAIEHIDEVQNEIDRLNE
QASEEILKVEQKYNKLRQPFFQKRSELIAKIPNFWVTTFVNHPQVSALLGEEDEEALHYL
TRVEVTEFEDIKSGYRIDFYFDENPYFENKVLSKEFHLNESGDPSSKSTEIKWKSGKDLT
KRSSQTQNKASRKRQHEEPESFFTWFTDHSDAGADELGEVIKDDIWPNPLQYYLVPDMDD
EEGEGEEDDDDDEEEEGLEDIDEEGDEDEGEEDEDDDEGEEGEEDEGEDD
Target Bioclass
Other
Family
Nucleosome assembly protein (NAP) family
Subcellular location
Cytoplasm, cytosol
Function
Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher.
Uniprot ID
Q01105
Ensemble ID
ENST00000322030.13
HGNC ID
HGNC:10760
ChEMBL ID
CHEMBL4295798

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
AZ-9
 Probe Info  		12.01  LDD0393  [1]
FBPP2
 Probe Info  		9.01  LDD0318  [2]
C-Sul
 Probe Info  		11.72  LDD0066  [3]
FBP2
 Probe Info  		3.54  LDD0323  [2]
ONAyne
 Probe Info  		K177(0.00); K83(0.00); K132(0.00); K172(0.00)  LDD0273  [4]
Alkylaryl probe 3
 Probe Info  		16.68  LDD0382  [5]
HHS-482
 Probe Info  		Y140(1.76)  LDD0285  [6]
HHS-475
 Probe Info  		Y140(0.91); Y73(0.99); Y119(1.10)  LDD0264  [7]
AMP probe
 Probe Info  		K167(0.00); K132(0.00)  LDD0200  [8]
ATP probe
 Probe Info  		K167(0.00); K132(0.00); K83(0.00); K150(0.00)  LDD0199  [8]
m-APA
 Probe Info  		H118(0.00); H102(0.00); H157(0.00)  LDD2233  [9]
CY-1
 Probe Info  		E86(0.00); K83(0.00); Q82(0.00); R84(0.00)  LDD0246  [10]
ATP probe
 Probe Info  		K83(0.00); K154(0.00); K15(0.00); K167(0.00)  LDD0035  [11]
NHS
 Probe Info  		K132(0.00); K68(0.00); K167(0.00); K189(0.00)  LDD0010  [12]
SF
 Probe Info  		K189(0.00); K72(0.00)  LDD0028  [13]
STPyne
 Probe Info  		K68(0.00); K167(0.00)  LDD0009  [12]
Ox-W18
 Probe Info  		N.A.  LDD2175  [14]
1c-yne
 Probe Info  		K167(0.00); K154(0.00); K68(0.00)  LDD0228  [15]
Acrolein
 Probe Info  		H47(0.00); H157(0.00)  LDD0217  [16]
Crotonaldehyde
 Probe Info  		N.A.  LDD0219  [16]
Methacrolein
 Probe Info  		N.A.  LDD0218  [16]
HHS-465
 Probe Info  		K167(0.00); K172(0.00); K177(0.00); K72(0.00)  LDD2240  [17]
PAL-AfBPP Probe
Click To Hide/Show 72 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C022
 Probe Info  		7.78  LDD1728  [18]
C052
 Probe Info  		5.10  LDD1750  [18]
C053
 Probe Info  		5.58  LDD1751  [18]
C055
 Probe Info  		13.45  LDD1752  [18]
C056
 Probe Info  		18.51  LDD1753  [18]
C059
 Probe Info  		4.99  LDD1756  [18]
C063
 Probe Info  		14.93  LDD1760  [18]
C064
 Probe Info  		6.87  LDD1761  [18]
C071
 Probe Info  		8.88  LDD1767  [18]
C072
 Probe Info  		8.11  LDD1768  [18]
C085
 Probe Info  		5.17  LDD1777  [18]
C087
 Probe Info  		14.32  LDD1779  [18]
C092
 Probe Info  		22.47  LDD1783  [18]
C106
 Probe Info  		28.44  LDD1793  [18]
C107
 Probe Info  		8.57  LDD1794  [18]
C108
 Probe Info  		8.82  LDD1795  [18]
C112
 Probe Info  		40.50  LDD1799  [18]
C134
 Probe Info  		21.71  LDD1816  [18]
C143
 Probe Info  		13.09  LDD1825  [18]
C145
 Probe Info  		8.46  LDD1827  [18]
C147
 Probe Info  		8.22  LDD1829  [18]
C160
 Probe Info  		10.70  LDD1840  [18]
C161
 Probe Info  		15.24  LDD1841  [18]
C165
 Probe Info  		12.91  LDD1845  [18]
C183
 Probe Info  		6.32  LDD1861  [18]
C187
 Probe Info  		95.67  LDD1865  [18]
C191
 Probe Info  		16.68  LDD1868  [18]
C193
 Probe Info  		5.86  LDD1869  [18]
C196
 Probe Info  		99.73  LDD1872  [18]
C201
 Probe Info  		35.51  LDD1877  [18]
C206
 Probe Info  		30.48  LDD1881  [18]
C210
 Probe Info  		80.45  LDD1884  [18]
C213
 Probe Info  		16.00  LDD1887  [18]
C214
 Probe Info  		5.94  LDD1888  [18]
C218
 Probe Info  		11.00  LDD1892  [18]
C220
 Probe Info  		52.35  LDD1894  [18]
C228
 Probe Info  		16.34  LDD1901  [18]
C229
 Probe Info  		11.63  LDD1902  [18]
C231
 Probe Info  		42.52  LDD1904  [18]
C232
 Probe Info  		44.32  LDD1905  [18]
C233
 Probe Info  		8.75  LDD1906  [18]
C244
 Probe Info  		17.75  LDD1917  [18]
C246
 Probe Info  		19.70  LDD1919  [18]
C284
 Probe Info  		21.86  LDD1954  [18]
C289
 Probe Info  		31.78  LDD1959  [18]
C293
 Probe Info  		16.56  LDD1963  [18]
C313
 Probe Info  		20.82  LDD1980  [18]
C317
 Probe Info  		9.32  LDD1983  [18]
C326
 Probe Info  		7.36  LDD1990  [18]
C348
 Probe Info  		11.71  LDD2009  [18]
C353
 Probe Info  		6.68  LDD2014  [18]
C354
 Probe Info  		10.20  LDD2015  [18]
C356
 Probe Info  		8.34  LDD2017  [18]
C361
 Probe Info  		24.76  LDD2022  [18]
C388
 Probe Info  		38.05  LDD2047  [18]
C390
 Probe Info  		25.81  LDD2049  [18]
C391
 Probe Info  		26.17  LDD2050  [18]
C403
 Probe Info  		15.24  LDD2061  [18]
C407
 Probe Info  		19.70  LDD2064  [18]
C413
 Probe Info  		16.56  LDD2069  [18]
C426
 Probe Info  		19.03  LDD2081  [18]
C429
 Probe Info  		24.93  LDD2084  [18]
C431
 Probe Info  		13.55  LDD2086  [18]
FFF probe11
 Probe Info  		20.00  LDD0471  [19]
FFF probe12
 Probe Info  		10.31  LDD0473  [19]
FFF probe13
 Probe Info  		17.50  LDD0475  [19]
FFF probe14
 Probe Info  		12.70  LDD0477  [19]
FFF probe2
 Probe Info  		14.31  LDD0463  [19]
FFF probe3
 Probe Info  		8.82  LDD0464  [19]
FFF probe4
 Probe Info  		14.18  LDD0466  [19]
FFF probe9
 Probe Info  		6.81  LDD0470  [19]
JN0003
 Probe Info  		20.00  LDD0469  [19]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa H47(0.00); H157(0.00)  LDD0222  [16]
 LDCM0185  Compound 17 HEK-293T 3.68  LDD0512  [19]
 LDCM0191  Compound 21 HEK-293T 4.45  LDD0508  [19]
 LDCM0190  Compound 34 HEK-293T 3.79  LDD0510  [19]
 LDCM0192  Compound 35 HEK-293T 3.01  LDD0509  [19]
 LDCM0193  Compound 36 HEK-293T 3.77  LDD0511  [19]
 LDCM0116  HHS-0101 DM93 Y140(0.91); Y73(0.99); Y119(1.10)  LDD0264  [7]
 LDCM0117  HHS-0201 DM93 Y119(0.87); Y73(1.00); Y140(1.18); Y146(1.89)  LDD0265  [7]
 LDCM0118  HHS-0301 DM93 Y140(0.95); Y73(1.04); Y119(1.49)  LDD0266  [7]
 LDCM0119  HHS-0401 DM93 Y140(0.85); Y73(0.96); Y119(0.99)  LDD0267  [7]
 LDCM0120  HHS-0701 DM93 Y119(0.80); Y140(0.96); Y73(1.00)  LDD0268  [7]
 LDCM0107  IAA HeLa H47(0.00); H157(0.00)  LDD0221  [16]
 LDCM0123  JWB131 DM93 Y140(1.76)  LDD0285  [6]
 LDCM0124  JWB142 DM93 Y140(3.31)  LDD0286  [6]
 LDCM0125  JWB146 DM93 Y140(1.00)  LDD0287  [6]
 LDCM0126  JWB150 DM93 Y140(3.58)  LDD0288  [6]
 LDCM0127  JWB152 DM93 Y140(1.02)  LDD0289  [6]
 LDCM0128  JWB198 DM93 Y140(0.33)  LDD0290  [6]
 LDCM0129  JWB202 DM93 Y140(1.21)  LDD0291  [6]
 LDCM0130  JWB211 DM93 Y140(1.41)  LDD0292  [6]
 LDCM0109  NEM HeLa H47(0.00); H157(0.00)  LDD0223  [16]
 LDCM0099  Phenelzine HEK-293T 16.68  LDD0382  [5]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 6 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Serine protease FAM111B (FAM111B) FAM111 family Q6SJ93
E3 ubiquitin-protein ligase Mdm2 (MDM2) MDM2/MDM4 family Q00987
Histone acetyltransferase KAT5 (KAT5) MYST (SAS/MOZ) family Q92993
Protein kinase C alpha type (PRKCA) AGC Ser/Thr protein kinase family P17252
Ras-related C3 botulinum toxin substrate 1 (RAC1) Rho family P63000
TATA box-binding protein-associated factor RNA polymerase I subunit C (TAF1C) . Q15572
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
14-3-3 protein gamma (YWHAG) 14-3-3 family P61981
Syntenin-1 (SDCBP) . O00560
Transcription factor
Click To Hide/Show 8 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Zinc finger protein 17 (ZNF17) Krueppel C2H2-type zinc-finger protein family P17021
Zinc finger protein 438 (ZNF438) Krueppel C2H2-type zinc-finger protein family Q7Z4V0
Paired box protein Pax-6 (PAX6) Paired homeobox family P26367
TATA-box-binding protein (TBP) TBP family P20226
Forkhead box protein O1 (FOXO1) . Q12778
Homeobox protein MOX-2 (MEOX2) . P50222
Nucleolar transcription factor 1 (UBTF) . P17480
THAP domain-containing protein 7 (THAP7) . Q9BT49
Other
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Borealin (CDCA8) Borealin family Q53HL2
cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A) CAMP-dependent kinase regulatory chain family P10644
TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B) RRN7/TAF1B family Q53T94
Sprouty-related, EVH1 domain-containing protein 1 (SPRED1) . Q7Z699
TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A) . Q15573

References

1 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.
2 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
3 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.
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 Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes. bioRxiv, 2020-06.
6 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.
7 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.
8 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.
9 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
10 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
11 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
12 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
13 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
14 Oxidative cyclization reagents reveal tryptophan cation- interactions. Nature. 2024 Mar;627(8004):680-687. doi: 10.1038/s41586-024-07140-6. Epub 2024 Mar 6.
Mass spectrometry data entry: PXD001377 , PXD005252
15 Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine. Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202112107. doi: 10.1002/anie.202112107. Epub 2021 Dec 16.
16 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.
17 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
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.