General Information of Target

Target ID LDTP04906
Target Name COP9 signalosome complex subunit 2 (COPS2)
Gene Name COPS2
Gene ID 9318
Synonyms
CSN2; TRIP15; COP9 signalosome complex subunit 2; SGN2; Signalosome subunit 2; Alien homolog; JAB1-containing signalosome subunit 2; Thyroid receptor-interacting protein 15; TR-interacting protein 15; TRIP-15
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSDMEDDFMCDDEEDYDLEYSEDSNSEPNVDLENQYYNSKALKEDDPKAALSSFQKVLEL
EGEKGEWGFKALKQMIKINFKLTNFPEMMNRYKQLLTYIRSAVTRNYSEKSINSILDYIS
TSKQMDLLQEFYETTLEALKDAKNDRLWFKTNTKLGKLYLEREEYGKLQKILRQLHQSCQ
TDDGEDDLKKGTQLLEIYALEIQMYTAQKNNKKLKALYEQSLHIKSAIPHPLIMGVIREC
GGKMHLREGEFEKAHTDFFEAFKNYDESGSPRRTTCLKYLVLANMLMKSGINPFDSQEAK
PYKNDPEILAMTNLVSAYQNNDITEFEKILKTNHSNIMDDPFIREHIEELLRNIRTQVLI
KLIKPYTRIHIPFISKELNIDVADVESLLVQCILDNTIHGRIDQVNQLLELDHQKRGGAR
YTALDKWTNQLNSLNQAVVSKLA
Target Bioclass
Other
Family
CSN2 family
Subcellular location
Cytoplasm
Function
Essential component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Involved in early stage of neuronal differentiation via its interaction with NIF3L1.
Uniprot ID
P61201
Ensemble ID
ENST00000299259.10
HGNC ID
HGNC:30747

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HCT15 SNV: p.Q430H .
IGROV1 SNV: p.R100L .
MDAMB436 SNV: p.T153R .
TE4 SNV: p.Q193L DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 23 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info 
15.00  LDD0402  [1]
ONAyne
 Probe Info 
K415(1.35)  LDD0274  [2]
IPM
 Probe Info 
N.A.  LDD0241  [3]
Probe 1
 Probe Info 
Y218(11.18); Y265(25.46); Y421(54.42)  LDD3495  [4]
DBIA
 Probe Info 
C399(5.39)  LDD3314  [5]
BTD
 Probe Info 
C179(2.12)  LDD1700  [6]
DA-P3
 Probe Info 
5.21  LDD0183  [7]
AHL-Pu-1
 Probe Info 
C179(2.30)  LDD0168  [8]
HHS-475
 Probe Info 
Y118(0.54); Y318(0.65)  LDD0264  [9]
5E-2FA
 Probe Info 
H255(0.00); H346(0.00); H230(0.00)  LDD2235  [10]
ATP probe
 Probe Info 
K415(0.00); K253(0.00); K70(0.00); K81(0.00)  LDD0199  [11]
4-Iodoacetamidophenylacetylene
 Probe Info 
C392(0.00); C179(0.00)  LDD0038  [12]
IA-alkyne
 Probe Info 
N.A.  LDD0032  [13]
Lodoacetamide azide
 Probe Info 
C392(0.00); C179(0.00)  LDD0037  [12]
SF
 Probe Info 
Y118(0.00); Y218(0.00)  LDD0028  [14]
STPyne
 Probe Info 
N.A.  LDD0009  [15]
1c-yne
 Probe Info 
K426(0.00); K300(0.00); K441(0.00)  LDD0228  [16]
1d-yne
 Probe Info 
N.A.  LDD0357  [16]
Acrolein
 Probe Info 
C179(0.00); H255(0.00); H334(0.00); H346(0.00)  LDD0217  [17]
Methacrolein
 Probe Info 
N.A.  LDD0218  [17]
W1
 Probe Info 
N.A.  LDD0236  [3]
AOyne
 Probe Info 
15.00  LDD0443  [18]
NAIA_5
 Probe Info 
C240(0.00); C392(0.00)  LDD2223  [19]
PAL-AfBPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FFF probe13
 Probe Info 
13.03  LDD0475  [20]
FFF probe14
 Probe Info 
20.00  LDD0477  [20]
FFF probe2
 Probe Info 
5.88  LDD0463  [20]
FFF probe3
 Probe Info 
5.29  LDD0464  [20]
STS-2
 Probe Info 
1.00  LDD0139  [21]
OEA-DA
 Probe Info 
4.78  LDD0046  [22]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0548  1-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-2-nitroethan-1-one MDA-MB-231 C179(0.54)  LDD2142  [6]
 LDCM0519  1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-2-nitroethan-1-one MDA-MB-231 C179(0.94)  LDD2112  [6]
 LDCM0524  2-Cyano-N-(2-morpholin-4-yl-ethyl)-acetamide MDA-MB-231 C179(1.13)  LDD2117  [6]
 LDCM0539  3-(4-Isopropylpiperazin-1-yl)-3-oxopropanenitrile MDA-MB-231 C179(0.69)  LDD2132  [6]
 LDCM0025  4SU-RNA HEK-293T C179(2.30)  LDD0168  [8]
 LDCM0545  Acetamide MDA-MB-231 C179(0.52)  LDD2138  [6]
 LDCM0156  Aniline NCI-H1299 13.53  LDD0403  [1]
 LDCM0498  BS-3668 MDA-MB-231 C179(0.56)  LDD2091  [6]
 LDCM0108  Chloroacetamide HeLa C179(0.00); H334(0.00); H255(0.00); H346(0.00)  LDD0222  [17]
 LDCM0031  Epigallocatechin gallate HEK-293T 5.21  LDD0183  [7]
 LDCM0116  HHS-0101 DM93 Y118(0.54); Y318(0.65)  LDD0264  [9]
 LDCM0117  HHS-0201 DM93 Y118(0.90); Y318(1.69)  LDD0265  [9]
 LDCM0118  HHS-0301 DM93 Y118(0.58)  LDD0266  [9]
 LDCM0119  HHS-0401 DM93 Y118(1.13)  LDD0267  [9]
 LDCM0120  HHS-0701 DM93 Y118(0.65)  LDD0268  [9]
 LDCM0107  IAA HeLa H255(0.00); H346(0.00); H334(0.00); H413(0.00)  LDD0221  [17]
 LDCM0022  KB02 HEK-293T C179(0.96)  LDD1492  [23]
 LDCM0023  KB03 HEK-293T C179(0.92)  LDD1497  [23]
 LDCM0024  KB05 IGR37 C399(5.39)  LDD3314  [5]
 LDCM0109  NEM HeLa H334(0.00); H346(0.00); H255(0.00)  LDD0223  [17]
 LDCM0496  Nucleophilic fragment 11a MDA-MB-231 C179(0.61)  LDD2089  [6]
 LDCM0499  Nucleophilic fragment 12b MDA-MB-231 C179(0.61)  LDD2092  [6]
 LDCM0500  Nucleophilic fragment 13a MDA-MB-231 C179(0.83)  LDD2093  [6]
 LDCM0506  Nucleophilic fragment 16a MDA-MB-231 C179(1.06)  LDD2099  [6]
 LDCM0507  Nucleophilic fragment 16b MDA-MB-231 C179(0.80)  LDD2100  [6]
 LDCM0511  Nucleophilic fragment 18b MDA-MB-231 C179(0.90)  LDD2104  [6]
 LDCM0513  Nucleophilic fragment 19b MDA-MB-231 C179(0.75)  LDD2106  [6]
 LDCM0515  Nucleophilic fragment 20b MDA-MB-231 C179(0.86)  LDD2108  [6]
 LDCM0516  Nucleophilic fragment 21a MDA-MB-231 C179(0.68)  LDD2109  [6]
 LDCM0518  Nucleophilic fragment 22a MDA-MB-231 C179(0.82)  LDD2111  [6]
 LDCM0522  Nucleophilic fragment 24a MDA-MB-231 C179(0.47)  LDD2115  [6]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C179(0.96)  LDD2123  [6]
 LDCM0532  Nucleophilic fragment 29a MDA-MB-231 C179(0.86)  LDD2125  [6]
 LDCM0534  Nucleophilic fragment 30a MDA-MB-231 C179(1.08)  LDD2127  [6]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C179(1.56)  LDD2136  [6]
 LDCM0211  Nucleophilic fragment 3b MDA-MB-231 C179(2.12)  LDD1700  [6]
 LDCM0546  Nucleophilic fragment 40 MDA-MB-231 C179(0.93)  LDD2140  [6]
 LDCM0550  Nucleophilic fragment 5a MDA-MB-231 C179(2.54)  LDD2144  [6]
 LDCM0552  Nucleophilic fragment 6a MDA-MB-231 C179(0.90)  LDD2146  [6]
 LDCM0554  Nucleophilic fragment 7a MDA-MB-231 C179(0.45)  LDD2148  [6]
 LDCM0556  Nucleophilic fragment 8a MDA-MB-231 C179(0.74); C276(0.41)  LDD2150  [6]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
NADH dehydrogenase flavoprotein 1, mitochondrial (NDUFV1) Complex I 51 kDa subunit family P49821
COP9 signalosome complex subunit 3 (COPS3) CSN3 family Q9UNS2
CREB-binding protein (CREBBP) . Q92793
Histone acetyltransferase p300 (EP300) . Q09472
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Wolframin (WFS1) . O76024
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
26S proteasome non-ATPase regulatory subunit 11 (PSMD11) Proteasome subunit S9 family O00231

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 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
3 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
4 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
5 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
6 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
7 A chemical probe unravels the reactive proteome of health-associated catechols. Chem Sci. 2023 Jul 22;14(32):8635-8643. doi: 10.1039/d3sc00888f. eCollection 2023 Aug 16.
Mass spectrometry data entry: PXD043348
8 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
9 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.
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 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.
12 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
13 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
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 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
16 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.
17 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.
18 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.
19 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
20 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.
21 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.
22 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
23 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402