Details of the Target

General Information of Target

Target ID LDTP06618
Target Name ATP-dependent Clp protease proteolytic subunit, mitochondrial (CLPP)
Gene Name CLPP
Gene ID 8192
Synonyms
ATP-dependent Clp protease proteolytic subunit, mitochondrial; EC 3.4.21.92; Endopeptidase Clp
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MWPGILVGGARVASCRYPALGPRLAAHFPAQRPPQRTLQNGLALQRCLHATATRALPLIP
IVVEQTGRGERAYDIYSRLLRERIVCVMGPIDDSVASLVIAQLLFLQSESNKKPIHMYIN
SPGGVVTAGLAIYDTMQYILNPICTWCVGQAASMGSLLLAAGTPGMRHSLPNSRIMIHQP
SGGARGQATDIAIQAEEIMKLKKQLYNIYAKHTKQSLQVIESAMERDRYMSPMEAQEFGI
LDKVLVHPPQDGEDEPTLVQKEPVEAAPAAEPVPAST
Target Bioclass
Enzyme
Family
Peptidase S14 family
Subcellular location
Mitochondrion matrix
Function
Protease component of the Clp complex that cleaves peptides and various proteins in an ATP-dependent process. Has low peptidase activity in the absence of CLPX. The Clp complex can degrade CSN1S1, CSN2 and CSN3, as well as synthetic peptides (in vitro) and may be responsible for a fairly general and central housekeeping function rather than for the degradation of specific substrates. Cleaves PINK1 in the mitochondrion.
Uniprot ID
Q16740
Ensemble ID
ENST00000245816.11
HGNC ID
HGNC:2084
ChEMBL ID
CHEMBL4523305

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 17 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		11.21  LDD0402  [1]
CY-1
 Probe Info  		100.00  LDD0243  [2]
N1
 Probe Info  		100.00  LDD0242  [2]
TH211
 Probe Info  		Y73(7.94); Y229(8.01)  LDD0260  [3]
TH216
 Probe Info  		Y73(6.53)  LDD0259  [3]
STPyne
 Probe Info  		K211(10.00)  LDD0277  [4]
Probe 1
 Probe Info  		Y76(274.91); Y206(8.74)  LDD3495  [5]
DBIA
 Probe Info  		C86(0.94)  LDD1509  [6]
5E-2FA
 Probe Info  		H178(0.00); H247(0.00)  LDD2235  [7]
ATP probe
 Probe Info  		N.A.  LDD0199  [8]
KY-26
 Probe Info  		N.A.  LDD0301  [9]
IA-alkyne
 Probe Info  		N.A.  LDD0150  [10]
SF
 Probe Info  		Y76(0.00); Y73(0.00)  LDD0028  [11]
1c-yne
 Probe Info  		N.A.  LDD0228  [12]
Acrolein
 Probe Info  		N.A.  LDD0217  [13]
Crotonaldehyde
 Probe Info  		N.A.  LDD0219  [13]
AOyne
 Probe Info  		15.00  LDD0443  [14]
PAL-AfBPP Probe
Click To Hide/Show 101 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C001
 Probe Info  		20.68  LDD1711  [15]
C007
 Probe Info  		16.00  LDD1716  [15]
C010
 Probe Info  		5.35  LDD1719  [15]
C018
 Probe Info  		5.28  LDD1726  [15]
C022
 Probe Info  		19.03  LDD1728  [15]
C028
 Probe Info  		18.77  LDD1734  [15]
C039
 Probe Info  		7.01  LDD1739  [15]
C040
 Probe Info  		9.38  LDD1740  [15]
C055
 Probe Info  		49.87  LDD1752  [15]
C063
 Probe Info  		21.71  LDD1760  [15]
C067
 Probe Info  		5.10  LDD1763  [15]
C068
 Probe Info  		6.59  LDD1764  [15]
C070
 Probe Info  		9.19  LDD1766  [15]
C072
 Probe Info  		11.47  LDD1768  [15]
C095
 Probe Info  		6.96  LDD1786  [15]
C102
 Probe Info  		11.79  LDD1790  [15]
C106
 Probe Info  		22.01  LDD1793  [15]
C107
 Probe Info  		10.20  LDD1794  [15]
C108
 Probe Info  		9.25  LDD1795  [15]
C110
 Probe Info  		8.75  LDD1797  [15]
C111
 Probe Info  		6.63  LDD1798  [15]
C129
 Probe Info  		8.69  LDD1811  [15]
C130
 Probe Info  		15.35  LDD1812  [15]
C134
 Probe Info  		22.16  LDD1816  [15]
C135
 Probe Info  		11.96  LDD1817  [15]
C139
 Probe Info  		16.56  LDD1821  [15]
C143
 Probe Info  		15.56  LDD1825  [15]
C145
 Probe Info  		8.46  LDD1827  [15]
C147
 Probe Info  		7.36  LDD1829  [15]
C153
 Probe Info  		18.13  LDD1834  [15]
C158
 Probe Info  		9.71  LDD1838  [15]
C160
 Probe Info  		9.85  LDD1840  [15]
C163
 Probe Info  		16.45  LDD1843  [15]
C169
 Probe Info  		37.53  LDD1849  [15]
C174
 Probe Info  		7.94  LDD1854  [15]
C177
 Probe Info  		18.13  LDD1856  [15]
C183
 Probe Info  		7.41  LDD1861  [15]
C187
 Probe Info  		22.16  LDD1865  [15]
C193
 Probe Info  		8.82  LDD1869  [15]
C194
 Probe Info  		10.48  LDD1870  [15]
C196
 Probe Info  		11.08  LDD1872  [15]
C197
 Probe Info  		8.34  LDD1873  [15]
C198
 Probe Info  		21.56  LDD1874  [15]
C205
 Probe Info  		7.46  LDD1880  [15]
C219
 Probe Info  		26.72  LDD1893  [15]
C220
 Probe Info  		16.80  LDD1894  [15]
C225
 Probe Info  		19.84  LDD1898  [15]
C228
 Probe Info  		14.83  LDD1901  [15]
C229
 Probe Info  		30.70  LDD1902  [15]
C233
 Probe Info  		38.59  LDD1906  [15]
C234
 Probe Info  		9.92  LDD1907  [15]
C235
 Probe Info  		18.38  LDD1908  [15]
C238
 Probe Info  		15.45  LDD1911  [15]
C239
 Probe Info  		6.82  LDD1912  [15]
C240
 Probe Info  		13.36  LDD1913  [15]
C243
 Probe Info  		54.95  LDD1916  [15]
C245
 Probe Info  		21.41  LDD1918  [15]
C246
 Probe Info  		42.22  LDD1919  [15]
C252
 Probe Info  		15.03  LDD1925  [15]
C258
 Probe Info  		7.78  LDD1931  [15]
C265
 Probe Info  		22.78  LDD1936  [15]
C271
 Probe Info  		14.72  LDD1941  [15]
C286
 Probe Info  		8.69  LDD1956  [15]
C288
 Probe Info  		12.30  LDD1958  [15]
C305
 Probe Info  		20.68  LDD1974  [15]
C310
 Probe Info  		15.89  LDD1977  [15]
C339
 Probe Info  		10.41  LDD2002  [15]
C340
 Probe Info  		7.01  LDD2003  [15]
C342
 Probe Info  		27.86  LDD2004  [15]
C349
 Probe Info  		18.00  LDD2010  [15]
C351
 Probe Info  		8.22  LDD2012  [15]
C353
 Probe Info  		7.52  LDD2014  [15]
C355
 Probe Info  		62.25  LDD2016  [15]
C356
 Probe Info  		21.11  LDD2017  [15]
C357
 Probe Info  		10.34  LDD2018  [15]
C366
 Probe Info  		22.47  LDD2027  [15]
C373
 Probe Info  		5.78  LDD2033  [15]
C380
 Probe Info  		17.51  LDD2039  [15]
C386
 Probe Info  		11.31  LDD2045  [15]
C388
 Probe Info  		49.87  LDD2047  [15]
C391
 Probe Info  		12.55  LDD2050  [15]
C394
 Probe Info  		6.15  LDD2053  [15]
C405
 Probe Info  		7.46  LDD2063  [15]
C419
 Probe Info  		18.90  LDD2074  [15]
C420
 Probe Info  		16.68  LDD2075  [15]
C426
 Probe Info  		17.63  LDD2081  [15]
C429
 Probe Info  		29.45  LDD2084  [15]
C430
 Probe Info  		5.35  LDD2085  [15]
C431
 Probe Info  		16.11  LDD2086  [15]
C433
 Probe Info  		5.98  LDD2088  [15]
FFF probe11
 Probe Info  		15.42  LDD0471  [16]
FFF probe13
 Probe Info  		20.00  LDD0475  [16]
FFF probe14
 Probe Info  		20.00  LDD0477  [16]
FFF probe15
 Probe Info  		20.00  LDD0478  [16]
FFF probe3
 Probe Info  		20.00  LDD0464  [16]
FFF probe4
 Probe Info  		20.00  LDD0466  [16]
FFF probe6
 Probe Info  		20.00  LDD0468  [16]
FFF probe7
 Probe Info  		20.00  LDD0483  [16]
JN0003
 Probe Info  		17.06  LDD0469  [16]
OEA-DA
 Probe Info  		20.00  LDD0046  [17]
STS-1
 Probe Info  		N.A.  LDD0068  [18]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0226  AC11 HEK-293T C86(0.94)  LDD1509  [6]
 LDCM0237  AC12 HEK-293T C86(1.02)  LDD1510  [6]
 LDCM0278  AC19 HEK-293T C86(0.79)  LDD1517  [6]
 LDCM0280  AC20 HEK-293T C86(0.91)  LDD1519  [6]
 LDCM0287  AC27 HEK-293T C86(0.86)  LDD1526  [6]
 LDCM0288  AC28 HEK-293T C86(1.15)  LDD1527  [6]
 LDCM0290  AC3 HEK-293T C86(1.03)  LDD1529  [6]
 LDCM0296  AC35 HEK-293T C86(0.91)  LDD1535  [6]
 LDCM0297  AC36 HEK-293T C86(0.88)  LDD1536  [6]
 LDCM0301  AC4 HEK-293T C86(1.16)  LDD1540  [6]
 LDCM0305  AC43 HEK-293T C86(0.89)  LDD1544  [6]
 LDCM0306  AC44 HEK-293T C86(1.14)  LDD1545  [6]
 LDCM0314  AC51 HEK-293T C86(0.97)  LDD1553  [6]
 LDCM0315  AC52 HEK-293T C86(0.98)  LDD1554  [6]
 LDCM0322  AC59 HEK-293T C86(1.05)  LDD1561  [6]
 LDCM0324  AC60 HEK-293T C86(1.08)  LDD1563  [6]
 LDCM0156  Aniline NCI-H1299 12.76  LDD0403  [1]
 LDCM0108  Chloroacetamide HeLa H178(0.00); H168(0.00)  LDD0222  [13]
 LDCM0371  CL102 HEK-293T C86(0.95)  LDD1575  [6]
 LDCM0375  CL106 HEK-293T C86(1.18)  LDD1579  [6]
 LDCM0380  CL110 HEK-293T C86(0.75)  LDD1584  [6]
 LDCM0384  CL114 HEK-293T C86(1.11)  LDD1588  [6]
 LDCM0388  CL118 HEK-293T C86(1.35)  LDD1592  [6]
 LDCM0393  CL122 HEK-293T C86(1.57)  LDD1597  [6]
 LDCM0397  CL126 HEK-293T C86(1.05)  LDD1601  [6]
 LDCM0401  CL14 HEK-293T C86(0.98)  LDD1605  [6]
 LDCM0406  CL19 HEK-293T C86(1.24)  LDD1610  [6]
 LDCM0407  CL2 HEK-293T C86(1.20)  LDD1611  [6]
 LDCM0408  CL20 HEK-293T C86(1.50)  LDD1612  [6]
 LDCM0414  CL26 HEK-293T C86(1.16)  LDD1618  [6]
 LDCM0420  CL31 HEK-293T C86(0.96)  LDD1624  [6]
 LDCM0421  CL32 HEK-293T C86(1.36)  LDD1625  [6]
 LDCM0433  CL43 HEK-293T C86(1.26)  LDD1637  [6]
 LDCM0434  CL44 HEK-293T C86(1.26)  LDD1638  [6]
 LDCM0441  CL50 HEK-293T C86(1.02)  LDD1645  [6]
 LDCM0446  CL55 HEK-293T C86(1.27)  LDD1649  [6]
 LDCM0447  CL56 HEK-293T C86(1.49)  LDD1650  [6]
 LDCM0454  CL62 HEK-293T C86(1.59)  LDD1657  [6]
 LDCM0459  CL67 HEK-293T C86(1.18)  LDD1662  [6]
 LDCM0460  CL68 HEK-293T C86(1.42)  LDD1663  [6]
 LDCM0462  CL7 HEK-293T C86(1.33)  LDD1665  [6]
 LDCM0467  CL74 HEK-293T C86(1.09)  LDD1670  [6]
 LDCM0472  CL79 HEK-293T C86(1.03)  LDD1675  [6]
 LDCM0473  CL8 HEK-293T C86(1.37)  LDD1676  [6]
 LDCM0474  CL80 HEK-293T C86(1.20)  LDD1677  [6]
 LDCM0480  CL86 HEK-293T C86(1.08)  LDD1683  [6]
 LDCM0486  CL91 HEK-293T C86(1.20)  LDD1689  [6]
 LDCM0487  CL92 HEK-293T C86(1.18)  LDD1690  [6]
 LDCM0493  CL98 HEK-293T C86(1.30)  LDD1696  [6]
 LDCM0189  Compound 16 HEK-293T 27.40  LDD0492  [16]
 LDCM0182  Compound 18 HEK-293T 11.49  LDD0501  [16]
 LDCM0184  Compound 20 HEK-293T 9.97  LDD0503  [16]
 LDCM0191  Compound 21 HEK-293T 5.12  LDD0493  [16]
 LDCM0187  Compound 32 HEK-293T 7.17  LDD0507  [16]
 LDCM0188  Compound 33 HEK-293T 10.88  LDD0505  [16]
 LDCM0190  Compound 34 HEK-293T 12.35  LDD0497  [16]
 LDCM0192  Compound 35 HEK-293T 8.51  LDD0509  [16]
 LDCM0193  Compound 36 HEK-293T 8.81  LDD0494  [16]
 LDCM0194  Compound 37 HEK-293T 4.12  LDD0498  [16]
 LDCM0196  Compound 39 HEK-293T 9.13  LDD0496  [16]
 LDCM0197  Compound 40 HEK-293T 11.49  LDD0495  [16]
 LDCM0181  Compound 41 HEK-293T 5.63  LDD0502  [16]
 LDCM0427  Fragment51 HEK-293T C86(1.27)  LDD1631  [6]
 LDCM0107  IAA HeLa H168(0.00); H247(0.00)  LDD0221  [13]
 LDCM0022  KB02 BICR-22 C206(1.49)  LDD2266  [19]
 LDCM0023  KB03 CAL-27 C206(1.16)  LDD2703  [19]
 LDCM0024  KB05 CAL-27 C206(1.22)  LDD3120  [19]
 LDCM0109  NEM HeLa N.A.  LDD0223  [13]

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
ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial (CLPX) ClpX chaperone family O76031
Probable E3 ubiquitin-protein ligase DTX2 (DTX2) Deltex family Q86UW9
Prolyl 4-hydroxylase subunit alpha-3 (P4HA3) P4HA family Q7Z4N8
Proteasome subunit beta type-1 (PSMB1) Peptidase T1B family P20618
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PPP2CA) PPP phosphatase family P67775
Ataxin-3 (ATXN3) . P54252
Transporter and channel
Click To Hide/Show 7 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Amyloid-beta precursor protein (APP) APP family P05067
Huntingtin (HTT) Huntingtin family P42858
Junctophilin-3 (JPH3) Junctophilin family Q8WXH2
Phospholipid scramblase 4 (PLSCR4) Phospholipid scramblase family Q9NRQ2
Alpha-synuclein (SNCA) Synuclein family P37840
Transportin-3 (TNPO3) . Q9Y5L0
Wolframin (WFS1) . O76024
Other
Click To Hide/Show 7 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) Fibulin family Q12805
EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) Fibulin family O95967
Progranulin (GRN) Granulin family P28799
Ganglioside-induced differentiation-associated protein 1 (GDAP1) GST superfamily Q8TB36
Nuclear transport factor 2 (NUTF2) . P61970
TAR DNA-binding protein 43 (TARDBP) . Q13148
Uncharacterized protein C14orf119 (C14orf119) . Q9NWQ9

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
N-formylmethionine Small molecular drug DB04464

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 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.
3 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.
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 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.
6 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
7 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
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 Direct Target Site Identification of a Sulfonyl-Triazole Covalent Kinase Probe by LC-MS Chemical Proteomics. Anal Chem. 2021 Sep 7;93(35):11946-11955. doi: 10.1021/acs.analchem.1c01591. Epub 2021 Aug 25.
10 Sequence-Based Prediction of Cysteine Reactivity Using Machine Learning. Biochemistry. 2018 Jan 30;57(4):451-460. doi: 10.1021/acs.biochem.7b00897. Epub 2017 Oct 26.
11 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
12 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.
13 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.
14 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.
15 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
16 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.
17 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
18 Proteome profiling reveals potential cellular targets of staurosporine using a clickable cell-permeable probe. Chem Commun (Camb). 2011 Oct 28;47(40):11306-8. doi: 10.1039/c1cc14824a. Epub 2011 Sep 16.
19 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