General Information of Target

Target ID LDTP10924
Target Name Prohibitin-2 (PHB2)
Gene Name PHB2
Gene ID 11331
Synonyms
BAP; REA; Prohibitin-2; B-cell receptor-associated protein BAP37; D-prohibitin; Repressor of estrogen receptor activity
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MASASTQPAALSAEQAKVVLAEVIQAFSAPENAVRMDEARDNACNDMGKMLQFVLPVATQ
IQQEVIKAYGFSCDGEGVLKFARLVKSYEAQDPEIASLSGKLKALFLPPMTLPPHGPAAG
GSVAAS
Target Bioclass
Other
Family
Prohibitin family
Subcellular location
Mitochondrion inner membrane
Function
Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors and sex steroid hormones in the nucleus.; In the mitochondria, together with PHB, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as a chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner. Also regulates cytochrome-c oxidase assembly (COX) and mitochondrial respiration. Binding to sphingoid 1-phosphate (SPP) modulates its regulator activity. Has a key role of mitophagy receptor involved in targeting mitochondria for autophagic degradation. Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6.; In the nucleus, serves as transcriptional co-regulator (Probable). Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases. Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity.; In the plasma membrane, is involved in IGFBP6-induced cell migration. Cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation.; (Microbial infection) Involved in human enterovirus 71/EV-71 infection by enhancing the autophagy mechanism during the infection.
Uniprot ID
Q99623
Ensemble ID
ENST00000440277.6
HGNC ID
HGNC:30306
ChEMBL ID
CHEMBL4295931

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 24 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
HDSF-alk
 Probe Info 
1.92  LDD0197  [2]
P8
 Probe Info 
10.00  LDD0451  [3]
AZ-9
 Probe Info 
2.32  LDD0393  [4]
FBPP2
 Probe Info 
3.11  LDD0318  [5]
CHEMBL5175495
 Probe Info 
13.39  LDD0196  [6]
CY4
 Probe Info 
100.00  LDD0244  [7]
N1
 Probe Info 
100.00  LDD0242  [7]
TH211
 Probe Info 
Y77(5.33)  LDD0260  [8]
C-Sul
 Probe Info 
3.59  LDD0066  [9]
FBP2
 Probe Info 
3.45  LDD0317  [5]
YN-1
 Probe Info 
100.00  LDD0444  [10]
ONAyne
 Probe Info 
K216(0.00); K89(0.00); K250(0.00); K296(0.00)  LDD0273  [11]
OPA-S-S-alkyne
 Probe Info 
K200(2.34); K218(2.79); K216(2.79); K262(3.03)  LDD3494  [12]
Probe 1
 Probe Info 
Y248(29.89)  LDD3495  [13]
Jackson_14
 Probe Info 
2.13  LDD0123  [14]
ATP probe
 Probe Info 
K89(0.00); K262(0.00)  LDD0199  [15]
ATP probe
 Probe Info 
N.A.  LDD0035  [16]
NHS
 Probe Info 
K262(0.00); K200(0.00); K6(0.00); K244(0.00)  LDD0010  [17]
SF
 Probe Info 
K216(0.00); K296(0.00); K89(0.00)  LDD0028  [18]
STPyne
 Probe Info 
K262(0.00); K200(0.00)  LDD0009  [17]
Ox-W18
 Probe Info 
N.A.  LDD2175  [19]
1c-yne
 Probe Info 
K200(0.00); K147(0.00); K24(0.00); K262(0.00)  LDD0228  [20]
Acrolein
 Probe Info 
H69(0.00); H47(0.00)  LDD0217  [21]
Crotonaldehyde
 Probe Info 
H47(0.00); H69(0.00)  LDD0219  [21]
PAL-AfBPP Probe
Click To Hide/Show 45 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DR-1
 Probe Info 
7.81  LDD0398  [22]
ILS-1 PP
 Probe Info 
2.68  LDD0417  [23]
C003
 Probe Info 
11.96  LDD1713  [24]
C017
 Probe Info 
6.23  LDD1725  [24]
C040
 Probe Info 
15.78  LDD1740  [24]
C055
 Probe Info 
15.03  LDD1752  [24]
C056
 Probe Info 
19.70  LDD1753  [24]
C063
 Probe Info 
12.55  LDD1760  [24]
C094
 Probe Info 
33.36  LDD1785  [24]
C112
 Probe Info 
39.12  LDD1799  [24]
C143
 Probe Info 
12.21  LDD1825  [24]
C161
 Probe Info 
11.39  LDD1841  [24]
C169
 Probe Info 
20.97  LDD1849  [24]
C201
 Probe Info 
35.51  LDD1877  [24]
C210
 Probe Info 
58.49  LDD1884  [24]
C228
 Probe Info 
17.15  LDD1901  [24]
C231
 Probe Info 
22.47  LDD1904  [24]
C235
 Probe Info 
22.63  LDD1908  [24]
C238
 Probe Info 
19.43  LDD1911  [24]
C246
 Probe Info 
13.00  LDD1919  [24]
C278
 Probe Info 
49.52  LDD1948  [24]
C285
 Probe Info 
20.11  LDD1955  [24]
C289
 Probe Info 
32.45  LDD1959  [24]
C349
 Probe Info 
12.47  LDD2010  [24]
C350
 Probe Info 
30.48  LDD2011  [24]
C355
 Probe Info 
23.92  LDD2016  [24]
C356
 Probe Info 
7.89  LDD2017  [24]
C362
 Probe Info 
51.27  LDD2023  [24]
C388
 Probe Info 
69.55  LDD2047  [24]
C390
 Probe Info 
41.93  LDD2049  [24]
C407
 Probe Info 
11.24  LDD2064  [24]
FFF probe11
 Probe Info 
20.00  LDD0471  [25]
FFF probe13
 Probe Info 
20.00  LDD0475  [25]
FFF probe14
 Probe Info 
16.43  LDD0477  [25]
FFF probe2
 Probe Info 
20.00  LDD0463  [25]
FFF probe3
 Probe Info 
19.73  LDD0464  [25]
FFF probe4
 Probe Info 
14.34  LDD0466  [25]
FFF probe6
 Probe Info 
8.25  LDD0467  [25]
FFF probe9
 Probe Info 
5.92  LDD0470  [25]
JN0003
 Probe Info 
20.00  LDD0469  [25]
STS-1
 Probe Info 
N.A.  LDD0137  [26]
STS-2
 Probe Info 
N.A.  LDD0138  [26]
TM-F
 Probe Info 
A65(0.00); G67(0.00); H69(0.00)  LDD0020  [27]
Photoindomethacin
 Probe Info 
N.A.  LDD0154  [28]
OEA-DA
 Probe Info 
6.48  LDD0046  [29]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa H69(0.00); H47(0.00)  LDD0222  [21]
 LDCM0107  IAA HeLa H69(0.00); H47(0.00)  LDD0221  [21]
 LDCM0109  NEM HeLa H69(0.00); H47(0.00)  LDD0223  [21]
 LDCM0016  Ranjitkar_cp1 MDA-MB-231 2.13  LDD0123  [14]

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
Dual specificity protein phosphatase 6 (DUSP6) Protein-tyrosine phosphatase family Q16828
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Prohibitin 1 (PHB1) Prohibitin family P35232
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Estrogen receptor (ESR1) Nuclear hormone receptor family P03372

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Capsaicin Small molecular drug DB06774
Investigative
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Rocaglamide Small molecular drug DB15495
Didesmethylrocaglamide . DB15496

References

1 Labeling Preferences of Diazirines with Protein Biomolecules. J Am Chem Soc. 2021 May 5;143(17):6691-6700. doi: 10.1021/jacs.1c02509. Epub 2021 Apr 20.
Mass spectrometry data entry: PXD025140
2 Fatty Acyl Sulfonyl Fluoride as an Activity-Based Probe for Profiling Fatty Acid-Associated Proteins in Living Cells. Chembiochem. 2022 Feb 16;23(4):e202100628. doi: 10.1002/cbic.202100628. Epub 2021 Dec 30.
3 Comparison of Different Competitive Proteome Profiling Approaches in Target Identification of Covalent Inhibitors. Chembiochem. 2022 Dec 16;23(24):e202200389. doi: 10.1002/cbic.202200389. Epub 2022 Nov 22.
4 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.
5 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
6 Charting the Chemical Space of Acrylamide-Based Inhibitors of zDHHC20. ACS Med Chem Lett. 2022 Sep 26;13(10):1648-1654. doi: 10.1021/acsmedchemlett.2c00336. eCollection 2022 Oct 13.
7 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.
8 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.
9 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.
10 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.
11 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
12 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
13 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.
14 Appendage and Scaffold Diverse Fully Functionalized Small-Molecule Probes via a Minimalist Terminal Alkyne-Aliphatic Diazirine Isocyanide. J Org Chem. 2018 Sep 21;83(18):11245-11253. doi: 10.1021/acs.joc.8b01831. Epub 2018 Aug 31.
15 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.
16 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
17 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
18 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
19 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
20 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.
21 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.
22 Quantitative Proteomics Reveals Cellular Off-Targets of a DDR1 Inhibitor. ACS Med Chem Lett. 2020 Feb 5;11(4):535-540. doi: 10.1021/acsmedchemlett.9b00658. eCollection 2020 Apr 9.
23 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
24 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
25 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.
26 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.
27 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
28 Small Molecule Interactome Mapping by Photoaffinity Labeling Reveals Binding Site Hotspots for the NSAIDs. J Am Chem Soc. 2018 Mar 28;140(12):4259-4268. doi: 10.1021/jacs.7b11639. Epub 2018 Mar 15.
Mass spectrometry data entry: PXD007094
29 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