Details of the Target

General Information of Target

Target ID LDTP01474
Target Name Ubiquitin carboxyl-terminal hydrolase 19 (USP19)
Gene Name USP19
Gene ID 10869
Synonyms
KIAA0891; ZMYND9; Ubiquitin carboxyl-terminal hydrolase 19; EC 3.4.19.12; Deubiquitinating enzyme 19; Ubiquitin thioesterase 19; Ubiquitin-specific-processing protease 19; Zinc finger MYND domain-containing protein 9
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSGGASATGPRRGPPGLEDTTSKKKQKDRANQESKDGDPRKETGSRYVAQAGLEPLASGD
PSASASHAAGITGSRHRTRLFFPSSSGSASTPQEEQTKEGACEDPHDLLATPTPELLLDW
RQSAEEVIVKLRVGVGPLQLEDVDAAFTDTDCVVRFAGGQQWGGVFYAEIKSSCAKVQTR
KGSLLHLTLPKKVPMLTWPSLLVEADEQLCIPPLNSQTCLLGSEENLAPLAGEKAVPPGN
DPVSPAMVRSRNPGKDDCAKEEMAVAADAATLVDEPESMVNLAFVKNDSYEKGPDSVVVH
VYVKEICRDTSRVLFREQDFTLIFQTRDGNFLRLHPGCGPHTTFRWQVKLRNLIEPEQCT
FCFTASRIDICLRKRQSQRWGGLEAPAARVGGAKVAVPTGPTPLDSTPPGGAPHPLTGQE
EARAVEKDKSKARSEDTGLDSVATRTPMEHVTPKPETHLASPKPTCMVPPMPHSPVSGDS
VEEEEEEEKKVCLPGFTGLVNLGNTCFMNSVIQSLSNTRELRDFFHDRSFEAEINYNNPL
GTGGRLAIGFAVLLRALWKGTHHAFQPSKLKAIVASKASQFTGYAQHDAQEFMAFLLDGL
HEDLNRIQNKPYTETVDSDGRPDEVVAEEAWQRHKMRNDSFIVDLFQGQYKSKLVCPVCA
KVSITFDPFLYLPVPLPQKQKVLPVFYFAREPHSKPIKFLVSVSKENSTASEVLDSLSQS
VHVKPENLRLAEVIKNRFHRVFLPSHSLDTVSPSDTLLCFELLSSELAKERVVVLEVQQR
PQVPSVPISKCAACQRKQQSEDEKLKRCTRCYRVGYCNQLCQKTHWPDHKGLCRPENIGY
PFLVSVPASRLTYARLAQLLEGYARYSVSVFQPPFQPGRMALESQSPGCTTLLSTGSLEA
GDSERDPIQPPELQLVTPMAEGDTGLPRVWAAPDRGPVPSTSGISSEMLASGPIEVGSLP
AGERVSRPEAAVPGYQHPSEAMNAHTPQFFIYKIDSSNREQRLEDKGDTPLELGDDCSLA
LVWRNNERLQEFVLVASKELECAEDPGSAGEAARAGHFTLDQCLNLFTRPEVLAPEEAWY
CPQCKQHREASKQLLLWRLPNVLIVQLKRFSFRSFIWRDKINDLVEFPVRNLDLSKFCIG
QKEEQLPSYDLYAVINHYGGMIGGHYTACARLPNDRSSQRSDVGWRLFDDSTVTTVDESQ
VVTRYAYVLFYRRRNSPVERPPRAGHSEHHPDLGPAAEAAASQASRIWQELEAEEEPVPE
GSGPLGPWGPQDWVGPLPRGPTTPDEGCLRYFVLGTVAALVALVLNVFYPLVSQSRWR
Target Bioclass
Enzyme
Family
Peptidase C19 family
Subcellular location
Endoplasmic reticulum membrane
Function
Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked ubiquitin chains.
Uniprot ID
O94966
Ensemble ID
ENST00000398888.6
HGNC ID
HGNC:12617
ChEMBL ID
CHEMBL4523156

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
m-APA
 Probe Info  		15.00  LDD0402  [1]
DA-P2
 Probe Info  		4.98  LDD0348  [2]
C-Sul
 Probe Info  		7.02  LDD0066  [3]
DBIA
 Probe Info  		C936(1.73)  LDD3310  [4]
BTD
 Probe Info  		C338(1.18)  LDD2107  [5]
DA-P3
 Probe Info  		4.25  LDD0180  [2]
HHS-475
 Probe Info  		Y584(0.15); Y992(0.89)  LDD0264  [6]
BDBM50514113
 Probe Info  		1.49  LDD0041  [7]
5E-2FA
 Probe Info  		N.A.  LDD2235  [8]
4-Iodoacetamidophenylacetylene
 Probe Info  		C102(0.00); C833(0.00); C759(0.00)  LDD0038  [9]
IA-alkyne
 Probe Info  		N.A.  LDD0032  [10]
IPIAA_L
 Probe Info  		N.A.  LDD0031  [11]
Lodoacetamide azide
 Probe Info  		C833(0.00); C759(0.00)  LDD0037  [9]
JW-RF-010
 Probe Info  		N.A.  LDD0026  [12]
TFBX
 Probe Info  		N.A.  LDD0027  [12]
IPM
 Probe Info  		N.A.  LDD0005  [13]
SF
 Probe Info  		Y992(0.00); K993(0.00)  LDD0028  [14]
VSF
 Probe Info  		N.A.  LDD0007  [13]
Acrolein
 Probe Info  		N.A.  LDD0217  [15]
Methacrolein
 Probe Info  		C338(0.00); C1042(0.00)  LDD0218  [15]
W1
 Probe Info  		N.A.  LDD0236  [16]
AOyne
 Probe Info  		11.70  LDD0443  [17]
NAIA_5
 Probe Info  		N.A.  LDD2223  [18]
HHS-465
 Probe Info  		K993(0.00); Y992(0.00)  LDD2240  [19]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0524  2-Cyano-N-(2-morpholin-4-yl-ethyl)-acetamide MDA-MB-231 C1138(0.95)  LDD2117  [5]
 LDCM0156  Aniline NCI-H1299 11.47  LDD0403  [1]
 LDCM0108  Chloroacetamide HeLa H335(0.00); C1042(0.00)  LDD0222  [15]
 LDCM0028  Dobutamine HEK-293T 4.25  LDD0180  [2]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C817(1.00); C821(0.99)  LDD1702  [5]
 LDCM0031  Epigallocatechin gallate HEK-293T 18.67  LDD0183  [2]
 LDCM0116  HHS-0101 DM93 Y584(0.15); Y992(0.89)  LDD0264  [6]
 LDCM0117  HHS-0201 DM93 Y992(1.71); Y584(1.96)  LDD0265  [6]
 LDCM0118  HHS-0301 DM93 Y992(0.58); Y584(0.87)  LDD0266  [6]
 LDCM0119  HHS-0401 DM93 Y992(0.20)  LDD0267  [6]
 LDCM0120  HHS-0701 DM93 Y992(1.49); Y584(2.05)  LDD0268  [6]
 LDCM0022  KB02 HEK-293T C1042(0.90); C466(1.03); C833(0.91); C1017(0.97)  LDD1492  [20]
 LDCM0023  KB03 HEK-293T C1042(1.11); C466(1.28); C833(1.28); C1017(1.16)  LDD1497  [20]
 LDCM0024  KB05 COLO792 C936(1.73)  LDD3310  [4]
 LDCM0030  Luteolin HEK-293T 7.20  LDD0182  [2]
 LDCM0514  Nucleophilic fragment 20a MDA-MB-231 C338(1.18)  LDD2107  [5]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C1138(1.01); C338(0.66)  LDD2123  [5]
 LDCM0550  Nucleophilic fragment 5a MDA-MB-231 C338(1.27)  LDD2144  [5]
 LDCM0029  Quercetin HEK-293T 7.87  LDD0181  [2]
 LDCM0002  Ward_cp1 U2OS 1.49  LDD0041  [7]

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 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
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 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
5 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
6 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.
7 Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells. ACS Chem Biol. 2016 Dec 16;11(12):3268-3272. doi: 10.1021/acschembio.6b00766. Epub 2016 Oct 31.
8 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
9 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
10 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
11 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
12 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
13 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
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 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.
16 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.
17 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.
18 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
19 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
20 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