Details of the Target

General Information of Target

Target ID LDTP03788
Target Name Protein phosphatase 1A (PPM1A)
Gene Name PPM1A
Gene ID 5494
Synonyms
PPPM1A; Protein phosphatase 1A; EC 3.1.3.16; Protein phosphatase 2C isoform alpha; PP2C-alpha; Protein phosphatase IA
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGAFLDKPKMEKHNAQGQGNGLRYGLSSMQGWRVEMEDAHTAVIGLPSGLESWSFFAVYD
GHAGSQVAKYCCEHLLDHITNNQDFKGSAGAPSVENVKNGIRTGFLEIDEHMRVMSEKKH
GADRSGSTAVGVLISPQHTYFINCGDSRGLLCRNRKVHFFTQDHKPSNPLEKERIQNAGG
SVMIQRVNGSLAVSRALGDFDYKCVHGKGPTEQLVSPEPEVHDIERSEEDDQFIILACDG
IWDVMGNEELCDFVRSRLEVTDDLEKVCNEVVDTCLYKGSRDNMSVILICFPNAPKVSPE
AVKKEAELDKYLECRVEEIIKKQGEGVPDLVHVMRTLASENIPSLPPGGELASKRNVIEA
VYNRLNPYKNDDTDSTSTDDMW
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
PP2C family
Subcellular location
Nucleus
Function
Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.
TTD ID
T55260
Uniprot ID
P35813
DrugMap ID
TTLA7IX
Ensemble ID
ENST00000325642.7
HGNC ID
HGNC:9275
ChEMBL ID
CHEMBL2437

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
EFO27 SNV: p.M1? .
HCT15 SNV: p.V130I .
HEC1 SNV: p.D273N .
HEC1B SNV: p.D273N .
HSC3 SNV: p.R155S .
LS180 SNV: p.C71Y .
MEWO SNV: p.P169L .
NCIH196 SNV: p.D380E .
RKO SNV: p.A352S .
SUPT1 SNV: p.R335H .
UMUC3 SNV: p.E173Q .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 15 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		15.00  LDD0402  [1]
TH211
 Probe Info  		Y202(10.77)  LDD0260  [2]
Probe 1
 Probe Info  		Y202(22.22)  LDD3495  [3]
DBIA
 Probe Info  		C363(1.75)  LDD3370  [4]
BTD
 Probe Info  		C314(0.39)  LDD2151  [5]
Acrolein
 Probe Info  		N.A.  LDD0221  [6]
5E-2FA
 Probe Info  		N.A.  LDD2235  [7]
4-Iodoacetamidophenylacetylene
 Probe Info  		C290(0.00); C314(0.00); C144(0.00)  LDD0038  [8]
IA-alkyne
 Probe Info  		C290(0.00); C314(0.00); C144(0.00)  LDD0036  [8]
Lodoacetamide azide
 Probe Info  		C290(0.00); C314(0.00); C144(0.00)  LDD0037  [8]
NAIA_4
 Probe Info  		N.A.  LDD2226  [9]
Compound 11
 Probe Info  		N.A.  LDD2213  [10]
TFBX
 Probe Info  		N.A.  LDD0148  [11]
AOyne
 Probe Info  		15.00  LDD0443  [12]
NAIA_5
 Probe Info  		C204(0.00); C290(0.00); C314(0.00); C144(0.00)  LDD2223  [9]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
VE-P
 Probe Info  		N.A.  LDD0396  [13]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0237  AC12 HEK-293T C72(1.00)  LDD1510  [14]
 LDCM0259  AC14 HEK-293T C72(1.24)  LDD1512  [14]
 LDCM0270  AC15 HEK-293T C72(1.10)  LDD1513  [14]
 LDCM0280  AC20 HEK-293T C72(1.06)  LDD1519  [14]
 LDCM0282  AC22 HEK-293T C72(1.05)  LDD1521  [14]
 LDCM0283  AC23 HEK-293T C72(1.05)  LDD1522  [14]
 LDCM0288  AC28 HEK-293T C72(1.07)  LDD1527  [14]
 LDCM0291  AC30 HEK-293T C72(1.12)  LDD1530  [14]
 LDCM0292  AC31 HEK-293T C72(1.18)  LDD1531  [14]
 LDCM0297  AC36 HEK-293T C72(1.03)  LDD1536  [14]
 LDCM0299  AC38 HEK-293T C72(1.17)  LDD1538  [14]
 LDCM0300  AC39 HEK-293T C72(1.07)  LDD1539  [14]
 LDCM0301  AC4 HEK-293T C72(1.04)  LDD1540  [14]
 LDCM0306  AC44 HEK-293T C72(0.97)  LDD1545  [14]
 LDCM0308  AC46 HEK-293T C72(1.06)  LDD1547  [14]
 LDCM0309  AC47 HEK-293T C72(1.06)  LDD1548  [14]
 LDCM0315  AC52 HEK-293T C72(0.96)  LDD1554  [14]
 LDCM0317  AC54 HEK-293T C72(1.19)  LDD1556  [14]
 LDCM0318  AC55 HEK-293T C72(1.04)  LDD1557  [14]
 LDCM0323  AC6 HEK-293T C72(1.02)  LDD1562  [14]
 LDCM0324  AC60 HEK-293T C72(0.94)  LDD1563  [14]
 LDCM0326  AC62 HEK-293T C72(1.08)  LDD1565  [14]
 LDCM0327  AC63 HEK-293T C72(1.01)  LDD1566  [14]
 LDCM0334  AC7 HEK-293T C72(1.01)  LDD1568  [14]
 LDCM0156  Aniline NCI-H1299 13.97  LDD0403  [1]
 LDCM0632  CL-Sc Hep-G2 C204(20.00); C314(1.55); C314(1.07)  LDD2227  [9]
 LDCM0367  CL1 HEK-293T C72(1.05)  LDD1571  [14]
 LDCM0368  CL10 HEK-293T C72(1.02)  LDD1572  [14]
 LDCM0369  CL100 HEK-293T C72(0.99)  LDD1573  [14]
 LDCM0370  CL101 HEK-293T C72(0.97)  LDD1574  [14]
 LDCM0372  CL103 HEK-293T C72(1.07)  LDD1576  [14]
 LDCM0373  CL104 HEK-293T C72(1.06)  LDD1577  [14]
 LDCM0374  CL105 HEK-293T C72(1.06)  LDD1578  [14]
 LDCM0376  CL107 HEK-293T C72(1.04)  LDD1580  [14]
 LDCM0377  CL108 HEK-293T C72(1.03)  LDD1581  [14]
 LDCM0378  CL109 HEK-293T C72(1.01)  LDD1582  [14]
 LDCM0379  CL11 HEK-293T C72(1.14)  LDD1583  [14]
 LDCM0381  CL111 HEK-293T C72(1.13)  LDD1585  [14]
 LDCM0382  CL112 HEK-293T C72(1.06)  LDD1586  [14]
 LDCM0383  CL113 HEK-293T C72(1.24)  LDD1587  [14]
 LDCM0385  CL115 HEK-293T C72(1.04)  LDD1589  [14]
 LDCM0386  CL116 HEK-293T C72(1.08)  LDD1590  [14]
 LDCM0387  CL117 HEK-293T C72(1.03)  LDD1591  [14]
 LDCM0389  CL119 HEK-293T C72(1.10)  LDD1593  [14]
 LDCM0391  CL120 HEK-293T C72(1.07)  LDD1595  [14]
 LDCM0392  CL121 HEK-293T C72(1.01)  LDD1596  [14]
 LDCM0394  CL123 HEK-293T C72(1.00)  LDD1598  [14]
 LDCM0395  CL124 HEK-293T C72(1.04)  LDD1599  [14]
 LDCM0396  CL125 HEK-293T C72(0.98)  LDD1600  [14]
 LDCM0398  CL127 HEK-293T C72(0.95)  LDD1602  [14]
 LDCM0399  CL128 HEK-293T C72(1.04)  LDD1603  [14]
 LDCM0400  CL13 HEK-293T C72(0.86)  LDD1604  [14]
 LDCM0402  CL15 HEK-293T C72(1.00)  LDD1606  [14]
 LDCM0403  CL16 HEK-293T C72(1.12)  LDD1607  [14]
 LDCM0408  CL20 HEK-293T C72(0.90)  LDD1612  [14]
 LDCM0410  CL22 HEK-293T C72(1.19)  LDD1614  [14]
 LDCM0411  CL23 HEK-293T C72(1.01)  LDD1615  [14]
 LDCM0413  CL25 HEK-293T C72(0.98)  LDD1617  [14]
 LDCM0415  CL27 HEK-293T C72(1.14)  LDD1619  [14]
 LDCM0416  CL28 HEK-293T C72(0.99)  LDD1620  [14]
 LDCM0418  CL3 HEK-293T C72(1.08)  LDD1622  [14]
 LDCM0421  CL32 HEK-293T C72(0.95)  LDD1625  [14]
 LDCM0423  CL34 HEK-293T C72(1.10)  LDD1627  [14]
 LDCM0424  CL35 HEK-293T C72(1.07)  LDD1628  [14]
 LDCM0426  CL37 HEK-293T C72(1.15)  LDD1630  [14]
 LDCM0428  CL39 HEK-293T C72(0.98)  LDD1632  [14]
 LDCM0429  CL4 HEK-293T C72(0.94)  LDD1633  [14]
 LDCM0430  CL40 HEK-293T C72(1.10)  LDD1634  [14]
 LDCM0434  CL44 HEK-293T C72(0.96)  LDD1638  [14]
 LDCM0436  CL46 HEK-293T C72(1.04)  LDD1640  [14]
 LDCM0437  CL47 HEK-293T C72(1.04)  LDD1641  [14]
 LDCM0439  CL49 HEK-293T C72(0.94)  LDD1643  [14]
 LDCM0443  CL52 HEK-293T C72(1.13)  LDD1646  [14]
 LDCM0447  CL56 HEK-293T C72(0.96)  LDD1650  [14]
 LDCM0449  CL58 HEK-293T C72(1.12)  LDD1652  [14]
 LDCM0450  CL59 HEK-293T C72(1.05)  LDD1653  [14]
 LDCM0453  CL61 HEK-293T C72(1.14)  LDD1656  [14]
 LDCM0455  CL63 HEK-293T C72(1.03)  LDD1658  [14]
 LDCM0456  CL64 HEK-293T C72(0.94)  LDD1659  [14]
 LDCM0460  CL68 HEK-293T C72(0.87)  LDD1663  [14]
 LDCM0463  CL70 HEK-293T C72(1.14)  LDD1666  [14]
 LDCM0464  CL71 HEK-293T C72(1.05)  LDD1667  [14]
 LDCM0466  CL73 HEK-293T C72(0.96)  LDD1669  [14]
 LDCM0469  CL76 HEK-293T C72(0.96)  LDD1672  [14]
 LDCM0473  CL8 HEK-293T C72(0.67)  LDD1676  [14]
 LDCM0474  CL80 HEK-293T C72(1.04)  LDD1677  [14]
 LDCM0476  CL82 HEK-293T C72(1.16)  LDD1679  [14]
 LDCM0477  CL83 HEK-293T C72(1.01)  LDD1680  [14]
 LDCM0479  CL85 HEK-293T C72(0.99)  LDD1682  [14]
 LDCM0481  CL87 HEK-293T C72(0.96)  LDD1684  [14]
 LDCM0482  CL88 HEK-293T C72(1.13)  LDD1685  [14]
 LDCM0487  CL92 HEK-293T C72(0.98)  LDD1690  [14]
 LDCM0489  CL94 HEK-293T C72(1.11)  LDD1692  [14]
 LDCM0490  CL95 HEK-293T C72(0.83)  LDD1693  [14]
 LDCM0492  CL97 HEK-293T C72(0.92)  LDD1695  [14]
 LDCM0494  CL99 HEK-293T C72(1.02)  LDD1697  [14]
 LDCM0495  E2913 HEK-293T C72(1.13)  LDD1698  [14]
 LDCM0625  F8 Ramos C314(0.28); C144(1.30)  LDD2187  [15]
 LDCM0572  Fragment10 Ramos C314(0.75); C144(0.40)  LDD2189  [15]
 LDCM0573  Fragment11 Ramos C314(0.90); C144(0.42)  LDD2190  [15]
 LDCM0574  Fragment12 Ramos C314(1.69); C144(0.34)  LDD2191  [15]
 LDCM0575  Fragment13 Ramos C314(0.65); C144(0.89)  LDD2192  [15]
 LDCM0576  Fragment14 Ramos C314(1.09); C204(0.48); C144(0.58)  LDD2193  [15]
 LDCM0579  Fragment20 Ramos C314(0.69); C144(0.26)  LDD2194  [15]
 LDCM0580  Fragment21 Ramos C314(1.31); C144(1.32)  LDD2195  [15]
 LDCM0582  Fragment23 Ramos C314(2.00); C204(1.02); C144(1.08)  LDD2196  [15]
 LDCM0578  Fragment27 Ramos C314(0.98)  LDD2197  [15]
 LDCM0586  Fragment28 Ramos C314(0.49); C204(0.83); C144(1.86)  LDD2198  [15]
 LDCM0588  Fragment30 Ramos C314(1.80); C144(0.48)  LDD2199  [15]
 LDCM0589  Fragment31 Ramos C314(1.05); C144(0.93)  LDD2200  [15]
 LDCM0590  Fragment32 Ramos C314(0.35); C144(0.38)  LDD2201  [15]
 LDCM0468  Fragment33 HEK-293T C72(0.99)  LDD1671  [14]
 LDCM0596  Fragment38 Ramos C314(0.39); C144(0.59)  LDD2203  [15]
 LDCM0566  Fragment4 Ramos C314(0.70); C204(0.55); C144(1.00)  LDD2184  [15]
 LDCM0610  Fragment52 Ramos C144(0.53)  LDD2204  [15]
 LDCM0614  Fragment56 Ramos C314(0.56); C144(0.48)  LDD2205  [15]
 LDCM0569  Fragment7 Ramos C314(0.51); C204(0.46); C144(0.83)  LDD2186  [15]
 LDCM0571  Fragment9 Ramos C314(1.05); C204(1.00); C144(0.29)  LDD2188  [15]
 LDCM0107  IAA HeLa N.A.  LDD0221  [6]
 LDCM0022  KB02 HEK-293T C72(1.02)  LDD1492  [14]
 LDCM0023  KB03 HEK-293T C72(0.92)  LDD1497  [14]
 LDCM0024  KB05 OCI-AML-2 C363(1.75)  LDD3370  [4]
 LDCM0109  NEM HeLa N.A.  LDD0223  [6]
 LDCM0557  Nucleophilic fragment 8b MDA-MB-231 C314(0.39)  LDD2151  [5]

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
Mitogen-activated protein kinase 1 (MAPK1) CMGC Ser/Thr protein kinase family P28482
Mitogen-activated protein kinase 14 (MAPK14) CMGC Ser/Thr protein kinase family Q16539
Epidermal growth factor receptor (EGFR) Tyr protein kinase family P00533
Insulin-like growth factor 1 receptor (IGF1R) Tyr protein kinase family P08069
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Beta-arrestin-1 (ARRB1) Arrestin family P49407
Beta-arrestin-2 (ARRB2) Arrestin family P32121
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Mothers against decapentaplegic homolog 2 (SMAD2) Dwarfin/SMAD family Q15796
Other
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Axin-1 (AXIN1) . O15169
Ran-binding protein 3 (RANBP3) . Q9H6Z4

The Drug(s) Related To This Target

Phase 3
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Vp-102 . D01HZQ

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 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.
3 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.
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 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.
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 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
9 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
10 Multiplexed CuAAC Suzuki-Miyaura Labeling for Tandem Activity-Based Chemoproteomic Profiling. Anal Chem. 2021 Feb 2;93(4):2610-2618. doi: 10.1021/acs.analchem.0c04726. Epub 2021 Jan 20.
Mass spectrometry data entry: PXD022279
11 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
12 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.
13 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.
14 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
15 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578