Details of the Target

General Information of Target

Target ID LDTP01734
Target Name Diphosphoinositol polyphosphate phosphohydrolase 1 (NUDT3)
Gene Name NUDT3
Gene ID 11165
Synonyms
DIPP; DIPP1; Diphosphoinositol polyphosphate phosphohydrolase 1; DIPP-1; EC 3.6.1.52; Diadenosine hexaphosphate hydrolase; Ap6A hydrolase; EC 3.6.1.61; Endopolyphosphatase; EC 3.6.1.10; Nucleoside diphosphate-linked moiety X motif 3; Nudix motif 3; m7GpppN-mRNA hydrolase; EC 3.6.1.62; m7GpppX diphosphatase; EC 3.6.1.59
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MMKLKSNQTRTYDGDGYKKRAACLCFRSESEEEVLLVSSSRHPDRWIVPGGGMEPEEEPS
VAAVREVCEEAGVKGTLGRLVGIFENQERKHRTYVYVLIVTEVLEDWEDSVNIGRKREWF
KIEDAIKVLQYHKPVQASYFETLRQGYSANNGTPVVATTYSVSAQSSMSGIR
Target Type
Literature-reported
Target Bioclass
Enzyme
Family
Nudix hydrolase family, DIPP subfamily
Subcellular location
Cytoplasm
Function
Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. InsP6 (inositol hexakisphosphate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) and diadenosine 5',5'''- P1,P5-pentaphosphate (Ap5A) being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Acts as a decapping enzyme that modulates the stability of a subset of mRNAs implicated in cell motility. Hydrolyzes monomethylated capped RNA after both the alpha- and beta-phosphates generating m7GMP + ppRNA and m7GDP + pRNA. Can hydrolyze unmethylated capped RNAs. Divalent cations zinc, magnesium and manganese determine its substrate specificity. Exhibits diphosphoinositol polyphosphate phosphohydrolase in the presence of magnesium ions, diadenosine hexaphosphate hydrolase activity in the presence of manganese ions and endopolyphosphatase activity in the presence of zinc ions. Plays an important role in limiting DNA damage and maintaining cell survival upon oxidative stress via its endopolyphosphatase activity.
TTD ID
T26748
Uniprot ID
O95989
DrugMap ID
TT69I0C
Ensemble ID
ENST00000607016.2
HGNC ID
HGNC:8050
ChEMBL ID
CHEMBL4295689

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 11 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C68(0.71)  LDD3310  [1]
AHL-Pu-1
 Probe Info  		C68(2.03)  LDD0171  [2]
HHS-475
 Probe Info  		Y131(0.86)  LDD0264  [3]
ATP probe
 Probe Info  		K133(0.00); K18(0.00)  LDD0199  [4]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [5]
IA-alkyne
 Probe Info  		N.A.  LDD0036  [5]
Lodoacetamide azide
 Probe Info  		C23(0.00); C25(0.00); C68(0.00)  LDD0037  [5]
Acrolein
 Probe Info  		N.A.  LDD0217  [6]
Methacrolein
 Probe Info  		N.A.  LDD0218  [6]
NAIA_5
 Probe Info  		N.A.  LDD2223  [7]
HHS-465
 Probe Info  		N.A.  LDD2240  [8]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0026  4SU-RNA+native RNA DM93 C68(2.03)  LDD0171  [2]
 LDCM0214  AC1 HEK-293T C68(0.99)  LDD1507  [9]
 LDCM0259  AC14 HEK-293T C68(1.10)  LDD1512  [9]
 LDCM0276  AC17 HEK-293T C68(0.83)  LDD1515  [9]
 LDCM0281  AC21 HEK-293T C68(0.92)  LDD1520  [9]
 LDCM0282  AC22 HEK-293T C68(0.96)  LDD1521  [9]
 LDCM0284  AC24 HEK-293T C68(0.99)  LDD1523  [9]
 LDCM0285  AC25 HEK-293T C68(0.93)  LDD1524  [9]
 LDCM0289  AC29 HEK-293T C68(0.97)  LDD1528  [9]
 LDCM0291  AC30 HEK-293T C68(0.95)  LDD1530  [9]
 LDCM0293  AC32 HEK-293T C68(0.98)  LDD1532  [9]
 LDCM0294  AC33 HEK-293T C68(0.81)  LDD1533  [9]
 LDCM0298  AC37 HEK-293T C68(1.06)  LDD1537  [9]
 LDCM0299  AC38 HEK-293T C68(1.02)  LDD1538  [9]
 LDCM0302  AC40 HEK-293T C68(0.93)  LDD1541  [9]
 LDCM0303  AC41 HEK-293T C68(0.87)  LDD1542  [9]
 LDCM0307  AC45 HEK-293T C68(0.97)  LDD1546  [9]
 LDCM0308  AC46 HEK-293T C68(0.83)  LDD1547  [9]
 LDCM0310  AC48 HEK-293T C68(0.98)  LDD1549  [9]
 LDCM0311  AC49 HEK-293T C68(0.90)  LDD1550  [9]
 LDCM0312  AC5 HEK-293T C68(1.00)  LDD1551  [9]
 LDCM0316  AC53 HEK-293T C68(0.97)  LDD1555  [9]
 LDCM0317  AC54 HEK-293T C68(0.97)  LDD1556  [9]
 LDCM0319  AC56 HEK-293T C68(1.02)  LDD1558  [9]
 LDCM0320  AC57 HEK-293T C68(0.95)  LDD1559  [9]
 LDCM0323  AC6 HEK-293T C68(0.92)  LDD1562  [9]
 LDCM0325  AC61 HEK-293T C68(0.92)  LDD1564  [9]
 LDCM0326  AC62 HEK-293T C68(0.92)  LDD1565  [9]
 LDCM0328  AC64 HEK-293T C68(1.02)  LDD1567  [9]
 LDCM0345  AC8 HEK-293T C68(0.98)  LDD1569  [9]
 LDCM0248  AKOS034007472 HEK-293T C68(1.00)  LDD1511  [9]
 LDCM0356  AKOS034007680 HEK-293T C68(0.92)  LDD1570  [9]
 LDCM0275  AKOS034007705 HEK-293T C68(0.94)  LDD1514  [9]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [6]
 LDCM0367  CL1 HEK-293T C68(0.90)  LDD1571  [9]
 LDCM0368  CL10 HEK-293T C68(1.09)  LDD1572  [9]
 LDCM0369  CL100 HEK-293T C68(0.79)  LDD1573  [9]
 LDCM0370  CL101 HEK-293T C68(0.87)  LDD1574  [9]
 LDCM0371  CL102 HEK-293T C68(0.85)  LDD1575  [9]
 LDCM0373  CL104 HEK-293T C68(0.91)  LDD1577  [9]
 LDCM0374  CL105 HEK-293T C68(0.75)  LDD1578  [9]
 LDCM0375  CL106 HEK-293T C68(0.80)  LDD1579  [9]
 LDCM0377  CL108 HEK-293T C68(1.27)  LDD1581  [9]
 LDCM0378  CL109 HEK-293T C68(0.96)  LDD1582  [9]
 LDCM0380  CL110 HEK-293T C68(0.91)  LDD1584  [9]
 LDCM0382  CL112 HEK-293T C68(1.11)  LDD1586  [9]
 LDCM0383  CL113 HEK-293T C68(0.94)  LDD1587  [9]
 LDCM0384  CL114 HEK-293T C68(0.88)  LDD1588  [9]
 LDCM0386  CL116 HEK-293T C68(0.77)  LDD1590  [9]
 LDCM0387  CL117 HEK-293T C68(0.81)  LDD1591  [9]
 LDCM0388  CL118 HEK-293T C68(0.86)  LDD1592  [9]
 LDCM0390  CL12 HEK-293T C68(0.89)  LDD1594  [9]
 LDCM0391  CL120 HEK-293T C68(0.99)  LDD1595  [9]
 LDCM0392  CL121 HEK-293T C68(0.88)  LDD1596  [9]
 LDCM0393  CL122 HEK-293T C68(0.83)  LDD1597  [9]
 LDCM0395  CL124 HEK-293T C68(0.83)  LDD1599  [9]
 LDCM0396  CL125 HEK-293T C68(0.84)  LDD1600  [9]
 LDCM0397  CL126 HEK-293T C68(0.85)  LDD1601  [9]
 LDCM0399  CL128 HEK-293T C68(0.98)  LDD1603  [9]
 LDCM0400  CL13 HEK-293T C68(0.87)  LDD1604  [9]
 LDCM0401  CL14 HEK-293T C68(1.07)  LDD1605  [9]
 LDCM0403  CL16 HEK-293T C68(1.09)  LDD1607  [9]
 LDCM0404  CL17 HEK-293T C68(0.77)  LDD1608  [9]
 LDCM0407  CL2 HEK-293T C68(1.00)  LDD1611  [9]
 LDCM0409  CL21 HEK-293T C68(0.85)  LDD1613  [9]
 LDCM0410  CL22 HEK-293T C68(1.04)  LDD1614  [9]
 LDCM0412  CL24 HEK-293T C68(0.97)  LDD1616  [9]
 LDCM0413  CL25 HEK-293T C68(0.92)  LDD1617  [9]
 LDCM0414  CL26 HEK-293T C68(0.85)  LDD1618  [9]
 LDCM0416  CL28 HEK-293T C68(1.13)  LDD1620  [9]
 LDCM0417  CL29 HEK-293T C68(0.92)  LDD1621  [9]
 LDCM0422  CL33 HEK-293T C68(0.80)  LDD1626  [9]
 LDCM0423  CL34 HEK-293T C68(0.96)  LDD1627  [9]
 LDCM0425  CL36 HEK-293T C68(1.04)  LDD1629  [9]
 LDCM0426  CL37 HEK-293T C68(0.99)  LDD1630  [9]
 LDCM0429  CL4 HEK-293T C68(0.80)  LDD1633  [9]
 LDCM0430  CL40 HEK-293T C68(1.04)  LDD1634  [9]
 LDCM0431  CL41 HEK-293T C68(0.90)  LDD1635  [9]
 LDCM0435  CL45 HEK-293T C68(0.80)  LDD1639  [9]
 LDCM0436  CL46 HEK-293T C68(0.92)  LDD1640  [9]
 LDCM0438  CL48 HEK-293T C68(1.01)  LDD1642  [9]
 LDCM0439  CL49 HEK-293T C68(0.95)  LDD1643  [9]
 LDCM0440  CL5 HEK-293T C68(0.85)  LDD1644  [9]
 LDCM0441  CL50 HEK-293T C68(0.85)  LDD1645  [9]
 LDCM0443  CL52 HEK-293T C68(0.85)  LDD1646  [9]
 LDCM0444  CL53 HEK-293T C68(0.82)  LDD1647  [9]
 LDCM0448  CL57 HEK-293T C68(0.83)  LDD1651  [9]
 LDCM0449  CL58 HEK-293T C68(0.93)  LDD1652  [9]
 LDCM0452  CL60 HEK-293T C68(0.91)  LDD1655  [9]
 LDCM0453  CL61 HEK-293T C68(1.08)  LDD1656  [9]
 LDCM0454  CL62 HEK-293T C68(0.82)  LDD1657  [9]
 LDCM0456  CL64 HEK-293T C68(0.82)  LDD1659  [9]
 LDCM0457  CL65 HEK-293T C68(0.89)  LDD1660  [9]
 LDCM0461  CL69 HEK-293T C68(0.87)  LDD1664  [9]
 LDCM0463  CL70 HEK-293T C68(0.93)  LDD1666  [9]
 LDCM0465  CL72 HEK-293T C68(1.05)  LDD1668  [9]
 LDCM0466  CL73 HEK-293T C68(0.75)  LDD1669  [9]
 LDCM0467  CL74 HEK-293T C68(0.88)  LDD1670  [9]
 LDCM0469  CL76 HEK-293T C68(0.98)  LDD1672  [9]
 LDCM0470  CL77 HEK-293T C68(0.87)  LDD1673  [9]
 LDCM0475  CL81 HEK-293T C68(1.04)  LDD1678  [9]
 LDCM0476  CL82 HEK-293T C68(1.01)  LDD1679  [9]
 LDCM0478  CL84 HEK-293T C68(0.88)  LDD1681  [9]
 LDCM0479  CL85 HEK-293T C68(0.80)  LDD1682  [9]
 LDCM0480  CL86 HEK-293T C68(0.98)  LDD1683  [9]
 LDCM0482  CL88 HEK-293T C68(0.86)  LDD1685  [9]
 LDCM0483  CL89 HEK-293T C68(0.90)  LDD1686  [9]
 LDCM0484  CL9 HEK-293T C68(0.89)  LDD1687  [9]
 LDCM0488  CL93 HEK-293T C68(0.90)  LDD1691  [9]
 LDCM0489  CL94 HEK-293T C68(0.85)  LDD1692  [9]
 LDCM0491  CL96 HEK-293T C68(0.86)  LDD1694  [9]
 LDCM0492  CL97 HEK-293T C68(0.82)  LDD1695  [9]
 LDCM0493  CL98 HEK-293T C68(0.91)  LDD1696  [9]
 LDCM0427  Fragment51 HEK-293T C68(1.05)  LDD1631  [9]
 LDCM0116  HHS-0101 DM93 Y131(0.86)  LDD0264  [3]
 LDCM0117  HHS-0201 DM93 Y131(0.77)  LDD0265  [3]
 LDCM0118  HHS-0301 DM93 Y131(0.79)  LDD0266  [3]
 LDCM0119  HHS-0401 DM93 Y131(0.75)  LDD0267  [3]
 LDCM0120  HHS-0701 DM93 Y131(0.80)  LDD0268  [3]
 LDCM0107  IAA HeLa N.A.  LDD0221  [6]
 LDCM0022  KB02 HEK-293T C68(0.95)  LDD1492  [9]
 LDCM0023  KB03 HEK-293T C68(1.00)  LDD1497  [9]
 LDCM0024  KB05 COLO792 C68(0.71)  LDD3310  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
DNA damage-inducible transcript 4-like protein (DDIT4L) DDIT4 family Q96D03

References

1 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
2 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
3 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.
4 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.
5 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
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 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
8 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
9 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