Target Information
| Target General Information | Top | |||||
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| Target ID |
T26748
(Former ID: TTDR00710)
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| Target Name |
Diphosphoinositol polyphosphate phosphohydrolase 2 (NUDT3)
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| Synonyms |
NUDT3; Diphosphoinositol polyphosphate phosphohydrolase; DIPP2
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| Gene Name |
NUDT3
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| Target Type |
Literature-reported target
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[1] | ||||
| 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 hexakisphophate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with Ap6A and 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.
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| BioChemical Class |
Acid anhydrides hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.6.1.52
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| Sequence |
MMKLKSNQTRTYDGDGYKKRAACLCFRSESEEEVLLVSSSRHPDRWIVPGGGMEPEEEPS
VAAVREVCEEAGVKGTLGRLVGIFENQERKHRTYVYVLIVTEVLEDWEDSVNIGRKREWF KIEDAIKVLQYHKPVQASYFETLRQGYSANNGTPVVATTYSVSAQSSMSGIR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Myo-inositol hexaphosphate | Ligand Info | |||||
| Structure Description | Human Diphosphoinositol polyphosphate phosphohydrolase 1 | PDB:2FVV | ||||
| Method | X-ray diffraction | Resolution | 1.25 Å | Mutation | No | [2] |
| PDB Sequence |
QTRTYDGDGY
17 KKRAACLCFR27 SESEEEVLLV37 SSSRHPDRWI47 VPGGGMEPEE57 EPSVAAVREV 67 CEEAGVKGTL77 GRLVGIFENQ87 ERKHRTYVYV97 LIVTEVLEDW107 EDSVNIGRKR 117 EWFKIEDAIK127 VLQYHKPVQA137 SYFET
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: (1R,2S,3R,4R,5S,6S)-4-hydroxy-2,3,5,6-tetrakis(phosphonooxy)cyclohexyl trihydrogen diphosphate | Ligand Info | |||||
| Structure Description | Diphosphoinositol polyphosphate phosphohydrolase 1 (DIPP1/NUDT3) in complex with 3-diphosphoinositol 1,2,4,5-tetrakisphosphate (3-PP-IP4), Mg and Fluoride ion | PDB:7TN4 | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [3] |
| PDB Sequence |
TRTYDGDGYK
18 KRAACLCFRS28 ESEEEVLLVS38 SSRHPDRWIV48 PGGGMEPEEE58 PSVAAVREVC 68 EEAGVKGTLG78 RLVGIFENQE88 RKHRTYVYVL98 IVTEVLEDWE108 DSVNIGRKRE 118 WFKIEDAIKV128 LQYHKPVQAS138 YFET
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| References | Top | |||||
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| REF 1 | Molecular cloning of a novel isoform of diphosphoinositol polyphosphate phosphohydrolase: a potential target of lithium therapy. Neuropsychopharmacology. 2001 Jun;24(6):640-51. | |||||
| REF 2 | Crystal structure of human diphosphoinositol phosphatase 1. Proteins. 2009 Oct;77(1):242-6. | |||||
| REF 3 | Structural and catalytic analyses of the InsP(6) kinase activities of higher plant ITPKs. FASEB J. 2022 Jul;36(7):e22380. | |||||
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