Overview
| Uniprot ID | O95989 |
|---|
| Protein Name | Diphosphoinositol polyphosphate phosphohydrolase 1 |
|---|
| Gene Name | NUDT3 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 5 |
***MMKLKSNQTRTY |
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 (PubMed:10585413, PubMed:12370170, PubMed:9822604). InsP6 (inositol hexakisphosphate) is not a substrate (PubMed:9822604). Acts as a negative regulator of the ERK1/2 pathway (By similarity). 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 (PubMed:10419486, PubMed:12370170). The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A (PubMed:12370170). Also able to hydrolyze 5-phosphoribose 1-diphosphate (PubMed:12370170). Acts as a decapping enzyme that modulates the stability of a subset of mRNAs implicated in cell motility (PubMed:26932476). Hydrolyzes monomethylated capped RNA after both the alpha- and beta-phosphates generating m7GMP + ppRNA and m7GDP + pRNA (PubMed:32727897). Can hydrolyze unmethylated capped RNAs (By similarity). Divalent cations zinc, magnesium and manganese determine its substrate specificity (PubMed:34788624). 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 (PubMed:34788624). Plays an important role in limiting DNA damage and maintaining cell survival upon oxidative stress via its endopolyphosphatase activity (PubMed:34788624)
Protein Sequence
10
MMKLKSNQTR
20
TYDGDGYKKR
30
AACLCFRSES
40
EEEVLLVSSS
50
RHPDRWIVPG
60
GGMEPEEEPS
70
VAAVREVCEE
80
AGVKGTLGRL
90
VGIFENQERK
100
HRTYVYVLIV
110
TEVLEDWEDS
120
VNIGRKREWF
130
KIEDAIKVLQ
140
YHKPVQASYF
150
ETLRQGYSAN
160
NGTPVVATTY
170
SVSAQSSMSG
IR
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0098978 |
glutamatergic synapse |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0140932 |
5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase activity |
| Molecular Function |
GO:0140933 |
5'-(N(7)-methylguanosine 5'-triphospho)-[mRNA] hydrolase activity |
| Molecular Function |
GO:0034431 |
bis(5'-adenosyl)-hexaphosphatase activity |
| Molecular Function |
GO:0034432 |
bis(5'-adenosyl)-pentaphosphatase activity |
| Molecular Function |
GO:0008486 |
diphosphoinositol-polyphosphate diphosphatase activity |
| Molecular Function |
GO:0000298 |
endopolyphosphatase activity |
| Molecular Function |
GO:0052842 |
inositol diphosphate pentakisphosphate diphosphatase activity |
| Molecular Function |
GO:0052840 |
inositol diphosphate tetrakisphosphate diphosphatase activity |
| Molecular Function |
GO:0052848 |
inositol-3,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity |
| Molecular Function |
GO:0052845 |
inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity |
| Molecular Function |
GO:0000287 |
magnesium ion binding |
| Molecular Function |
GO:0030145 |
manganese ion binding |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:1901911 |
adenosine 5'-(hexahydrogen pentaphosphate) catabolic process |
| Biological Process |
GO:0007267 |
cell-cell signaling |
| Biological Process |
GO:1901909 |
diadenosine hexaphosphate catabolic process |
| Biological Process |
GO:1901907 |
diadenosine pentaphosphate catabolic process |
| Biological Process |
GO:0015961 |
diadenosine polyphosphate catabolic process |
| Biological Process |
GO:0071544 |
diphosphoinositol polyphosphate catabolic process |
| Biological Process |
GO:0071543 |
diphosphoinositol polyphosphate metabolic process |
| Biological Process |
GO:0110154 |
RNA decapping |
Reference
[1] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.