DDP1 (YOR163W) encodes the Saccharomyces cerevisiae diphosphoinositol polyphosphate phosphohydrolase, a Nudix (MutT motif) hydrolase orthologous to human DIPP1-3 (NUDT3/4/10/11). Ddp1 removes the beta-phosphate from the pyrophosphate groups of inositol pyrophosphates, converting PP-InsP5 (IP7) back to IP6 and [PP]2-InsP4 (IP8) to PP-InsP5, thereby opposing the Kcs1 and Vip1 kinases. The same active site hydrolyses diadenosine hexa- and pentaphosphates (Ap6A preferred, Ap5A) and adenosine tetra-/pentaphosphates, and Ddp1 also has inorganic polyphosphate endopolyphosphatase activity and in vitro mRNA decapping activity. It requires divalent cations (Mg2+, Mn2+, Zn2+) and localises to the cytoplasm and nucleus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000298 endopolyphosphatase activity | IDA PMID:21775424 Identification of an evolutionarily conserved family of inor... | ACCEPT | Summary: IDA from Lonetti et al. 2011: Ddp1 has robust inorganic polyphosphate endopolyphosphohydrolase activity, conserved in human DIPP1-3. A genuine in vitro activity of this Nudix hydrolase; its in vivo contribution relative to Ppn1/Ppn2/Ppx1 is less clear. Supporting Evidence: PMID:21775424 we demonstrate that DDP1, encoding diadenosine and diphosphoinositol phosphohydrolase, possesses a robust poly-P endopolyphosphohydrolase activity |
| GO:0000298 endopolyphosphatase activity | IDA PMID:31175919 Ppn2 endopolyphosphatase overexpressed in Saccharomyces cere... | ACCEPT | Summary: IDA from Andreeva et al. 2019: Ddp1 purified from an overexpressing yeast strain shows endopolyphosphatase (and very low exopolyphosphatase) activity, distinct from Ppn1/Ppn2. Supporting Evidence: PMID:31175919 Ppn2, Ppn1, and Ddp1 had endopolyphosphatase activities, whereas Ppx1 did not. |
| GO:0000298 endopolyphosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (RHEA:22452 / EC 3.6.1.10) from the UniProt catalytic-activity annotation, itself based on Andreeva et al. 2019. Correct. Supporting Evidence: PMID:31175919 Ppn2, Ppn1, and Ddp1 had endopolyphosphatase activities, whereas Ppx1 did not. |
| GO:0005634 nucleus | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA from the genome-wide GFP localization study; Ddp1-GFP was scored in cytoplasm and nucleus. Plausible for a small soluble Nudix hydrolase. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories file:yeast/DDP1/DDP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in nucleus) from PTN000290326 (human DIPP1/NUDT3, Drosophila Aps). Consistent with the yeast GFP data. Supporting Evidence: file:yeast/DDP1/DDP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0191), from the GFP study. Supporting Evidence: file:yeast/DDP1/DDP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA from the genome-wide GFP localization study (cytoplasm). Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories file:yeast/DDP1/DDP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in cytoplasm) from PTN000290326 (human DIPP1, Arabidopsis NUDT13, etc.). Consistent with yeast GFP data. Supporting Evidence: file:yeast/DDP1/DDP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0086), from the GFP study. Supporting Evidence: file:yeast/DDP1/DDP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-402 (inositol phosphate biosynthesis) assigning the PP-InsP hydrolysis reactions to the cytosol. Consistent with cytoplasmic GFP signal. Supporting Evidence: file:yeast/DDP1/DDP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus |
| GO:0006798 polyphosphate catabolic process | IDA PMID:21775424 Identification of an evolutionarily conserved family of inor... | KEEP AS NON CORE | Summary: IDA from Lonetti et al. 2011 for polyphosphate catabolic process, based on the in vitro endopolyphosphatase activity of Ddp1. The activity is real, but the major yeast polyP-degrading enzymes are Ppn1, Ppn2 and Ppx1; Ddp1's physiological share of polyP turnover is not established, so this is kept as a non-core process. Supporting Evidence: PMID:21775424 we demonstrate that DDP1, encoding diadenosine and diphosphoinositol phosphohydrolase, possesses a robust poly-P endopolyphosphohydrolase activity PMID:31175919 Ppn2, Ppn1, and Ddp1 had endopolyphosphatase activities, whereas Ppx1 did not. |
| GO:0008486 diphosphoinositol-polyphosphate diphosphatase activity | IDA PMID:10419486 The diadenosine hexaphosphate hydrolases from Schizosaccharo... | ACCEPT | Summary: IDA from Safrany et al. 1999: purified Ddp1 (YOR163w) efficiently hydrolyses diphosphorylated inositol polyphosphates (PP-InsP5, [PP]2-InsP4). Core activity, defining the DIPP (diphosphoinositol polyphosphate phosphohydrolase) subfamily. Supporting Evidence: PMID:10419486 we have now discovered that they have an important additional function, namely, the efficient hydrolysis of diphosphorylated inositol polyphosphates file:yeast/DDP1/DDP1-uniprot.txt cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 |
| GO:0008486 diphosphoinositol-polyphosphate diphosphatase activity | IEA GO_REF:0000003 | ACCEPT | Summary: IEA from EC 3.6.1.52 mapping. Correct. Supporting Evidence: file:yeast/DDP1/DDP1-uniprot.txt Reaction=diphospho-myo-inositol polyphosphate + H2O = myo-inositol |
| GO:0008486 diphosphoinositol-polyphosphate diphosphatase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-402: Ddp1 hydrolyses [PP]2-IP4 to PP-IP5 and PP-IP5 to IP6 (EC 3.6.1.52). Correct. Supporting Evidence: PMID:10419486 we have now discovered that they have an important additional function, namely, the efficient hydrolysis of diphosphorylated inositol polyphosphates file:yeast/DDP1/DDP1-uniprot.txt cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 |
| GO:0015961 diadenosine polyphosphate catabolic process | IDA PMID:10085096 The Saccharomyces cerevisiae YOR163w gene encodes a diadenos... | ACCEPT | Summary: IDA from Cartwright & McLennan 1999: recombinant Ddp1 hydrolyses Ap6A (preferred) and Ap5A; diadenosine polyphosphate catabolism is a direct consequence of its own catalysis. Supporting Evidence: PMID:10085096 we have shown the product to be a (di)adenosine polyphosphate hydrolase with a previously undescribed substrate specificity PMID:10085096 Its function may be to eliminate potentially toxic dinucleoside polyphosphates during sporulation. |
| GO:0015961 diadenosine polyphosphate catabolic process | IDA PMID:9450008 The MutT motif-containing ORF163w protein from the yeast Sac... | ACCEPT | Summary: IDA from Cartwright & McLennan 1997 (abstract not available in cache): first report that ORF YOR163w encodes a (di)nucleoside polyphosphate hydrolase. Consistent with the later detailed characterisation. Supporting Evidence: PMID:9450008 encodes a (di)nucleoside polyphosphate hydrolase |
| GO:0016462 pyrophosphatase activity | IEA GO_REF:0000002 | MODIFY | Summary: IEA from InterPro IPR047198 (DDP-type Nudix domain) to pyrophosphatase activity. Correct but uninformative; Ddp1's characterised pyrophosphatase activity is hydrolysis of the diphosphate (pyrophosphate) groups of inositol pyrophosphates and diadenosine polyphosphates. Proposed replacements: diphosphoinositol-polyphosphate diphosphatase activity Supporting Evidence: PMID:10419486 we have now discovered that they have an important additional function, namely, the efficient hydrolysis of diphosphorylated inositol polyphosphates |
| GO:0032958 inositol phosphate biosynthetic process | RCA GO_REF:0000123 | MODIFY | Summary: RCA from YeastPathways PWY3O-402 (inositol phosphate biosynthesis superpathway). Ddp1 removes the beta-phosphate from inositol pyrophosphates (PP-IP5 -> IP6, [PP]2-IP4 -> PP-IP5), i.e. it degrades the diphosphoinositol polyphosphates rather than building inositol phosphates; the biosynthetic process term is inherited from the superpathway. The correct process is diphosphoinositol polyphosphate catabolic process. Proposed replacements: diphosphoinositol polyphosphate catabolic process Supporting Evidence: PMID:10419486 we have now discovered that they have an important additional function, namely, the efficient hydrolysis of diphosphorylated inositol polyphosphates file:yeast/DDP1/DDP1-uniprot.txt cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 |
| GO:0034431 bis(5'-adenosyl)-hexaphosphatase activity | EXP PMID:10419486 The diadenosine hexaphosphate hydrolases from Schizosaccharo... | ACCEPT | Summary: EXP from Safrany et al. 1999: purified Ddp1 hydrolyses Ap6A as well as PP-InsPs. Core activity. Supporting Evidence: PMID:10419486 we have now discovered that they have an important additional function, namely, the efficient hydrolysis of diphosphorylated inositol polyphosphates |
| GO:0034431 bis(5'-adenosyl)-hexaphosphatase activity | IDA PMID:10085096 The Saccharomyces cerevisiae YOR163w gene encodes a diadenos... | ACCEPT | Summary: IDA from Cartwright & McLennan 1999: Ap6A is the preferred substrate (Km 56 uM). Supporting Evidence: PMID:10085096 we have shown the product to be a (di)adenosine polyphosphate hydrolase with a previously undescribed substrate specificity PMID:10085096 is the preferred substrate, and hydrolysis in H218O shows that ADP and adenosine 5'-tetraphosphate are produced |
| GO:0034431 bis(5'-adenosyl)-hexaphosphatase activity | IDA PMID:9450008 The MutT motif-containing ORF163w protein from the yeast Sac... | ACCEPT | Summary: IDA from Cartwright & McLennan 1997; YOR163w encodes a (di)nucleoside polyphosphate hydrolase. Supporting Evidence: PMID:9450008 encodes a (di)nucleoside polyphosphate hydrolase |
| GO:0034431 bis(5'-adenosyl)-hexaphosphatase activity | IEA GO_REF:0000116 | ACCEPT | Summary: IEA (RHEA:32047) from UniProt catalytic activity. Correct. Supporting Evidence: PMID:10085096 is the preferred substrate, and hydrolysis in H218O shows that ADP and adenosine 5'-tetraphosphate are produced |
| GO:0034432 bis(5'-adenosyl)-pentaphosphatase activity | IDA PMID:10085096 The Saccharomyces cerevisiae YOR163w gene encodes a diadenos... | ACCEPT | Summary: IDA from Cartwright & McLennan 1999: Ap5A is also hydrolysed. Supporting Evidence: PMID:10085096 adenosine 5'-pentaphosphate, and adenosine 5'-tetraphosphate are also substrates |
| GO:0034432 bis(5'-adenosyl)-pentaphosphatase activity | IDA PMID:9450008 The MutT motif-containing ORF163w protein from the yeast Sac... | ACCEPT | Summary: IDA from Cartwright & McLennan 1997 (abstract not cached); consistent with the later characterisation showing Ap5A hydrolysis. Supporting Evidence: PMID:9450008 encodes a (di)nucleoside polyphosphate hydrolase |
| GO:0052845 inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000290326 (human DIPP1/NUDT3, mouse, rat, S. pombe Aps1). The DIPP subfamily removes the 5-beta-phosphate of 5-PP-InsP5 regenerating IP6; Ddp1 is shown to cleave beta-phosphates from PP-InsP5, so the inherited specific activity is consistent. Supporting Evidence: file:yeast/DDP1/DDP1-uniprot.txt cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 PMID:10419486 we have now discovered that they have an important additional function, namely, the efficient hydrolysis of diphosphorylated inositol polyphosphates |
| GO:0071544 diphosphoinositol polyphosphate catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000290326 (human DIPP1). Correct and core; Ddp1 is the main yeast inositol pyrophosphate phosphatase of the Nudix family. Supporting Evidence: PMID:10419486 we have now discovered that they have an important additional function, namely, the efficient hydrolysis of diphosphorylated inositol polyphosphates |
| GO:1901909 diadenosine hexaphosphate catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000290326 (human DIPP1, S. pombe Aps1). Correct; Ap6A is the preferred dinucleotide substrate of Ddp1. Supporting Evidence: PMID:10085096 we have shown the product to be a (di)adenosine polyphosphate hydrolase with a previously undescribed substrate specificity |
| GO:1990174 phosphodiesterase decapping endonuclease activity | IDA PMID:23353937 Multiple Nudix family proteins possess mRNA decapping activi... | KEEP AS NON CORE | Summary: IDA from Song et al. 2013: Ddp1 shows mRNA decapping activity in vitro on capped RNA, like its mouse homologue Nudt3. This is an in vitro observation; no in vivo role of Ddp1 in mRNA decay has been shown. The curator's choice of the phosphodiesterase decapping endonuclease term (release of intact cap) versus a pyrophosphatase-type decapping term cannot be checked from the abstract; retained as non-core. Supporting Evidence: PMID:23353937 revealed that the yeast homolog of Nudt3, Ddp1p, also possesses decapping activity in vitro |
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Download this section (compressed HTML)Q: Which of Ddp1's substrates (inositol pyrophosphates, Ap6A/Ap5A, polyphosphate, capped RNA) is physiologically dominant, and do they compete in vivo?
Q: Does Ddp1 preferentially hydrolyse the 1-PP (Vip1) or 5-PP (Kcs1) position of IP7/IP8 in yeast?
Experiment: Quantify IP7/IP8 isomers (CE-MS), Ap6A and polyP in ddp1 null and catalytic-dead strains, alone and combined with ppn1 ppn2 ppx1, to define in vivo substrates.
Diadenosine and diphosphoinositol polyphosphate phosphatase; hydrolyzes diphosphorylated inositol polyphosphates and diadenosine polyphosphates; high specificity for diadenosine hexa- and pentaphosphates; contains endopolyphosphatase activity with a high affinity for polyphosphates, an activity also observed for its human DIPP homologs; possesses mRNA decapping activity; nudix hydrolase family member; protein abundance increases in response to DNA replication stress
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