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MetaCyc Enzyme: diphosphoinositol polyphosphate phosphohydrolase 3β

Gene: NUDT11 Accession Number: HS05381 (MetaCyc)

Synonyms: hDIPP3beta, FLJ10628, DIPP3B, APS1, diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 3-beta

Species: Homo sapiens

Summary:
Two closely related but previously uncharacterized proteins similar to NUDT3 were discovered by two labs independently. One lab named them DIPP3α and DIPP3β [Hidaka02] while the other named them hAps2 and hAps1 [Leslie02]. The proteins, which are encoded by the NUDT10 and NUDT11 genes, respectively, differ from each other by a single amino acid. The genes reside on the X chromosome only 152 kbp apart [Hidaka02].

Both proteins are cytoplasmic, and both metabolize diadenosine-polyphosphates and diphosphoinositol polyphosphates. Northern hybridizations revealed strong expression in the testis, medium expression in the brain, and very low expression in other tissues [Hidaka02].

The NUDT11 gene was cloned into an expression vector with a GST-tag and expressed in Escherichia coli , and the recombinant protein was purified [Leslie02]. Activity required Mn2+.

Based on [Leslie02], adenosine dinucleosides were by far the preferred substrates for this enzyme. 5',5'''-diadenosine hexaphosphate and 5',5'''-diadenosine pentaphosphate were hydrolyzed to AMP and adenosine pentaphosphate and adenosine tetraphosphate, respectively. adenosine pentaphosphate was further hydrolyzed to adenosine tetraphosphate and then to ATP, making the final products ATP and AMP. Despite the sequence similarity to NUDT3 and NUDT4, this study found that the enzyme had little activity towards diphosphoinositol phosphates. Surprisingly, the study by [Hidaka02] found exactly the opposite, suggesting that diphosphoinositol phosphates are the preferred in vivo substrates for the enzyme.

The enzyme also has 5-phospho-α-D-ribose 1-diphosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate [Fisher02].

Locations: cytosol

Map Position: [49,120,728 -> 49,121,219]

Molecular Weight of Polypeptide: 18.559 kD (from nucleotide sequence), 25.0 kD (experimental) [Hidaka02 ]

Unification Links: Entrez-Nucleotide:AK001490 , Entrez-Nucleotide:BC009942 , Mint:MINT-3053121 , PhosphoSite:Q96G61 , PhylomeDB:Q96G61 , Pride:Q96G61 , Protein Model Portal:Q96G61 , SMR:Q96G61 , String:9606.ENSP00000365160 , UniProt:Q96G61

Relationship Links: InterPro:IN-FAMILY:IPR000086 , InterPro:IN-FAMILY:IPR015797 , InterPro:IN-FAMILY:IPR020084 , Pfam:IN-FAMILY:PF00293 , Prosite:IN-FAMILY:PS00893 , Prosite:IN-FAMILY:PS51462

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0005829 - cytosol [Leslie02]

Credits:
Created 28-Oct-2009 by Caspi R , SRI International


Enzymatic reaction of: diphosphoinositol pentakisphosphate phosphohydrolase (diphosphoinositol polyphosphate phosphohydrolase 3β)

1D-myoinositol 5-diphosphate 1,2,3,4,6-pentakisphosphate + H2O <=> 1D-myo-inositol 1,2,3,4,5,6-hexakisphosphate + phosphate + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Activators (Unknown Mechanism): Mn2+ [Leslie02]

Kinetic Parameters:

Substrate
Km (μM)
Citations
1D-myoinositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
0.053
[Hidaka02]


Enzymatic reaction of: bis(diphospho)inositol tetrakisphosphate phosphohydrolase (diphosphoinositol polyphosphate phosphohydrolase 3β)

1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate + H2O <=> 1D-myoinositol 5-diphosphate 1,2,3,4,6-pentakisphosphate + phosphate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Activators (Unknown Mechanism): Mn2+ [Leslie02]


Enzymatic reaction of: adenosine tetraphosphate phosphohydrolase (diphosphoinositol polyphosphate phosphohydrolase 3β)

EC Number: 3.6.1.14

adenosine tetraphosphate + H2O <=> ATP + phosphate + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Activators (Unknown Mechanism): Mn2+ [Leslie02]


Enzymatic reaction of: adenosine pentaphosphate phosphohydrolase (diphosphoinositol polyphosphate phosphohydrolase 3β)

EC Number: 3.6.1.14

adenosine pentaphosphate + H2O <=> adenosine tetraphosphate + phosphate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Activators (Unknown Mechanism): Mn2+ [Leslie02]


Enzymatic reaction of: diadenosine pentaphosphate phosphohydrolase (diphosphoinositol polyphosphate phosphohydrolase 3β)

EC Number: 3.6.1.60

5',5'''-diadenosine pentaphosphate + H2O <=> adenosine tetraphosphate + AMP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Activators (Unknown Mechanism): Mn2+ [Leslie02]


Enzymatic reaction of: diadenosine hexaphosphate phosphohydrolase (diphosphoinositol polyphosphate phosphohydrolase 3β)

EC Number: 3.6.1.60

5',5'''-diadenosine hexaphosphate + H2O <=> adenosine pentaphosphate + AMP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Activators (Unknown Mechanism): Mn2+ [Leslie02]

Kinetic Parameters:

Substrate
Km (μM)
Citations
5',5'''-diadenosine hexaphosphate
43.0
[Hidaka02]


Enzymatic reaction of: 5-phosphoribosyl 1-pyrophosphate pyrophosphatase (diphosphoinositol polyphosphate phosphohydrolase 3β)

5-phospho-α-D-ribose 1-diphosphate + H2O <=> α-D-ribose 1,5-bisphosphate + phosphate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

Reversibility of this reaction is unspecified.


References

Fisher02: Fisher DI, Safrany ST, Strike P, McLennan AG, Cartwright JL (2002). "Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate." J Biol Chem 277(49);47313-7. PMID: 12370170

Hidaka02: Hidaka K, Caffrey JJ, Hua L, Zhang T, Falck JR, Nickel GC, Carrel L, Barnes LD, Shears SB (2002). "An adjacent pair of human NUDT genes on chromosome X are preferentially expressed in testis and encode two new isoforms of diphosphoinositol polyphosphate phosphohydrolase." J Biol Chem 277(36);32730-8. PMID: 12105228

Leslie02: Leslie NR, McLennan AG, Safrany ST (2002). "Cloning and characterisation of hAps1 and hAps2, human diadenosine polyphosphate-metabolising Nudix hydrolases." BMC Biochem 3;20. PMID: 12121577


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Nov 28, 2014, biocyc13.