Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 3.6.1.17 - bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) and Organism(s) Homo sapiens and UniProt Accession P50583

for references in articles please use BRENDA:EC3.6.1.17
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments
Also acts on bis(5'-xanthosyl)-tetraphosphate and, more slowly, on bis(5'-adenosyl)-tetraphosphate and bis(5'-uridyl)-tetraphosphate [cf. EC 3.6.1.41 bis(5'-nucleosyl)-tetraphosphatase (symmetrical)]
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
UNIPROT: P50583
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
ap4a hydrolase, nudt2, diadenosine tetraphosphatase, enpp4, ap4aase, ndx-4, ct771, dinucleoside tetraphosphatase, ap4a-hydrolase, dipp1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ap4A-hydrolase
-
asymmetrical diadenosine tetraphosphate hydrolase
-
(asymmetrical) dinucleoside tetraphosphatase
-
-
Ap4A hydrolase
AP4AASE
-
-
-
-
asymmetrical Ap4A hydrolase
-
-
bis(5'-adenosyl)-tetraphosphatase
-
-
-
-
bis(5'-guanosyl)-tetraphosphatase
-
-
-
-
bis(5'-nucleosyl)-tetraphosphatase (asymmetrical)
-
-
bis(5-guanosyl)tetraphosphatase
-
-
-
-
Diadenosine 5',5'''-P1,P4-tetraphosphate asymmetrical hydrolase
-
-
-
-
diadenosine P1,P4-tetraphosphatase
-
-
-
-
Diadenosine tetraphosphatase
-
-
-
-
diguanosine tetraphosphatase
-
-
-
-
diguanosinetetraphosphatase (asymmetrical)
-
-
-
-
diguanosinetetraphosphate guanosylhydrolase
-
-
-
-
dinucleoside tetraphosphatase
-
-
-
-
dinucleosidetetraphosphatase (asymmetrical)
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphorous acid anhydride hydrolysis
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
P1,P4-bis(5'-nucleosyl)-tetraphosphate nucleotidohydrolase
Also acts on bis(5'-xanthosyl)-tetraphosphate and, more slowly, on bis(5'-adenosyl)-tetraphosphate and bis(5'-uridyl)-tetraphosphate [cf. EC 3.6.1.41 bis(5'-nucleosyl)-tetraphosphatase (symmetrical)]
CAS REGISTRY NUMBER
COMMENTARY hide
37289-29-5
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
P1,P4-bis(5'-adenosyl) tetraphosphate + H2O
ATP + AMP
show the reaction diagram
-
-
-
?
2'-deoxyadenosine adenosine tetraphosphate + H2O
ATP + 2'-dAMP + 2'-dATP + AMP
show the reaction diagram
-
-
80% dAMP, 20% AMP
?
A-5'-p-alpha,beta,alpha',beta'-bis(oxymethylene)p-5'-A + H2O
2 alpha,beta-oxymethylene-ADP
show the reaction diagram
-
diadenosine polyphosphate analog
-
-
?
Ap4A + H2O
?
show the reaction diagram
-
-
-
-
?
Ap5A + H2O
?
show the reaction diagram
-
-
-
-
?
Ap6A + H2O
Ap5 + AMP
show the reaction diagram
-
-
-
-
?
betabeta'-methyleneoxy-Ap4A + H2O
AMP + beta,gamma-methyleneoxy-ATP
show the reaction diagram
-
diadenosine polyphosphate analog
-
-
?
di-2,6-diaminopurine beta-D-ribofuranoside tetraphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
diadenosine 5',5''-P1,P4-tetraphosphate + H2O
ATP + AMP
show the reaction diagram
-
-
-
-
?
diadenosine 5',5''-P1,P5-pentaphosphate + H2O
adenosine 5'-tetraphosphate + AMP
show the reaction diagram
-
-
-
-
?
diadenosine 5',5'-P1,P4-tetraphosphate + H2O
ATP + AMP
show the reaction diagram
-
-
-
-
?
P1,P3-bis(5'-adenosyl)triphosphate + H2O
AMP + ADP
show the reaction diagram
-
-
-
?
P1,P4-bis(5'-(2'-deoxy)adenosyl) tetraphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
P1,P4-bis(5'-adenosyl) tetraphosphate + H2O
ATP + AMP
show the reaction diagram
P1,P4-bis(5'-adenosyl)tetraphosphate + H2O
AMP + ATP
show the reaction diagram
-
-
-
?
P1,P4-bis(5'-guanosyl)tetraphosphate + H2O
GTP + GMP
show the reaction diagram
-
-
-
?
P1,P5-bis(5'-adenosyl) pentaphosphate + H2O
ADP + ATP
show the reaction diagram
-
-
-
-
?
P1,P5-bis(5'-adenosyl)pentaphosphate + H2O
AMP + adenosine 5'-tetraphosphate
show the reaction diagram
-
-
-
?
additional information
?
-
enzyme is a diphosphoinositol polyphosphate phosphohydrolase, EC 3.6.1.52
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
P1,P4-bis(5'-adenosyl) tetraphosphate + H2O
ATP + AMP
show the reaction diagram
-
-
-
?
diadenosine 5',5'-P1,P4-tetraphosphate + H2O
ATP + AMP
show the reaction diagram
-
-
-
-
?
P1,P4-bis(5'-adenosyl) tetraphosphate + H2O
ATP + AMP
show the reaction diagram
P1,P4-bis(5'-guanosyl)tetraphosphate + H2O
GTP + GMP
show the reaction diagram
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
activated by physiological concentration, maximal activity at 2 mM
Co2+
-
60% of activity
Zn2+
-
50% of activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2,3,4-tetra(adenosine-5'-O-phospho)erythritol
-
-
1,2,3,4-tetra(adenosine-5'-O-phosphorothio)erythritol
-
-
1,2,3-tri(adenosine-5'-O-phosphorothio)glycerol
-
-
1,3-di(adenosine-5'-O-phospho)-2-phospho-glycerol
-
-
1,3-di(adenosine-5'-O-phospho)-2-phosphorothio-glycerol
-
-
1,3-di(adenosine-5'-O-phospho)glycerol
-
-
1,4-di(adenosine-5'-O-phospho)erythritol
-
-
1,4-di(adenosine-5'-O-phosphorothio)erythritol
-
-
A-5'-p-alpha,beta,alpha',beta'-bis(oxymethylene)p-5'-A
-
competitive inhibitor
A-5'-p-beta,beta'-methyleneoxy-p-5'-A
-
competitive inhibitor
adenosine 5'-tetraphosphate
Ca2+
-
Ki: 0.3 mM
di(adenosine-5'-O-phosphorothio)-di(adenosine-5'-phospho)pentaerythritol
-
-
diadenosine 5',5'''-P1,P4-tetraphosphate
-
-
diadenosine triphosphate
-
competitive, also phosphonate analogues of the substance
fluoride
guanosine 5'-tetraphosphate
-
Ki: 0.01 mM
inositol 1-[(phosphorylmethyl)phosphonic acid]-2,3,4,5,6-pentaphosphate
competitive
inositol 1-[(phosphorylmethyl)phosphonic acid]-2,3,5,6-tetraphosphate
competitive
inositol 4-butyl-1-[(phosphorylmethyl)phosphonic acid]-2,3,5,6-tetraphosphate
competitive
Zn2+
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.038
Ap4A
-
pH 7.4, 37°C
0.098
Ap5A
-
pH 7.4, 37°C
0.04
Ap6A
-
pH 7.4, 37°C
0.002
diadenosine 5',5'-P1,P4-tetraphosphate
-
-
0.0007 - 0.04
P1,P4-bis(5'-adenosyl) tetraphosphate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.031
1,2,3,4-tetra(adenosine-5'-O-phospho)erythritol
-
pH 7.6, 30°C
0.018
1,2,3,4-tetra(adenosine-5'-O-phosphorothio)erythritol
-
pH 7.6, 30°C
0.037
1,2,3-tri(adenosine-5'-O-phosphorothio)glycerol
-
pH 7.6, 30°C
0.066
1,3-di(adenosine-5'-O-phospho)-2-phospho-glycerol
-
pH 7.6, 30°C
0.032
1,3-di(adenosine-5'-O-phospho)-2-phosphorothio-glycerol
-
pH 7.6, 30°C
0.109
1,3-di(adenosine-5'-O-phospho)glycerol
-
pH 7.6, 30°C
0.142
1,4-di(adenosine-5'-O-phospho)erythritol
-
pH 7.6, 30°C
0.0015
1,4-di(adenosine-5'-O-phosphorothio)erythritol
-
pH 7.6, 30°C
0.0025
A-5'-p-alpha,beta,alpha',beta'-bis(oxymethylene)p-5'-A
-
-
0.0021
A-5'-p-beta,beta'-methyleneoxy-p-5'-A
-
-
0.3
Ca2+
-
-
0.0037
di(adenosine-5'-O-phosphorothio)-di(adenosine-5'-phospho)pentaerythritol
-
pH 7.6, 30°C
0.02
fluoride
-
-
0.01
guanosine 5'-tetraphosphate
-
-
0.00011
inositol 1-[(phosphorylmethyl)phosphonic acid]-2,3,4,5,6-pentaphosphate
pH not specified in the publication, temperature not specified in the publication
0.00027
inositol 1-[(phosphorylmethyl)phosphonic acid]-2,3,5,6-tetraphosphate
pH not specified in the publication, temperature not specified in the publication
0.000023
inositol 4-butyl-1-[(phosphorylmethyl)phosphonic acid]-2,3,5,6-tetraphosphate
pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0001
-
crude extract
0.00022
-
crude extract
18.5
-
purified enzyme
52
-
purified enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 8
-
degradation of Ap4A
7.6
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.1 - 8.6
-
pH 6.1: about 75% of maximal activity, pH 8.6: about 10% of maximal activity, degradation of Ap4A
6.5 - 8.5
-
half maximum activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
bound to prostasome-membranes through a GPI-anchor
Manually annotated by BRENDA team
present on surface of vascular endothelium
Manually annotated by BRENDA team
additional information
-
spermatozoa do not possess this hydrolytic activity, but they can aquire it after fusion with prostasomes
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
Ap4A-hydrolase is involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. SARS coronavirus protein 7a interacts with human Ap4A-hydrolase in the cytoplasm
physiological function
the primary and secondary waves of platelet aggregation and dense granule release are strongly induced by nanomolar ENPP4 in the presence of Ap3A, while Ap3A alone initiates a primary wave of aggregation followed by rapid disaggregation. ENPP4 mediates platelet aggregation via release of ADP from Ap3A and activation of ADP receptors
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
AP4A_HUMAN
147
0
16829
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
18000
-
SDS-PAGE, immunoblot
19200
-
SDS-PAGE, gel filtration
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structure determined by NMR spectroscopy
structure of wild-type and E58A mutant human Ap4A hydrolase, to 2.7 and 2.1 A resolution, respectively. Similar to the canonical Nudix fold, human Ap4A hydrolase shows the common alphabetaalpha-sandwich architecture. Two sulfate ions and one diphosphate coordinated with some conserved residues are observed in the active cleft
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E58A
crystallization data
T70A
active site mutant, has no effect on platelet aggregation and secretion
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
fused to glutathione S-transferase and expressed in E. coli
expression in insect cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pinto, R.M.; Costas, M.J.; Fernandez, A.; Canales, J.; Garcia-Agundez, J.A.; Camselle, J.C.
Dinucleoside tetraphosphatase from human blood cells: Purification and characterization as a high specific activity enzyme recognized by an anti-rat tetraphosphatase antibody
FEBS Lett.
287
85-88
1991
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Lazewska, D.; Starzynska, E.; Guranowski, A.
Human placental (asymmetrical) diadenosine 5',5'''-P1,P4-tetraphosphate hydrolase: Purification to homogenity and some properties
Protein Expr. Purif.
4
45-51
1993
Homo sapiens
Manually annotated by BRENDA team
Guranowski, A.; Galbas, M.; Hartmann, R.; Justesen, J.
Selective degradation of 2'-adenylated diadenosine tri- and tetraphosphates, Ap3A and Ap4A, by two specific human dinucleoside polyphosphate hydrolases
Arch. Biochem. Biophys.
373
218-224
2000
Homo sapiens
Manually annotated by BRENDA team
Guranowski, A.; Starzynska, E.; McLennan, A.G.; Baraniak, J.; Stec, W.J.
Adenosine-5'-O-phosphorylated and adenosine-5'-O-phosphorothioylated polyols as strong inhibitors of (symmetrical) and (asymmetrical) dinucleoside tetraphosphatases
Biochem. J.
373
635-640
2003
Homo sapiens, Lupinus angustifolius
Manually annotated by BRENDA team
Minelli, A.; Allegrucci, C.; Liguori, L.; Ronquist, G.
Ecto-diadenosine polyphosphate hydrolase activity on human prostasomes
Prostate
51
1-9
2002
Homo sapiens
Manually annotated by BRENDA team
Swarbrick, J.D.; Buyya, S.; Gunawardana, D.; Gayler, K.R.; McLennan, A.G.; Gooley, P.R.
Structure and substrate-binding mechanism of human Ap4A hydrolase
J. Biol. Chem.
280
8471-8481
2005
Homo sapiens (P50583), Homo sapiens
Manually annotated by BRENDA team
Guranowski, A.; Starzynska, E.; Pietrowska-Borek, M.; Rejman, D.; Blackburn, G.M.
Novel diadenosine polyphosphate analogs with oxymethylene bridges replacing oxygen in the polyphosphate chain: potential substrates and/or inhibitors of Ap4A hydrolases
FEBS J.
276
1546-1553
2009
Homo sapiens, Lupinus angustifolius
Manually annotated by BRENDA team
Vasilenko, N.; Moshynskyy, I.; Zakhartchouk, A.
SARS coronavirus protein 7a interacts with human Ap4A-hydrolase
Virol. J.
7
31
2010
Homo sapiens (P50583), Homo sapiens
Manually annotated by BRENDA team
Wu, M.; Chong, L.S.; Capolicchio, S.; Jessen, H.J.; Resnick, A.C.; Fiedler, D.
Elucidating diphosphoinositol polyphosphate function with nonhydrolyzable analogues
Angew. Chem. Int. Ed. Engl.
53
7192-7197
2014
Homo sapiens (O95989)
Manually annotated by BRENDA team
Ge, H.; Chen, X.; Yang, W.; Niu, L.; Teng, M.
Crystal structure of wild-type and mutant human Ap4A hydrolase
Biochem. Biophys. Res. Commun.
432
16-21
2013
Homo sapiens (P50583), Homo sapiens
Manually annotated by BRENDA team
Albright, R.A.; Chang, W.C.; Robert, D.; Ornstein, D.L.; Cao, W.; Liu, L.; Redick, M.E.; Young, J.I.; De La Cruz, E.M.; Braddock, D.T.
NPP4 is a procoagulant enzyme on the surface of vascular endothelium
Blood
120
4432-4440
2012
Homo sapiens (Q9Y6X5)
Manually annotated by BRENDA team