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Information on EC 2.7.4.6 - nucleoside-diphosphate kinase and Organism(s) Homo sapiens and UniProt Accession P15531

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IUBMB Comments
Many nucleoside diphosphates can act as acceptors, while many ribo- and deoxyribonucleoside triphosphates can act as donors.
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This record set is specific for:
Homo sapiens
UNIPROT: P15531
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
nm23-h1, nucleoside diphosphate kinase, ndp kinase, nm23-h2, ndpk-b, ndpk2, nucleoside diphosphokinase, ndk-1, nucleoside-diphosphate kinase, nucleoside diphosphate kinase a, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NDP kinase A
-
nucleoside diphosphate kinase
-
nucleoside diphosphate kinase A
-
nucleoside diphosphate kinase B
-
kinase, nucleoside diphosphate (phosphorylating)
-
-
-
-
NDPK-D
NM23
-
-
NM23 metastasis suppressor
-
exhibits Ndk activity
Nm23-H1
-
-
nucleoside 5'-diphosphate kinase
-
-
-
-
nucleoside diphosphate (UDP) kinase
-
-
-
-
nucleoside diphosphate kinase
nucleoside diphosphate kinase B
-
nucleoside diphosphate kinase D
-
nucleoside diphosphokinase
-
-
-
-
nucleoside-diphosphate kinase 3
-
nucleotide phosphate kinase
-
-
-
-
UDP kinase
-
-
-
-
uridine diphosphate kinase
-
-
-
-
additional information
-
the enzyme belongs to the nucleoside diphosphate kinase family
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
show the reaction diagram
ping pong mechanism with formation of an enzyme intermediate phosphorylated at His118
ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:nucleoside-diphosphate phosphotransferase
Many nucleoside diphosphates can act as acceptors, while many ribo- and deoxyribonucleoside triphosphates can act as donors.
CAS REGISTRY NUMBER
COMMENTARY hide
9026-51-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + GDP
ADP + GTP
show the reaction diagram
assay by spontaneous release of GDP from G proteins. This GDP serves as a substrate for phosphotransfer by the NDPK, and the formed GTP then binds back to the G protein. NDPK is able to transfer phosphate also onto denatured proteins and thus also on the covalently linked GDP
-
-
r
ATP + NDP
ADP + NTP
show the reaction diagram
ATP + 8-bromo-IDP
ADP + ?
show the reaction diagram
ATP + CDP
ADP + CTP
show the reaction diagram
-
-
-
-
?
ATP + dTDP
ADP + dTTP
show the reaction diagram
-
-
-
?
ATP + GDP
ADP + GTP
show the reaction diagram
-
-
-
-
?
ATP + NDP
ADP + NTP
show the reaction diagram
ATP + TDP
ADP + TTP
show the reaction diagram
gamma-S-ATP + GDP
ADP + gamma-S-GTP
show the reaction diagram
-
poor substrate
-
-
?
gamma-S-GTP + GDP
GDP + gamma-S-GTP
show the reaction diagram
-
poor substrate
-
-
?
GTP + CDP
GDP + CTP
show the reaction diagram
-
-
-
-
?
GTP + dGDP
GDP + dGTP
show the reaction diagram
-
-
-
-
?
GTP + dTDP
GDP + dTTP
show the reaction diagram
-
-
-
-
?
NDP + NTP
NTP + NDP
show the reaction diagram
NTP + nucleoside diphosphate
NDP + NTP
show the reaction diagram
additional information
?
-
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
ATP + NDP
ADP + NTP
show the reaction diagram
MgATP promotes correct folding and association
-
-
?
ATP + GDP
ADP + GTP
show the reaction diagram
-
-
-
-
?
ATP + NDP
ADP + NTP
show the reaction diagram
ATP + TDP
ADP + TTP
show the reaction diagram
-
-
-
r
NDP + NTP
NTP + NDP
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
MgATP promotes correct folding and association
Ca2+
-
requirement, about half as effective as Mg2+, Mn2+ or Co2+, pI 7.3-enzyme variant
Zn2+
-
not
additional information
-
no activation by Cu2+ or monovalent cations
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8-bromo-IDP
-
in excess
ellagic acid
-
inhibits NDPK and suppresses MDA-MB-435S cell growth
epigallocatechin gallate
-
EGCG, inhibits NDPK and suppresses MDA-MB-435S cell growth
GMP
-
erythrocytic kinase, kinetics
p-chloromercuribenzoate
theophylline
-
-
additional information
-
no inhibition by papaverine
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
forskolin
forskolin enhances NDPK-B interaction with CFTR 3fold in 16HBE14o- cells
additional information
-
nucleoside triphosphate, especially GTP, promotes the dynamic self-assembly of isozyme NDPKB into ordered 20-25 nm diameter filaments in vitro
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.033 - 0.06
8-bromo-IDP
0.024
ADP
-
cosubstrate GTP
0.2 - 0.38
ATP
-
cosubstrate dTDP, two different assays
0.21 - 0.39
dTDP
-
cosubstrate ATP, two different assays
0.12
GTP
-
cosubstrate ADP
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002 - 0.003
ellagic acid
Homo sapiens
-
-
0.008 - 0.01
epigallocatechin gallate
Homo sapiens
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
550
-
isozyme A6, 25°C
740
-
isozyme B6, 25°C
additional information
-
specific activities of a variety of animals, plants and microorganisms
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9
-
-
7.2
-
assembly assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
assay at
25
-
assay at
37
-
assembly assay at
additional information
-
temperature-dependence of NDP kinases
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
low expression
Manually annotated by BRENDA team
intermediate expression
Manually annotated by BRENDA team
intermediate expression
Manually annotated by BRENDA team
in hepatocarcinoma derived cell lines, NME4 expression is lower in cell lines with high metastatic potential
Manually annotated by BRENDA team
intermediate expression
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
intermediate expression
Manually annotated by BRENDA team
-
isoforms A,B in the ratio 1:3
Manually annotated by BRENDA team
highest expression
Manually annotated by BRENDA team
high expression
Manually annotated by BRENDA team
intermediate expression
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
additional information
HeLa cells are naturally almost devoid of NDPK-D
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
the enzyme is secreted
-
Manually annotated by BRENDA team
structural basis of NDPK-D/mitochondrial membrane interactions via binding of cardiolipin, overview
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
NME1 depletion impacts migration and differentiation but not proliferation in neuroblastoma cells. Candidate targets of NME1 histidine kinase activity include ENO1, GAPDH, and PKM
malfunction
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
NDKA_HUMAN
152
0
17149
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
100000
-
erythrocytic enzyme variant pI 8.3, gel filtration
105000
-
gel filtration
19000
-
x * 19000 + x * 20500, SDS-PAGE
20500
-
x * 19000 + x * 20500, SDS-PAGE
80000
-
erythrocytic enzyme variants pI 5.4 and pI 6.8, gel filtration
80000 - 100000
-
erythrocytic enzyme variants
84000
-
erythrocytic enzyme variants pI 6.3 and pI 7.3, gel filtration
93000
-
erythrocytic enzyme variant pI 5.8, gel filtration
additional information
-
comparison of kinase amino acid sequences
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
hexamer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
phosphoprotein
-
GTP (but not ATP) promotes serine phosphorylation of NDPK. Further rising [AMP] promotes serine phosphorylation (only with GTP) but inhibits histidine phosphorylation of NDPK from both donors, phosphorylation is inhibited when the reaction is performed in the presence of 1 mM AMP
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant H118G/F60W in complex with ADP, Ca2+ and phosphate
-
wild-type and mutant S120G in complex with ADP, no significant changes between wild-type and mutant even in the surroundings of the catalytic His residue
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H118N/S120G
site-directed mutagenesis, the mutant is inactive and expressed as insoluble protein in inclusion bodies
S120G
naturally mutation occuring in neuroblastoma, the mutant has a folding defect, the urea-denatured protein cannot refold in vitro
H118C
-
the mutant of isozyme NDPKB is catalytically inactive
H118G/F60W
-
mutant engineered for following intrinsic fluorescence during substrate binding, crystallization data
K135L
-
isoform B, mutation in dimeric interface, defective DNA-binding and reduced stability of enzyme
N69H
-
isoform B, mutation in dimeric interface, defective DNA-binding and reduced stability of enzyme
R34G
-
isoform B, mutation in dimeric interface, defective DNA-binding and reduced stability of enzyme
R90D
site-directed mutagenesis, the mutant does not bind to cardiolipin
S120G
-
mutant identified in aggressive neuroblastomas, crystallization data
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
3 h, 50% loss of activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and mutant enzymes by anion exchange chromatography
affinity chromatography on Cibacron Red 3B-P-Sepharose
-
marked isoelectric variability with pIs from 5.4 to 8.3
-
native enzyme partially by mitochondrion preparation
Ni-NTA column chromatography
-
recombinant His-tagged wild-type and mutant NDPKB by nickel affinity chromatography
-
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant enzymes
expressed in Escherichia coli
-
expression of GST-fusion NM23 protein in Escherichia coli
-
expression of His-tagged wild-type and mutant NDPKB
-
overview
-
recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3)
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in human airway cells exposed to hypoxia (3% oxygen) membrane-bound and cytosolic NDPK is inhibited
-
overexpression of NME4 mRNA in several types of tumors
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
renaturation of subunit polypeptides A and B generates several isozymes
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
NME1 expression is associated with reduced overall and event-free survival of neuroblastoma patients and with the strongest associations of any of the NME family member genes. NME1 expression is also higher in tumors with MYCN oncogene amplification and in tumors from patients with stage 4 disease. Isoforms NME1/NMe2 and multiple phosphorylated His-containing proteins are found in all tested neuroblastoma cell lines and in xenograft neuroblastoma tumors. NME1 expression is asssociated with neuroblastoma cell migration and differentiation
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lam, S.C.T.; Packham, M.A.
Isolation and kinetic studies of nucleoside diphosphokinase from human platelets and effects of cAMP phosphodiesterase inhibitors
Biochem. Pharmacol.
35
4449-4455
1986
Homo sapiens
Manually annotated by BRENDA team
Presecan, E.; Vonica, A.; Lascu, I.
Nucleoside diphosphate kinase from human erythrocytes: purification, molecular mass and subunit structure
FEBS Lett.
250
629-632
1989
Homo sapiens
Manually annotated by BRENDA team
Gilles, A.M.; Presecan, E.; Vonica, A.; Lascu, I.
Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme
J. Biol. Chem.
266
8784-8789
1991
Homo sapiens
Manually annotated by BRENDA team
Hemmerich, S.; Pecht, I.
Oligomeric structure and autophosphorylation of nucleoside diphosphate kinase from rat mucosal mast cells
Biochemistry
31
4580-4587
1992
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Agarwal, R.P.; Robison, B.; Parks, R.E.
Nucleoside diphosphokinase from human erythrocytes
Methods Enzymol.
51
376-386
1978
Homo sapiens
Manually annotated by BRENDA team
Parks, R.E.; Agarwal, R.P.
Nucleoside diphosphokinases
The Enzymes,3rd Ed. (Boyer,P. D. ,ed. )
8
307-333
1973
Anguilla rostrata, Avian myeloblastosis virus, Papio sp., Bacillus subtilis, Beta vulgaris subsp. vulgaris, Bos taurus, Saccharomyces cerevisiae, Vicia faba, Canis lupus familiaris, Gallus gallus, Columba livia, Oryctolagus cuniculus, Streptococcus pneumoniae, Escherichia coli, Felis catus, Helianthus tuberosus, Homo sapiens, Hordeum vulgare, Impatiens holstii, Micrococcus luteus, Platyrrhini, Mus musculus, Myxine glutinosa, Phoca vitulina, Pisum sativum, Rattus norvegicus, Saccharomyces pastorianus, Saccharum officinarum, Schistosoma mansoni, Solanum tuberosum, Squalus acanthias, Sus scrofa, Triticum aestivum
-
Manually annotated by BRENDA team
Schaertl, S.; Konrad, M.; Geeves, M.A.
Substrate specificity of human nucleoside-diphosphate kinase revealed by transient kinetic analysis
J. Biol. Chem.
273
5662-5669
1998
Homo sapiens
Manually annotated by BRENDA team
Chen, Y.; Gallois-Montbrun, S.; Schneider, B.; Veron, M.; Morera, S.; Deville-Bonne, D.; Janin, J.
Nucleotide Binding to Nucleoside Diphosphate Kinases: X-ray Structure of Human NDPK-A in Complex with ADP and Comparison to Protein Kinases
J. Mol. Biol.
332
915-926
2003
Homo sapiens
Manually annotated by BRENDA team
Bourdais, J.; Biondi, R.; Sarfati, S.; Guerreiro, C.; Lascu, I.; Janin, J.; Veron, M.
Cellular phosphorylation of anti-HIV nucleosides. Role of nucleoside diphosphate kinase
J. Biol. Chem.
271
7887-7890
1996
Homo sapiens
Manually annotated by BRENDA team
Kim, S.Y.; Song, E.J.; Chang, K.H.; Kim, E.; Chae, S.K.; Lee, H.; Lee, K.J.
Oligomeric structures determine the biochemical characteristics of human nucleoside diphosphate kinases
J. Biochem. Mol. Biol.
34
355-364
2001
Homo sapiens
-
Manually annotated by BRENDA team
Lacombe, M.L.; Milon, L.; Munier, A.; Mehus, J.G.; Lambeth, D.O.
The human Nm23/nucleoside diphosphate kinases
J. Bioenerg. Biomembr.
32
247-258
2000
Homo sapiens
Manually annotated by BRENDA team
Janin, J.; Deville-Bonne, D.
Nucleoside-diphosphate kinase: structural and kinetic analysis of reaction pathway and phosphohistidine intermediate
Methods Enzymol.
354
118-134
2002
Bos taurus, Dictyostelium discoideum, Drosophila melanogaster, Homo sapiens, Myxococcus xanthus, Rattus norvegicus
Manually annotated by BRENDA team
Fischbach, M.A.; Settleman, J.
Specific biochemical inactivation of oncogenic Ras proteins by nucleoside diphosphate kinase
Cancer Res.
63
4089-4094
2003
Escherichia coli, Homo sapiens
Manually annotated by BRENDA team
Giraud, M.F.; Georgescauld, F.; Lascu, I.; Dautant, A.
Crystal structures of S120G mutant and wild type of human nucleoside diphosphate kinase A in complex with ADP
J. Bioenerg. Biomembr.
38
261-264
2006
Homo sapiens
Manually annotated by BRENDA team
Mocan, I.; Georgescauld, F.; Gonin, P.; Thoraval, D.; Cervoni, L.; Giartosio, A.; Dabernat-Arnaud, S.; Crouzet, M.; Lacombe, M.; Lascu, I.
Protein phosphorylation corrects the folding defect of the neuroblastoma (S120G) mutant of human nucleoside diphosphate kinase A/Nm23-H1
Biochem. J.
403
149-156
2007
Homo sapiens (P15531), Homo sapiens
Manually annotated by BRENDA team
Morin-Leisk, J.; Lee, T.H.
Nucleotide-dependent self-assembly of nucleoside diphosphate kinase (NDPK) in vitro
Biochim. Biophys. Acta
1784
2045-2051
2008
Homo sapiens
Manually annotated by BRENDA team
Rumjahn, S.M.; Javed, M.A.; Wong, N.; Law, W.E.; Buxton, I.L.
Purinergic regulation of angiogenesis by human breast carcinoma-secreted nucleoside diphosphate kinase
Br. J. Cancer
97
1372-1380
2007
Homo sapiens
Manually annotated by BRENDA team
Tokarska-Schlattner, M.; Boissan, M.; Munier, A.; Borot, C.; Mailleau, C.; Speer, O.; Schlattner, U.; Lacombe, M.L.
The nucleoside diphosphate kinase D (NM23-H4) binds the inner mitochondrial membrane with high affinity to cardiolipin and couples nucleotide transfer with respiration
J. Biol. Chem.
283
26198-26207
2008
Rattus norvegicus, Homo sapiens (O00746), Homo sapiens
Manually annotated by BRENDA team
Wieland, T.
Interaction of nucleoside diphosphate kinase B with heterotrimeric G protein betagamma dimers: consequences on G protein activation and stability
Naunyn Schmiedebergs Arch. Pharmacol.
374
373-383
2007
Rattus norvegicus, Homo sapiens (P15531)
Manually annotated by BRENDA team
Schlattner, U.; Tokarska-Schlattner, M.; Ramirez, S.; Brueckner, A.; Kay, L.; Polge, C.; Epand, R.F.; Lee, R.M.; Lacombe, M.L.; Epand, R.M.
Mitochondrial kinases and their molecular interaction with cardiolipin
Biochim. Biophys. Acta
1788
2032-2047
2009
Homo sapiens (O00746)
Manually annotated by BRENDA team
Treharne, K.J.; Best, O.G.; Mehta, A.
The phosphorylation status of membrane-bound nucleoside diphosphate kinase in epithelia and the role of AMP
Mol. Cell. Biochem.
329
107-114
2009
Ovis aries, Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Francois-Moutal, L.; Maniti, O.; Marcillat, O.; Granjon, T.
New insights into lipid-nucleoside diphosphate kinase-D interaction mechanism: protein structural changes and membrane reorganisation
Biochim. Biophys. Acta
1828
906-915
2013
Homo sapiens
Manually annotated by BRENDA team
Conery, A.R.; Sever, S.; Harlow, E.
Nucleoside diphosphate kinase Nm23-H1 regulates chromosomal stability by activating the GTPase dynamin during cytokinesis
Proc. Natl. Acad. Sci. USA
107
15461-15466
2010
Homo sapiens
Manually annotated by BRENDA team
Borthwick, L.A.; Kerbiriou, M.; Taylor, C.J.; Cozza, G.; Lascu, I.; Postel, E.H.; Cassidy, D.; Trouve, P.; Mehta, A.; Robson, L.; Muimo, R.
Role of interaction and nucleoside diphosphate kinase B in regulation of the cystic fibrosis transmembrane conductance regulator function by cAMP-dependent protein kinase A
PLoS ONE
11
e0149097
2016
Homo sapiens (P22392)
Manually annotated by BRENDA team
Adam, K.; Lesperance, J.; Hunter, T.; Zage, P.
The potential functional roles of NME1 histidine kinase activity in neuroblastoma pathogenesis
Int. J. Mol. Sci.
21
3319
2020
Homo sapiens (P15531)
Manually annotated by BRENDA team
Hoff, S.; Epting, D.; Falk, N.; Schroda, S.; Braun, D.A.; Halbritter, J.; Hildebrandt, F.; Kramer-Zucker, A.; Bergmann, C.; Walz, G.; Lienkamp, S.S.
The nucleoside-diphosphate kinase NME3 associates with nephronophthisis proteins and is required for ciliary function during renal development
J. Biol. Chem.
293
15243-15255
2018
Xenopus laevis, Homo sapiens (Q13232), Homo sapiens, Danio rerio (Q9PTF3), Danio rerio
Manually annotated by BRENDA team
Lacombe, M.L.; Tokarska-Schlattner, M.; Boissan, M.; Schlattner, U.
The mitochondrial nucleoside diphosphate kinase (NDPK-D/NME4), a moonlighting protein for cell homeostasis
Lab. Invest.
98
582-588
2018
Xenopus laevis, Homo sapiens (O00746), Mus musculus (Q9WV84)
Manually annotated by BRENDA team