BRENDA - Enzyme Database show
show all sequences of 2.7.11.30

A small dibromotyrosine derivative purified from Pseudoceratina sp. suppresses TGF-beta responsiveness by inhibiting TGF-beta type I receptor serine/threonine kinase activity

Chen, C.L.; Kao, Y.C.; Yang, P.H.; Sung, P.J.; Wen, Z.H.; Chen, J.J.; Huang, Y.B.; Chen, P.Y.; J. Cell. Biochem. 117, 2800-2814 (2016)

Data extracted from this reference:

Application
Application
Commentary
Organism
pharmacology
enzyme inhibitor (1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile is a potential therapeutic agent for fibrotic disease and cancer treatment
Homo sapiens
Cloned(Commentary)
Commentary
Organism
gene ALK5, transient recombinant expression of FLAG-tagged enzyme mutant T202D in HEKT293 cells
Homo sapiens
Engineering
Amino acid exchange
Commentary
Organism
T202D
site-directed mutagenesis
Homo sapiens
Inhibitors
Inhibitors
Commentary
Organism
Structure
(1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile
the small dibromotyrosine derivative purified from Pseudoceratina sp. suppresses TGF-beta responsiveness by inhibiting TGF-beta type I receptor serine/threonine kinase activity. The compound inhibits the TGF-beta-stimulated transcriptional activations of 3TP-Lux and decreases phosphorylated Smad2/3 levels and the nuclear translocation of Smad2/3 increased by TGF-beta. The compound inhibits TGF-beta-induced EMT and wound healing of A-549 cells and is a potential therapeutic agent for fibrotic disease and cancer treatment. The compound has no effects on TGF-beta receptor synthesis but attenuates TGF-beta-induced transcriptional activation in Mv1Lu cells and TGF-beta-induced expression of fibronectin and PAI-1 in A549 and NMuMG cells and TGF-beta-induced cell migration
Homo sapiens
Metals/Ions
Metals/Ions
Commentary
Organism
Structure
Mg2+
required
Homo sapiens
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ATP + Smad2
Homo sapiens
-
ADP + phosphorylated Smad2
-
-
?
ATP + Smad3
Homo sapiens
-
ADP + phosphorylated Smad3
-
-
?
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
P36897
-
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
A-549 cell
-
Homo sapiens
-
epithelial cell
-
Homo sapiens
-
Mv1Lu cell
-
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ATP + Smad2
-
740796
Homo sapiens
ADP + phosphorylated Smad2
-
-
-
?
ATP + Smad3
-
740796
Homo sapiens
ADP + phosphorylated Smad3
-
-
-
?
Cofactor
Cofactor
Commentary
Organism
Structure
ATP
-
Homo sapiens
Application (protein specific)
Application
Commentary
Organism
pharmacology
enzyme inhibitor (1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile is a potential therapeutic agent for fibrotic disease and cancer treatment
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
gene ALK5, transient recombinant expression of FLAG-tagged enzyme mutant T202D in HEKT293 cells
Homo sapiens
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
ATP
-
Homo sapiens
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
T202D
site-directed mutagenesis
Homo sapiens
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
(1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile
the small dibromotyrosine derivative purified from Pseudoceratina sp. suppresses TGF-beta responsiveness by inhibiting TGF-beta type I receptor serine/threonine kinase activity. The compound inhibits the TGF-beta-stimulated transcriptional activations of 3TP-Lux and decreases phosphorylated Smad2/3 levels and the nuclear translocation of Smad2/3 increased by TGF-beta. The compound inhibits TGF-beta-induced EMT and wound healing of A-549 cells and is a potential therapeutic agent for fibrotic disease and cancer treatment. The compound has no effects on TGF-beta receptor synthesis but attenuates TGF-beta-induced transcriptional activation in Mv1Lu cells and TGF-beta-induced expression of fibronectin and PAI-1 in A549 and NMuMG cells and TGF-beta-induced cell migration
Homo sapiens
Metals/Ions (protein specific)
Metals/Ions
Commentary
Organism
Structure
Mg2+
required
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ATP + Smad2
Homo sapiens
-
ADP + phosphorylated Smad2
-
-
?
ATP + Smad3
Homo sapiens
-
ADP + phosphorylated Smad3
-
-
?
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
A-549 cell
-
Homo sapiens
-
epithelial cell
-
Homo sapiens
-
Mv1Lu cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ATP + Smad2
-
740796
Homo sapiens
ADP + phosphorylated Smad2
-
-
-
?
ATP + Smad3
-
740796
Homo sapiens
ADP + phosphorylated Smad3
-
-
-
?
Expression
Organism
Commentary
Expression
Homo sapiens
(1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile has no effects on TGF-beta receptor synthesis
additional information
Expression (protein specific)
Organism
Commentary
Expression
Homo sapiens
(1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile has no effects on TGF-beta receptor synthesis
additional information
Other publictions for EC 2.7.11.30
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [C]
Temperature Range [C]
Temperature Stability [C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [C] (protein specific)
Temperature Range [C] (protein specific)
Temperature Stability [C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
740796
Chen
A small dibromotyrosine deriva ...
Homo sapiens
J. Cell. Biochem.
117
2800-2814
2016
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1
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740900
Sun
GsSRK, a G-type lectin S-recep ...
Glycine soja
J. Plant Physiol.
170
505-515
2013
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1
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4
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1
1
1
1
1
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740256
Zhou
Reduced SMAD7 leads to overact ...
Homo sapiens
Cancer Res.
71
955-963
2011
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1
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2
2
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702898
Haneen
Mutation analysis of 'Endoglin ...
Homo sapiens
BMC Med. Genet.
10
53
2009
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1
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1
1
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703244
Long
Altered bone morphogenetic pro ...
Rattus norvegicus
Circulation
119
566-576
2009
-
1
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2
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2
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1
1
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1
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704485
Upton
Bone morphogenetic protein (BM ...
Homo sapiens
J. Biol. Chem.
284
15794-15804
2009
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1
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1
1
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705441
Mahmoud
Endoglin and activin receptor- ...
Mus musculus
Lab. Invest.
89
15-25
2009
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4
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1
2
2
1
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690773
Watanabe
Insulin gene is a target in ac ...
Homo sapiens
Biochem. Biophys. Res. Commun.
377
867-872
2008
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1
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1
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5
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1
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691269
Kim
Synthesis and biological evalu ...
Rattus norvegicus
Bioorg. Med. Chem. Lett.
18
2122-2127
2008
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52
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691460
Zhou
Inhibition of the TGF-beta rec ...
Homo sapiens
Blood
112
3434-3443
2008
-
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1
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1
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1
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2
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4
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4
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691532
Xu
TGF-beta receptor kinase inhib ...
Homo sapiens
Br. J. Haematol.
142
192-201
2008
-
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1
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1
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2
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6
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6
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3
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691833
Fujiwara
Implications of mutations of a ...
Homo sapiens
Circ. J.
72
127-133
2008
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5
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692159
Bueno
Semi-mechanistic modelling of ...
Homo sapiens
Eur. J. Cancer
44
142-150
2008
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1
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1
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1
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4
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6
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1
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693034
Zhao
Smad4-dependent TGF-beta signa ...
Homo sapiens
J. Biol. Chem.
283
11293-11301
2008
-
-
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1
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2
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1
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7
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3
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7
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3
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693381
Young
The activin receptor-like kina ...
Ovis aries
J. Endocrinol.
196
251-261
2008
-
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1
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1
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1
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694090
Xu
Cyclin G2 is degraded through ...
Homo sapiens
Mol. Biol. Cell
19
4968-4979
2008
-
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706906
Li
Down-regulation of transformin ...
Homo sapiens
World J. Gastroenterol.
14
2894-2899
2008
-
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1
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2
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2
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664721
Zhang
Activin receptor-like kinase 7 ...
Rattus norvegicus
Diabetologia
49
506-518
2006
3
-
1
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1
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3
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5
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1
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1
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664088
Peng
Kinetic characterization of no ...
Homo sapiens
Biochemistry
44
2293-2304
2005
-
-
1
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1
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4
4
-
1
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-
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2
-
1
1
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9
1
1
-
-
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1
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1
3
-
4
-
-
1
1
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1
-
4
4
3
4
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1
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1
1
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9
1
1
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1
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-
-
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-
-
-
-
664715
Desgrosellier
Activin receptor-like kinase 2 ...
Gallus gallus
Dev. Biol.
280
201-210
2005
1
-
1
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1
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-
-
-
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1
-
1
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3
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3
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2
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665640
Ungefroren
Transforming growth factor-bet ...
Homo sapiens
J. Biol. Chem.
280
2644-2652
2005
1
-
-
-
-
-
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4
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3
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665699
Lux
Human retroviral gag- and gag- ...
Homo sapiens
J. Biol. Chem.
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2005
1
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1
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1
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1
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-
666443
Halder
A specific inhibitor of TGF-be ...
Homo sapiens
Neoplasia
7
509-521
2005
1
-
-
-
-
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1
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1
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1
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2
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1
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1
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1
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1
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663984
Ge
Selective inhibitors of type I ...
Homo sapiens
Biochem. Pharmacol.
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41-50
2004
2
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1
-
1
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-
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1
1
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2
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3
-
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3
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3
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1
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1
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1
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2
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1
1
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1
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1
1
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2
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3
-
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3
-
1
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1
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-
-
-
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-
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-
664036
Ottesen
Semisynthesis of phosphovarian ...
Homo sapiens
Biochemistry
43
5698-5706
2004
2
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-
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-
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1
2
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2
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2
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4
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1
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1
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1
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2
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1
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1
2
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2
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4
-
1
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1
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-
-
-
-
-
-
-
-
664318
Sawyer
Synthesis and activity of new ...
Homo sapiens, Mus musculus
Bioorg. Med. Chem. Lett.
14
3581-3584
2004
2
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1
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-
-
6
-
2
-
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2
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2
-
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1
-
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2
-
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2
-
2
-
-
-
2
-
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2
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6
2
-
1
2
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-
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6
6
-
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2
-
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2
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1
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2
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2
-
2
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2
-
-
-
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-
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-
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-
665532
Kim
Activin receptor-like kinase-7 ...
Homo sapiens
J. Biol. Chem.
279
28458-28465
2004
1
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1
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3
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1
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1
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3
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3
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2
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5
-
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1
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1
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1
1
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3
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1
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1
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3
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2
-
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5
-
-
-
-
-
-
-
-
-
-
-
-
-
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665554
Yakymovych
Smad2 phosphorylation by type ...
Mus musculus
J. Biol. Chem.
279
35781-35787
2004
1
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-
-
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-
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1
2
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2
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1
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-
-
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2
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5
-
1
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1
-
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1
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1
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1
-
-
-
-
-
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1
2
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2
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-
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2
-
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5
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
666283
Forrester
Tegumental expression of a nov ...
Schistosoma mansoni
Mol. Biochem. Parasitol.
136
149-156
2004
-
-
1
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-
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1
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3
-
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4
-
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1
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1
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4
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
666359
Mazerbourg
Growth differentiation factor- ...
Rattus norvegicus
Mol. Endocrinol.
18
653-665
2004
2
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1
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1
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2
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1
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3
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2
-
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-
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3
-
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4
-
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1
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2
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1
1
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1
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2
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1
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3
-
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3
-
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4
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
664282
Roberts
Identification of novel isofor ...
Homo sapiens
Biol. Reprod.
68
1719-1726
2003
2
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1
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1
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1
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2
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8
-
-
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-
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2
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1
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1
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1
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8
-
-
-
-
-
-
-
-
-
-
-
-
-
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-
-
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-
665481
Liu
Smads 2 and 3 are differential ...
Rattus norvegicus
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278
11721-11728
2003
1
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1
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1
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5
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1
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1
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1
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1
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5
-
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665487
Harrison
Identification of a functional ...
Homo sapiens
J. Biol. Chem.
278
21129-21135
2003
2
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1
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27
-
-
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1
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1
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1
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-
-
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1
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1
1
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-
-
-
-
-
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1
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2
-
1
1
-
27
-
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1
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1
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1
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1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
666312
Goumans
Activin receptor-like kinase ( ...
Mus musculus
Mol. Cell
12
817-828
2003
2
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1
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1
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1
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1
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5
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1
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-
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1
1
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5
-
-
-
-
-
-
-
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1
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2
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1
1
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1
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1
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1
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5
-
-
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-
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1
1
-
5
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
666512
Fink
TGF-beta-induced nuclear local ...
Homo sapiens
Oncogene
22
1317-1323
2003
1
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-
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-
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1
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3
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1
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5
-
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5
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1
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1
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1
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1
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3
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5
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5
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