Information on EC 2.7.11.30 - receptor protein serine/threonine kinase and Organism(s) Homo sapiens

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The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.11.30
-
RECOMMENDED NAME
GeneOntology No.
receptor protein serine/threonine kinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Phosphorylation
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[receptor-protein] phosphotransferase
The transforming growth factor beta (TGF-beta) family of cytokines regulates cell proliferation, differentiation, recognition and death. Signalling occurs by the binding of ligand to the type II receptor, which is the constitutively active kinase. Bound TGF-beta is then recognized by receptor I, which is phosphorylated and can propagate the signal to downstream substrates [1,3].
CAS REGISTRY NUMBER
COMMENTARY hide
146702-86-5
-
152060-53-2
-
154907-75-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
-
SMAD7 is a negative regulator of TGF-beta receptor I (TBRI) kinase. The enzyme increases Smad7 via increased TGF-beta signaling
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + KKVLTQMGSPSIRCS(P)SV(P)S
ADP + ?
show the reaction diagram
-
Smad3-derived peptide substrate
-
-
?
ATP + KKVLTQMGSPSIRCS(P)SVA
ADP + ?
show the reaction diagram
-
Smad3-derived peptide substrate
-
-
?
ATP + KKVLTQMGSPSIRCS(P)SVS
ADP + ?
show the reaction diagram
-
Smad3-derived peptide substrate
-
-
?
ATP + KMGSPSVRCS(P)SMS
ADP + ?
show the reaction diagram
TGF-beta-induced phosphorylation by TbetaRI receptor kinase of the Smad2-derived, phosphorylated peptide substrate containing Ser465 phosphorylation site, poor activity with nonphosphorylated peptide substrate
-
-
?
ATP + KVLTQMGSPSIRCS(P)SVS
ADP + ?
show the reaction diagram
-
Smad3-derived peptide substrate
-
-
?
ATP + KVLTQMGSPSIRCSSV(P)S
ADP + ?
show the reaction diagram
-
Smad3-derived peptide substrate
-
-
?
ATP + KVLTQMGSPSVRCS(P)SMS
ADP + ?
show the reaction diagram
-
Smad2-derived peptide substrate
-
-
?
ATP + KVLTQMGSPSVRCSSMS
ADP + ?
show the reaction diagram
-
Smad2-derived peptide substrate
-
-
?
ATP + KVLTQMGSPSVRCSSMS(P)S
ADP + ?
show the reaction diagram
-
Smad2-derived peptide substrate
-
-
?
ATP + Smad
ADP + phosphorylated Smad
show the reaction diagram
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
ATP + [actividin receptor]
ADP + [actividin receptor] phosphate
show the reaction diagram
ATP + [TGF-beta receptor II]
ADP + [TGF-beta receptor II] phosphate
show the reaction diagram
ATP + [TGF-beta receptor I]
ADP + [TGF-beta receptor I] phosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + Smad
ADP + phosphorylated Smad
show the reaction diagram
-
involved in ALK5 activation of p38 MAPK signaling and of GADDbeta45 and BGN expression induced by TGF-beta
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
ATP + [actividin receptor]
ADP + [actividin receptor] phosphate
show the reaction diagram
ATP + [TGF-beta receptor II]
ADP + [TGF-beta receptor II] phosphate
show the reaction diagram
-
regulation and metabolism, overview
-
-
?
ATP + [TGF-beta receptor I]
ADP + [TGF-beta receptor I] phosphate
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(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
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4(quinolin-4-yl)-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.00005-0.0013 mM
4-phenyl substituted pyrazole inhibitors
-
inhibitory potency of 4-phenyl substituted pyrazole derivatives, IC50 of 30-555 nM, overview
-
4-phenyl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.000005-0.0195 mM
calphostin C
-
-
LY-2157299
-
LY-2157299 inhibits TGF-beta mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells. In vivo administration of LY-2157299 ameliorates anemia in a TGF-beta overexpressing transgenic mouse model of bone marrow failure. Treatment with LY-2157199 stimulates hematopoiesis from primary myelodysplastic syndrome bone marrow specimens
LY2109761
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TGF-beta receptor kinase inhibitor LY2109761 reverses the anti-apoptotic effects of TGF-beta1 in myelo-monocytic leukaemic cells, it LY2109761 enhanced apoptosis only in the presence of exogenously added TGF-beta1
LY2157299
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inhibits Smad3 and Smad3 phosphorylation and antagonizes TGF-beta receptor I kinase activity in vivo in human cancer cells implanted into nude mice, pharmacokinetic model, overview
LY364947
LY566578
-
competitive to ATP, noncompetitive to the peptide substrate, IC50 is 70 nM, mechanism
LY580276
-
competitive to ATP, noncompetitive to the peptide substrate, IC50 is 580 nM, mechanism
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PD98059
-
-
PEG10
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ancient retroviral/retrotransposon element intergrated as a single copy gene in to human chromosome 7q21, encodes two splicing varaiants PEG10-RF1 and PEG10-RF1/2, gag- and gag-pol-like proteins that interact with TGF-beta family proteins, DNA and amino acid sequence deteramination and analysis of PEG10-RF1, PEG10-RF1 inhibits ALK1 and ALK5 signaling by direct interaction, overview
Rapamycin
-
-
SB-431542
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specific TGF-beta receptor kinase inhibitor, a potent antitumor agent for human cancers, induces anchorage-independent cell growth in TGF-beta growth-inhibited cells, and colony formation in growth-induced cells, overview
SB203580
-
-
SD-208
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
actividin
-
actividin A
-
required for activity in a complex formed with ALK4 and ActRIIB or ActRII, identification of the functional binding site
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actividin B
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required for activity in a complex formed with ALK4 and ActRIIB or ActRII, identification of the functional binding site
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SARA protein
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i.e. Smad anchor for receptor activation protein, binding site for co-modulator Smad4, modulates self-association of partially phosphorylated Smad2 preventing premature release of monophosphorylated substrate, interaction with Smad2 via the Smad2 MH2 domain
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TGF-beta
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TGF-beta 3
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binds and activates ALK5
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0057 - 0.0088
ATP
0.26
KKVLTQMGSPSIRCS(P)SVS
-
pH 7.5, 30°C, recombinant wild-type ALK5
0.331
KVLTQMGSPSVRCS(P)SMS
-
pH 7.5, 30°C, recombinant wild-type ALK5
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000028
LY364947
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pH 7.5, 30°C, recombinant mutant T204D ALK5, inhibition of autophosphorylation
0.000038
LY566578
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pH 7.5, 30°C, recombinant mutant T204D ALK5, inhibition of autophosphorylation
0.000037
LY580276
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pH 7.5, 30°C, recombinant mutant T204D ALK5, inhibition of autophosphorylation
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00005 - 0.0013
4(quinolin-4-yl)-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
Homo sapiens;
-
IC50 of 0.00005-0.0013 mM
0.00003 - 0.000555
4-phenyl substituted pyrazole inhibitors
Homo sapiens;
-
inhibitory potency of 4-phenyl substituted pyrazole derivatives, IC50 of 30-555 nM, overview
-
0.000005 - 0.0195
4-phenyl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
Homo sapiens;
-
IC50 of 0.000005-0.0195 mM
0.000051 - 0.000175
LY364947
0.00007
LY566578
Homo sapiens;
-
competitive to ATP, noncompetitive to the peptide substrate, IC50 is 70 nM, mechanism
0.00058
LY580276
Homo sapiens;
-
competitive to ATP, noncompetitive to the peptide substrate, IC50 is 580 nM, mechanism
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22 - 30
-
assay at
25
-
assay at
30
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
from patients of German origin with tentative diagnosis of hereditary hemorrhagic telangiectasia
Manually annotated by BRENDA team
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ALK3
Manually annotated by BRENDA team
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anaplastic carcinoma lung cell
Manually annotated by BRENDA team
low ALK7 expression level
Manually annotated by BRENDA team
-
hepatoma cell line
Manually annotated by BRENDA team
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a myeloid leukemic cell line
Manually annotated by BRENDA team
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pancreatic Smad4 null cell line, expression of Smad2 and Smad3
Manually annotated by BRENDA team
-
an ovarian surface epithelial cell line
Manually annotated by BRENDA team
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an ovarian surface epithelial cell line
Manually annotated by BRENDA team
-
a myeloid leukemic cell line
Manually annotated by BRENDA team
high ALK7 expression level
Manually annotated by BRENDA team
-
breast carcinoma cell line, derived from malignant pleural effusions
Manually annotated by BRENDA team
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breast carcinoma cell line, derived from malignant pleural effusions
Manually annotated by BRENDA team
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breast Smad4 null cell line, expression of Smad2 and Smad3
Manually annotated by BRENDA team
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osteosarcoma cell line
Manually annotated by BRENDA team
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a myelo-monocytic leukemic cell line
Manually annotated by BRENDA team
-
carcinoma breast cell
Manually annotated by BRENDA team
-
an ovarian cancer cell line
Manually annotated by BRENDA team
-
and beta cell lines
Manually annotated by BRENDA team
-
a myelo-monocytic leukemic cell line
Manually annotated by BRENDA team
-
a myelo-monocytic leukemic cell line
Manually annotated by BRENDA team
-
diverse VACO cell lines, Smad4 null cell lines, expression analysis of Smad2, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
65000
-
ALK1 protein, determined by SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
ALK5 performs autophosphorylation, wild-type and mutant T204D enzymes
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged transforming growth factor-beta type I receptor kinase domain mutant T204D from insect Sf9 cells by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant ALK5 from Spodoptera frugiperda Sf9 cells by nickel affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
activin receptor-like kinase 1 gene, ALK1 is located on chromosome 12q13, DNA and amino acid sequence determination of wild-type and mutant enzymes, genotyping
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ALK7, DNA and amino acid sequence determination and analysis, genetic organization, determination of several isoforms by alternative splicing of ALK7
co-expression and co-localization of ALK1 mutant Q201D and cytoplasmic PEG10-RF1 mutant YFP in COS-1 cells, expression of ALK1 and ALK5 with PEG10-RF1 in a two-hydrid system in Saccharomyces cerevisiae, overview
-
expression of HA-tagged wild-type ALK7 in rat FaO hepatoma cells and transiently of HA-tagged ALK mutant T194D in human Hep3B hepatoma cells using the adenovirus infection method, expression leads in both cases to an apoptosis-positive phenotype, expression of inactive ALK7 mutant K222R dos not cause an altered phenotype
-
expression of His-tagged transforming growth factor-beta type I receptor kinase domain mutant T204D in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
expression of His-tagged wild-type and mutant ALK5 in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
functional co-expression of TGF-beta and the soluble intracellular domain of the TGF-beta type I receptor in murine mammary gland epithelial cells and in mink lung epithelial cells inducing growth inhibition
-
gene ALK5, transient recombinant expression of FLAG-tagged enzyme mutant T202D in HEKT293 cells
-
surface expression of wild-type and mutant ALK4 type I receptors in HEK293T cells, expression of wild-type and mutant ALK4 type I receptors in mink lung epithelial cells, Mv1Lu cells
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transient expression of wild-type and mutant enzymes in COS-7 cells, and in Min-6 and Hep-G2 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
(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
-
down-regulation of ALK1 in LX-2 cells by the herbal compound Cpd861, cells are treated with TGF-beta1 (5 ng/ml) Cpd861 (0.1 mg/ml), TGF-beta1 (5 ng/ml) plus Cpd861 (an extract of 10 herbs traditionally applied as chinese medicine, 5 ng/ml) for 24 h to investigate the effect of Cpd861 on the TGF-beta1/ALK1 pathway
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reduction of endogenous ALK1 expression significantly attenuates BMP9-mediated phosphorylation of Smad1/5 and Smad2
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the ALK1 gene is constitutively expressed in LX-2 cells and TGF-beta1 does not further increase its expression
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A78G
-
site-directed mutagenesis, the mutation affects binding of actividin
D89A
-
site-directed mutagenesis, the mutation does not affect binding of actividin
E74A
-
site-directed mutagenesis, the mutation affects binding of actividin
E88A
-
site-directed mutagenesis, the mutation does not affect binding of actividin
F82A
-
site-directed mutagenesis, the mutation slightly affects binding of actividin
G79A
-
site-directed mutagenesis, the mutation affects binding of actividin
H312Q
-
naturally occuring mutation in Japanese pulmonary arterial hypertension patients
I70A
-
site-directed mutagenesis, the mutation of a residue from the ALK4 extracellular domain affects the binding of activin and the substantial effects of the dominant negative truncated ALK4 mutant
K222R
-
inactive mutant
K72A
-
site-directed mutagenesis, the mutation does not affect binding of actividin
K80A
-
site-directed mutagenesis, the mutation affects binding of actividin
L381P
-
naturally occuring mutation in Japanese pulmonary arterial hypertension patients
L40A
-
site-directed mutagenesis, the mutation of a residue from the ALK4 extracellular domain affects the binding of activin and the substantial effects of the dominant negative truncated ALK4 mutant
L75A
-
site-directed mutagenesis, the mutation of a residue from the ALK4 extracellular domain affects the binding of activin and the substantial effects of the dominant negative truncated ALK4 mutant
L85A
-
site-directed mutagenesis, the mutation affects binding of actividin
L90A
-
site-directed mutagenesis, the mutation does not affect binding of actividin
M53A
-
site-directed mutagenesis, the mutation slightly affects binding of actividin
P71A
-
site-directed mutagenesis, the mutation affects binding of actividin
P77A
-
site-directed mutagenesis, the mutation of a residue from the ALK4 extracellular domain affects the binding of activin and the substantial effects of the dominant negative truncated ALK4 mutant
P81A
-
site-directed mutagenesis, the mutation does not affect binding of actividin
Q201D
-
constitutively active ALK1 mutant
R479Q
-
naturally occuring mutation in Japanese pulmonary arterial hypertension patients
R484Q
-
naturally occuring mutation in Japanese pulmonary arterial hypertension patients
R91A
-
site-directed mutagenesis, the mutation affects binding of actividin
S38A
-
site-directed mutagenesis, the mutation slightly affects binding of actividin
S55A
-
site-directed mutagenesis, the mutation affects binding of actividin
S86A
-
site-directed mutagenesis, the mutation affects binding of actividin
S87A
-
site-directed mutagenesis, the mutation affects binding of actividin
T202D
-
site-directed mutagenesis
T204D
-
constitutively active ALK5 mutant
T93A
-
site-directed mutagenesis, the mutation affects binding of actividin
V73A
-
site-directed mutagenesis, the mutation of a residue from the ALK4 extracellular domain affects the binding of activin and the substantial effects of the dominant negative truncated ALK4 mutant
V76A
-
site-directed mutagenesis, the mutation affects binding of actividin
Y83A
-
site-directed mutagenesis, the mutation affects binding of actividin
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
-
next to the Curaçao criteria, genetic analysis contributes as an essential tool to a reliable diagnosis of clinically affected hereditary hemorrhagic telangiectasia patients and clinically unsymptomatic hereditary hemorrhagic telangiectasia patients, thus helping to take early preventive measures even before the occurrence of first clinical symptoms, the PCR-SSP technique can facilitate this high task of genetic analysis in routine hereditary hemorrhagic telangiectasia diagnostics and underlines the importance of using molecular diagnosis for early identification of individuals carrying mutations and being at risk of vascular complications
medicine
-
therapeutic potential of TBRI inhibitors in myelodysplastic syndrome, MDS. The myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by cytologic dysplasia and ineffective hematopoiesis
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