Information on EC 2.7.11.30 - receptor protein serine/threonine kinase

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The expected taxonomic range for this enzyme is: Bilateria

EC NUMBER
COMMENTARY
2.7.11.30
-
RECOMMENDED NAME
GeneOntology No.
receptor protein serine/threonine kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + [receptor-protein] = ADP + [receptor-protein] phosphate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Phosphorylation
-
-
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].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
activin receptor-like kinase 1
-
-
activin receptor-like kinase 1
P37023
-
activin receptor-like kinase 1
-
-
activin receptor-like kinase 1 gene
P37023
-
activin receptor-like kinase 2
-
-
activin receptor-like kinase 5
-
-
activin receptor-like kinase 5
-
-
activin receptor-like kinase 5
-
-
activin receptor-like kinase 5
-
-
activin receptor-like kinase 6
-
-
activin receptor-like kinase 7
-
-
activin receptor-like kinase 7
Q8NER5
-
activin receptor-like kinase 7
-
-
activin receptor-like kinase-5
-
-
activin receptor-like kinase-7
-
-
activin receptor-like-kinase 1
-
-
activin-like kinase receptor 1
-
-
activin-like kinase receptor 4
-
-
ACTR-IC
Q8NER5
-
ACVRL1
P37023
-
ACVRL1
-
-
ALK1
P37023
-
ALK4
-
-
ALK5
-
-
alk5 kinase
P36897
-
ALK6
-
-
ALK7
Q8NER5
-
BMP type I receptor
-
-
BMP type II receptor
-
-
BMP type II receptor
-
-
BMPR-II
-
-
BMPR2
P37023
-
BMPRII
-
-
bone morphogenetic protein receptor II gene
P37023
-
bone morphogenetic protein type II receptor
-
-
bone morphogenetic protein type II receptor
-
-
ESK2
-
-
-
-
MIS type II receptor
-
-
-
-
MRII
-
-
-
-
receptor serine/threonine kinase
Q6GZL5
-
RSTK
Q6GZL5
-
serine/threonine receptor kinase
-
-
Serine/threonine-protein kinase receptor R1
-
-
-
-
Serine/threonine-protein kinase receptor R4
-
-
-
-
Serine/threonine-protein kinase receptor R5
-
-
-
-
Serine/threonine-protein kinase receptor R6
-
-
-
-
SKR1
-
-
-
-
SKR2
-
-
-
-
SKR3
-
-
-
-
SKR4
-
-
-
-
SKR5
-
-
-
-
SKR6
-
-
-
-
SmRK2
Q6GZL5
-
TbetaKI
-
-
TbetaR-I
-
-
TbetaR-I
-
-
TbetaR-II
-
-
TbetaRI
-
-
TbetaRI
-
-
TbetaRI kinase
-
-
TbetaRI receptor kinase
-
-
TbetaRII
-
-
TBRI
P36897
-
TGF-beta receptor
-
-
TGF-beta receptor
-
-
TGF-beta receptor
-
-
TGF-beta receptor 1
Q8NER5
-
TGF-beta receptor I
-
-
TGF-beta receptor I
-
-
TGF-beta receptor I kinase
-
-
TGF-beta receptor I kinase
P36897
-
TGF-beta receptor II
-
-
TGF-beta receptor II kinase
-
-
TGF-beta receptor kinase
-
-
TGF-beta type I receptor
-
-
-
-
TGF-beta type I receptor
-
-
TGF-beta type I receptor kinase
-
-
TGF-beta type I receptor kinase
-
-
TGF-beta type I receptor kinase
-
-
TGF-beta type II receptor
-
-
-
-
TGF-beta type-I receptor
-
-
TGFbetaRI/II kinase
-
-
transforming growth factor beta type-I receptor
-
-
transforming growth factor-beta receptor
-
-
transforming growth factor-beta receptor
-
-
transforming growth factor-beta receptor
-
-
transforming growth factor-beta receptor 1
Q8NER5
-
transforming growth factor-beta receptor I
-
-
transforming growth factor-beta receptor I
-
-
transforming growth factor-beta receptor II
-
-
transforming growth factor-beta type 1 receptor kinase
-
-
transforming growth factor-beta type I receptor
-
-
transforming growth factor-beta type I receptor kinase
-
-
transforming growth factor-beta type1 receptor kinase
-
-
TRKI
-
-
TSK-7L
-
-
-
-
type I receptor kinase
-
-
type I receptor TGF-beta kinase
-
-
type I serine/threonine kinase
-
-
type II receptor serine/threonine kinase
Q6GZL5
-
MISRII
-
-
-
-
additional information
-
ALK7 is a type I serine/threonine kinase receptor belonging to the TGF-beta family of proteins
additional information
-
the enzyme belongs to the TGF-beta superfamily of enzymes
additional information
Q6GZL5
the RSTK belong to the TGF-beta family of receptor serine/threonine kinases
CAS REGISTRY NUMBER
COMMENTARY
146702-86-5
-
152060-53-2
-
154907-75-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
ALK4 is a type I transmembrane serine/threonine kinase receptor
-
-
Manually annotated by BRENDA team
gene ACVRIC, activin receptor type 1C precursor, four GenBank entries; several isoforms by alternative splicing
SwissProt
Manually annotated by BRENDA team
wild-type and endoglin +/- mice
-
-
Manually annotated by BRENDA team
Booroola ewes
-
-
Manually annotated by BRENDA team
female Sprague-Dawley rats
SwissProt
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
3 isozymes
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome) is an autosomal dominant disorder which is clinically characterised by recurrent epistaxis, mucocutaneous telangiectasia and visceral arteriovenous malformations, genetic linkage studies identify 2 genes primarily related to hereditary hemorrhagic telangiectasia: endoglin and activin receptor-like kinase 1, 10 different ACVRL1 mutations can be identified in 12 out of 41 hereditary hemorrhagic telangiectasia patients, including 2 deletions, 2 insertions, 1 splice site mutation and 5 missense mutations
malfunction
-
mutations in the TGF-type I receptor, activin receptor-like kinase (ALK)-1, cause hereditary hemorrhagic telangiectasia but have also been found in some cases of severe pulmonary arterial hypertension
malfunction
-
mutations in transforming growth factor-beta (TGF-beta) receptor superfamily members underlie conditions characterized by vascular dysplasia
malfunction
-
association of ACVRL1 mutations with a vascular disease, familial pulmonary artery hypertension
physiological function
-
activin receptor-like-kinase 1 is a receptor for ligands of the transforming growth factor-beta family
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
P36897
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
-
-, involved in ALK5 activation of p38 MAPK signaling and of GADDbeta45 and BGN expression induced by TGF-beta
-
-
?
ATP + Smad1
ADP + phosphorylated Smad1
show the reaction diagram
-
phosphorylation by ALK1
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
-
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
ALK7, ALK7 is involved in regulation of cell proliferation and apoptosis, regulation, overview
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
P80204
GDF-9-induced phosphorylation
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
phosphorylation by ALK5
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
step in the MAPK signaling pathway via JNK and p38
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
TGF-beta- or actividin-induced phosphorylation
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
P36897
TGF-beta-induced phosphorylation by TbetaRI receptor kinase at both phosphorylation sites Ser465 and Ser467 leads to release of Smad2 from membrane-anchored protein SARA and signaling co-mediator Smad4, translocation into the nucleus, and regulation of target gene expression
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
TGF-beta-mediated activation of Smad2 by the TGF-beta receptor
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
TGF-beta-mediated activation of Smad2 by the TGF-beta receptor
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
phosphorylation by ALK7
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
phosphorylation by the TGF-beta receptor
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
recombinant GST-fusion Smad2 substrate expressed in Escherichia coli, TGF-beta- or actividin-induced phosphorylation of the two C-terminal Ser residues in the Ser-Ser-Xaa-Ser motif
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
P36897
TGF-beta-induced phosphorylation by TbetaRI receptor kinase at two phosphorylation sites Ser465 and Ser467 within the MH2 domain, activity with Smad2 analogues, overview
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
TGF-beta-induced phosphorylation of Arg462 and Cys463 by TbetaR-I, no activity with Smad2 mutant R462I/C463A by TbetaR-I, Smad2 is no substrate of TbetaR-II and BMP type II receptor
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
the substrate is a tumor suppressor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
-
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
ALK7
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
P80204
GDF-9-induced phosphorylation
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
phosphorylation by ALK5
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
step in the MAPK signaling pathway via JNK and p38
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
TGF-beta-mediated activation of Smad3 by the TGF-beta receptor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
TGF-beta-mediated activation of Smad3 by the TGF-beta receptor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
phosphorylation by ALK7
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
phosphorylation by the TGF-beta receptor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
TGF-beta-induced C-terminal phosphorylation
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
the substrate is a tumor suppressor
-
-
?
ATP + Smad5
ADP + phosphorylated Smad5
show the reaction diagram
-
phosphorylation by ALK1
-
-
?
ATP + [actividin receptor]
ADP + [actividin receptor] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [actividin receptor]
ADP + [actividin receptor] phosphate
show the reaction diagram
-
activins regulate pancreatic development, differentiation and insulin secretion, insulin gene is a target in activin receptor-like kinase 7 signaling pathway in pancreatic beta-cells, SBE and A/GG elements of the human insulin promoter are involved in the regulation of the ALK7 signal, regulation, overview
-
-
?
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
-
-
-
-
?
ATP + [TGF-beta receptor I]
ADP + [TGF-beta receptor I] phosphate
show the reaction diagram
-
TGF-beta signalling pathway regulation, overview
-
-
?
additional information
?
-
-
activin receptor-like kinase-7, ALK7, induces apoptosis through activation of MAPKs, e.g. SEK1, in a Smad3-dependent mechanism in hepatoma cells
-
-
-
additional information
?
-
-
ALK4 forms a complex with type II serine/threonine transmembrane receptor ActRIIB or ActRII and activin for initiation of signaling, ALK3 forms a complex with bone morphogenetic protein-2
-
-
-
additional information
?
-
-
ALK7 induces apoptosis of pancreatic beta cells and beta cell lines via Smad2-caspase3 pathways causing diabetes of type 1 and 2, ALK7 activation suppresses Akt activation
-
-
-
additional information
?
-
P80204
diverse ligand members of the TGF-beta family interact with a limited number of receptors in a combinatorial manner to activate two downstream Smad pathways
-
-
-
additional information
?
-
-
in TGF-beta signaling, phosphorylated Smad2 and Smad3 form a complex with tumor suppressor Smad4, the complex is translocated to the nucleus, nuclear translocation of Smad2 and Smad3 in absence of Smad4 is not sufficient for TGF-beta-induced transcriptional responses, Smad4 mutations occur in some human cancers and inactivate the TGF-beta signaling, overview
-
-
-
additional information
?
-
-
TGF-beta is responsible for induction of growth arrest in cells via the transforming growth factor-beta receptor I, the inhibition can be blocked by cell treatment with SD-093overview
-
-
-
additional information
?
-
-
TGF-beta mediates activation of Smad2 and Smad3 in a differentiated way dependent on the developmental and activationstages of the cells, regulation, overview
-
-
-
additional information
?
-
-
TGF-beta regulates the activation state of endothelium via two opposing type I receptor/Smad pathways: ALK1 induces Smad1/5 phosphorylation leading to increased endothelial cell proliferation and migration, while ALK5 promotes Smad2/3 activation and inhibits both processes, regulation overview
-
-
-
additional information
?
-
P36897
TGF-beta signaling is involved in a wide range of cellular processes and various disease states in humans, R-Smad phosphorylation plays a key role
-
-
-
additional information
?
-
-
TGF-beta signals via its receptor type I and type II, ALK5 mediates most of the TGF-beta signaling, misexpression of ALK2, being constitutively active, in nontransforming ventricular, endocardial cells causes epithelial-mesenchymal transformation, EMT, which can be inhibited by Smad6, since ALK2 alone is sufficient to cause EMT, overview
-
-
-
additional information
?
-
-
the enzyme is involved in p38 MAPK activation
-
-
-
additional information
?
-
-
the TGF-beta receptor kinase is involved in transforming growth in advanced carcinogenesis and in epithelial-to-mesenchymal cell transition, EMT, overview
-
-
-
additional information
?
-
-
the TGF-beta type I receptor/ALK5-dependent activation of the GADD45beta gene mediates the induction of biglycan expression by TGF-beta, th TGF-beta type II receptor is required for for TGF-beta binding and signaling induction activity, overview
-
-
-
additional information
?
-
-
ALK2 and ALK5 are type I receptors
-
-
-
additional information
?
-
-
ALK5 performs autophosphorylation, substrate specificities of recombinant wild-type and mutant T204D ALK5, ALK5 is the intracellular domain of the transforming growth factor beta type-I receptor
-
-
-
additional information
?
-
P80204
GDF-9 does not induce phosphorylation of Smad1
-
-
-
additional information
?
-
-
substrate specificity of transforming growth factor-beta receptor I
-
-
-
additional information
?
-
P37023
ALK1 mutations cause hereditary hemorrhagic telangiectasia in association with pulmonary arterial hypertension, PAH, in patients
-
-
-
additional information
?
-
-
ALK6 modulates follicle-stimulating hormone secretion
-
-
-
additional information
?
-
-
ALK7 is a receptor for nodal and activin AB and B, overview. The insulin promoter is activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1, PDX-1, in the ALK7 pathway, overview
-
-
-
additional information
?
-
-
cyclin G2 mRNA is strongly up-regulated by Nodal and ALK7, Nodal and ALK7 decrease the expression of Skp1 and Skp2 and increase cyclin G2 levels. The antiproliferative effect of Nodal/ALK7 on ovarian cancer cells is in part mediated by cyclin G2, regulation, overview
-
-
-
additional information
?
-
-
signaling by RON, a phosphotyrosine kinase receptor, cooperates with Smad4-independent TGF-beta signaling to promote cell motility and invasion, knocking down RON expression in Smad4-deficient cells suppresses TGF-beta-mediated motility and invasion. Functional inactivation by site-directed mutations of two Smad binding sites on the RON promoter inhibits TGF-beta-mediated repression of RON promoter activity, cross-talk of Smad4-independent TGF-beta signaling and the RON pathway promotes an invasive phenotype, overview
-
-
-
additional information
?
-
-
TGF-beta receptor kinase inhibitor LY2109761 reverses the anti-apoptotic effects of TGF-beta1 in myelo-monocytic leukaemic cells, overview
-
-
-
additional information
?
-
-
the TGF-beta pathway is overactivated in myelodysplastic syndrome, MDS, involving ineffective hematopoiesis leading to peripheral cytopenias. Suppression of the TGF-beta signaling leads to in vitro enhancement of hematopoiesis, overview. TBRi inhibition can improve anemia in a model of bone marrow failure, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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 + Smad1
ADP + phosphorylated Smad1
show the reaction diagram
-
phosphorylation by ALK1
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
-
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
ALK7 is involved in regulation of cell proliferation and apoptosis, regulation, overview
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
P80204
GDF-9-induced phosphorylation
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
phosphorylation by ALK5
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
step in the MAPK signaling pathway via JNK and p38
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
TGF-beta- or actividin-induced phosphorylation
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
P36897
TGF-beta-induced phosphorylation by TbetaRI receptor kinase at both phosphorylation sites Ser465 and Ser467 leads to release of Smad2 from membrane-anchored protein SARA and signaling co-mediator Smad4, translocation into the nucleus, and regulation of target gene expression
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
TGF-beta-mediated activation of Smad2 by the TGF-beta receptor
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
show the reaction diagram
-
TGF-beta-mediated activation of Smad2 by the TGF-beta receptor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
-
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
ALK7
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
P80204
GDF-9-induced phosphorylation
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
phosphorylation by ALK5
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
step in the MAPK signaling pathway via JNK and p38
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
TGF-beta-mediated activation of Smad3 by the TGF-beta receptor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
TGF-beta-mediated activation of Smad3 by the TGF-beta receptor
-
-
?
ATP + Smad5
ADP + phosphorylated Smad5
show the reaction diagram
-
phosphorylation by ALK1
-
-
?
ATP + [actividin receptor]
ADP + [actividin receptor] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [actividin receptor]
ADP + [actividin receptor] phosphate
show the reaction diagram
-
activins regulate pancreatic development, differentiation and insulin secretion, insulin gene is a target in activin receptor-like kinase 7 signaling pathway in pancreatic beta-cells, SBE and A/GG elements of the human insulin promoter are involved in the regulation of the ALK7 signal, regulation, overview
-
-
?
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
-
-
-
-
?
ATP + [TGF-beta receptor I]
ADP + [TGF-beta receptor I] phosphate
show the reaction diagram
-
TGF-beta signalling pathway regulation, overview
-
-
?
additional information
?
-
-
activin receptor-like kinase-7, ALK7, induces apoptosis through activation of MAPKs, e.g. SEK1, in a Smad3-dependent mechanism in hepatoma cells
-
-
-
additional information
?
-
-
ALK4 forms a complex with type II serine/threonine transmembrane receptor ActRIIB or ActRII and activin for initiation of signaling, ALK3 forms a complex with bone morphogenetic protein-2
-
-
-
additional information
?
-
-
ALK7 induces apoptosis of pancreatic beta cells and beta cell lines via Smad2-caspase3 pathways causing diabetes of type 1 and 2, ALK7 activation suppresses Akt activation
-
-
-
additional information
?
-
P80204
diverse ligand members of the TGF-beta family interact with a limited number of receptors in a combinatorial manner to activate two downstream Smad pathways
-
-
-
additional information
?
-
-
in TGF-beta signaling, phosphorylated Smad2 and Smad3 form a complex with tumor suppressor Smad4, the complex is translocated to the nucleus, nuclear translocation of Smad2 and Smad3 in absence of Smad4 is not sufficient for TGF-beta-induced transcriptional responses, Smad4 mutations occur in some human cancers and inactivate the TGF-beta signaling, overview
-
-
-
additional information
?
-
-
TGF-beta is responsible for induction of growth arrest in cells via the transforming growth factor-beta receptor I, the inhibition can be blocked by cell treatment with SD-093overview
-
-
-
additional information
?
-
-
TGF-beta mediates activation of Smad2 and Smad3 in a differentiated way dependent on the developmental and activationstages of the cells, regulation, overview
-
-
-
additional information
?
-
-
TGF-beta regulates the activation state of endothelium via two opposing type I receptor/Smad pathways: ALK1 induces Smad1/5 phosphorylation leading to increased endothelial cell proliferation and migration, while ALK5 promotes Smad2/3 activation and inhibits both processes, regulation overview
-
-
-
additional information
?
-
P36897
TGF-beta signaling is involved in a wide range of cellular processes and various disease states in humans, R-Smad phosphorylation plays a key role
-
-
-
additional information
?
-
-
TGF-beta signals via its receptor type I and type II, ALK5 mediates most of the TGF-beta signaling, misexpression of ALK2, being constitutively active, in nontransforming ventricular, endocardial cells causes epithelial-mesenchymal transformation, EMT, which can be inhibited by Smad6, since ALK2 alone is sufficient to cause EMT, overview
-
-
-
additional information
?
-
-
the enzyme is involved in p38 MAPK activation
-
-
-
additional information
?
-
-
the TGF-beta receptor kinase is involved in transforming growth in advanced carcinogenesis and in epithelial-to-mesenchymal cell transition, EMT, overview
-
-
-
additional information
?
-
-
the TGF-beta type I receptor/ALK5-dependent activation of the GADD45beta gene mediates the induction of biglycan expression by TGF-beta, th TGF-beta type II receptor is required for for TGF-beta binding and signaling induction activity, overview
-
-
-
additional information
?
-
P37023
ALK1 mutations cause hereditary hemorrhagic telangiectasia in association with pulmonary arterial hypertension, PAH, in patients
-
-
-
additional information
?
-
-
ALK6 modulates follicle-stimulating hormone secretion
-
-
-
additional information
?
-
-
ALK7 is a receptor for nodal and activin AB and B, overview. The insulin promoter is activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1, PDX-1, in the ALK7 pathway, overview
-
-
-
additional information
?
-
-
cyclin G2 mRNA is strongly up-regulated by Nodal and ALK7, Nodal and ALK7 decrease the expression of Skp1 and Skp2 and increase cyclin G2 levels. The antiproliferative effect of Nodal/ALK7 on ovarian cancer cells is in part mediated by cyclin G2, regulation, overview
-
-
-
additional information
?
-
-
signaling by RON, a phosphotyrosine kinase receptor, cooperates with Smad4-independent TGF-beta signaling to promote cell motility and invasion, knocking down RON expression in Smad4-deficient cells suppresses TGF-beta-mediated motility and invasion. Functional inactivation by site-directed mutations of two Smad binding sites on the RON promoter inhibits TGF-beta-mediated repression of RON promoter activity, cross-talk of Smad4-independent TGF-beta signaling and the RON pathway promotes an invasive phenotype, overview
-
-
-
additional information
?
-
-
TGF-beta receptor kinase inhibitor LY2109761 reverses the anti-apoptotic effects of TGF-beta1 in myelo-monocytic leukaemic cells, overview
-
-
-
additional information
?
-
-
the TGF-beta pathway is overactivated in myelodysplastic syndrome, MDS, involving ineffective hematopoiesis leading to peripheral cytopenias. Suppression of the TGF-beta signaling leads to in vitro enhancement of hematopoiesis, overview. TBRi inhibition can improve anemia in a model of bone marrow failure, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
-
Mn2+
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1-(1,3-benzodioxol-5-yl)-2-(6-ethylpyridin-2-yl)ethanone
-
-
1-(1,3-benzodioxol-5-yl)-2-(6-methylpyridin-2-yl)ethanone
-
-
1-(1,3-benzodioxol-5-yl)-2-bromo-2-(6-ethylpyridin-2-yl)ethanone
-
-
1-(1,3-benzodioxol-5-yl)-2-bromo-2-(6-methylpyridin-2-yl)ethanone
-
-
1-(1,3-benzodioxol-5-yl)-2-bromo-2-pyridin-2-ylethanone
-
-
1-(1,3-benzodioxol-5-yl)-2-pyridin-2-ylethanone
-
-
2,6-lutidine
-
i.e. 2,6-dimethylpyridine
2-(6-ethylpyridin-2-yl)-1-quinoxalin-6-ylethanone
-
-
2-(6-methylpyridin-2-yl)-1-quinoxalin-6-ylethanone
-
-
2-bromo-2-(6-ethylpyridin-2-yl)-1-quinoxalin-6-ylethanone
-
-
2-bromo-2-(6-methylpyridin-2-yl)-1-quinoxalin-6-ylethanone
-
-
2-bromo-2-pyridin-2-yl-1-quinoxalin-6-ylethanone
-
-
2-pyridin-2-yl-1-quinoxalin-6-ylethanone
-
-
3-((4-(6-methylpyridin-2-yl)-5-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide
-
IN-1233, inhibitor specifically inhibits TGF-beta signaling via ALK-5 by acting as a competitive inhibitor of the ATP-binding site, inhibition of activin receptor-like kinase-5 signaling in vivo with the selective small-molecule inhibitor prevents pulmonary arterial hypertension, right ventricular hypertrophy, and vascular remodeling after monocrotaline injection and inhibits the progression of established pulmonary arterial hypertension in this model
3-([[4-(1,3-benzodioxol-5-yl)-5-(6-ethylpyridin-2-yl)-1,3-thiazol-2-yl]amino]methyl)benzamide
-
-
3-([[4-(1,3-benzodioxol-5-yl)-5-(6-ethylpyridin-2-yl)-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
3-([[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1,3-thiazol-2-yl]amino]methyl)benzamide
-
-
3-([[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
3-([[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1,3-thiazol-2-yl]amino]methyl)benzamide
-
-
3-([[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
3-([[5-(6-ethylpyridin-2-yl)-4-quinoxalin-6-yl-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
3-([[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
3-[[(5-pyridin-2-yl-4-quinoxalin-6-yl-1,3-thiazol-2-yl)amino]methyl]benzamide
-
-
3-[[(5-pyridin-2-yl-4-quinoxalin-6-yl-1,3-thiazol-2-yl)amino]methyl]benzonitrile
-
-
3-[[5-(6-ethylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl]benzamide
-
-
3-[[5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl]benzamide
-
-
4(quinolin-4-yl)-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.00005-0.0013 mM
4(quinolin-4-yl)-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.00015-0.0051 mM, overview
4-(1,3-benzodioxol-5-yl)-5-(6-ethylpyridin-2-yl)-1,3-thiazol-2-amine
-
-
4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1,3-thiazol-2-amine
-
-
4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1,3-thiazol-2-amine
-
-
4-([[4-(1,3-benzodioxol-5-yl)-5-(6-ethylpyridin-2-yl)-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
4-([[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
4-([[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
4-([[5-(6-ethylpyridin-2-yl)-4-quinoxalin-6-yl-1,3-thiazol-2-yl]amino]methyl)benzamide
-
-
4-([[5-(6-ethylpyridin-2-yl)-4-quinoxalin-6-yl-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
4-([[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1,3-thiazol-2-yl]amino]methyl)benzamide
-
-
4-([[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1,3-thiazol-2-yl]amino]methyl)benzonitrile
-
-
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
4-phenyl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.00011-0.020 mM, overview
4-[[(5-pyridin-2-yl-4-quinoxalin-6-yl-1,3-thiazol-2-yl)amino]methyl]benzamide
-
-
4-[[(5-pyridin-2-yl-4-quinoxalin-6-yl-1,3-thiazol-2-yl)amino]methyl]benzonitrile
-
-
5-(6-ethylpyridin-2-yl)-4-quinoxalin-6-yl-1,3-thiazol-2-amine
-
-
5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1,3-thiazol-2-amine
-
-
5-pyridin-2-yl-4-quinoxalin-6-yl-1,3-thiazol-2-amine
-
-
6-ethyl-2-methylpyridine
-
i.e. 2-ethyl-6-methylpyridine
calphostin C
-
-
LY2109761
-
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
-
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
-
competitive to ATP, noncompetitive to the peptide substrate, IC50 is 175 nM, mechanism
LY364947
-
IC50 is 51 nM
LY364947
-
IC50 is 31 nM
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
-
PEG10
-
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
-
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
SD-208
-
inhibition of the TBRI kinase inhibits TGF-beta-mediated smad2 activation in hematopoietic progenitors, alleviates anemia, and stimulates hematopoiesis in vivo in bone marrow
SD-208
-
inhibitor reduces the monocrotaline-induced increase in RV systolic pressure, but the effects on established pulmonary arterial hypertension are modest, and no convincing evidence for in vivo inhibition of TGF-beta-driven target genes is presented
SD-208
-
selektive ALK5 kinase inhibitor
Smad7
P80204
inhibits induction of receptor activation/signaling by GDF-9 in vivo
-
LY580276
-
-
-
additional information
-
a dominant negative SEK1 mutant abolishes the ALK7-induced apoptosis
-
additional information
-
ALK1 mediates inhibition of the ALK5/Smad2/3 pathway
-
additional information
P80204
no inhibition of GDF-9-induced receptor activation by Smad6
-
additional information
-
LY294002 completely abolishes the ALK7 mutant T194D/Smad3-induced synergistic effect by inhibiting interaction between the Smad3-Linker and PDX-1
-
additional information
-
inhibitory potency of 5-(pyridin-2-yl)thiazole inhibitors, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
actividin
-
activates Smad2 phosphorylation via type I receptor kinases
-
actividin
Q8NER5
TGF-beta receptor I and ALK7 possess an actividin receptor-binding domain
-
actividin
-
binds and activates the type I receptor ALK7
-
actividin A
-
required for activity in a complex formed with ALK4 and ActRIIB or ActRII, identification of the functional binding site
-
actividin B
-
required for activity in a complex formed with ALK4 and ActRIIB or ActRII, identification of the functional binding site
-
ALK5
-
is important for ALK1/TGF-beta signaling
-
nodal
Q8NER5
-
-
SARA protein
-
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
-
TGF-beta
-
i.e. transforming growth factor-beta, interacts with and activates type I transforming growth factor-beta receptor
-
TGF-beta
-
binds to and activates TbetaRI receptor kinase that phosphorylates Smad2
-
TGF-beta
-
-
-
TGF-beta
-
-
-
TGF-beta
-
binds and activates the TGF-family receptor kinases of type I and type II, e.g. type I receptor ALK7
-
TGF-beta
-
binds and activates the TGF-beta receptor, treatment of cells with TGF-beta increaes the production of matrix proteins
-
TGF-beta
-
-
-
TGF-beta
-
a potent regulator of cell proliferation, differentiation, motility, and apoptosis, binds to and activates serine/threonine receptors that phosphorylate Smad2 and Smad3
-
TGF-beta
-
activates the TGF-beta type I receptor kinase by binding, affects BGN and GADDbeta45 expression in PANC-1 and M-63 cells via ALK5 and Smad phosphorylation/activation, overview
-
TGF-beta
-
activates the type II and type I membrane receptors, e.g. ALK1 and ALK5
-
TGF-beta
P80204
interacts with and activates type I actividin receptor-like kinase 5, ALK5
-
TGF-beta
-
binds and activates the TGF-beta receptor kinase, promotes transforming growth in advanced carcinogenesis, influences transcription activity of cells
-
TGF-beta
-
activates the TGF-beta receptor by direct binding
-
TGF-beta 3
-
binds and activates ALK5
-
growth differentiation factor-9
P80204
i.e. GDF-9, interacts with bone morphogenetic protein type II receptor, and activates type I actividin receptor-like kinase 5, ALK5, GDF-9 belongs to the TGF-beta family, no stimulation of receptors ALK1, ALK2, ALK3, and ALKA6 by GDF-9
-
additional information
-
increased D-glucose and palmitate concentrations increase the ALK7 enzyme expression in INS-1 cells
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0057
-
ATP
-
pH 7.5, 30C, recombinant mutant T204D ALK5
0.0088
-
ATP
-
pH 7.5, 30C, recombinant wild-type ALK5
0.26
-
KKVLTQMGSPSIRCS(P)SVS
-
pH 7.5, 30C, recombinant wild-type ALK5
0.331
-
KVLTQMGSPSVRCS(P)SMS
-
pH 7.5, 30C, recombinant wild-type ALK5
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2.8e-05
-
LY364947
-
pH 7.5, 30C, recombinant mutant T204D ALK5, inhibition of autophosphorylation
3.8e-05
-
LY566578
-
pH 7.5, 30C, recombinant mutant T204D ALK5, inhibition of autophosphorylation
-
3.7e-05
-
LY580276
-
pH 7.5, 30C, recombinant mutant T204D ALK5, inhibition of autophosphorylation
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.4e-05
-
3-((4-(6-methylpyridin-2-yl)-5-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide
-
-
5e-05
0.0013
4(quinolin-4-yl)-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.00005-0.0013 mM
0.00015
0.0051
4(quinolin-4-yl)-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.00015-0.0051 mM, overview
3e-05
0.000555
4-phenyl substituted pyrazole inhibitors
-
inhibitory potency of 4-phenyl substituted pyrazole derivatives, IC50 of 30-555 nM, overview
-
5e-06
0.0195
4-phenyl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.000005-0.0195 mM
0.00011
0.02
4-phenyl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.00011-0.020 mM, overview
3.1e-05
-
LY364947
-
IC50 is 31 nM
5.1e-05
-
LY364947
-
IC50 is 51 nM
0.000175
-
LY364947
-
competitive to ATP, noncompetitive to the peptide substrate, IC50 is 175 nM, mechanism
7e-05
-
LY566578
-
competitive to ATP, noncompetitive to the peptide substrate, IC50 is 70 nM, mechanism
-
0.00058
-
LY580276
-
competitive to ATP, noncompetitive to the peptide substrate, IC50 is 580 nM, mechanism
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
30
-
assay at
22
-
-
assay at
25
-
-
assay at
30
-
-
assay at
30
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Q6GZL5, -
e.g. on the dorsal surface of male parasites, and on the dorsal and ventral surfaces of female parasites
Manually annotated by BRENDA team
-
from patients of German origin with tentative diagnosis of hereditary hemorrhagic telangiectasia
Manually annotated by BRENDA team
-
CD34+ and stromal cells
Manually annotated by BRENDA team
-
pancreatic Smad4 null cell line, expression of Smad2 and Smad3
Manually annotated by BRENDA team
-
anaplastic carcinoma lung cell
Manually annotated by BRENDA team
-
pancreatic Smad4 null cell line, expression of Smad2 and Smad3
Manually annotated by BRENDA team
-
ALK2, nontransforming ventricular, misexpression of LAK2 in endocardial cells
Manually annotated by BRENDA team
-
embryonic cells
Manually annotated by BRENDA team
Q8NER5
low ALK7 expression level
Manually annotated by BRENDA team
-
ALK2 and ALK5, atrioventricular cushion of developing heart
Manually annotated by BRENDA team
-
hepatoma cell line
Manually annotated by BRENDA team
-
primary, differential TGF-beta-mediated activation of Smad2 and Smad3 in activated and non-activated cells, overview
Manually annotated by BRENDA team
-
a myeloid leukemic cell line
Manually annotated by BRENDA team
-
bone marrow stromal cells
Manually annotated by BRENDA team
-
pancreatic Smad4 null cell line, expression of Smad2 and Smad3
Manually annotated by BRENDA team
Q6GZL5, -
surface, primary expression of type II receptor serine/threonine kinase, SmRK2
Manually annotated by BRENDA team
-
an ovarian surface epithelial cell line
Manually annotated by BRENDA team
-
an ovarian surface epithelial cell line
Manually annotated by BRENDA team
-
hematopoietic cells
Manually annotated by BRENDA team
-
a myeloid leukemic cell line
Manually annotated by BRENDA team
Q8NER5
high ALK7 expression level
Manually annotated by BRENDA team
-
breast carcinoma cell line, derived from malignant pleural effusions
Manually annotated by BRENDA team
-
breast carcinoma cell line, derived from malignant pleural effusions
Manually annotated by BRENDA team
-
breast Smad4 null cell line, expression of Smad2 and Smad3
Manually annotated by BRENDA team
-
enbryonic fibroblast cell line
Manually annotated by BRENDA team
-
osteosarcoma cell line
Manually annotated by BRENDA team
-
carcinoma breast cell
Manually annotated by BRENDA team
-
fibroblast cell line
Manually annotated by BRENDA team
-
an ovarian cancer cell line
Manually annotated by BRENDA team
P80204
small antral follicle of estrogen-treated rats
Manually annotated by BRENDA team
-
pancreatic cancer cell line
Manually annotated by BRENDA team
-
and beta cell lines
Manually annotated by BRENDA team
-
primary cell culture, immunohistochemic analysis for ALK6 detection
Manually annotated by BRENDA team
Q8NER5
high ALK7 expression level, co-expression of nodal in different gestational stages
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
-
a myelo-monocytic leukemic cell line
Manually annotated by BRENDA team
additional information
-
expression analysis of ALK7 in different cells types, overview
Manually annotated by BRENDA team
additional information
-
ALK6 does not co-localize with gondotroph cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
with a large cytoplasmic domain
Manually annotated by BRENDA team
-
transmembrane protein
Manually annotated by BRENDA team
-
with a cytoplasmic domain
Manually annotated by BRENDA team
Q6GZL5, -
the isozymes all possess an extracellular domain
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
65000
-
-
ALK1 protein, determined by SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 55000-72000, different cell sources, SDS-PAGE
additional information
-
ALK5 is the intracellular domain of the transforming growth factor beta type-I receptor
additional information
-
ALK3 crystal structure model analysis
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
ALK5 performs autophosphorylation, wild-type and mutant T204D enzymes
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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 ACCESSION NO.
LITERATURE
transient expression of ALK2 and ALK5 in C3H10T1/2 cells using the adenovirus transfection system
-
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
-
ALK7, DNA and amino acid sequence determination and analysis, genetic organization, determination of several isoforms by alternative splicing of ALK7
Q8NER5
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
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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
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expression of His-tagged wild-type and mutant ALK5 in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
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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
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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
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expression of ALK1 and ALK5 in 293T cells, Hep-G2 cells, and in COS-7 cells using the adenovirus transfection system
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expressed in P-19 cells
P80204
expression of ALK7 in COS cells, native expression analysis of ALK7 in different cells types
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DNA and amino acid sequence determination and analysis of type II receptor serine/threonine kinase, SmRK2, which is expressed in three different transcripts: one encoding a full-length receptor with 5'- and 3'-UTRs, a second one encoding a longer form containing no 3'-UTR and no stop codon, and a third truncated version encoding the first 53 amino acids of the N-terminus, phylogenetic tree, expression of GST-tagged SmRK2 in Escherichia coli strain BL21(DE3)
Q6GZL5, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
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
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in endoglin +/- mice, ACVRL1 is expressed in small regions of the distal arteries where endoglin is below detectable limits, co-expression of ACVRL1 and endoglin and associated pSmad1/5/8 signalling in the endothelial cells of distal arterioles
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exposure to monocrotaline and chronic hypoxia leads to a reduction in the expression of BMPR-II mRNA in rat lungs by day 21
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ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A78G
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site-directed mutagenesis, the mutation affects binding of actividin
D89A
-
site-directed mutagenesis, the mutation does not affect binding of actividin
E74A
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site-directed mutagenesis, the mutation affects binding of actividin
E88A
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site-directed mutagenesis, the mutation does not affect binding of actividin
F82A
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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
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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
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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
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
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site-directed mutagenesis, the mutation does not affect binding of actividin
Q201D
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constitutively active ALK1 mutant
R479Q
-
naturally occuring mutation in Japanese pulmonary arterial hypertension patients
R484Q
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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
T194D
-
constitutive active ALK7 mutant
T194D
-
site-directed mutagenesis of ALK7
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
additional information
-
misexpression of ALK2 in nontransforming ventricular, endocardial cells causes epithelial-mesenchymal transformation, EMT, which can be decreased by overexpression of inhibitor Smad6
M53A
-
site-directed mutagenesis, the mutation slightly affects binding of actividin
additional information
-
functional co-expression of TGF-beta and the soluble intracellular domain of the TGF-beta type I receptor in murine mammary gland epithelial cells induces transdifferentiation of epithelial cells to mesenchymal cells, overview
additional information
Q8NER5
construction of a truncated mutant ALK7
additional information
-
construction of a truncated dominant negative ALK4 mutant
additional information
-
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
additional information
-
knockout of TBRI by shRNA suppression using a lentiviral construct leads to decreased smad2 activtaion and reverses the suppressive effects of TGF-beta on hematopoiesis, overview
additional information
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ALK1 mutations cause hereditary hemorrhagic telangiectasia in association with pulmonary arterial hypertension, PAH, in patients, determination of polymorphisms in Japanese pulmonary arterial hypertension patients, phenotypes, overview
Y83A
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site-directed mutagenesis, the mutation affects binding of actividin
additional information
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knockdown of ALK5 expression in embryonic endothelial cells by antisense oligonucleotides results in inhibition of both TGF-beta-induced Smad 2 and Smad1/5 phosphorylation, an ALk5mutant defective in Smad activation rescues TGF-beta/ALK1-induced signaling in ALK5 null mutant endothelial cells
additional information
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activin receptor-like kinase 6 Booroola mutation enhances suppressive effects of bone morphogenetic protein 2, BMP2, BMP4, BMP6 and growth and differentiation factor-9 on FSH release from ovine primary pituitary cell cultures
additional information
P80204
conferring of responsiveness to GDF-9-mediated stimulation of ALK5 and Smad3 phosphorylation in normally unresponsive COS-7 cells by overexpression of the three proteins, no responsiveness by co-expression with BMPRII receptor, expression of GDF-9 in a CAGA-luciferase reporter construct in P19 cells reveals that GDF-9 binds to BMP-activated type II receptors but its downstream actions are mediated by the type I receptor ALK5, overview, expression of ALK5 siRNA inhibits GDF-9-induced stimulation in granulosa cells
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
diagnostics
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next to the Curaao 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
-
potential for activin receptor-like kinase-5 inhibition in prevention and progression of disease, inhibition of activin receptor-like kinase-5 signaling in vivo with the selective small-molecule inhibitor IN-1233 prevented pulmonary arterial hypertension, right ventricular hypertrophy, and vascular remodeling after monocrotaline injection and inhibited the progression of established pulmonary arterial hypertension in this model