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Information on EC 2.7.11.30 - receptor protein serine/threonine kinase and Organism(s) Rattus norvegicus and UniProt Accession P80204
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2.7.11.30 receptor protein serine/threonine kinaseIUBMB Comments
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].
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Word Map
- 2.7.11.30
-
necroptosis
- pulmonary
- arterial
- hypertension
- endothelial
- smads
- tgf-beta1
- necrosis
- mlkl
- hereditary
- tnf
- fibrosis
- telangiectasia
-
hemorrhagic
- endoglin
- collagen
- malformation
-
arteriovenous
- caspase-8
-
idiopathic
-
domain-like
-
smad2/3
-
tgf-beta-induced
- osteoblast
- factor-beta1
- myofibroblasts
-
tgf-beta-mediated
-
necrostatin-1s
- bmp2
-
autocrine
- epistaxis
- fadd
- bmpr1a
-
tnf-induced
-
anaplastic
-
pseudokinase
-
heteromeric
-
serine-threonine
-
pasmcs
- tak1
- noggin
-
smad-dependent
-
mucocutaneous
- monocrotaline
- tgfbr1
- medicine
-
fkbp12
-
mixed-lineage
- pharmacology
-
receptor-regulated
- ciap2
- diagnostics
-
alk-positive
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
ripk1, bmpr2, ripk3, tgf-beta receptor, tbetarii, alk-1, acvrl1, bmpr-ii, bmprii, tbetar-ii, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ESK2
-
-
-
-
MIS type II receptor
-
-
-
-
MISRII
-
-
-
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MRII
-
-
-
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Serine/threonine-protein kinase receptor R1
-
-
-
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Serine/threonine-protein kinase receptor R4
-
-
-
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Serine/threonine-protein kinase receptor R5
-
-
-
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Serine/threonine-protein kinase receptor R6
-
-
-
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SKR1
-
-
-
-
SKR2
-
-
-
-
SKR3
-
-
-
-
SKR4
-
-
-
-
SKR5
-
-
-
-
SKR6
-
-
-
-
TGF-beta type I receptor
-
-
-
-
TGF-beta type II receptor
-
-
-
-
TSK-7L
-
-
-
-
additional information
-
the enzyme belongs to the TGF-beta superfamily of enzymes
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
146702-86-5
-
152060-53-2
-
154907-75-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + Smad2
ADP + phosphorylated Smad2
GDF-9-induced phosphorylation
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
GDF-9-induced phosphorylation
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
-
ALK7 is involved in regulation of cell proliferation and apoptosis, regulation, overview
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
-
TGF-beta-mediated activation of Smad2 by the TGF-beta receptor
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
-
phosphorylation by the TGF-beta receptor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
-
TGF-beta-mediated activation of Smad3 by the TGF-beta receptor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
-
phosphorylation by the TGF-beta receptor
-
-
?
additional information
?
-
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
?
-
GDF-9 does not induce phosphorylation of Smad1
-
-
?
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
?
-
-
TGF-beta mediates activation of Smad2 and Smad3 in a differentiated way dependent on the developmental and activationstages of the cells, regulation, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + Smad2
ADP + phosphorylated Smad2
GDF-9-induced phosphorylation
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
GDF-9-induced phosphorylation
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
-
ALK7 is involved in regulation of cell proliferation and apoptosis, regulation, overview
-
-
?
ATP + Smad2
ADP + phosphorylated Smad2
-
TGF-beta-mediated activation of Smad2 by the TGF-beta receptor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
-
TGF-beta-mediated activation of Smad3 by the TGF-beta receptor
-
-
?
additional information
?
-
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
?
-
-
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
?
-
-
TGF-beta mediates activation of Smad2 and Smad3 in a differentiated way dependent on the developmental and activationstages of the cells, regulation, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Smad7
inhibits induction of receptor activation/signaling by GDF-9 in vivo
-
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-([[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-[[(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
-
-
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
additional information
no inhibition of GDF-9-induced receptor activation by Smad6
-
additional information
-
inhibitory potency of 5-(pyridin-2-yl)thiazole inhibitors, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
growth differentiation factor-9
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
-
TGF-beta
interacts with and activates type I actividin receptor-like kinase 5, ALK5
-
additional information
-
increased D-glucose and palmitate concentrations increase the ALK7 enzyme expression in INS-1 cells
-
TGF-beta
-
binds and activates the TGF-beta receptor, treatment of cells with TGF-beta increaes the production of matrix proteins
-
TGF-beta
-
binds and activates the TGF-family receptor kinases of type I and type II, e.g. type I receptor ALK7
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000034
3-((4-(6-methylpyridin-2-yl)-5-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide
Rattus norvegicus
-
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
primary, differential TGF-beta-mediated activation of Smad2 and Smad3 in activated and non-activated cells, overview
additional information
-
expression analysis of ALK7 in different cells types, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TGFR1_RAT
501
2
56000
Swiss-Prot
Secretory Pathway (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of ALK7 in COS cells, native expression analysis of ALK7 in different cells types
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
exposure to monocrotaline and chronic hypoxia leads to a reduction in the expression of BMPR-II mRNA in rat lungs by day 21
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zhang, N.; Kumar, M.; Xu, G.; Ju, W.; Yoon, T.; Xu, E.; Huang, X.; Gaisano, H.; Peng, C.; Wang, Q.
Activin receptor-like kinase 7 induces apoptosis of pancreatic beta cells and beta cell lines
Diabetologia
49
506-518
2006
Rattus norvegicus
Liu, C.; Gaca, M.D.; Swenson, E.S.; Vellucci, V.F.; Reiss, M.; Wells, R.G.
Smads 2 and 3 are differentially activated by transforming growth factor-beta (TGF-beta) in quiescent and activated hepatic stellate cells. Constitutive nuclear localization of Smads in activated cells is TGF-beta-independent
J. Biol. Chem.
278
11721-11728
2003
Rattus norvegicus
Mazerbourg, S.; Klein, C.; Roh, J.; Kaivo-Oja, N.; Mottershead, D.G.; Korchynskyi, O.; Ritvos, O.; Hsueh, A.J.
Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5
Mol. Endocrinol.
18
653-665
2004
Rattus norvegicus (P80204)
Kim, D.K.; Choi, J.H.; An, Y.J.; Lee, H.S.
Synthesis and biological evaluation of 5-(pyridin-2-yl)thiazoles as transforming growth factor-beta type1 receptor kinase inhibitors
Bioorg. Med. Chem. Lett.
18
2122-2127
2008
Rattus norvegicus
Long, L.; Crosby, A.; Yang, X.; Southwood, M.; Upton, P.D.; Kim, D.K.; Morrell, N.W.
Altered bone morphogenetic protein and transforming growth factor-beta signaling in rat models of pulmonary hypertension: potential for activin receptor-like kinase-5 inhibition in prevention and progression of disease
Circulation
119
566-576
2009
Rattus norvegicus
EXTERNAL LINKS (specific for EC-Number 2.7.11.30)
Transporter Classification Database (TCDB): 8.A.23.1.27
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