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Information on EC 2.7.11.30 - receptor protein serine/threonine kinase and Organism(s) Mus musculus
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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: Mus musculus
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
-
-
-
-
MRII
-
-
-
-
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
-
-
-
-
TGF-beta type I receptor
-
-
-
-
TGF-beta type II receptor
-
-
-
-
TSK-7L
-
-
-
-
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
-
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 + Smad3
ADP + phosphorylated Smad3
-
TGF-beta-induced C-terminal phosphorylation
-
-
?
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
?
-
-
the enzyme is involved in p38 MAPK activation
-
-
?
additional information
?
-
-
substrate specificity of transforming growth factor-beta receptor I
-
-
?
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
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
?
-
-
the enzyme is involved in p38 MAPK activation
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4(quinolin-4-yl)-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.00015-0.0051 mM, overview
4-phenyl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
-
IC50 of 0.00011-0.020 mM, overview
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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 type II and type I membrane receptors, e.g. ALK1 and ALK5
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00015 - 0.0051
4(quinolin-4-yl)-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
Mus musculus
-
IC50 of 0.00015-0.0051 mM, overview
0.00011 - 0.02
4-phenyl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole derivatives
Mus musculus
-
IC50 of 0.00011-0.020 mM, overview
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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). AVR2B_MOUSE
536
1
60542
Swiss-Prot
Secretory Pathway (Reliability: 1)
BMPR2_MOUSE
1038
1
115020
Swiss-Prot
Secretory Pathway (Reliability: 2)
BMR1A_MOUSE
532
1
60063
Swiss-Prot
Secretory Pathway (Reliability: 1)
BMR1B_MOUSE
502
1
56944
Swiss-Prot
other Location (Reliability: 2)
AMHR2_MOUSE
568
1
61195
Swiss-Prot
Secretory Pathway (Reliability: 3)
TGFR2_MOUSE
567
1
64219
Swiss-Prot
Secretory Pathway (Reliability: 4)
AVR2A_MOUSE
513
1
57890
Swiss-Prot
Secretory Pathway (Reliability: 1)
TGFR1_MOUSE
503
2
56179
Swiss-Prot
Secretory Pathway (Reliability: 2)
ACV1B_MOUSE
505
1
56700
Swiss-Prot
Secretory Pathway (Reliability: 1)
ACV1C_MOUSE
493
2
54700
Swiss-Prot
Secretory Pathway (Reliability: 1)
ACVL1_MOUSE
502
0
56519
Swiss-Prot
Mitochondrion (Reliability: 4)
ACVR1_MOUSE
509
1
57226
Swiss-Prot
Secretory Pathway (Reliability: 2)
Q3UG22_MOUSE
567
1
64146
TrEMBL
Secretory Pathway (Reliability: 4)
Q9CU19_MOUSE
189
1
21067
TrEMBL
other Location (Reliability: 4)
A0A2R8W6H9_MOUSE
448
1
47982
TrEMBL
Secretory Pathway (Reliability: 3)
Q8BRS2_MOUSE
592
1
67136
TrEMBL
Secretory Pathway (Reliability: 3)
Q8C7A7_MOUSE
451
1
50169
TrEMBL
Secretory Pathway (Reliability: 2)
E9Q418_MOUSE
434
1
48888
TrEMBL
other Location (Reliability: 3)
Q3TZF1_MOUSE
505
1
56700
TrEMBL
Secretory Pathway (Reliability: 1)
F6V9X7_MOUSE
190
0
20484
TrEMBL
other Location (Reliability: 5)
B7ZNG1_MOUSE
451
1
50491
TrEMBL
other Location (Reliability: 1)
A2AJR5_MOUSE
413
0
46124
TrEMBL
Secretory Pathway (Reliability: 1)
Q3UP52_MOUSE
209
0
23640
TrEMBL
other Location (Reliability: 5)
Q53Z43_MOUSE
532
1
60063
TrEMBL
Secretory Pathway (Reliability: 1)
Q3USS1_MOUSE
491
1
55894
TrEMBL
Mitochondrion (Reliability: 2)
Q3U485_MOUSE
426
1
47906
TrEMBL
other Location (Reliability: 4)
Q8BRV4_MOUSE
513
1
57916
TrEMBL
Secretory Pathway (Reliability: 1)
Q91YV1_MOUSE
502
1
56483
TrEMBL
Mitochondrion (Reliability: 5)
Q3UG09_MOUSE
768
0
84871
TrEMBL
other Location (Reliability: 1)
A2AJR6_MOUSE
336
0
37228
TrEMBL
Secretory Pathway (Reliability: 1)
Q8BQS9_MOUSE
592
1
67108
TrEMBL
Secretory Pathway (Reliability: 4)
Q9CVP4_MOUSE
215
0
24353
TrEMBL
other Location (Reliability: 3)
Q4FJL1_MOUSE
503
2
56179
TrEMBL
Secretory Pathway (Reliability: 2)
Q9D5H8_MOUSE
420
1
47575
TrEMBL
other Location (Reliability: 2)
Q3V348_MOUSE
363
0
41112
TrEMBL
other Location (Reliability: 2)
Q60607_MOUSE
500
1
56439
TrEMBL
Secretory Pathway (Reliability: 1)
A2AI38_MOUSE
513
1
57890
TrEMBL
Secretory Pathway (Reliability: 1)
Q543C0_MOUSE
592
1
67122
TrEMBL
Secretory Pathway (Reliability: 3)
Q91ZR8_MOUSE
567
1
64247
TrEMBL
Secretory Pathway (Reliability: 4)
B2RRZ4_MOUSE
502
1
56944
TrEMBL
other Location (Reliability: 2)
Q3UER5_MOUSE
580
1
65357
TrEMBL
Secretory Pathway (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
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
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of ALK1 and ALK5 in 293T cells, Hep-G2 cells, and in COS-7 cells using the adenovirus transfection system
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sawyer, J.S.; Beight, D.W.; Britt, K.S.; Anderson, B.D.; Campbell, R.M.; Goodson, T.Jr.; Herron, D.K.; Li, H.Y.; McMillen, W.T.; Mort, N.; Parsons, S.; Smith, E.C.; Wagner, J.R.; Yan, L.; Zhang, F.; Yingling, J.M.
Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain
Bioorg. Med. Chem. Lett.
14
3581-3584
2004
Homo sapiens, Mus musculus
Yakymovych, I.; Heldin, C.H.; Souchelnytskyi, S.
Smad2 phosphorylation by type I receptor. Contribution of arginine 462 and cysteine 463 In the C terminus of Smad2 for specificity
J. Biol. Chem.
279
35781-35787
2004
Mus musculus
Goumans, M.J.; Valdimarsdottir, G.; Itoh, S.; Lebrin, F.; Larsson, J.; Mummery, C.; Karlsson, S.; ten Dijke, P.
Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFbeta/ALK5 signaling
Mol. Cell
12
817-828
2003
Mus musculus
EXTERNAL LINKS (specific for EC-Number 2.7.11.30)
Transporter Classification Database (TCDB): 8.A.23.1.27
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