transforming growth factor beta receptor 2 | Type II receptor serine/threonine kinases | IUPHAR/BPS Guide to PHARMACOLOGY

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transforming growth factor beta receptor 2

Target not currently curated in GtoImmuPdb

Target id: 1795

Nomenclature: transforming growth factor beta receptor 2

Abbreviated Name: TGFBR2

Family: Type II receptor serine/threonine kinases

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Quaternary Structure: Complexes
Transforming growth factor β receptor
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 592 3p22 TGFBR2 transforming growth factor beta receptor 2
Mouse 1 592 9F3 Tgfbr2 transforming growth factor, beta receptor II
Rat 1 567 8q32 Tgfbr2 transforming growth factor
Gene and Protein Information Comments
The 592 amino acid human isoform is the longest isoform (A). Isoform B is shorter (567 animo acids) and has refseq NP_003233. The mouse similarly has two protein isoforms: isoform 1 in the table above and isoform 2 (567 animo acids) with refseq NP_083851.
Previous and Unofficial Names
MFS2 | tbetaR-II | TbetaRII | TBR-II | TGF-beta 2 | TGFβ receptor II | TGF-beta receptor type-2 | TGF-beta receptor type II | TGFβR-II | TGF-beta type II receptor | Tgfbr2T | TGFR-2 | transforming growth factor | transforming growth factor beta receptor II | transforming growth factor, beta receptor II (70/80kDa)
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Solution structure and backbone dynamics of the TGFbeta type II receptor extracellular domain.
PDB Id:  1PLO
Resolution:  0.0Å
Species:  Human
References:  3
Enzyme Reaction
EC Number: 2.7.11.30
Natural/Endogenous Ligands
TGFβ3 {Sp: Human}

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LY2109761 Hs Inhibition 6.5 pKi 7
pKi 6.5 (Ki 3x10-7 M) [7]
compound 13a [PMID: 23639540] Hs Inhibition 8.9 pIC50 4
pIC50 8.9 (IC50 1.37x10-9 M) [4]
compound 13d [PMID: 23639540] Hs Inhibition 7.6 pIC50 4
pIC50 7.6 (IC50 2.6x10-8 M) [4]
galunisertib Hs Inhibition 6.7 pIC50 9
pIC50 6.7 (IC50 2.08x10-7 M) [9]
Description: Value determined usinfg the DiscoverX KINOMEscan platform.
compound 15b [PMID: 16539403] Hs Inhibition 6.4 pIC50 6
pIC50 6.4 (IC50 3.52x10-7 M) [6]
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
TGFβ3 {Sp: Human} Hs Agonist 6.5 pKd 5
pKd 6.5 (Kd 2.94x10-7 M) [5]
Description: Using a SPR assay and immobilised ligand.
H. polygyrus TGF-β mimic Hs Agonist 5.5 pKd 5
pKd 5.5 (Kd 2.96x10-6 M) [5]
Description: Measured using a SPR assay and immobilised ligand.
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,8

Key to terms and symbols Click column headers to sort
Target used in screen: TGFBR2
Ligand Sp. Type Action Value Parameter
NVP-TAE684 Hs Inhibitor Inhibition 6.6 pKd
PP-242 Hs Inhibitor Inhibition 6.6 pKd
AST-487 Hs Inhibitor Inhibition 6.6 pKd
PD-173955 Hs Inhibitor Inhibition 6.6 pKd
Ki-20227 Hs Inhibitor Inhibition 6.5 pKd
tamatinib Hs Inhibitor Inhibition 6.5 pKd
lestaurtinib Hs Inhibitor Inhibition 6.3 pKd
canertinib Hs Inhibitor Inhibition 6.1 pKd
PLX-4720 Hs Inhibitor Inhibition 6.1 pKd
fedratinib Hs Inhibitor Inhibition 6.0 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: ...1

Key to terms and symbols Click column headers to sort
Target used in screen: nd/TGFBR2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 10.1
dorsomorphin Hs Inhibitor Inhibition 18.7
alsterpaullone Hs Inhibitor Inhibition 19.4
TWS119 Hs Inhibitor Inhibition 42.6
K-252a Hs Inhibitor Inhibition 47.6
aloisine A Hs Inhibitor Inhibition 55.0
JAK inhibitor I Hs Inhibitor Inhibition 58.2
Cdk4 inhibitor Hs Inhibitor Inhibition 61.8
compound 52 [PMID: 9677190] Hs Inhibitor Inhibition 70.2
SB 218078 Hs Inhibitor Inhibition 70.3
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Colorectal cancer, hereditary nonpolyposis, type 6; HNPCC6
Synonyms: Hereditary nonpolyposis colon cancer [Orphanet: ORPHA144]
OMIM: 614331
Orphanet: ORPHA144
Disease:  Esophageal cancer
Disease Ontology: DOID:5041
OMIM: 133239
Disease:  Loeys-Dietz syndrome 2; LDS2
Synonyms: Aortic aneurysm, familial thoratic 3; AAT3 [OMIM: 610168]
Familial thoracic aortic aneurysm and aortic dissection [Orphanet: ORPHA91387]
Loeys-Dietz syndrome [Orphanet: ORPHA60030] [Disease Ontology: DOID:0050466]
Marfan syndrome type 2 [Orphanet: ORPHA284973]
Disease Ontology: DOID:0050466
OMIM: 610168
Orphanet: ORPHA60030, ORPHA284973, ORPHA91387

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1039-45. [PMID:22037377]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

3. Deep S, Walker KP, Shu Z, Hinck AP. (2003) Solution structure and backbone dynamics of the TGFbeta type II receptor extracellular domain. Biochemistry, 42 (34): 10126-39. [PMID:12939140]

4. Engers DW, Frist AY, Lindsley CW, Hong CC, Hopkins CR. (2013) Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg. Med. Chem. Lett., 23 (11): 3248-52. [PMID:23639540]

5. Johnston CJC, Smyth DJ, Kodali RB, White MPJ, Harcus Y, Filbey KJ, Hewitson JP, Hinck CS, Ivens A, Kemter AM et al.. (2017) A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells. Nat Commun, 8 (1): 1741. [PMID:29170498]

6. Li HY, Wang Y, Heap CR, King CH, Mundla SR, Voss M, Clawson DK, Yan L, Campbell RM, Anderson BD et al.. (2006) Dihydropyrrolopyrazole transforming growth factor-beta type I receptor kinase domain inhibitors: a novel benzimidazole series with selectivity versus transforming growth factor-beta type II receptor kinase and mixed lineage kinase-7. J. Med. Chem., 49 (6): 2138-42. [PMID:16539403]

7. Melisi D, Ishiyama S, Sclabas GM, Fleming JB, Xia Q, Tortora G, Abbruzzese JL, Chiao PJ. (2008) LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Mol. Cancer Ther., 7 (4): 829-40. [PMID:18413796]

8. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]

9. Yingling JM, McMillen WT, Yan L, Huang H, Sawyer JS, Graff J, Clawson DK, Britt KS, Anderson BD, Beight DW et al.. (2018) Preclinical assessment of galunisertib (LY2157299 monohydrate), a first-in-class transforming growth factor-β receptor type I inhibitor. Oncotarget, 9 (6): 6659-6677. [PMID:29467918]

How to cite this page

Type II receptor serine/threonine kinases: transforming growth factor beta receptor 2. Last modified on 16/08/2018. Accessed on 22/07/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1795.