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transforming growth factor beta receptor 2

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Target id: 1795

Nomenclature: transforming growth factor beta receptor 2

Abbreviated Name: TGFBR2

Family: Type II receptor serine/threonine kinases

Contents:

Quaternary Structure: Complexes
Transforming growth factor β receptor
Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 567 3p24.1 TGFBR2 transforming growth factor beta receptor 2
Mouse 1 592 9 68.39 cM Tgfbr2 transforming growth factor, beta receptor II
Rat 1 567 8q32 Tgfbr2 transforming growth factor, beta receptor 2
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 Click here for help
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 Click here for help
Alphafold P37173 (Hs), Q62312 (Mm), P38438 (Rn)
BRENDA 2.7.11.30
ChEMBL Target CHEMBL4267 (Hs)
Ensembl Gene ENSG00000163513 (Hs), ENSMUSG00000032440 (Mm), ENSRNOG00000013265 (Rn)
Entrez Gene 7048 (Hs), 21813 (Mm), 81810 (Rn)
Human Protein Atlas ENSG00000163513 (Hs)
KEGG Enzyme 2.7.11.30
KEGG Gene hsa:7048 (Hs), mmu:21813 (Mm), rno:81810 (Rn)
OMIM 190182 (Hs)
Orphanet ORPHA120069 (Hs)
Pharos P37173 (Hs)
RefSeq Nucleotide NM_001024847 (Hs), NM_009371 (Mm), NM_031132 (Rn)
RefSeq Protein NP_001020018 (Hs), NP_033397 (Mm), NP_083851 (Mm), NP_112394 (Rn)
UniProtKB P37173 (Hs), Q62312 (Mm), P38438 (Rn)
Wikipedia TGFBR2 (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.11.30
Natural/Endogenous Ligands Click here for help
TGFβ3 {Sp: Human}

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LY2109761 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pKi 7
⤷ pKi 6.5 (Ki 3x10-7 M) [7]
compound 13a [PMID: 23639540] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pIC50 4
⤷ pIC50 8.9 (IC50 1.37x10-9 M) [4]
compound 13d [PMID: 23639540] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 4
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [4]
galunisertib Small molecule or natural product Click here for species-specific activity table 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] Small molecule or natural product Click here for species-specific activity table 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} Peptide Click here for species-specific activity table Ligand is endogenous in the given species 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 Peptide Click here for species-specific activity table Immunopharmacology Ligand 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 Click here for help
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
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.6 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
Ki-20227 Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
PLX-4720 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure 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 Click here for help
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 Small molecule or natural product Hs Inhibitor Inhibition 10.1
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 18.7
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 19.4
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 42.6
K-252a Small molecule or natural product Hs Inhibitor Inhibition 47.6
aloisine A Small molecule or natural product Hs Inhibitor Inhibition 55.0
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 58.2
Cdk4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 61.8
compound 52 [PMID: 9677190] Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 70.2
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 70.3
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Immuno Process:  Antigen presentation
Immuno Process:  Tissue repair
Clinically-Relevant Mutations and Pathophysiology Click here for help
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 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1795.