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bone morphogenetic protein receptor type IA

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Target id: 1786

Nomenclature: bone morphogenetic protein receptor type IA

Abbreviated Name: BMPR1A

Family: Type I receptor serine/threonine kinases

Contents:

Quaternary Structure: Complexes
Bone morphogenetic protein receptors
Growth/differentiation factor receptors
Anti-Müllerian hormone receptors
Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 532 10q23.2 BMPR1A bone morphogenetic protein receptor type 1A
Mouse 1 532 14 20.81 cM Bmpr1a bone morphogenetic protein receptor, type 1A
Rat 1 532 16p15 Bmpr1a bone morphogenetic protein receptor type 1A
Previous and Unofficial Names Click here for help
BMP receptor IA | CD292 | SKR5 | activin receptor-like kinase 3 | bone morphogenetic protein 4 receptor | BMP-2/BMP-4 receptor | ALK3 | ACVRLK3 | serine/threonine-protein kinase receptor R5 | bone morphogenetic protein receptor
Database Links Click here for help
Alphafold P36894 (Hs), P36895 (Mm), Q78EA7 (Rn)
BRENDA 2.7.11.30
ChEMBL Target CHEMBL5275 (Hs)
Ensembl Gene ENSG00000107779 (Hs), ENSMUSG00000021796 (Mm), ENSRNOG00000052469 (Rn)
Entrez Gene 657 (Hs), 12166 (Mm), 81507 (Rn)
Human Protein Atlas ENSG00000107779 (Hs)
KEGG Enzyme 2.7.11.30
KEGG Gene hsa:657 (Hs), mmu:12166 (Mm), rno:81507 (Rn)
OMIM 601299 (Hs)
Orphanet ORPHA119048 (Hs)
Pharos P36894 (Hs)
RefSeq Nucleotide NM_004329 (Hs), NM_009758 (Mm), NM_030849 (Rn)
RefSeq Protein NP_004320 (Hs), NP_033888 (Mm), NP_110476 (Rn)
UniProtKB P36894 (Hs), P36895 (Mm), Q78EA7 (Rn)
Wikipedia BMPR1A (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of a TGF-beta ligand-receptor complex between growth/differentiation factor 5 and bone morphogenetic protein receptor type-1A
PDB Id:  3QB4
Resolution:  2.28Å
Species:  Human
References: 
Enzyme Reaction Click here for help
EC Number: 2.7.11.30
Natural/Endogenous Ligands Click here for help
Müllerian inhibiting substance {Sp: Human}
Comments: Other endogenous ligands may include growth/differentiation factor-6 [2].

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 13d [PMID: 23639540] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >8.3 pIC50 4
⤷ pIC50 >8.3 (IC50 <5x10-9 M) [4]
compound 13r [PMID: 23639540] Small molecule or natural product Click here for species-specific activity table Hs Inhibition >8.3 pIC50 4
⤷ pIC50 >8.3 (IC50 <5x10-9 M) [4]
compound 13a [PMID: 23639540] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 4
⤷ pIC50 8.0 (IC50 1.04x10-8 M) [4]
K02288 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 6
⤷ pIC50 7.5 (IC50 3.43x10-8 M) [6]
zilurgisertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 pIC50 1
⤷ pIC50 6.0 (IC50 9.14x10-7 M) [1]
LDN-214117 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.9 pIC50 5
⤷ pIC50 5.9 (IC50 1.171x10-6 M) [5]
ML347 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.0 pIC50 4
⤷ pIC50 5.0 (IC50 1.08x10-5 M) [4]
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: 3,7
Key to terms and symbols Click column headers to sort
Target used in screen: BMPR1A
Ligand Sp. Type Action Value Parameter
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Chromosome 10q23 deletion syndrome
Synonyms: Juvenile polyposis of infancy [Orphanet: ORPHA79076]
OMIM: 612242
Orphanet: ORPHA79076
Disease:  Generalized juvenile polyposis/juvenile polyposis coli
Synonyms: Juvenile polypolis syndrome; JPS [OMIM: 174900]
OMIM: 174900
Orphanet: ORPHA329971
Disease:  Hereditary nonpolyposis colon cancer
Orphanet: ORPHA144
Disease:  Polyposis syndrome, hereditary mixed, 2; HMPS2
OMIM: 610069
Orphanet: ORPHA157794

References

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1. Arista L, Babu S, Bian J, Cui K, Dillon MP, Lattmann R, Li J, Liao L, Lizos D, Ramos R et al.. (2021) Aminopyridine derivatives and their use as selective alk-2 inhibitors. Patent number: US20210155606A1. Assignee: Novartis AG. Priority date: 20/07/2016. Publication date: 27/05/2021.

2. Asai-Coakwell M, March L, Dai XH, Duval M, Lopez I, French CR, Famulski J, De Baere E, Francis PJ, Sundaresan P et al.. (2013) Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. Hum Mol Genet, 22 (7): 1432-42. [PMID:23307924]

3. 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]

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. Mohedas AH, Wang Y, Sanvitale CE, Canning P, Choi S, Xing X, Bullock AN, Cuny GD, Yu PB. (2014) Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J Med Chem, 57 (19): 7900-15. [PMID:25101911]

6. Witten MR, Wu L, Lai CT, Kapilashrami K, Pusey M, Gallagher K, Chen Y, Yao W. (2022) Inhibition of ALK2 with bicyclic pyridyllactams. Bioorg Med Chem Lett, 55: 128452. [PMID:34780900]

7. 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]

How to cite this page

Type I receptor serine/threonine kinases: bone morphogenetic protein receptor type IA. Last modified on 19/03/2024. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1786.