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erb-b2 receptor tyrosine kinase 3

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Target not currently curated in GtoImmuPdb

Target id: 1798

Nomenclature: erb-b2 receptor tyrosine kinase 3

Abbreviated Name: HER3

Family: Type I RTKs: ErbB (epidermal growth factor) receptor family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1342 12q13.2 ERBB3 erb-b2 receptor tyrosine kinase 3
Mouse 1 1339 10 77.1 cM Erbb3 erb-b2 receptor tyrosine kinase 3
Rat 1 1339 7q11 Erbb3 erb-b2 receptor tyrosine kinase 3
Previous and Unofficial Names Click here for help
lethal congenital contracture syndrome 2 | Glial growth factor receptor | LCCS2 | v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3
Database Links Click here for help
Alphafold P21860 (Hs), Q61526 (Mm), Q62799 (Rn)
BRENDA 2.7.10.1
CATH/Gene3D 3.80.20.20
ChEMBL Target CHEMBL5838 (Hs)
Ensembl Gene ENSG00000065361 (Hs), ENSMUSG00000018166 (Mm), ENSRNOG00000004964 (Rn)
Entrez Gene 2065 (Hs), 13867 (Mm), 29496 (Rn)
Human Protein Atlas ENSG00000065361 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:2065 (Hs), mmu:13867 (Mm), rno:29496 (Rn)
OMIM 190151 (Hs)
Orphanet ORPHA160236 (Hs)
Pharos P21860 (Hs)
RefSeq Nucleotide NM_001005915 (Hs), NM_010153 (Mm), NM_017218 (Rn)
RefSeq Protein NP_001005915 (Hs), NP_034283 (Mm), NP_058914 (Rn)
UniProtKB P21860 (Hs), Q61526 (Mm), Q62799 (Rn)
Wikipedia ERBB3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the HER3 (ERBB3) Extracellular Domain
PDB Id:  1M6B
Resolution:  2.6Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the ERBB3 kinase domain in complex with AMP-PNP
PDB Id:  3LMG
Ligand:  AMP-PNP
Resolution:  2.8Å
Species:  Human
References:  9
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Natural/Endogenous Ligands Click here for help
neuregulin-1 {Sp: Human}
neuregulin-2 {Sp: Human}

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
sapitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 1
⤷ pIC50 8.4 (IC50 4x10-9 M) [1]
TX2-121-1 Small molecule or natural product Primary target of this compound Hs Binding 7.3 pIC50 6
⤷ pIC50 7.3 (IC50 4.9x10-8 M) [6]
Inhibitor Comments
TX2-121-1 (PubChem CID 78243759), a compound structurally related to TX1-85-1, is similarly reported to down-regulate HER3-dependent signalling [6].
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
elgemtumab Peptide Primary target of this compound Hs Binding 10.6 – 11.4 pKd 5
⤷ pKd 10.6 – 11.4 (Kd 2.6x10-11 – 4x10-12 M) [5]
seribantumab Peptide Primary target of this compound Hs Binding 9.1 pKd 8
⤷ pKd 9.1 (Kd 7.69x10-10 M) [8]
istiratumab Peptide Primary target of this compound Click here for species-specific activity table Hs Binding >9.0 pKd 4
⤷ pKd >9.0 (Kd <1x10-9 M) [4]
MM-111 Peptide Primary target of this compound Click here for species-specific activity table Hs Binding 7.8 pKd 7
⤷ pKd 7.8 (Kd 1.561x10-8 M) [7]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
TX1-85-1 Small molecule or natural product Primary target of this compound Hs Binding 7.6 pIC50 6
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [6]
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: 3,10
Key to terms and symbols Click column headers to sort
Target used in screen: ERBB3
Ligand Sp. Type Action Value Parameter
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.1 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 8.1 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.7 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
erlotinib 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 »
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Lethal congenital contractural syndrome 2; LCCS2
OMIM: 607598
Orphanet: ORPHA137776

References

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1. Barlaam B, Anderton J, Ballard P, Bradbury RH, Hennequin LF, Hickinson DM, Kettle JG, Kirk G, Klinowska T, Lambert-van der Brempt C et al.. (2013) Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR, HER2, and HER3 Receptors. ACS Med Chem Lett, 4 (8): 742-6. [PMID:24900741]

2. Cho HS, Leahy DJ. (2002) Structure of the extracellular region of HER3 reveals an interdomain tether. Science, 297 (5585): 1330-3. [PMID:12154198]

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. Fitzgerald JB, Johnson BW, Baum J, Adams S, Iadevaia S, Tang J, Rimkunas V, Xu L, Kohli N, Rennard R et al.. (2014) MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol Cancer Ther, 13 (2): 410-25. [PMID:24282274]

5. Garner AP, Sprague EAR, Ettenberg SA, Kunz C, Haubst N, Elis W. (2014) Antibodies for epidermal growth factor receptor 3 (HER3). Patent number: US8735551 B2. Assignee: Novartis Ag.. Priority date: 20/08/2010. Publication date: 27/05/2014.

6. Lim SM, Xie T, Westover KD, Ficarro SB, Tae HS, Gurbani D, Sim T, Marto JA, Jänne PA, Crews CM et al.. (2015) Development of small molecules targeting the pseudokinase Her3. Bioorg Med Chem Lett, 25 (16): 3382-9. [PMID:26094118]

7. McDonagh CF, Huhalov A, Harms BD, Adams S, Paragas V, Oyama S, Zhang B, Luus L, Overland R, Nguyen S et al.. (2012) Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3. Mol Cancer Ther, 11 (3): 582-93. [PMID:22248472]

8. Schoeberl B, Pace EA, Fitzgerald JB, Harms BD, Xu L, Nie L, Linggi B, Kalra A, Paragas V, Bukhalid R et al.. (2009) Therapeutically targeting ErbB3: a key node in ligand-induced activation of the ErbB receptor-PI3K axis. Sci Signal, 2 (77): ra31. [PMID:19567914]

9. Shi F, Telesco SE, Liu Y, Radhakrishnan R, Lemmon MA. (2010) ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proc Natl Acad Sci USA, 107 (17): 7692-7. [PMID:20351256]

10. 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 RTKs: ErbB (epidermal growth factor) receptor family: erb-b2 receptor tyrosine kinase 3. Last modified on 11/07/2016. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1798.