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Target not currently curated in GtoImmuPdb
Target id: 1799
Nomenclature: erb-b2 receptor tyrosine kinase 4
Abbreviated Name: HER4
Family: Type I RTKs: ErbB (epidermal growth factor) receptor family
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 1 | 1308 | 2q34 | ERBB4 | erb-b2 receptor tyrosine kinase 4 | |
Mouse | 1 | 1308 | 1 33.8 cM | Erbb4 | erb-b2 receptor tyrosine kinase 4 | |
Rat | 1 | 1308 | 9q32-q33 | Erbb4 | erb-b2 receptor tyrosine kinase 4 |
Previous and Unofficial Names |
Her4 | v-erb-b2 avian erythroblastic leukemia viral oncogene 4 | v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 |
Database Links | |
Alphafold | Q15303 (Hs), Q61527 (Mm), Q62956 (Rn) |
BRENDA | 2.7.10.1 |
CATH/Gene3D | 3.80.20.20 |
ChEMBL Target | CHEMBL3009 (Hs) |
DrugBank Target | Q15303 (Hs) |
Ensembl Gene | ENSG00000178568 (Hs), ENSMUSG00000062209 (Mm), ENSRNOG00000014248 (Rn) |
Entrez Gene | 2066 (Hs), 13869 (Mm), 59323 (Rn) |
Human Protein Atlas | ENSG00000178568 (Hs) |
KEGG Enzyme | 2.7.10.1 |
KEGG Gene | hsa:2066 (Hs), mmu:13869 (Mm), rno:59323 (Rn) |
OMIM | 600543 (Hs) |
Orphanet | ORPHA370064 (Hs) |
Pharos | Q15303 (Hs) |
RefSeq Nucleotide | NM_001042599 (Hs), NM_010154 (Mm), NM_021687 (Rn) |
RefSeq Protein | NP_001036064 (Hs), NP_034284 (Mm), NP_067719 (Rn) |
UniProtKB | Q15303 (Hs), Q61527 (Mm), Q62956 (Rn) |
Wikipedia | ERBB4 (Hs) |
Selected 3D Structures | |||||||||||
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Enzyme Reaction | ||||
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Natural/Endogenous Ligands |
betacellulin {Sp: Human} |
epiregulin {Sp: Human} |
HB-EGF {Sp: Human} |
neuregulin-1 {Sp: Human} |
neuregulin-2 {Sp: Human} |
neuregulin-3 {Sp: Human} |
neuregulin-4 {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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 5,16 |
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Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Target used in screen: ERBB4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 1,6 |
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Target used in screen: ErbB4/ERBB4(HER4) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immuno Process Associations | ||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||
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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. Barf T, Kaptein A. (2012) Irreversible protein kinase inhibitors: balancing the benefits and risks. J Med Chem, 55 (14): 6243-62. [PMID:22621397]
3. Bradshaw JM, McFarland JM, Paavilainen VO, Bisconte A, Tam D, Phan VT, Romanov S, Finkle D, Shu J, Patel V et al.. (2015) Prolonged and tunable residence time using reversible covalent kinase inhibitors. Nat Chem Biol, 11 (7): 525-31. [PMID:26006010]
4. Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR et al.. (2016) Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med, 374 (4): 323-32. [PMID:26641137]
5. 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]
6. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]
7. Gavai AV, Fink BE, Fairfax DJ, Martin GS, Rossiter LM, Holst CL, Kim SH, Leavitt KJ, Mastalerz H, Han WC et al.. (2009) Discovery and preclinical evaluation of [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid, (3S)-3-morpholinylmethyl ester (BMS-599626), a selective and orally efficacious inhibitor of human epidermal growth factor receptor 1 and 2 kinases. J Med Chem, 52 (21): 6527-30. [PMID:19821562]
8. Huang Z, Dong Y. (2012) Quinazoline derivatives substituted by aniline, preparation method and use thereof. Patent number: WO2012027960A1. Assignee: Shandong Xuanzhu Pharma Co Ltd. Priority date: 30/08/2011. Publication date: 30/03/2012.
9. Klutchko SR, Zhou H, Winters RT, Tran TP, Bridges AJ, Althaus IW, Amato DM, Elliott WL, Ellis PA, Meade MA et al.. (2006) Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB family of tyrosine kinase receptors. J Med Chem, 49 (4): 1475-85. [PMID:16480284]
10. Kulukian A, Lee P, Taylor J, Rosler R, de Vries P, Watson D, Forero-Torres A, Peterson S. (2020) Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models. Mol Cancer Ther, 19 (4): 976-987. [PMID:32241871]
11. Li X, Zuo Y, Tang G, Wang Y, Zhou Y, Wang X, Guo T, Xia M, Ding N, Pan Z. (2014) Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem, 57 (12): 5112-28. [PMID:24915291]
12. Nam HJ, Kim HP, Yoon YK, Hur HS, Song SH, Kim MS, Lee GS, Han SW, Im SA, Kim TY et al.. (2011) Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer. Cancer Lett, 302 (2): 155-65. [PMID:21306821]
13. Qiu C, Tarrant MK, Choi SH, Sathyamurthy A, Bose R, Banjade S, Pal A, Bornmann WG, Lemmon MA, Cole PA et al.. (2008) Mechanism of activation and inhibition of the HER4/ErbB4 kinase. Structure, 16 (3): 460-7. [PMID:18334220]
14. Ren Y, Zheng J, Fan S, Wang L, Cheng M, Shi D, Zhang W, Tang R, Yu Y, Jiao L et al.. (2017) Anti-tumor efficacy of theliatinib in esophageal cancer patient-derived xenografts models with epidermal growth factor receptor (EGFR) overexpression and gene amplification. Oncotarget, 8 (31): 50832-50844. [PMID:28881608]
15. Traxler P, Allegrini PR, Brandt R, Brueggen J, Cozens R, Fabbro D, Grosios K, Lane HA, McSheehy P, Mestan J et al.. (2004) AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res, 64 (14): 4931-41. [PMID:15256466]
16. 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]
17. Wood ER, Shewchuk LM, Ellis B, Brignola P, Brashear RL, Caferro TR, Dickerson SH, Dickson HD, Donaldson KH, Gaul M et al.. (2008) 6-Ethynylthieno[3,2-d]- and 6-ethynylthieno[2,3-d]pyrimidin-4-anilines as tunable covalent modifiers of ErbB kinases. Proc Natl Acad Sci USA, 105 (8): 2773-8. [PMID:18287036]
18. Xie H, Lin L, Tong L, Jiang Y, Zheng M, Chen Z, Jiang X, Zhang X, Ren X, Qu W et al.. (2011) AST1306, a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, exhibits antitumor activity both in vitro and in vivo. PLoS ONE, 6 (7): e21487. [PMID:21789172]
19. Zhou W, Ercan D, Chen L, Yun CH, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R et al.. (2009) Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature, 462 (7276): 1070-4. [PMID:20033049]
Type I RTKs: ErbB (epidermal growth factor) receptor family: erb-b2 receptor tyrosine kinase 4. Last modified on 19/04/2023. Accessed on 03/11/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1799.