Details of the Target

General Information of Target

Target ID LDTP03138
Target Name Receptor tyrosine-protein kinase erbB-3 (ERBB3)
Gene Name ERBB3
Gene ID 2065
Synonyms
HER3; Receptor tyrosine-protein kinase erbB-3; EC 2.7.10.1; Proto-oncogene-like protein c-ErbB-3; Tyrosine kinase-type cell surface receptor HER3
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVM
GNLEIVLTGHNADLSFLQWIREVTGYVLVAMNEFSTLPLPNLRVVRGTQVYDGKFAIFVM
LNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNG
RSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQD
TDCFACRHFNDSGACVPRCPQPLVYNKLTFQLEPNPHTKYQYGGVCVASCPHNFVVDQTS
CVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGN
LDFLITGLNGDPWHKIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGG
RSLYNRGFSLLIMKNLNVTSLGFRSLKEISAGRIYISANRQLCYHHSLNWTKVLRGPTEE
RLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEP
REFAHEAECFSCHPECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPI
YKYPDVQNECRPCHENCTQGCKGPELQDCLGQTLVLIGKTHLTMALTVIAGLVVIFMMLG
GTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVF
GTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPG
SSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNV
LLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVT
VWELMTFGAEPYAGLRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDENIRPTFKE
LANEFTRMARDPPRYLVIKRESGPGIAPGPEPHGLTNKKLEEVELEPELDLDLDLEAEED
NLATTTLGSALSLPVGTLNRPRGSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPR
PVSLHPMPRGCLASESSEGHVTGSEAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLL
TPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLSSVLGTEEEDEDEEYEYM
NRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDY
EYMNRQRDGGGPGGDYAAMGACPASEQGYEEMRAFQGPGHQAPHVHYARLKTLRSLEATD
SAFDNPDYWHSRLFPKANAQRT
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
Protein kinase superfamily, Tyr protein kinase family, EGF receptor subfamily
Subcellular location
Secreted; Cell membrane
Function
Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase. May also be activated by CSPG5. Involved in the regulation of myeloid cell differentiation.
TTD ID
T86350
Uniprot ID
P21860
DrugMap ID
TTDC8N2
Ensemble ID
ENST00000267101.8
HGNC ID
HGNC:3431
ChEMBL ID
CHEMBL5838

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
AU565 SNV: p.E952Q DBIA    Probe Info 
COLO800 SNV: p.S765R .
HCT116 SNV: p.Q261Ter .
HCT15 SNV: p.N126K; p.R667H; p.P1142H DBIA    Probe Info 
HEC1 SNV: p.R475W; p.E1018D .
HEC1B SNV: p.R475W .
IGROV1 SNV: p.K742E DBIA    Probe Info 
JURKAT SNV: p.S1049N; p.H1100Y .
KYSE150 SNV: p.D297Y .
LNCaP clone FGC SNV: p.K177N .
MFE296 Deletion: p.C186VfsTer20 .
MFE319 SNV: p.W902Ter .
MOLT4 SNV: p.R193Ter; p.R679Ter .
NCIH1792 Deletion: p.V104_R106del .
NUGC3 SNV: p.G1273R .
PF382 SNV: p.N487S .
UMUC3 SNV: p.M91I; p.P689S .
WM2664 Insertion: p.L326TfsTer7 .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C331(2.49)  LDD3311  [1]
AHL-Pu-1
 Probe Info  		C1282(20.00)  LDD0170  [2]
IA-alkyne
 Probe Info  		N.A.  LDD0162  [3]
NAIA_5
 Probe Info  		C331(0.00); C259(0.00); C1091(0.00); C778(0.00)  LDD2223  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0025  4SU-RNA DM93 C1282(20.00)  LDD0170  [2]
 LDCM0026  4SU-RNA+native RNA DM93 C1282(11.31); C1091(4.15); C1066(20.00)  LDD0171  [2]
 LDCM0632  CL-Sc Hep-G2 C740(20.00); C1091(0.55); C1078(0.36)  LDD2227  [4]
 LDCM0022  KB02 22RV1 C331(2.31)  LDD2243  [1]
 LDCM0023  KB03 22RV1 C331(2.50)  LDD2660  [1]
 LDCM0024  KB05 G361 C331(2.49)  LDD3311  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 13 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) PI3/PI4-kinase family P42336
Beta-adrenergic receptor kinase 1 (GRK2) AGC Ser/Thr protein kinase family P25098
Tyrosine-protein kinase ABL2 (ABL2) Tyr protein kinase family P42684
Epidermal growth factor receptor (EGFR) Tyr protein kinase family P00533
Receptor tyrosine-protein kinase erbB-2 (ERBB2) Tyr protein kinase family P04626
Receptor tyrosine-protein kinase erbB-3 (ERBB3) Tyr protein kinase family P21860
Receptor tyrosine-protein kinase erbB-4 (ERBB4) Tyr protein kinase family Q15303
Proto-oncogene tyrosine-protein kinase Src (SRC) Tyr protein kinase family P12931
Tyrosine-protein kinase HCK (HCK) Tyr protein kinase family P08631
Tyrosine-protein kinase SYK (SYK) Tyr protein kinase family P43405
Tensin-2 (TNS2) PTEN phosphatase protein family Q63HR2
Tensin-3 (TNS3) PTEN phosphatase protein family Q68CZ2
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) . P19174
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Heat shock protein HSP 90-beta (HSP90AB1) Heat shock protein 90 family P08238
Protein S100-B (S100B) S-100 family P04271
Immunoglobulin
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) . Q96JA1
Other
Click To Hide/Show 14 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Adapter molecule crk (CRK) CRK family P46108
Crk-like protein (CRKL) CRK family P46109
Growth factor receptor-bound protein 2 (GRB2) GRB2/sem-5/DRK family P62993
Growth factor receptor-bound protein 7 (GRB7) GRB7/10/14 family Q14451
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) PI3K p85 subunit family P27986
Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2) PI3K p85 subunit family O00459
Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3) PI3K p85 subunit family Q92569
Ras and Rab interactor 1 (RIN1) RIN (Ras interaction/interference) family Q13671
Protein S100-A4 (S100A4) S-100 family P26447
SH2B adapter protein 3 (SH2B3) SH2B adapter family Q9UQQ2
Cytoplasmic protein NCK2 (NCK2) . O43639
Ras GTPase-activating protein 1 (RASA1) . P20936
SHC-transforming protein 1 (SHC1) . P29353
SHC-transforming protein 3 (SHC3) . Q92529

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Tucatinib . DB11652
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Ezn-3920 . D0VV5X

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
3 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
4 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264