General Information of Target

Target ID LDTP05347
Target Name Pro-neuregulin-1, membrane-bound isoform (NRG1)
Gene Name NRG1
Gene ID 3084
Synonyms
GGF; HGL; HRGA; NDF; SMDF; Pro-neuregulin-1, membrane-bound isoform; Pro-NRG1) [Cleaved into: Neuregulin-1; Acetylcholine receptor-inducing activity; ARIA; Breast cancer cell differentiation factor p45; Glial growth factor; Heregulin; HRG; Neu differentiation factor; Sensory and motor neuron-derived factor)]
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MSERKEGRGKGKGKKKERGSGKKPESAAGSQSPALPPRLKEMKSQESAAGSKLVLRCETS
SEYSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGN
DSASANITIVESNEIITGMPASTEGAYVSSESPIRISVSTEGANTSSSTSTSTTGTSHLV
KCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCQPGFTGARCTENVPMKVQNQEKAEELYQ
KRVLTITGICIALLVVGIMCVVAYCKTKKQRKKLHDRLRQSLRSERNNMMNIANGPHHPN
PPPENVQLVNQYVSKNVISSEHIVEREAETSFSTSHYTSTAHHSTTVTQTPSHSWSNGHT
ESILSESHSVIVMSSVENSRHSSPTGGPRGRLNGTGGPRECNSFLRHARETPDSYRDSPH
SERYVSAMTTPARMSPVDFHTPSSPKSPPSEMSPPVSSMTVSMPSMAVSPFMEEERPLLL
VTPPRLREKKFDHHPQQFSSFHHNPAHDSNSLPASPLRIVEDEEYETTQEYEPAQEPVKK
LANSRRAKRTKPNGHIANRLEVDSNTSSQSSNSESETEDERVGEDTPFLGIQNPLAASLE
ATPAFRLADSRTNPAGRFSTQEEIQARLSSVIANQDPIAV
Target Type
Clinical trial
Target Bioclass
Immunoglobulin
Family
Neuregulin family
Subcellular location
Secreted; Nucleus; Membrane; Cell membrane
Function
Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4. Binds to ERBB3. Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1. Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons.
TTD ID
T65198
Uniprot ID
Q02297
DrugMap ID
TTEH395
Ensemble ID
ENST00000287842.7
HGNC ID
HGNC:7997

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
22RV1 Deletion: p.K91SfsTer24 .
CORL23 SNV: p.A597V .
DU4475 SNV: p.N75I .
FUOV1 SNV: p.V261M .
HCT15 SNV: p.T217I; p.K228N .
HEC1 SNV: p.K12N; p.S403G .
HEC1B SNV: p.S403G .
HT115 SNV: p.V306A .
LNCaP clone FGC SNV: p.L607M .
LS180 Deletion: p.K91SfsTer24 .
MEWO SNV: p.G119E .
NCIH1299 SNV: p.N378S .
OVK18 Deletion: p.K91SfsTer24 .
SKMEL3 SNV: p.G145E .
SKOV3 SNV: p.N75D .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info 
K82(5.56); K90(3.15); K91(2.22)  LDD0277  [1]
DBIA
 Probe Info 
C409(3.66)  LDD3376  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 42-MG-BA C409(3.84)  LDD2244  [2]
 LDCM0023  KB03 42-MG-BA C409(3.16)  LDD2661  [2]
 LDCM0024  KB05 ONS-76 C409(3.66)  LDD3376  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
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
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Lysosomal-associated transmembrane protein 4B (LAPTM4B) LAPTM4/LAPTM5 transporter family Q86VI4
Membrane-spanning 4-domains subfamily A member 4A (MS4A4A) MS4A family Q96JQ5
Other
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Protein jagunal homolog 1 (JAGN1) Jagunal family Q8N5M9
Transmembrane protein 54 (TMEM54) TMEM54 family Q969K7
B-cell differentiation antigen CD72 (CD72) . P21854

The Drug(s) Related To This Target

Phase 3
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Neucardin . D00ZPR
Phase 1
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Ggf . D08WNO
Ggf-2 . D0H0YZ

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
2 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