Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEH395)

DTT Name Pro-neuregulin-1 (Pro-NRG1)
Synonyms SMDF (20-241); Pro-neuregulin-1, membrane-bound isoform (20-241); NDF (20-241); Heregulin (20-241); HRGA (20-241); HGL (20-241); GGF (20-241)
Gene Name NRG1
DTT Type
Clinical trial target
 [1]
UniProt ID
NRG1_HUMAN
TTD ID
T65198
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSERKEGRGKGKGKKKERGSGKKPESAAGSQSPALPPRLKEMKSQESAAGSKLVLRCETS
SEYSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGN
DSASANITIVESNEIITGMPASTEGAYVSSESPIRISVSTEGANTSSSTSTSTTGTSHLV
KCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCQPGFTGARCTENVPMKVQNQEKAEELYQ
KRVLTITGICIALLVVGIMCVVAYCKTKKQRKKLHDRLRQSLRSERNNMMNIANGPHHPN
PPPENVQLVNQYVSKNVISSEHIVEREAETSFSTSHYTSTAHHSTTVTQTPSHSWSNGHT
ESILSESHSVIVMSSVENSRHSSPTGGPRGRLNGTGGPRECNSFLRHARETPDSYRDSPH
SERYVSAMTTPARMSPVDFHTPSSPKSPPSEMSPPVSSMTVSMPSMAVSPFMEEERPLLL
VTPPRLREKKFDHHPQQFSSFHHNPAHDSNSLPASPLRIVEDEEYETTQEYEPAQEPVKK
LANSRRAKRTKPNGHIANRLEVDSNTSSQSSNSESETEDERVGEDTPFLGIQNPLAASLE
ATPAFRLADSRTNPAGRFSTQEEIQARLSSVIANQDPIAV
Function
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. Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors.
KEGG Pathway
ErbB signaling pathway (hsa04012 )
Reactome Pathway
PI3K events in ERBB4 signaling (R-HSA-1250342 )
SHC1 events in ERBB4 signaling (R-HSA-1250347 )
Nuclear signaling by ERBB4 (R-HSA-1251985 )
PIP3 activates AKT signaling (R-HSA-1257604 )
GRB2 events in ERBB2 signaling (R-HSA-1963640 )
PI3K events in ERBB2 signaling (R-HSA-1963642 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
RAF/MAP kinase cascade (R-HSA-5673001 )
SHC1 events in ERBB2 signaling (R-HSA-1250196 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
3 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Neucardin DME617W Heart failure BD10-BD13 Phase 3 [1]
GGF DMVWYOU Congestive heart failure BD10 Phase 1b [2]
GGF-2 DMDMPKC Heart failure BD10-BD13 Phase 1 [1]
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References

1 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
2 Glial growth factor/neuregulin inhibits Schwann cell myelination and induces demyelination. J Cell Biol. 2001 Mar 19;152(6):1289-99.