NRG3

Protein identityUniProt · HPA

UniProt accession

P56975

Gene

NRG3

Ensembl

ENSG00000185737

Chromosome

10

Canonical length

720 aa

Protein class

Cancer-related genes, Plasma proteins, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Vesicles

Secretome location

Secreted in brain

OverviewNCBI Gene

This gene is a member of the neuregulin gene family. This gene family encodes ligands for the transmembrane tyrosine kinase receptors ERBB3 and ERBB4 - members of the epidermal growth factor receptor family. Ligand binding activates intracellular signaling cascades and the induction of cellular responses including proliferation, migration, differentiation, and survival or apoptosis. This gene encodes neuregulin 3 (NRG3). NRG3 has been shown to activate the tyrosine phosphorylation of its cognate receptor, ERBB4, and is thought to influence neuroblast proliferation, migration and differentiation by signalling through ERBB4. NRG3 also promotes mammary differentiation during embryogenesis. Linkage studies have implicated this gene as a susceptibility locus for schizophrenia and schizoaffective disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but their biological validity has not been verified.[provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

720 residues, UniProt reviewed canonical sequence.

>P56975|NRG3
     1  MSEGAAAASP PGAASAAAAS AEEGTAAAAA AAAAGGGPDG GGEGAAEPPR ELRCSDCIVW
    61  NRQQTWLCVV PLFIGFIGLG LSLMLLKWIV VGSVKEYVPT DLVDSKGMGQ DPFFLSKPSS
   121  FPKAMETTTT TTSTTSPATP SAGGAASSRT PNRISTRLTT ITRAPTRFPG HRVPIRASPR
   181  STTARNTAAP ATVPSTTAPF FSSSTLGSRP PVPGTPSTQA MPSWPTAAYA TSSYLHDSTP
   241  SWTLSPFQDA ASSSSSSSSS ATTTTPETST SPKFHTTTYS TERSEHFKPC RDKDLAYCLN
   301  DGECFVIETL TGSHKHCRCK EGYQGVRCDQ FLPKTDSILS DPTDHLGIEF MESEEVYQRQ
   361  VLSISCIIFG IVIVGMFCAA FYFKSKKQAK QIQEQLKVPQ NGKSYSLKAS STMAKSENLV
   421  KSHVQLQNYS KVERHPVTAL EKMMESSFVG PQSFPEVPSP DRGSQSVKHH RSLSSCCSPG
   481  QRSGMLHRNA FRRTPPSPRS RLGGIVGPAY QQLEESRIPD QDTIPCQGIE VRKTISHLPI
   541  QLWCVERPLD LKYSSSGLKT QRNTSINMQL PSRETNPYFN SLEQKDLVGY SSTRASSVPI
   601  IPSVGLEETC LQMPGISEVK SIKWCKNSYS ADVVNVSIPV SDCLIAEQQE VKILLETVQE
   661  QIRILTDARR SEDYELASVE TEDSASENTA FLPLSPTAKS EREAQFVLRN EIQRDSALTK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NRG3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.67

Highest tissue expression

16 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.46

gnomAD pLI

0.11

gnomAD missense Z

-0.26

DepMap mean gene effect

0

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• animal organ development
• ERBB4 signaling pathway
• ERBB4-ERBB4 signaling pathway
• intracellular signal transduction
• mammary placode formation
• modulation of chemical synaptic transmission
• negative regulation of neuron migration
• pattern specification process
• regulation of cell growth
• synapse assembly
• chemorepulsion involved in interneuron migration from the subpallium to the cortex

Molecular functions

• chemorepellent activity
• growth factor activity
• receptor ligand activity
• receptor tyrosine kinase binding
• transmembrane receptor protein tyrosine kinase activator activity

Cellular components

• extracellular region
• extracellular space
• glutamatergic synapse
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-like domain
• Neuregulin

KeywordsUniProt

• Cell membrane
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Growth factor
• Membrane
• Secreted
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of NRG3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ERBB4