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FLASH GENE
Symbol NRG1 contributors: mct/shn - updated : 03-08-2015
HGNC name neuregulin 1
HGNC id 7997
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • NRG1 type 1, immunoglobulin-like and EGF-like domain
  • a kringle-like sequence
    • conjugated GlycoP
    isoforms Precursor precursors are expressed predominately within cortical neurons, soluble neuregulin accumulates preferentially on the surface of white matter astrocytes (PMID: 19150438)
    HOMOLOGY
    interspecies ortholog to Nrg1, Mus musculus
    ortholog to Nrg1, Rattus norvegicus
    ortholog to nrg1, Danio rerio
    Homologene
    FAMILY
  • neuregulin family
    • CATEGORY regulatory , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text type I membrane protein or soluble form
    basic FUNCTION
  • required for generation of neural crest-derived neurons in cranial ganglia and for trabeculation of the heart ventricle (
  • essential role of CRD-NRG-1-mediated signaling for coordinating nerve, target, and Schwann cell interactions in the normal maintenance of peripheral synapses (
  • role in muscle spindle differentiation (
  • indirect NEU/ERBB2 p185 activator (see ERBB2)
  • regulator of expression of ligand and voltage gated channels in neurons and skeletal muscle, stimulating glucose transport translocation and transporter expression in muscle cells, essential for trabeculation of cardiac ventricle
  • involved in the myelination and regulating axonal myelin sheath thickness
  • promoting cell death of prostate cancer cells
  • may regulate skeletal myogenesis and this regulation is dependent on the state of differentiation of the myocytes
  • required for spermatogonial amplification and differentiation
  • plays an important role in oncogenesis
  • induces glial cell line-derived neurotrophic growth factor-independent, non-branching growth and differentiation of ureteric bud epithelia
  • may also play a key role in the proliferation of neuronal progenitors in CNS development (regulate proliferation but not apoptosis)
  • plays critical roles in the development of the embryonic cerebral cortex via regulation of cortical cell migration and patterning
  • development of oligodendrocytes and neurones from olig2-expressing precursor cells (
  • role in the signaling network implicated in enteric nervous system development and maintenance which is also in line with its role as a modifier of the RET gene
  • NRG1 signaling is functional and cytoprotective in brain microvascular endothelial cells
  • playing a plays a critical role in myelination that is regulatrd by ERBB2 and ERBB2IP
  • is a novel mediator of MUC5AC and MUC5B expression in bronchial epithelial cells
  • may be the principal tumour suppressor gene that leads to the loss of 8p in many breast and other epithelial cancers
  • like NRG3, plays critical roles in the development of the embryonic cerebral cortex via regulation of cortical cell migration and patterning
  • stimulates the formation of new synapses and strengthens existing synapses and may be critical for basal synapse formation
  • exerts its signaling activity by binding to its cognate receptors, ERBB2/ERBB3 heterodimers or ERBB4 homodimers
  • zebrafish Neuregulin 1 controls Schwann cell migration and is required in neurons for migration
  • new role for NRG1/ERBB4 signaling in regulating oligodendrocyte precursors migration selectively during early stages of CNS development
  • is an axon-derived factor that is critical for Schwann cell (SC) development and myelinogenesis in a manner dependent on transmembrane tyrosine kinases ERBB2 and ERBB3
  • mediates the glucose repression of multiple genes through its direct binding to the specific promoter regions
  • potential role for NRG3 in brain development and function, which appears to be distinct from its paralog NRG1
  • NRG1 selectively increases GRM1-activated currents by inducing synthesis and trafficking to membrane of functional receptors
    • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS synaptogenesis
    PATHWAY
    metabolism
    signaling
  • autocrine signaling loop between NOTCH1 and NRG1 that controls melanoma growth
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Her2 and Her3 (
  • epidermal growth factor, EGF (
  • LIM kinase 1, LIMK1 (
  • activating their tyrosine kinase receptor (ERBB2-4), enhancer of CHRND, CHRNE in muscle enhancer of GRIN2C, CHRNA7 in neurons
  • ERBB4
  • GDNF (required for effective formation of long spermatogonial chain)
  • link between GJB1 expression and NRG1 regulation of Schwann cells proliferation that does not involve GJB1-mediated intercellular communication
  • interacting with BACE1 (processing of NRG1 by BACE1 rather than ADAM10 is more critical for the regulation of myelination)
  • PARD3 regulates RAC1 activation by BDNF but not by NRG1-Type III in Schwann cells, although both ligands activate RAC1
  • NRG/ERBB signaling maintains high efficacy of synaptic transmission by stabilizing the postsynaptic apparatus via phosphorylation of DTNA
  • NOTCH1 directly regulates the transcription of NRG1 by binding to its promoter region
  • NRG1 is the ligand for ERBB3 and 4, members of the epidermal growth factor family of receptors that are involved in the genesis and progression of a number of cancers
  • ERBIN is required for remyelination of regenerated axons after injury, probably by regulating ERBB2 and NRG1 levels
  • induces expression of the muscle spindle-specific gene EGR3 by stimulating the transcriptional activity of CREB1 and SRF
  • NRG1 inhibited the GDNF-induced neuronal differentiation and GDNF negatively regulated NRG1-signaling by down-regulating the expression of its receptor, ERBB2
  • NRG1 signaling promotes dendritic spine growth through kalirin
  • imbalanced NRG1 isoforms and downregulated ERBIN may contribute to the dysregulation of ERBB2 signaling in the development of diabetic peripheral neuropathy (DPN)
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SCZD6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional fusion      
    chimeric protein gamma heregulin (ERBG) by fusion with STIP1 (5'-STIP1-NRG1-3') in translocation t(8;11) (p12;q13
    constitutional     --low  
    in amyotrophic lateral sclerosis and Parkinson's disease, in cerebral fluid
    constitutional     --over  
    in Alzheimer's disease
    tumoral        
    silenced by methylation in breast cancers
    Susceptibility
  • to schizophrenia (
  • to late onset Alzheimer's disease with psychoses
  • to Hirschsprung's disease
    • Variant & Polymorphism SNP
  • increasing the risk of late onset Alzheimer's disease families with psychoses
  • SNP increasing the risk of schizophrenia
  • interaction between variants in NRG1 and ERBB4 might contribute to susceptibility for schizophrenia
  • SNP increasing the risk of Hirschsprung's disease
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquiredheart failure
    potential use of NRG1s as novel therapy for heart failure
    respiratorylung 
    may represent a novel therapeutic target for mucus hypersecretion in respiratory diseases
    ANIMAL & CELL MODELS
  • in cysteine-rich domain-NRG-1-/-mice, peripheral projections defasciculated and displayed aberrant branching patterns within their targets (
  • knock-down of nrg1 caused near total loss of olig2-positive cerebellar neurones, but caused no apparent loss of spinal motor neurones (
  • misexpression of human NRG1 type III in zebrafish transgenic embryos results in ectopic Schwann cell migration, allowing them to aberrantly enter the central nervous system
  • in murine juvenile testes Ra and Fsh induced meiosis indirectly through Sertoli cells when Nrg1 and Nrg3 were upregulated, as Nrg1 amplified itself and Nrg3