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FLASH GENE
Symbol NRG1 contributors: mct/shn - updated : 03-08-2015
HGNC name neuregulin 1
HGNC id 7997
Corresponding disease
SCZD6 schizophrenia 6
Location 8p12      Physical location : 31.497.267 - 32.622.558
Synonym name
  • glial growth factor
  • neu differentiation factor
  • heregulin, alpha (45kD, ERBB2 p185-activator)
  • sensory and motor neuron derived factor
  • neuregulin 1 isoform HRG-gamma
  • pro-neuregulin-1, membrane-bound isoform
  • Synonym symbol(s) NDF, HGL, HRGA, GGF, SMDF, ARIA, GGF2, HRG, HRG1, Pro-NRG1, MST131
    DNA
    TYPE functioning gene
    STRUCTURE 1125.74 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status provisional
    Map pter - D8S1810 - D8S2319 - NRG1 - D8S1758 - D8S259 - cen
    Physical map
    MGC8721 8p12 hypothetical protein MGC8721 LEPROTL1 8p21.2-p21.1 leptin receptor overlapping transcript-like 1 DCTN6 8p12-p11 dynactin 6 LOC392209 8 similar to heat shock protein (hsp-2) LOC92755 8p21.1 hypothetical gene LOC92755 RBPMS 8p12-p11 RNA binding protein with multiple splicing GTF2E2 8p12-p11 general transcription factor IIE, polypeptide 2, beta 34kDa GSR 8p21.1 glutathione reductase D8S2298E 8p12-p11.2 Homo sapiens reproduction 8 (D8S2298E), mRNA. PPP2CB 8p12-p11.2 protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform TEX15 8p12 testis expressed sequence 15 PURG 8p11 purine-rich element binding protein G WRN 8p12-p11.2 Werner syndrome LOC157589 8p12 similar to potassium channel tetramerisation domain containing 9 NRG1 8p21-p12 neuregulin 1 FUT10 8p12 fucosyltransferase 10 (alpha (1,3) fucosyltransferase) LOC84549 8p12 RNA binding protein FLJ23263 8p12 hypothetical protein FLJ23263 RNF122 8p12 ring finger protein 122 MGC1136 8p12 hypothetical protein MGC1136 LOC392210 8 similar to VENT-like homeobox 2; hemopoietic progenitor homeobox protein VENTX2 LOC392211 8 similar to Ribosomal protein L6 HCP21 8p12 cytochrome c, somatic pseudogene LOC137107 8p12 similar to ribosomal protein L10a LOC389646 8 hypothetical gene supported by X89401; NM_000982
    RNA
    TRANSCRIPTS type messenger
    text other alternative forms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 1694 22.6 211 - 1992 1350381
    also called HRG-gamma
    5 splicing 1987 45 422 nervous system, skeletal muscle 1993 8096067
  • soluble form
  • also called GGFHBS5 or GGF2
  • 3 splicing 2374 31 296 in the nervous system spinal cord, motoneuron, fetal lung, liver, kidney 2004 15044753
  • also called SMDF
  • a C-terminal EGF-like domain and a unique N-terminal sequence which lacks an Ig-like domain, cysteine-rich domain (CRD)
  • 12 splicing 3078 70.2 640 breast, ovary, testis, prostate, heart, muscle 2004 15044753
    also called erbB2 or HRG-alpha
    11 splicing 2377 - 420 - 1992 1350381
    also called HRG-beta2b
    12 splicing 3069 70 637 - 1992 1350381
    also called HRG-beta 2
    7 splicing 1740 26 241 brain spinal cord 1993 8096067
  • may be a nuclear isoform
  • also called HRG-beta 3, GGF or GGFHFB1
  • 13 splicing 3220 51 462 - 1994 7509448
    also called ndf43 or HRG-beta 1
    13 - 3093 - 645 - 1992 1350381
    also called HRG-beta1
    4 splicing 1592 - 177 - 1992 1350381
    also called HRG-gamma3
    5 splicing 1638 - 207 - 1992 1350381
    also called HRG-beta3b
    13 splicing 3211 - 459 - 1992 1350381
    also called ndf43b
    5 splicing 1643 - 194 - 1992 1350381
    also called HRG-gamma2
    11 splicing 2502 - 590 - 1992 1350381
    also called HRG-beta1d
    13 splicing 2604 - 624 - 1998 9491987
  • also called HRG-beta1b
  • promotes breast cancer cell proliferation through RAC1/ERK-dependent induction of CCND1 and CDKN1A
  • 12 splicing 2553 - 607 - 1992 1350381
    also called HRG-beta1c
    9 splicing 2411 - 308 - 1992 1350381
    also called ndf43c
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon   Homo sapiens
    Reproductivefemale systembreast   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Membranemucous membrane    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    Reproductiveepithelial cell
    cell lineage
    cell lines
    fluid/secretion cerebral spinal fluid
    at STAGE
    physiological period embryo
    Text embryonic tissues
    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