• Neuregulin 1 is important for synaptic plasticity, GABAergic function within the amygdala (to shut down anxiety), myelination (Schwann cell maturation, survival, and motility), heart function (cardiac growth factor), tumor suppression
• Neuregulin 1  increases  axonal 7 nAChR.
• Neuregulin 1 is decreased in schizophrenia.
• Neuregulin 1 decreases IL-1², IL-6, IL-10, IL-8, IL12-p70, and TNF-.

More detailed information:

• Neuregulin 1 (NRG1)

• Associated with

  • Schizophrenia [R]

  • Bipolar disorder [R]

  • Alzheimer’s disease (AD) [R]

  • Anxiety-like behaviors [R]

  • Heart development and maintenance problems [R]

    • Chronic heart failure and heart abnormality

  • Many fast growing tumors [R]

Advanced information:

• Migration of neuronal receptors in cerebral cortex [R]

• pi3K/Akt activates NRG1 ability to prevent release of Aβ1-42 -induced LDH release [R]

• pi3K/Akt activates NRG1 prevents accumulation of oxygen reactive species in the primary cortical neurons [R]

• NRG1 interacts with Receptor Tyrosine-protein Kinase erbB-3 (ERBB3) [R]

  • ErbB3 functions as an epidermal growth factor receptor [R]

• NRG1 interacts with LIM domain kinase 1 (LIMK1) [R]

  • LIMK1 works as an intracellular signaling pathway [R]

  • NRG1 to treat Alzheimer’s disease (AD) [R]

Use of recombinant human NRG1 (rhNRG-1) as a drug for treatment of chronic heart failure [R]

     Covered on Genetics Home Reference: Hirschsprung diseaseFrom NCBI Gene: Schizophrenia 6From UniProt: A chromosomal aberration involving NRG1 produces gamma-heregulin. Translocation t(8;11) with TENM4. The translocation fuses the 5'-end of TENM4 to NRG1 (isoform 8). The product of this translocation was first thought to be an alternatively spliced isoform. Gamma-heregulin is a soluble activating ligand for the ERBB2-ERBB3 receptor complex and acts as an autocrine growth factor in a specific breast cancer cell line (MDA-MB-175). Not detected in breast carcinoma samples, including ductal, lobular, medullary, and mucinous histological types, neither in other breast cancer cell lines.

     From NCBI Gene: The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Apr 2016] From UniProt: 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 (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). 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 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons.

The following transcription factors affect gene expression:

• AP-1
• c-Jun
• Max
• STAT5A
• Egr-1
• CREB
• deltaCREB
• NRF2

Tissue specificity:

Type I isoforms are the predominant forms expressed in the endocardium. Isoform alpha is expressed in breast, ovary, testis, prostate, heart, skeletal muscle, lung, placenta liver, kidney, salivary gland, small intestine and brain, but not in uterus, stomach, pancreas, and spleen. Isoform 3 is the predominant form in mesenchymal cells and in non-neuronal organs, whereas isoform 6 is the major neuronal form. Isoform 8 is expressed in spinal cord and brain. Isoform 9 is the major form in skeletal muscle cells; in the nervous system it is expressed in spinal cord and brain. Also detected in adult heart, placenta, lung, liver, kidney, and pancreas. Isoform 10 is expressed in nervous system: spinal cord motor neurons, dorsal root ganglion neurons, and brain. Predominant isoform expressed in sensory and motor neurons. Not detected in adult heart, placenta, lung, liver, skeletal muscle, kidney, and pancreas. Not expressed in fetal lung, liver and kidney. Type IV isoforms are brain-specific.

Developmental stage:

Detectable at early embryonic ages. Isoform 10 is highly expressed in developing spinal motor neurons and in developing cranial nerve nuclei. Expression is maintained only in both adult motor neurons and dorsal root ganglion neurons. Type IV isoforms are expressed in fetal brain.

Molecular Function:

• Transcription Cofactor Activity
• Protein Tyrosine Kinase Activity
• Ras Guanyl-Nucleotide Exchange Factor Activity
• Receptor Binding
• Cytokine Activity
• Integrin Binding
• Growth Factor Activity
• Protein Tyrosine Kinase Activator Activity
• Transmembrane Receptor Protein Tyrosine Kinase Activator Activity
• Receptor Tyrosine Kinase Binding
• Erbb-3 Class Receptor Binding
• Chemorepellent Activity
• Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Activity

Biological Processes:

• Mapk Cascade
• Activation Of Mapk Activity
• Cell Morphogenesis
• Startle Response
• Cardiac Conduction System Development
• Ventricular Trabecula Myocardium Morphogenesis
• Cell Communication
• Transmembrane Receptor Protein Tyrosine Kinase Signaling Pathway
• Activation Of Transmembrane Receptor Protein Tyrosine Kinase Activity
• Nervous System Development
• Synapse Assembly
• Peripheral Nervous System Development
• Locomotory Behavior
• Regulation Of Blood Pressure
• Cell Proliferation
• Positive Regulation Of Cell Proliferation
• Axon Ensheathment
• Embryo Development
• Negative Regulation Of Cardiac Muscle Cell Apoptotic Process
• Neural Crest Cell Development
• Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Glucose Transport
• Glial Cell Fate Commitment
• Chemorepulsion Involved In Interneuron Migration From The Subpallium To The Cortex
• Positive Regulation Of Cell Growth
• Mammary Gland Development
• Positive Regulation Of Myelination
• Activation Of Protein Kinase B Activity
• Intracellular Signal Transduction
• Erbb Signaling Pathway
• Erbb2 Signaling Pathway
• Wound Healing
• Negative Regulation Of Protein Catabolic Process
• Myelination
• Regulation Of Protein Homodimerization Activity
• Regulation Of Protein Heterodimerization Activity
• Cellular Protein Complex Disassembly
• Neurotransmitter Receptor Metabolic Process
• Positive Regulation Of Axon Extension
• Positive Regulation Of Cell Adhesion
• Negative Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Positive Regulation Of Ras Protein Signal Transduction
• Phosphatidylinositol-Mediated Signaling
• Neuron Fate Commitment
• Oligodendrocyte Differentiation
• Negative Regulation Of Secretion
• Positive Regulation Of Striated Muscle Cell Differentiation
• Positive Regulation Of Protein Kinase B Signaling
• Cardiac Muscle Cell Differentiation
• Ventricular Cardiac Muscle Cell Differentiation
• Positive Regulation Of Cardiac Muscle Cell Proliferation
• Cardiac Muscle Cell Myoblast Differentiation
• Endocardial Cell Differentiation
• Positive Regulation Of Dendritic Spine Development
• Positive Regulation Of Calcineurin-Nfat Signaling Cascade
• Positive Regulation Of Protein Targeting To Mitochondrion
• Positive Regulation Of Protein Localization To Cell Surface
• Regulation Of Cell Motility
• Positive Regulation Of Cardiac Muscle Cell Differentiation
• Negative Regulation Of Neuron Migration
• Negative Regulation Of Extrinsic Apoptotic Signaling Pathway In Absence Of Ligand