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NRG1 Gene

protein-coding   GIFtS: 69
GCID: GC08P031554

Neuregulin 1


(Previous symbol: HGL)
  See NRG1-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Neuregulin 11 2     MSTP1312
HGL1 2 3 5     Glial Growth Factor2
HRGA2 3 5     Heregulin, Alpha (45kD, ERBB2 P185-Activator)2
GGF2 3     Neu Differentiation Factor2
NDF2 3     Neuregulin 1 Type IV Beta 1a2
SMDF2 3     Neuregulin 1 Type IV Beta 32
ARIA2 5     pro-NRG12
GGF22     Pro-Neuregulin-1, Membrane-Bound Isoform2
HRG2     Sensory And Motor Neuron Derived Factor2
HRG12     Pro-NRG13
MST1312     

External Ids:    HGNC: 79971   Entrez Gene: 30842   Ensembl: ENSG000001571687   OMIM: 1424455   UniProtKB: Q022973   

Export aliases for NRG1 gene to outside databases

Previous GC identifers: GC08P031402 GC08P032856 GC08P032463 GC08P031617 GC08P030042


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for NRG1 Gene:
The protein encoded by this gene was originally identified as a 44-kD glycoprotein that interacts with the
NEU/ERBB2 receptor tyrosine kinase to increase its phosphorylation on tyrosine residues. This protein is a
signaling protein that mediates cell-cell interactions and plays critical roles in the growth and development of
multiple organ systems. It is known that an extraordinary variety of different isoforms are produced from this
gene through alternative promoter usage and splicing. These isoforms are tissue-specifically expressed and differ
significantly in their structure, and thereby these isoforms are classified into types I, II, III, IV, V and VI.
The gene dysregulation has been linked to diseases such as cancer, schizophrenia and bipolar disorder (BPD).
(provided by RefSeq, May 2009)

GeneCards Summary for NRG1 Gene:
NRG1 (neuregulin 1) is a protein-coding gene. Diseases associated with NRG1 include schizophreniform disorder, and childhood-onset schizophrenia. GO annotations related to this gene include growth factor activity and receptor binding. An important paralog of this gene is NRG2.

UniProtKB/Swiss-Prot: NRG1_HUMAN, Q02297
Function: 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

Gene Wiki entry for NRG1 (Neuregulin 1) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000008.10  NT_167187.2  NC_018919.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the NRG1 gene promoter:
         CREB   AP-1   deltaCREB   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): NRG1 promoter sequence
   Search Chromatin IP Primers for NRG1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NRG1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 8p12   Ensembl cytogenetic band:  8p12   HGNC cytogenetic band: 8p21-p12

NRG1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NRG1 gene location

GeneLoc information about chromosome 8         GeneLoc Exon Structure

GeneLoc location for GC08P031554:  view genomic region     (about GC identifiers)

Start:
31,496,820 bp from pter      End:
32,622,558 bp from pter
Size:
1,125,739 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: NRG1_HUMAN, Q02297 (See protein sequence)
Recommended Name: Pro-neuregulin-1, membrane-bound isoform precursor  
Size: 640 amino acids; 70392 Da
Subunit: The cytoplasmic domain interacts with the LIM domain region of LIMK1 (By similarity). Interacts with
ERBB3 and ERBB4
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
Sequence caution: Sequence=AAA19955.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of
unknown origin in the N-terminal part; Sequence=AAC51756.1; Type=Erroneous initiation;
5 PDB 3D structures from and Proteopedia for NRG1:
1HAE (3D)        1HAF (3D)        1HRE (3D)        1HRF (3D)        3U7U (3D)    
Secondary accessions: A5YAK4 A5YAK5 A8K1L2 B7Z4Z3 E9PHH4 O14667 P98202 Q02298 Q02299 Q07110
Q07111 Q12779 Q12780 Q12781 Q12782 Q12783 Q12784 Q15491 Q7RTV9 Q7RTW0 Q7RTW1 Q7RTW2 Q8NFN1
Q8NFN2 Q8NFN3 Q9UPE3
Alternative splicing: 11 isoforms:  Q02297-1   Q02297-2   Q02297-3   Q02297-4   Q02297-6   Q02297-7   Q02297-8   Q02297-9   
Q02297-10   Q02297-11   Q02297-12   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for NRG1: NX_Q02297

Explore proteomics data for NRG1 at MOPED

Post-translational modifications: 

  • Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth
    factor form1
  • N- and O-glycosylated. Extensive glycosylation precedes the proteolytic cleavage (By similarity)1
  • Glycosylation2 at Asn120, Asn126, Asn164
  • Modification sites at PhosphoSitePlus

  • See NRG1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (17 alternative transcripts): 
    NP_001153467.1  NP_001153468.1  NP_001153471.1  NP_001153473.1  NP_001153474.1  NP_001153476.1  NP_001153477.1  NP_001153479.1  
    NP_001153480.1  NP_004486.2  NP_039250.2  NP_039251.2  NP_039252.2  NP_039253.1  NP_039254.1  NP_039256.2  
    NP_039258.1  

    ENSEMBL proteins: 
     ENSP00000430053   ENSP00000429582   ENSP00000434640   ENSP00000429067   ENSP00000430120  
     ENSP00000287842   ENSP00000428828   ENSP00000384620   ENSP00000432052   ENSP00000433289  
     ENSP00000433350   ENSP00000428546   ENSP00000430862   ENSP00000428411   ENSP00000343395  
     ENSP00000349275   ENSP00000287845   ENSP00000340497   ENSP00000439276  
    Reactome Protein details: Q02297

    NRG1 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant NRG1 Protein
    R&D Systems Recombinant & Natural Proteins for NRG1 (Neuregulin-1 Isoform SMDF, Neuregulin-1 alpha/NRG1 alpha, Neuregulin-1 beta 1/NRG1 beta 1, Neuregulin-1/NRG1)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for NRG1
    OriGene Custom MassSpec
    OriGene Custom Protein Services for NRG1
    GenScript Purified and Recombinant Proteins for NRG1
    Novus Biologicals NRG1 Proteins
    Novus Biologicals NRG1 Lysates
    Sino Biological Recombinant Protein for NRG1
    Sino Biological Cell Lysate for NRG1
    ProSpec Recombinant Protein for NRG1
    Cloud-Clone Corp. Proteins for NRG1

     
    Search eBioscience for Proteins for NRG1 

     
    antibodies-online proteins for NRG1 (22 products) 

     
    antibodies-online peptides for NRG1

    NRG1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of NRG1
    R&D Systems Antibodies for NRG1 (Neuregulin-1 Isoform SMDF, Neuregulin-1 alpha/NRG1 alpha, Neuregulin-1 beta 1/NRG1 beta 1, Neuregulin-1/NRG1, Neuregulin-1 Isoform GGF2)
    Cell Signaling Technology (CST) Antibodies for NRG1 
    OriGene Antibodies for NRG1
    OriGene Custom Antibody Services for NRG1
    Novus Biologicals NRG1 Antibodies
    Abcam antibodies for NRG1 (Q02297, Q15491)
    Cloud-Clone Corp. Antibodies for NRG1
    ThermoFisher Antibody for NRG1
    antibodies-online antibodies for NRG1 (110 products) 

    NRG1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    R&D Systems ELISAs for NRG1 (Neuregulin-1 beta 1/NRG1 beta 1, Neuregulin-1/NRG1)         (see all)
    GenScript Custom Assay Services for NRG1
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for NRG1
    Cloud-Clone Corp. CLIAs for NRG1
    Search eBioscience for ELISAs for NRG1 
    antibodies-online kits for NRG1 (41 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    ISET: Immunoglobulin superfamily / I-set domain containing

    Selected InterPro protein domains (see all 8):
     IPR003598 Ig_sub2
     IPR007110 Ig-like_dom
     IPR002154 Neuregulin_1_C
     IPR000742 EG-like_dom
     IPR013098 Ig_I-set

    Graphical View of Domain Structure for InterPro Entry Q02297

    ProtoNet protein and cluster: Q02297

    2 Blocks protein domains:
    IPB002154 Neuregulin family signature
    IPB003598 Immunoglobulin C-2 type


    UniProtKB/Swiss-Prot: NRG1_HUMAN, Q02297
    Domain: The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing.
    Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity)
    Domain: ERBB receptor binding is elicited entirely by the EGF-like domain
    Similarity: Belongs to the neuregulin family
    Similarity: Contains 1 EGF-like domain
    Similarity: Contains 1 Ig-like C2-type (immunoglobulin-like) domain


    Find genes that share domains with NRG1           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NRG1_HUMAN, Q02297
    Function: 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

         Genatlas biochemistry entry for NRG1:
    neuregulin 1 multipotent epidermal growth factor-like factor with several splice variants (44kDa),indirect
    NEU/ERBB2 p185 activator (see ERBB2)

         Summary: 
    During embryonic development, NRG1 as signaling molecule is secreted from the following cells:
                
    Heart: Endocardial Cells (Endocardium)

    It affects the following cells:
          selected tissues (see all 3)      fully expand
    Peripheral Nervous System: Schwann Precursor Cells (Peripheral Nerve Domain), Immature Schwann Cells (Peripheral Nerve Domain)      fully expand to see all 2 cells
    Neural Tube: Oligodendrocyte Precursor Cells (Anterior Entopeduncular Area), Oligodendrocyte Precursor Cells (Lateral Ganglionic Eminence)      fully expand to see all 4 cells

    NRG1 as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:
                
    Peripheral Nervous System: Schwann-like cells, Schwann-like cells

         Gene Ontology (GO): Selected molecular function terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003712transcription cofactor activity IDA15073182
    GO:0005102receptor binding IPI7514177
    GO:0005125cytokine activity TAS10372964
    GO:0005176ErbB-2 class receptor binding IEA--
    GO:0005515protein binding IPI7592681
         
    Find genes that share ontologies with NRG1           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for NRG1:
     Decreased TP53 protein express  Increased G1 DNA content  Increased cell death in breast 

         14 MGI mutant phenotypes (inferred from 14 alleles(MGI details for Nrg1):
     behavior/neurological  cardiovascular system  cellular  embryogenesis  endocrine/exocrine gland 
     growth/size/body  homeostasis/metabolism  integument  mortality/aging  muscle 
     nervous system  reproductive system  respiratory system  vision/eye 

    Find genes that share phenotypes with NRG1           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for NRG1: Nrg1tm1Zhou Nrg1tm1Leth Nrg1tm1Gne Nrg1tm1Cbm Nrg1tm1Lex Nrg1tm1Lwr
                                                         Nrg1tm2Zhou

       genOway: Develop your customized and physiologically relevant rodent model for NRG1

    miRNA
    Products:
        
    miRTarBase miRNAs that target NRG1:
    hsa-mir-124-3p (MIRT022506)

    Block miRNA regulation of human, mouse, rat NRG1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NRG1 (see all 40):
    hsa-miR-142-5p hsa-miR-3607-3p hsa-miR-429 hsa-miR-15a hsa-miR-124 hsa-miR-424 hsa-miR-506 hsa-miR-1183
    SwitchGear 3'UTR luciferase reporter plasmids (see all 2): NRG1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for NRG1
    Predesigned siRNA for gene silencing in human, mouse, rat NRG1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for NRG1

    Clone
    Products:
         
    OriGene clones in human, mouse for NRG1 (see all 97)
    OriGene ORF clones in mouse, rat for NRG1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 17): NRG1 (NM_004495)
    Sino Biological Human cDNA Clone for NRG1
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NRG1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NRG1

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for NRG1
    Browse ESI BIO Cell Lines and PureStem Progenitors for NRG1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NRG1

    Flow Cytometry
    Products:
       

     
    eBioscience FlowRNA Probe Sets ( VA1-12144) for NRG1 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    NRG1_HUMAN, Q02297: Pro-neuregulin-1, membrane-bound isoform: Cell membrane; Single-pass type I membrane
    protein. Note=Does not seem to be active
    NRG1_HUMAN, Q02297: Neuregulin-1: Secreted
    NRG1_HUMAN, Q02297: Isoform 8: Nucleus. Note=May be nuclear
    NRG1_HUMAN, Q02297: Isoform 9: Secreted. Note=Has a signal peptide
    NRG1_HUMAN, Q02297: Isoform 10: Membrane; Single-pass type I membrane protein. Note=May possess an internal
    uncleaved signal sequence
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    nucleus5
    plasma membrane5
    cytoskeleton2
    cytosol1
    mitochondrion1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region TAS--
    GO:0005615extracellular space IDA11389077
    GO:0005634nucleus IEA--
    GO:0005737cytoplasm IEA--
    GO:0005886plasma membrane ----

    Find genes that share ontologies with NRG1           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for NRG1 About   (see all 32)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1ErbB signaling pathway
    ErbB signaling pathway0.52
    EGFR Inhibitor Pathway, Pharmacodynamics0.49
    ErbB signaling pathway0.52
    2Development EGFR signaling pathway
    Development ERBB family signaling0.57
    GRB7 events in ERBB2 signaling0.00
    3Apoptotic Pathways in Synovial Fibroblasts
    Mitochondrial Apoptosis0.85
    Rac1 Pathway0.65
    Cellular Apoptosis Pathway0.85
    Glioma Invasiveness0.64
    Apoptotic Pathways in Synovial Fibroblasts0.84
    Actin-Based Motility by Rho Family GTPases0.62
    p53 Mediated Apoptosis0.84
    ERK5 Signaling0.61
    4Signaling by FGFR
    Signaling by FGFR0.91
    Signaling by PDGF0.87
    Signaling by FGFR in disease0.91
    Signaling by EGFR0.83
    Downstream signaling of activated FGFR0.91
    Signaling by EGFR in Cancer0.82
    Downstream signal transduction0.90
    NGF signalling via TRKA from the plasma membrane0.71
    5PI-3K cascade
    PI3K/AKT activation0.93
    PI3K/AKT Signaling in Cancer0.88
    GAB1 signalosome0.93
    PI3K events in ERBB4 signaling0.88
    Constitutive PI3K/AKT Signaling in Cancer0.88
    Role of LAT2/NTAL/LAB on calcium mobilization0.80
    PIP3 activates AKT signaling0.88
    Signaling by SCF-KIT0.72


    Find genes that share SuperPaths with NRG1           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for NRG1 (see all 58)
        Nuclear Receptor Activation by Vitamin-A
    Paxillin Interactions
    Telomerase Components in Cell Signaling
    Mitochondrial Apoptosis
    Molecular Mechanisms of Cancer

    1 Cell Signaling Technology (CST) Pathway for NRG1
        Tyrosine Kinases / Adaptors

    4 GeneGo (Thomson Reuters) Pathways for NRG1
        Development ERBB-family signaling
    Development Ligand-independent activation of ESR1 and ESR2
    Apoptosis and survival Role of CDK5 in neuronal death and survival
    Translation Non-genomic (rapid) action of Androgen Receptor

    4 BioSystems Pathways for NRG1
        MicroRNAs in cardiomyocyte hypertrophy
    ErbB signaling pathway
    Cardiac Progenitor Differentiation
    Glypican 1 network

    1 Sino Biological Pathway for NRG1
        EGFR Signaling Pathway

    Selected Reactome Pathways for NRG1 (see all 12)
        Downregulation of ERBB2:ERBB3 signaling
    GRB7 events in ERBB2 signaling
    GRB2 events in ERBB2 signaling
    PI3K events in ERBB2 signaling
    SHC1 events in ERBB2 signaling

    1 PharmGKB Pathway for NRG1
        EGFR Inhibitor Pathway, Pharmacodynamics

    1 Kegg Pathway  (Kegg details for NRG1):
        ErbB signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NRG1: 
              Neurogenesis in human mouse rat
              Growth Factors in human mouse rat
              Neurotrophins & Receptors in human mouse rat
              Common Cytokines in human mouse rat
              Inflammatory Response & Autoimmunity 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NRG1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 20)

    Selected Interacting proteins for NRG1 (Q022971, 2, 3 ENSP000003492754) via UniProtKB, MINT, STRING, and/or I2D (see all 571)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ERBB3P218601, 3, ENSP000002671014EBI-2460927,EBI-720706 I2D: score=2 STRING: ENSP00000267101
    ERBB2P046261, 3, ENSP000002695714EBI-2460927,EBI-641062 I2D: score=1 STRING: ENSP00000269571
    IKZF4Q9H2S93, ENSP000002620324I2D: score=1 STRING: ENSP00000262032
    ERBB4Q153033, ENSP000003422354I2D: score=2 STRING: ENSP00000342235
    EGFP011333, ENSP000002651714I2D: score=1 STRING: ENSP00000265171
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 51):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade IEA--
    GO:0000902cell morphogenesis IEA--
    GO:0003161cardiac conduction system development IEA--
    GO:0003222ventricular trabecula myocardium morphogenesis IDA17336907
    GO:0007154cell communication TAS17432114

    Find genes that share ontologies with NRG1           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for NRG1

    Selected Novoseek inferred chemical compound relationships for NRG1 gene (see all 62)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    hrgbeta1 91.4 10 9652748 (4), 11781840 (4)
    pd158780 81.2 3 15555917 (1), 16867224 (1), 18520822 (1)
    tyrosine 76.1 164 7514177 (4), 11807823 (3), 9168115 (2), 7535767 (2) (see all 98)
    trastuzumab 72.7 26 16847284 (4), 19497323 (3), 16533770 (2), 16489114 (1) (see all 15)
    phosphatidylinositol 61.6 23 7535767 (3), 10542266 (1), 10844033 (1), 10441522 (1) (see all 20)
    gefitinib 58 11 12684395 (2), 18682844 (1), 18351692 (1), 20215504 (1) (see all 7)
    lapatinib 53.5 4 14737100 (2), 15755991 (1)
    phosphotyrosine 44.5 4 10745024 (1), 17016520 (1), 10353604 (1)
    forskolin 43.7 42 15390106 (4), 9774641 (4), 14730697 (4), 12898530 (3) (see all 18)
    ly294002 41.4 13 18349105 (1), 19535045 (1), 12439862 (1), 14743465 (1) (see all 5)



    Find genes that share compounds with NRG1           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for NRG1 gene (17 alternative transcripts): 
    NM_001159995.1  NM_001159996.1  NM_001159999.1  NM_001160001.1  NM_001160002.1  NM_001160004.1  NM_001160005.1  NM_001160007.1  
    NM_001160008.1  NM_004495.3  NM_013956.3  NM_013957.3  NM_013958.3  NM_013959.3  NM_013960.3  NM_013962.2  
    NM_013964.3  

    Unigene Cluster for NRG1:

    Neuregulin 1
    Hs.453951  [show with all ESTs]
    Unigene Representative Sequence: NM_013960
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 21):
    ENST00000518104 ENST00000519301 ENST00000520407(uc003xip.3) ENST00000523534
    ENST00000523079(uc003xir.3 uc010lvl.3 uc010lvm.3 uc010lvn.3 uc003xis.3 uc011lbf.1)
    ENST00000287842 ENST00000521670 ENST00000405005 ENST00000518206(uc003xix.3)
    ENST00000522569 ENST00000520502(uc003xiy.3) ENST00000523041 ENST00000518084
    ENST00000522402 ENST00000519240 ENST00000523681 ENST00000338921 ENST00000356819(uc010lvo.2 uc003xiu.2 uc003xiw.2 uc010lvp.2)

    miRNA
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    hsa-miR-142-5p hsa-miR-3607-3p hsa-miR-429 hsa-miR-15a hsa-miR-124 hsa-miR-424 hsa-miR-506 hsa-miR-1183
    SwitchGear 3'UTR luciferase reporter plasmids (see all 2): NRG1 3' UTR sequence
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    GenScript: all cDNA clones in your preferred vector (see all 17): NRG1 (NM_004495)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NRG1
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    eBioscience FlowRNA Probe Sets ( VA1-12144) for NRG1 

    Additional mRNA sequence: 

    AB451331.1 AB451475.1 AF026146.1 AK097005.1 AK223435.1 AK289927.1 AK290730.1 AK293240.1 
    AK293270.1 AK298132.1 AY207002.1 BC006492.2 BC007675.2 BC064587.1 BC073871.1 BC144446.1 
    BC150609.1 BT007389.1 CR450288.1 EF372273.1 EF372274.1 EF372276.1 EF517295.1 EF517296.1 
    EF517297.1 EU359055.1 EU363508.1 EU363509.1 EU363510.1 GQ983557.1 GQ983558.1 L12260.1 
    L12261.1 L41827.1 M94165.1 M94166.1 M94167.1 M94168.1 S68256.1 U02325.1 
    U02326.1 U02327.1 U02328.1 U02329.1 U02330.1 

    14 DOTS entries:

    DT.115085  DT.92430137  DT.86854208  DT.97788670  DT.120633394  DT.100748793  DT.92430148  DT.95370230 
    DT.120633303  DT.95151463  DT.95370232  DT.86859456  DT.92050266  DT.92430140 

    Selected AceView cDNA sequences (see all 129):

    BC007675 BU624346 M94166 AI625796 BQ018711 AL533649 BX509829 NM_013956 
    BI918166 AW161051 NM_013964 U02327 BI822417 BF431949 BC073871 AI634664 
    AA833637 CB113134 BU621171 AI671746 F03816 BM548863 BM142279 BC064587 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for NRG1 (see all 8)    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b · 13c ^ 14 ^ 15 ^ 16 ^ 17
    SP1:                                                        -     -           -                                             
    SP2:                                                        -     -                                                         
    SP3:                                                              -           -                                             
    SP4:                                                                          -                                             
    SP5:                                                                                                                        


    ECgene alternative splicing isoforms for NRG1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    NRG1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    NRG1 Expression
    About this image


    NRG1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 7) fully expand
     
     Heart (Cardiovascular System)
             Endocardial Cells Endocardium
     
     Neural Tube (Nervous System)    fully expand to see all 4 entries
             Metencephalon
     
     NULL (Uncategorized)    fully expand to see all 2 entries
             Definitive endoderm-like cells
     
     Lung (Respiratory System)    fully expand to see all 2 entries
             Basal Cells Respiratory Bronchioles
     
     Blood (Hematopoietic System)
             Monocytes Peripheral Blood
    NRG1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NRG1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.453951

    UniProtKB/Swiss-Prot: NRG1_HUMAN, Q02297
    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

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NRG1: 
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              Neurotrophins & Receptors in human mouse rat
              Common Cytokines in human mouse rat
              Inflammatory Response & Autoimmunity 384HT in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for NRG1 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nrg15 neuregulin 1   --   8 (18.75 cM) 31818028 
    chicken
    (Gallus gallus)
    Aves NRG16
    Gallus gallus neuregulin 1 (NRG1), mRNA.
    64(a)
    1 ↔ 1
    Z(53782385-54246036)
    lizard
    (Anolis carolinensis)
    Reptilia NRG16
    neuregulin 1
    73(a)
    1 ↔ 1
    2(73855886-74105707)
    African clawed frog
    (Xenopus laevis)
    Amphibia nrg1-A2 neuregulin 1 81.62(n)    AF142632.1 
    zebrafish
    (Danio rerio)
    Actinopterygii BI879460.12   -- 75.84(n)    BI879460.1 


    ENSEMBL Gene Tree for NRG1 (if available)
    TreeFam Gene Tree for NRG1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NRG1 gene
    NRG22  NRG32  
    3 SIMAP similar genes for NRG1 using alignment to 34 protein entries:     NRG1_HUMAN (see all proteins):
    NRG3    NRG4    NRG2

    Find genes that share paralogs with NRG1           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for NRG1 (see all 23094)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 8 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs3675431501,2
    Cuntested131734622(+) ATGGCA/C/GACGCG 6 Q P R int1 mis10--------
    rs1475629391,2
    Cuntested131835051(+) GTAAGA/CAATTG 4 -- int10--------
    rs560556941,2
    C--30045735(+) GTGTG-/TG/T  
     GTGTGTG
    AGAGA
    4 -- int10--------
    rs1132139741,2
    C--30051699(+) TTTTC-/TTTTTT 4 -- int11Minor allele frequency- T:0.00CSA 2
    rs2003352921,2
    --30051702(+) CTTTT-/CTTTTT 4 -- int10--------
    rs581677321,2
    C--30051711(+) TTTTT-/T/TT  
            
    GAGAT
    4 -- int11NA 2
    rs2006117511,2
    C--30073377(-) TTCGAA/CAAAAA 4 -- int10--------
    rs117808921,2
    C,H--30111259(+) TAAttG/Tttttt 4 -- int10--------
    rs3683424091,2
    C--30111259(+) TAATT-/GTTTTT 4 -- int10--------
    rs1411472821,2
    C--30122286(+) TATGA-/TTTTTT 4 -- int10--------

    HapMap Linkage Disequilibrium report for NRG1 (31496820 - 31746820 bp, first 250kb of NRG1)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for NRG1 (see all 41):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2638529CNV Deletion19546169
    esv2657877CNV Deletion23128226
    esv2659448CNV Deletion23128226
    esv2736845CNV Deletion23290073
    esv991445CNV Deletion20482838
    esv2167886CNV Deletion18987734
    esv1693112CNV Deletion17803354
    esv4933CNV Deletion18987735
    esv2663032CNV Deletion23128226
    esv2736844CNV Deletion23290073

    Human Gene Mutation Database (HGMD): NRG1
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing NRG1
    DNA2.0 Custom Variant and Variant Library Synthesis for NRG1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 142445   
    OMIM disorders: 603013  
    UniProtKB/Swiss-Prot: NRG1_HUMAN, Q02297
  • Note=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

  • 6 diseases for NRG1:    
    About MalaCards
    schizophreniform disorder    childhood-onset schizophrenia    cannabis dependence    bipolar disorder
    schizophrenia    breast cancer

    1 disease from the University of Copenhagen DISEASES database for NRG1:
    Schizophrenia

    Find genes that share disorders with NRG1           About GenesLikeMe

    Selected Novoseek inferred disease relationships for NRG1 gene (see all 61)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    schizophrenia 79.2 432 16442083 (6), 18704261 (5), 19652122 (5), 19058791 (5) (see all 99)
    breast cancer 70.9 239 12569369 (5), 10536169 (4), 15645137 (4), 11328805 (4) (see all 99)
    other schizophrenia 57.6 3 15000348 (1)
    mammary tumor 57.3 12 8106145 (3), 12209601 (1), 7535767 (1), 12529413 (1) (see all 8)
    breast carcinoma 56.5 27 7514177 (2), 9285119 (2), 7579500 (2), 11313890 (1) (see all 18)
    bipolar disorder 55.9 35 16940976 (4), 15939841 (3), 18466881 (3), 19127563 (2) (see all 17)
    viral leukemia 47.3 2 12021921 (1)
    heart nervous 46.6 1 12370490 (1)
    psychotic 43.7 22 19127563 (3), 19184335 (2), 18466879 (1), 20182055 (1) (see all 12)
    tumors 42.2 72 8640840 (4), 7992839 (3), 8825123 (3), 16168116 (3) (see all 40)

    Genetic Association Database (GAD): NRG1
    Human Genome Epidemiology (HuGE) Navigator: NRG1 (110 documents)

    Export disorders for NRG1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for NRG1 gene, integrated from 10 sources (see all 857):
    (articles sorted by number of sources associating them with NRG1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Identification of heregulin, a specific activator of p185erbB2. (PubMed id 1350381)1, 2, 3, 9 Holmes W.E.... Vandlen R.L. (Science 1992)
    2. Sensory and motor neuron-derived factor. A novel heregulin variant highly expressed in sensory and motor neurons. (PubMed id 7782315)1, 2, 9 Ho W.-H.... Osheroff P.L. (J. Biol. Chem. 1995)
    3. Neuregulin 1 (NRG1 ) and schizophrenia: analysis of a US family sample and the evidence in the balance. (PubMed id 16219118)1, 4, 9 Duan J....Gejman P.V. (Psychol Med 2005)
    4. A neuregulin 1 variant is associated with increased lateral ventricle volume in patients with first-episode schizophrenia. (PubMed id 19058791)1, 4, 9 Mata I....Crespo-Facorro B. (Biol. Psychiatry 2009)
    5. Neuregulin-1 genotypes and eye movements in schizophrenia. (PubMed id 19575259)1, 4, 9 Haraldsson H.M....Petursson H. (Eur Arch Psychiatry Clin Neurosci 2010)
    6. Support for NRG1 as a susceptibility factor for schizophrenia in a northern Swedish isolated population. (PubMed id 19652122)1, 4, 9 Alaerts M....Del-Favero J. (Arch. Gen. Psychiatry 2009)
    7. Genetic association analysis of NRG1 with methamphetamine-induced psychosis in a Japanese population. (PubMed id 19394386)1, 4, 9 Okochi T....Iwata N. (amp 2009)
    8. Neuregulin-1 haplotype HAP(ICE) is associated with lower hippocampal volumes in schizophrenic patients and in non-affected family members. (PubMed id 18291420)1, 4, 9 Gruber O....Maier W. (J Psychiatr Res 2008)
    9. Does neuregulin-1 play a role in Type A behavior? The cardiovascular risk in young Finns study. (PubMed id 18798975)1, 4, 9 Service H.M....Keltikangas-JAorvinen L. (Behav Brain Funct 2008)
    10. Failure to replicate the association between NRG1 and schizophrenia using Japanese large sample. (PubMed id 18282690)1, 4, 9 Ikeda M....Iwata N. (Schizophr. Res. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 3084 HGNC: 7997 AceView: NRG1 Ensembl:ENSG00000157168 euGenes: HUgn3084
    ECgene: NRG1 Kegg: 3084 H-InvDB: NRG1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for NRG1 Pharmacogenomics, SNPs, Pathways
    Protein Spotlighthttp://web.expasy.org/spotlight/back_issues/129

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NRG1 gene:
    Search GeneIP for patents involving NRG1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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     Browse ESI BIO Cell Lines and PureStem Progenitors for NRG1
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     Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NRG1
     SwitchGear 3'UTR luciferase reporter plasmids for NRG1
     SwitchGear Promoter luciferase reporter plasmids for NRG1
     ThermoFisher Antibody for NRG1
     Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NRG1
     Browse compounds at ApexBio
     Search Addgene for plasmids for NRG1
      Search eBioscience for proteins for NRG1
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      eBioscience FlowRNA Probe Sets
     genOway: Develop your customized and physiologically relevant rodent model for NRG1
     antibodies-online antibodies for NRG1 (110 products)
     antibodies-online kits for NRG1 (41 products)
     antibodies-online peptides for NRG1
     antibodies-online proteins for NRG1 (22 products)
           
    GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014 , 7 Oct 2014

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