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Aliases for NRG1 Gene

Aliases for NRG1 Gene

  • Neuregulin 1 2 3
  • Pro-NRG1 3 4
  • HRGA 3 4
  • SMDF 3 4
  • HGL 3 4
  • GGF 3 4
  • NDF 3 4
  • NRG1 Intronic Transcript 2 (Non-Protein Coding) 2
  • Heregulin, Alpha (45kD, ERBB2 P185-Activator) 3
  • Pro-Neuregulin-1, Membrane-Bound Isoform 3
  • Sensory And Motor Neuron Derived Factor 3
  • Neu Differentiation Factor 3
  • ERBB2 P185-Activator) 6
  • Glial Growth Factor 3
  • NRG1-IT2 3
  • MSTP131 3
  • MST131 3
  • HRG1 3
  • GGF2 3
  • ARIA 3
  • HRG 3

External Ids for NRG1 Gene

Previous HGNC Symbols for NRG1 Gene

  • HGL
  • NRG1-IT2

Previous GeneCards Identifiers for NRG1 Gene

  • GC08P031402
  • GC08P032856
  • GC08P032463
  • GC08P031554
  • GC08P030042

Summaries for NRG1 Gene

Entrez Gene Summary for NRG1 Gene

  • The protein encoded by this gene is a membrane glycoprotein that 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, Jun 2014]

GeneCards Summary for NRG1 Gene

NRG1 (Neuregulin 1) is a Protein Coding gene. Diseases associated with NRG1 include schizophreniform disorder and schizophrenia. Among its related pathways are PI-3K cascade and PI-3K cascade. GO annotations related to this gene include receptor binding and growth factor activity. An important paralog of this gene is NRG3.

UniProtKB/Swiss-Prot for NRG1 Gene

  • 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 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NRG1 Gene

Genomics for NRG1 Gene

Regulatory Elements for NRG1 Gene

Genomic Location for NRG1 Gene

Start:
31,639,304 bp from pter
End:
32,765,040 bp from pter
Size:
1,125,737 bases
Orientation:
Plus strand

Genomic View for NRG1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NRG1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NRG1 Gene

Proteins for NRG1 Gene

  • Protein details for NRG1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q02297-NRG1_HUMAN
    Recommended name:
    Pro-neuregulin-1, membrane-bound isoform
    Protein Accession:
    Q02297
    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

    Protein attributes for NRG1 Gene

    Size:
    640 amino acids
    Molecular mass:
    70392 Da
    Quaternary structure:
    • The cytoplasmic domain interacts with the LIM domain region of LIMK1 (By similarity). Interacts with ERBB3 and ERBB4.
    SequenceCaution:
    • Sequence=AAA19955.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=AAC51756.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for NRG1 Gene

    Alternative splice isoforms for NRG1 Gene

neXtProt entry for NRG1 Gene

Proteomics data for NRG1 Gene at MOPED

Post-translational modifications for NRG1 Gene

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

No data available for DME Specific Peptides for NRG1 Gene

Domains for NRG1 Gene

Gene Families for NRG1 Gene

HGNC:
  • ISET :Immunoglobulin superfamily / I-set domain containing

Graphical View of Domain Structure for InterPro Entry

Q02297

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).
  • ERBB receptor binding is elicited entirely by the EGF-like domain
  • Contains 1 EGF-like domain.
  • Contains 1 Ig-like C2-type (immunoglobulin-like) domain.
Family:
  • Belongs to the neuregulin family.
genes like me logo Genes that share domains with NRG1: view

Function for NRG1 Gene

Molecular function for NRG1 Gene

GENATLAS Biochemistry: neuregulin 1 multipotent epidermal growth factor-like factor with several splice variants (44kDa),indirect NEU/ERBB2 p185 activator (see ERBB2)
UniProtKB/Swiss-Prot 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 Ontology (GO) - Molecular Function for NRG1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003712 transcription cofactor activity IDA 15073182
GO:0005102 receptor binding IPI 7514177
GO:0005125 cytokine activity TAS 10372964
GO:0005176 ErbB-2 class receptor binding IEA --
GO:0005515 protein binding IPI 7592681
genes like me logo Genes that share ontologies with NRG1: view
genes like me logo Genes that share phenotypes with NRG1: view

Animal Models for NRG1 Gene

MGI Knock Outs for NRG1:

miRNA for NRG1 Gene

miRTarBase miRNAs that target NRG1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for NRG1 Gene

Localization for NRG1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NRG1 Gene

Pro-neuregulin-1, membrane-bound isoform: Cell membrane; Single-pass type I membrane protein. Note=Does not seem to be active.
Neuregulin-1: Secreted.
Isoform 8: Nucleus. Note=May be nuclear.
Isoform 9: Secreted. Note=Has a signal peptide.
Isoform 10: Membrane; Single-pass type I membrane protein. Note=May possess an internal uncleaved signal sequence.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NRG1 Gene COMPARTMENTS Subcellular localization image for NRG1 gene
Compartment Confidence
extracellular 5
nucleus 5
plasma membrane 5
cytoskeleton 2
cytosol 1
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for NRG1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA 11389077
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane --
genes like me logo Genes that share ontologies with NRG1: view

Pathways for NRG1 Gene

SuperPathways for NRG1 Gene

Superpath Contained pathways
1 Apoptotic Pathways in Synovial Fibroblasts
2 Signaling by FGFR
3 PI-3K cascade
4 GPCR Pathway
5 ERK Signaling
genes like me logo Genes that share pathways with NRG1: view

Gene Ontology (GO) - Biological Process for NRG1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IEA --
GO:0000902 cell morphogenesis IEA --
GO:0003161 cardiac conduction system development IEA --
GO:0003222 ventricular trabecula myocardium morphogenesis IDA 17336907
GO:0007154 cell communication TAS 17432114
genes like me logo Genes that share ontologies with NRG1: view

Compounds for NRG1 Gene

(62) Novoseek inferred chemical compound relationships for NRG1 Gene

Compound -log(P) Hits PubMed IDs
hrgbeta1 91.4 8
pd158780 81.2 3
tyrosine 76.1 116
trastuzumab 72.7 21
phosphatidylinositol 61.6 22
genes like me logo Genes that share compounds with NRG1: view

Transcripts for NRG1 Gene

Unigene Clusters for NRG1 Gene

Neuregulin 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for NRG1 Gene

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:
SP6:
SP7:
SP8:

Relevant External Links for NRG1 Gene

GeneLoc Exon Structure for
NRG1
ECgene alternative splicing isoforms for
NRG1

Expression for NRG1 Gene

mRNA expression in normal human tissues for NRG1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for NRG1 Gene

SOURCE GeneReport for Unigene cluster for NRG1 Gene Hs.453951

mRNA Expression by UniProt/SwissProt for NRG1 Gene

Q02297-NRG1_HUMAN
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.
genes like me logo Genes that share expressions with NRG1: view

No data available for mRNA differential expression in normal tissues for NRG1 Gene

Orthologs for NRG1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NRG1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NRG1 35
  • 99.55 (n)
  • 99.5 (a)
NRG1 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NRG1 35
  • 90.64 (n)
  • 94.28 (a)
NRG1 36
  • 67 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NRG1 35
  • 91.69 (n)
  • 93.77 (a)
NRG1 36
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nrg1 16
Nrg1 36
  • 67 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NRG1 36
  • 85 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NRG1 36
  • 88 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nrg1 35
  • 89.06 (n)
  • 93.94 (a)
chicken
(Gallus gallus)
Aves NRG1 36
  • 64 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NRG1 36
  • 73 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia nrg1-A 35
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100496613 35
  • 72.37 (n)
  • 74.61 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.6383 35
zebrafish
(Danio rerio)
Actinopterygii nrg1 35
  • 60.13 (n)
  • 54.14 (a)
nrg1 36
  • 42 (a)
OneToOne
Species with no ortholog for NRG1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NRG1 Gene

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

Paralogs for NRG1 Gene

Paralogs for NRG1 Gene

genes like me logo Genes that share paralogs with NRG1: view

Variants for NRG1 Gene

Sequence variations from dbSNP and Humsavar for NRG1 Gene

SNP ID Clin Chr 08 pos Sequence Context AA Info Type MAF
rs109767 -- 31,966,251(-) AAGAT(A/G)TAGGT intron-variant
rs167857 -- 31,997,097(+) TATTG(A/T)TTTAA intron-variant
rs167858 -- 31,963,805(+) CCGCT(A/C)TCAGG intron-variant
rs167859 -- 31,977,019(+) GTGTT(C/T)GCATT intron-variant
rs170576 -- 31,935,539(-) gggtc(A/G)cacct intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NRG1 Gene

Variant ID Type Subtype PubMed ID
nsv890709 CNV Gain 21882294
nsv831280 CNV Loss 17160897
esv270947 CNV Insertion 20981092
esv2638529 CNV Deletion 19546169
esv2167886 CNV Deletion 18987734
esv4933 CNV Deletion 18987735
nsv398284 CNV Loss 16902084
esv991445 CNV Deletion 20482838
esv9668 CNV Loss 19470904
esv1693112 CNV Deletion 17803354
esv2736844 CNV Deletion 23290073
nsv6142 CNV Insertion 18451855
esv2677557 CNV Deletion 23128226
nsv831282 CNV Gain 17160897
esv1484590 CNV Insertion 17803354
esv274992 CNV Gain+Loss 21479260
nsv890710 CNV Loss 21882294
nsv528531 CNV Loss 19592680
nsv470207 CNV Gain 18288195
nsv465632 CNV Gain 19166990
esv2657877 CNV Deletion 23128226
nsv890711 CNV Gain 21882294
nsv522780 CNV Loss 19592680
nsv518140 CNV Loss 19592680
nsv397244 CNV Loss 16902084
esv275566 CNV Loss 21479260
esv2659448 CNV Deletion 23128226
dgv1177n67 CNV Loss 20364138
esv2736845 CNV Deletion 23290073
esv2663032 CNV Deletion 23128226
nsv510140 CNV Loss 20534489
nsv526564 CNV Loss 19592680
nsv398013 CNV Loss 16902084
esv270557 CNV Insertion 20981092
esv274055 CNV Insertion 20981092
esv1412340 CNV Insertion 17803354
esv275121 CNV Loss 21479260
nsv465633 CNV Loss 19166990
nsv397271 CNV Loss 16902084
nsv890712 CNV Gain 21882294
esv8345 CNV Gain 19470904

Relevant External Links for NRG1 Gene

HapMap Linkage Disequilibrium report
NRG1
Human Gene Mutation Database (HGMD)
NRG1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NRG1 Gene

Disorders for NRG1 Gene

(1) OMIM Diseases for NRG1 Gene (142445)

UniProtKB/Swiss-Prot

NRG1_HUMAN
  • 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.

(1) University of Copenhagen DISEASES for NRG1 Gene

(61) Novoseek inferred disease relationships for NRG1 Gene

Disease -log(P) Hits PubMed IDs
schizophrenia 79.2 237
breast cancer 70.9 171
other schizophrenia 57.6 1
mammary tumor 57.3 10
breast carcinoma 56.5 21

Relevant External Links for NRG1

Genetic Association Database (GAD)
NRG1
Human Genome Epidemiology (HuGE) Navigator
NRG1
genes like me logo Genes that share disorders with NRG1: view

Publications for NRG1 Gene

  1. Identification of heregulin, a specific activator of p185erbB2. (PMID: 1350381) Holmes W.E. … Vandlen R.L. (Science 1992) 2 3 4 23
  2. Neural expression and chromosomal mapping of Neu differentiation factor to 8p12-p21. (PMID: 8095334) Orr-Urtreger A. … Yarden Y. (Proc. Natl. Acad. Sci. U.S.A. 1993) 2 3 23
  3. Sensory and motor neuron-derived factor. A novel heregulin variant highly expressed in sensory and motor neurons. (PMID: 7782315) Ho W.-H. … Osheroff P.L. (J. Biol. Chem. 1995) 3 4 23
  4. Gamma-heregulin is the product of a chromosomal translocation fusing the DOC4 and HGL/NRG1 genes in the MDA-MB-175 breast cancer cell line. (PMID: 10523851) Wang X.-Z. … Ron D. (Oncogene 1999) 3 4 23
  5. Neuregulin 1 and susceptibility to Schizophrenia. (PMID: 12145742) Stefansson H. … Stefansson K. (Am. J. Hum. Genet. 2002) 3 4 23

Products for NRG1 Gene

Sources for NRG1 Gene

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