InnateDB Protein
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IDBP-598617.3
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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NRG1
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Protein Name
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neuregulin 1
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Synonyms
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ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA; MST131; MSTP131; NDF; NRG1-IT2; SMDF;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000433289
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InnateDB Gene
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IDBG-16182 (NRG1)
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Protein Structure
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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. {ECO:0000269PubMed:1348215, ECO:0000269PubMed:7902537}.
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Subcellular Localization |
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.
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Disease Associations |
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.
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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. {ECO:0000269PubMed:17565985}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 10 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.
Experimentally validated |
Total |
10
[view]
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Protein-Protein |
9
[view]
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Protein-DNA |
1
[view]
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
1 [view]
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Molecular Function |
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Biological Process |
GO:0003222
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ventricular trabecula myocardium morphogenesis
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GO:0007154
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cell communication
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GO:0007169
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transmembrane receptor protein tyrosine kinase signaling pathway
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GO:0007171
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activation of transmembrane receptor protein tyrosine kinase activity
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GO:0007173
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epidermal growth factor receptor signaling pathway
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GO:0007399
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nervous system development
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GO:0008283
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cell proliferation
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GO:0008543
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fibroblast growth factor receptor signaling pathway
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GO:0009790
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embryo development
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GO:0010667
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negative regulation of cardiac muscle cell apoptotic process
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GO:0014032
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neural crest cell development
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GO:0030307
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positive regulation of cell growth
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GO:0030879
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mammary gland development
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GO:0038095
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Fc-epsilon receptor signaling pathway
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GO:0038127
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ERBB signaling pathway
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GO:0042060
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wound healing
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GO:0043496
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regulation of protein homodimerization activity
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GO:0043497
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regulation of protein heterodimerization activity
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GO:0043624
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cellular protein complex disassembly
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GO:0045087
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innate immune response
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GO:0045785
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positive regulation of cell adhesion
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GO:0045892
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negative regulation of transcription, DNA-templated
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GO:0048011
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neurotrophin TRK receptor signaling pathway
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GO:0048015
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phosphatidylinositol-mediated signaling
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GO:0051048
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negative regulation of secretion
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GO:0051155
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positive regulation of striated muscle cell differentiation
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GO:0055007
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cardiac muscle cell differentiation
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GO:0055012
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ventricular cardiac muscle cell differentiation
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GO:0060045
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positive regulation of cardiac muscle cell proliferation
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GO:0060379
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cardiac muscle cell myoblast differentiation
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GO:0060956
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endocardial cell differentiation
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GO:0061098
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positive regulation of protein tyrosine kinase activity
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GO:2001240
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negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
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Cellular Component |
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PDB ID |
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InterPro |
IPR000742
Epidermal growth factor-like domain
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PFAM |
PF00008
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PRINTS |
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PIRSF |
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SMART |
SM00181
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TIGRFAMs |
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Modification |
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SwissProt |
Q02297
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PhosphoSite |
PhosphoSite-Q02297
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
3084
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UniGene |
Hs.691092
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RefSeq |
NP_039253
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HUGO |
HGNC:7997
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OMIM |
142445
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CCDS |
CCDS6087
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HPRD |
00802
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IMGT |
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EMBL |
AC021909
AC022833
AC022850
AC023948
AC068359
AC068931
AC083977
AC103675
AC104000
AC104029
AC113209
AF009227
AF026146
AF491780
AK289927
AK298132
BC064587
BC073871
BK000383
CH471080
EF372273
EF372274
L12260
L12261
L41827
M94165
M94166
M94167
M94168
U02325
U02326
U02327
U02328
U02329
U02330
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GenPept |
AAA19950
AAA19951
AAA19952
AAA19953
AAA19954
AAA19955
AAA58638
AAA58639
AAA58640
AAA58641
AAB59358
AAB59622
AAC41764
AAC51756
AAD01795
AAH64587
AAH73871
AAM71137
AAM71139
AAM71140
ABQ53539
ABQ53540
BAF82616
BAH12729
DAA00044
DAA00045
DAA00046
DAA00047
EAW63411
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