InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NRG1

Summary

InnateDB Protein

IDBP-473918.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NRG1

Protein Name

neuregulin 1

Synonyms

ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA; MST131; MSTP131; NDF; NRG1-IT2; SMDF;

Species

Homo sapiens

Ensembl Protein

ENSP00000428828

InnateDB Gene

IDBG-16182 (NRG1)

Protein Structure

UniProt Annotation

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}.

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.

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.

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}.

Comments

Interactions

Number of Interactions

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]
Protein-Protein	9 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003712	transcription cofactor activity
GO:0005102	receptor binding
GO:0005125	cytokine activity
GO:0005515	protein binding
GO:0008083	growth factor activity
GO:0030296	protein tyrosine kinase activator activity
GO:0030297	transmembrane receptor protein tyrosine kinase activator activity
GO:0030971	receptor tyrosine kinase binding
GO:0043125	ErbB-3 class receptor binding

Biological Process

GO:0003222	ventricular trabecula myocardium morphogenesis
GO:0007154	cell communication
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007171	activation of transmembrane receptor protein tyrosine kinase activity
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007399	nervous system development
GO:0008283	cell proliferation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0009790	embryo development
GO:0010667	negative regulation of cardiac muscle cell apoptotic process
GO:0014032	neural crest cell development
GO:0030307	positive regulation of cell growth
GO:0030879	mammary gland development
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038127	ERBB signaling pathway
GO:0042060	wound healing
GO:0043496	regulation of protein homodimerization activity
GO:0043497	regulation of protein heterodimerization activity
GO:0043624	cellular protein complex disassembly
GO:0045087	innate immune response
GO:0045785	positive regulation of cell adhesion
GO:0045892	negative regulation of transcription, DNA-templated
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0051048	negative regulation of secretion
GO:0051155	positive regulation of striated muscle cell differentiation
GO:0055007	cardiac muscle cell differentiation
GO:0055012	ventricular cardiac muscle cell differentiation
GO:0060045	positive regulation of cardiac muscle cell proliferation
GO:0060379	cardiac muscle cell myoblast differentiation
GO:0060956	endocardial cell differentiation
GO:0061098	positive regulation of protein tyrosine kinase activity
GO:2001240	negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005634	nucleus
GO:0016020	membrane
GO:0016324	apical plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000742 Epidermal growth factor-like domain
IPR002154 Neuregulin 1-related, C-terminal
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR013098 Immunoglobulin I-set
IPR013106 Immunoglobulin V-set domain
IPR013151 Immunoglobulin
IPR018250 Neuregulin

PFAM

PF00008
PF02158
PF07679
PF07686
PF00047

PRINTS

PR01089

PIRSF

SMART

SM00181
SM00408
SM00409

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt