Neuregulin (NRG1) Antibody – Mouse Monoclonal

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]

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. Ref.14 Ref.15

Subunit structure: The cytoplasmic domain interacts with the LIM domain region of LIMK1

By similarity. Interacts with ERBB3 and ERBB4. Ref.15 Ref.18

Subcellular location: 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.

Tissue specificity: Type I isoforms are the predominant forms expressed in the endocardium. Isoform alphais 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 expressedin 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. Ref.10

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. Ref.10

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.

Post-translational modification: Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.N- and O-glycosylated. Extensive glycosylation precedes the proteolytic cleavage

By similarity. Ref.14

Involvement in disease: 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.

Sequence similarities: Belongs to the neuregulin family.Contains 1 EGF-like domain.Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Sequence caution: The sequence AAA19955.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.The sequence AAC51756.1 differs from that shown. Reason: Erroneous initiation.