Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Nrg1. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Nrg1
  • participates in the following biological processes:
    • cardiac conduction system development ^[13]
    • cell morphogenesis ^[14]
    • MAPK cascade ^[17]
    • negative regulation of protein catabolic process ^[3]
    • positive regulation of protein kinase activity ^{[1, 8]}
    • positive regulation of protein kinase B signaling cascade ^[3]
    • positive regulation of Ras protein signal transduction ^[17]
  • performs the following molecular functions:
    • ErbB-2 class receptor binding ^[2]
  • is located in the following cellular components:
    • cytoplasm ^[10]
    • integral to plasma membrane ^[2]
    • neuromuscular junction ^[12]
    • plasma membrane ^[10]
    • synapse ^[8]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Nrg1
  • participates in the following biological processes:
    • glial cell differentiation ^{[7, 16]}
    • heart development ^{[4, 9, 11]}
    • locomotory behavior ^[5]
    • muscle organ development ^[6]
    • nervous system development ^[9]
    • neuron fate commitment ^[2]
    • neurotransmitter receptor metabolic process ^[15]
    • peripheral nervous system development ^{[4, 11]}
    • regulation of cell differentiation ^{[2, 18]}
    • synapse assembly ^[19]
• Researchers have inferred, based on genetic interactions, that the gene product of Nrg1
  • participates in the following biological processes:
    • cell migration based on interactions with Erbb4 ^[14]
  • performs the following molecular functions:
    • ErbB-2 class receptor binding based on interactions with Erbb4 ^[14]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Nrg1:
  • participates in the following biological processes:
    • activation of transmembrane receptor protein tyrosine kinase activity
    • cardiac muscle cell myoblast differentiation
    • cell proliferation
    • cellular protein complex disassembly
    • endocardial cell differentiation
    • ERBB signaling pathway
    • glucose transport
    • negative regulation of apoptotic process
    • negative regulation of cardiac muscle cell apoptotic process
    • negative regulation of secretion
    • negative regulation of transcription, DNA-dependent
    • positive regulation of cardiac muscle cell proliferation
    • positive regulation of cell adhesion
    • positive regulation of cell growth
    • positive regulation of protein tyrosine kinase activity
    • regulation of protein heterodimerization activity
    • transmembrane receptor protein tyrosine kinase signaling pathway
    • ventricular cardiac muscle cell differentiation
    • ventricular trabecula myocardium morphogenesis
    • wound healing
  • performs the following molecular functions:
    • ErbB-3 class receptor binding
    • growth factor activity
    • protein tyrosine kinase activator activity
    • receptor binding
    • transcription cofactor activity
  • is located in the following cellular components:
    • apical plasma membrane
    • extracellular space

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References

1. Balana ME et al. (1999) Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas Oncogene, 18:6370-9. (PubMed:10597237)
2. Calaora V et al. (2001) Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro. J Neurosci, 21:4740-51. (PubMed:11425901)
3. Cotter L et al. (2010) Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination. Science, 328:1415-8. (PubMed:20448149)
4. Erickson SL et al. (1997) ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice. Development, 124:4999-5011. (PubMed:9362461)
5. Gerlai R et al. (2000) Heregulin, but not ErbB2 or ErbB3, heterozygous mutant mice exhibit hyperactivity in multiple behavioral tasks Behav Brain Res, 109:219-27. (PubMed:10762692)
6. Hippenmeyer S et al. (2002) A role for neuregulin1 signaling in muscle spindle differentiation. Neuron, 36:1035-49. (PubMed:12495620)
7. Jevsek M et al. (2006) CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission. Proc Natl Acad Sci U S A, 103:6374-9. (PubMed:16606832)
8. Jo SA et al. (1995) Neuregulins are concentrated at nerve-muscle synapses and activate ACh-receptor gene expression. Nature, 373:158-61. (PubMed:7816098)
9. Kramer R et al. (1996) Neuregulins with an Ig-like domain are essential for mouse myocardial and neuronal development. Proc Natl Acad Sci U S A, 93:4833-8. (PubMed:8643489)
10. Liu X et al. (1998) Domain-specific gene disruption reveals critical regulation of neuregulin signaling by its cytoplasmic tail. Proc Natl Acad Sci U S A, 95:13024-9. (PubMed:9789034)
11. Meyer D et al. (1995) Multiple essential functions of neuregulin in development [see comments] [published erratum appears in Nature 1995 Dec 14;378(6558):753] Nature, 378:386-90. (PubMed:7477375)
12. Moscoso LM et al. (1995) Synapse-associated expression of an acetylcholine receptor-inducing protein, ARIA/heregulin, and its putative receptors, ErbB2 and ErbB3, in developing mammalian muscle. Dev Biol, 172:158-69. (PubMed:7589796)
13. Rentschler S et al. (2002) Neuregulin-1 promotes formation of the murine cardiac conduction system. Proc Natl Acad Sci U S A, 99:10464-9. (PubMed:12149465)
14. Rio C et al. (1997) Neuregulin and erbB receptors play a critical role in neuronal migration. Neuron, 19:39-50. (PubMed:9247262)
15. Sandrock AW Jr et al. (1997) Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivo. Science, 276:599-603. (PubMed:9110980)
16. Schmid RS et al. (2003) Neuregulin 1-erbB2 signaling is required for the establishment of radial glia and their transformation into astrocytes in cerebral cortex. Proc Natl Acad Sci U S A, 100:4251-6. (PubMed:12649319)
17. Tansey MG et al. (1996) ARIA/HRG regulates AChR epsilon subunit gene expression at the neuromuscular synapse via activation of phosphatidylinositol 3-kinase and Ras/MAPK pathway. J Cell Biol, 134:465-76. (PubMed:8707830)
18. Vartanian T et al. (1999) Failure of spinal cord oligodendrocyte development in mice lacking neuregulin. Proc Natl Acad Sci U S A, 96:731-5. (PubMed:9892702)
19. Wolpowitz D et al. (2000) Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses. Neuron, 25:79-91. (PubMed:10707974)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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