neuregulin-3 (NRG3)

Function

• direct ligand for the ERBB4 tyrosine kinase receptor
• binding results in ligand-stimulated tyrosine phosphorylation & activation of the receptor
• does not bind to the EGF receptor, ERBB2 receptor or ERBB3 receptor
• may be a survival factor for oligodendrocytes
• proteolytic cleavage close to the plasma membrane on the external face leads to the release of soluble growth factor form
• extensive glycosylation precedes the proteolytic cleavage
• isoform 3 is glycosylated
• interacts with ERBB4

Structure

• the cytoplasmic domain may be involved in regulation of trafficking & proteolytic processing
• regulation of proteolytic processing involves initial intracellular domain dimerization (putative)
• ERBB receptor binding is elicited entirely by the EGF-like domain (putative)
• belongs to the neuregulin family
• contains 1 EGF-like domain

Compartment

• pro-neuregulin-3
  • plaams membrane
  • single-pass type 1 membrane protein
  • does not seem to be active (putative)
• neuregulin-3: secreted (putative)
• isoform 3:
  • cell membrane
  • single-pass type 1 membrane protein
  • isoform 3 is also proteolytically released as a soluble form

Alternative splicing

named isoforms=4

Expression

• highly expressed in most regions of the brain
• not expressed or expressed at a low level in corpus callosum
• expressed at low level in testis
• not detected in heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, ovary, small intestine, colon & peripheral blood leukocytes
• isoform 3
  • expressed in fetal brain
  • not expressed in other fetal tissues

More general terms

• neuregulin
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=10718
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:10718
• OMIM: https://mirror.omim.org/entry/605533
• UniProt: http://www.uniprot.org/uniprot/P56975.html