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neuregulin-1; neu differentiation factor; heregulin; breast cancer cell differentiation factor p45; glial growth factor-2 (NRG1, GGF, HGL, HRG, HRGA, NDF, SMDF, ARIA)
Function:
1) direct ligand for ERBB3 & ERBB4 tyrosine kinase receptors
2) recruits ERBB1 & ERBB2 coreceptors
3) multiple isoforms perform diverse functions
a) growth & differentiation of epithelial, glial, neuronal, & skeletal muscle cells
b) expression of acetylcholine receptor in synaptic vesicles during formation of neuromuscular junctions
c) lobuloalveolar budding & milk production in mammary gland, differentiation of mammary tumor cells
d) Schwann cell proliferation
e) development of the myocardium
- trabeculation of developing heart
4) interacts with LIM domain region of LIMK1
5) extensive glycosylation precedes the proteolytic cleavage
Compartment:
- cell membrane, secreted, nucleus
- membrane-bound form may not be active
Alternative splicing:
- named isoforms=10
- additional isoforms seem to exist
Expression:
- secreted form(s) expressed in nervous system
- NOT expressed in adult heart, placenta, lung, liver, skeletal muscle, kidney, pancreas
- NOT expression in fetal lung, liver, kidney
- detectable at early embryonic ages
Pathology:
- chromosomal translocation t(8;11) involving NRG1 & ODZ4 produced gamma-heregulin
General
glial growth factor heregulin, or neu-differentiation factor
glycoprotein
neuregulin
Properties
SIZE: MW = 32 kD
entity length = 296 aa
COMPARTMENT: extracellular compartment
MOTIF: cysteine-rich region {58-91}
transmembrane domain {76-100}
threonine-rich region {211-232}
MOTIF: threonine residue (SEVERAL)
EGF domain {233-277}
MOTIF: cysteine residue {C237}
MODIFICATION: cysteine residue {C251}
cysteine residue {C245}
MODIFICATION: cysteine residue {C265}
cysteine residue {C251}
MODIFICATION: cysteine residue {C237}
cysteine residue {C265}
MODIFICATION: cysteine residue {C245}
cysteine residue {C267}
MODIFICATION: cysteine residue {C276}
cysteine residue {C276}
MODIFICATION: cysteine residue {C267}
Database Correlations
OMIM 142445
UniProt Q02297
PFAM correlations
Entrez Gene 3084
Kegg hsa:3084
References
- Marchionni MA, Goodearl AD, Chen MS, Bermingham-McDonogh O,
Kirk C, Hendricks M, Danehy F, Misumi D, Sudhalter J, Kobayashi K, et al.
Glial growth factors are alternatively spliced erbB2 ligands
expressed in the nervous system.
Nature. 1993 Mar 25;362(6418):312-8.
PMID: 8096067
- UniProt :accession Q02297
- Protein Spotlight; Tipping the mind - Issue 129 of June 2011
http://web.expasy.org/spotlight/back_issues/sptlt129.shtml