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

General

neuregulin phosphoprotein

Properties

SIZE: entity length = 720 aa MW = 78 kD COMPARTMENT: cellular membrane MOTIF: alanine-rich region {5-8} MOTIF: alanine residue (SEVERAL) alanine-rich region {13-21} MOTIF: alanine residue (SEVERAL) alanine-rich region {26-34} MOTIF: alanine residue (SEVERAL) threonine-rich region {105-285} MOTIF: threonine residue (SEVERAL) Ser phosphorylation site {S116} Ser phosphorylation site {S119} threonine-rich region {127-135} MOTIF: threonine residue (SEVERAL) serine-rich region {252-260} MOTIF: serine residue (SEVERAL) threonine-rich region {262-265} MOTIF: threonine residue (SEVERAL) EGF domain {286-329} MOTIF: cysteine residue {C290} MODIFICATION: cysteine residue {C304} cysteine residue {C298} MODIFICATION: cysteine residue {C317} cysteine residue {C304} MODIFICATION: cysteine residue {C290} cysteine residue {C317} MODIFICATION: cysteine residue {C298} cysteine residue {C319} MODIFICATION: cysteine residue {C328} cysteine residue {C328} MODIFICATION: cysteine residue {C319} transmembrane domain {361-381}

Database Correlations

OMIM 605533 UniProt P56975 Entrez Gene 10718 Kegg hsa:10718

References

UniProt :accession P56975