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NRG3 neuregulin 3 [ Homo sapiens (human) ]

Gene ID: 10718, updated on 26-May-2016
Official Symbol
NRG3provided by HGNC
Official Full Name
neuregulin 3provided by HGNC
Primary source
HGNC:HGNC:7999
See related
Ensembl:ENSG00000185737 HPRD:16115; MIM:605533; Vega:OTTHUMG00000018626
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HRG3; pro-NRG3
Summary
This gene is a member of the neuregulin gene family. This gene family encodes ligands for the transmembrane tyrosine kinase receptors ERBB3 and ERBB4 - members of the epidermal growth factor receptor family. Ligand binding activates intracellular signaling cascades and the induction of cellular responses including proliferation, migration, differentiation, and survival or apoptosis. This gene encodes neuregulin 3 (NRG3). NRG3 has been shown to activate the tyrosine phosphorylation of its cognate receptor, ERBB4, and is thought to influence neuroblast proliferation, migration and differentiation by signalling through ERBB4. NRG3 also promotes mammary differentiation during embryogenesis. Linkage studies have implicated this gene as a susceptibility locus for schizophrenia and schizoaffective disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but their biological validity has not been verified.[provided by RefSeq, Sep 2009]
Orthologs
Location:
10q23.1
Exon count:
15
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 10 NC_000010.11 (81875309..82987179)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (83635070..84746935)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105378389 Neighboring gene uncharacterized LOC105378390 Neighboring gene uncharacterized LOC105378391 Neighboring gene NRG3 antisense RNA 1 Neighboring gene uncharacterized LOC105378392 Neighboring gene microtubule affinity regulating kinase 2 pseudogene 15

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated (2011-12-21)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated (2011-12-21)

ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
Genome-wide association study of retinopathy in individuals without diabetes.
NHGRI GWA Catalog
Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits.
NHGRI GWA Catalog
Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.
NHGRI GWA Catalog
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
NHGRI GWA Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
NHGRI GWA Catalog
Whole genome association study identifies polymorphisms associated with QT prolongation during iloperidone treatment of schizophrenia.
NHGRI GWA Catalog
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  • Signaling by FGFR4, organism-specific biosystem (from REACTOME)
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  • Signaling by Insulin receptor, organism-specific biosystem (from REACTOME)
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  • Signaling by PDGF, organism-specific biosystem (from REACTOME)
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  • Signaling by PTK6, organism-specific biosystem (from REACTOME)
    Signaling by PTK6, organism-specific biosystemPTK6 (BRK) is an oncogenic non-receptor tyrosine kinase that functions downstream of ERBB2 (HER2) (Xiang et al. 2008, Peng et al. 2015) and other receptor tyrosine kinases, such as EGFR (Kamalati et ...
  • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
    Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
  • Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystem (from REACTOME)
    Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystemBinding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS...
  • Signaling by VEGF, organism-specific biosystem (from REACTOME)
    Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
  • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
  • Signalling by NGF, organism-specific biosystem (from REACTOME)
    Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
  • Signalling to ERKs, organism-specific biosystem (from REACTOME)
    Signalling to ERKs, organism-specific biosystemNeurotrophins utilize multiple pathways to activate ERKs (ERK1 and ERK2), a subgroup of the large MAP kinase (MAPK) family, from the plasma membrane. The major signalling pathways to ERKs are via RAS...
  • Signalling to RAS, organism-specific biosystem (from REACTOME)
    Signalling to RAS, organism-specific biosystemSignalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation...
  • Signalling to p38 via RIT and RIN, organism-specific biosystem (from REACTOME)
    Signalling to p38 via RIT and RIN, organism-specific biosystemRIT and RIN are two small guanine nucleotide binding proteins that share more than 50% sequence identity with RAS, including highly conserved core effector domains. Unlike RAS, the C termini of RIT a...
  • VEGFA-VEGFR2 Pathway, organism-specific biosystem (from REACTOME)
    VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...
  • VEGFR2 mediated cell proliferation, organism-specific biosystem (from REACTOME)
    VEGFR2 mediated cell proliferation, organism-specific biosystemVEGFR2 stimulates ERK not via GRB2-SOS-RAS, but via pY1175-dependent phosphorylation of PLC gamma and subsequent activation of PKCs. PKC plays an important mediatory role in the proliferative Ras/Raf...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
chemorepellent activity IEA
Inferred from Electronic Annotation
more info
 
growth factor activity NAS
Non-traceable Author Statement
more info
PubMed 
receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
 
receptor tyrosine kinase binding NAS
Non-traceable Author Statement
more info
PubMed 
transmembrane receptor protein tyrosine kinase activator activity NAS
Non-traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
activation of transmembrane receptor protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
 
animal organ development IBA
Inferred from Biological aspect of Ancestor
more info
 
chemorepulsion involved in interneuron migration from the subpallium to the cortex IEA
Inferred from Electronic Annotation
more info
 
intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
 
mammary placode formation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of neuron migration IEA
Inferred from Electronic Annotation
more info
 
pattern specification process IEA
Inferred from Electronic Annotation
more info
 
regulation of cell growth NAS
Non-traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
extracellular region NAS
Non-traceable Author Statement
more info
PubMed 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
 
integral component of plasma membrane NAS
Non-traceable Author Statement
more info
PubMed 
intracellular IEA
Inferred from Electronic Annotation
more info
 
Preferred Names
pro-neuregulin-3, membrane-bound isoform
Names
neuregulin 3 variant 1
neuregulin 3 variant 10
neuregulin 3 variant 11
neuregulin 3 variant 12
neuregulin 3 variant 13
neuregulin 3 variant 14
neuregulin 3 variant 3
neuregulin 3 variant 4
neuregulin 3 variant 5
neuregulin 3 variant 6
neuregulin 3 variant 7
neuregulin 3 variant 8
neuregulin 3 variant 9
neuregulin-3-like polypeptide

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_013373.1 RefSeqGene

    Range
    5001..1116866
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001010848.3NP_001010848.2  pro-neuregulin-3, membrane-bound isoform isoform 1

    See identical proteins and their annotated locations for NP_001010848.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AL589782, BC136811, DQ001411
    Consensus CDS
    CCDS31233.1
    UniProtKB/Swiss-Prot
    P56975
    UniProtKB/TrEMBL
    B9EGV5
    Related
    ENSP00000361214, OTTHUMP00000245406, ENST00000372141, OTTHUMT00000412261
    Conserved Domains (2) summary
    pfam02158
    Location:353676
    Neuregulin; Neuregulin family
    PHA02887
    Location:278331
    PHA02887; EGF-like protein; Provisional
  2. NM_001165972.1NP_001159444.1  pro-neuregulin-3, membrane-bound isoform isoform 2

    See identical proteins and their annotated locations for NP_001159444.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a protein (isoform 2) that is one amino acid shorter, compared to isoform 1.
    Source sequence(s)
    AA704915, AK122886, AL589782, BC136811, DB326565
    UniProtKB/TrEMBL
    B3KVG8, B9EGV5
    Conserved Domains (2) summary
    pfam02158
    Location:352675
    Neuregulin; Neuregulin family
    PHA02887
    Location:278331
    PHA02887; EGF-like protein; Provisional
  3. NM_001165973.1NP_001159445.1  pro-neuregulin-3, membrane-bound isoform isoform 3

    See identical proteins and their annotated locations for NP_001159445.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has multiple differences in the presence and absence of exons in the 5' and 3' ends, compared to variant 1. These differences produce a unique 5' UTR and cause translation initiation at a unique start codon, compared to variant 1. The encoded protein (isoform 3; also known as hFBNRG3) has a shorter and distinct N-terminus and 24 additional aa in its C-terminus, compared to isoform 1. Isoform 3 is exclusively expressed in fetal brain and may undergo N-terminal proteolytic processing following its insertion into the plasma membrane.
    Source sequence(s)
    AA704915, AK122886, AL589782, DB326565, DQ001411, DQ857894
    Consensus CDS
    CCDS53547.1
    UniProtKB/Swiss-Prot
    P56975
    UniProtKB/TrEMBL
    B3KVG8
    Related
    ENSP00000361215, OTTHUMP00000019990, ENST00000372142, OTTHUMT00000049103
    Conserved Domains (2) summary
    pfam02158
    Location:132479
    Neuregulin; Neuregulin family
    PHA02887
    Location:38110
    PHA02887; EGF-like protein; Provisional

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p2 Primary Assembly

    Range
    81875309..82987179
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011539172.1XP_011537474.1  

    Conserved Domains (2) summary
    pfam02158
    Location:353701
    Neuregulin; Neuregulin family
    PHA02887
    Location:278331
    PHA02887; EGF-like protein; Provisional
  2. XM_011539173.1XP_011537475.1  

    Conserved Domains (2) summary
    pfam02158
    Location:352700
    Neuregulin; Neuregulin family
    PHA02887
    Location:278331
    PHA02887; EGF-like protein; Provisional
  3. XM_011539175.1XP_011537477.1  

    Conserved Domains (2) summary
    pfam02158
    Location:353677
    Neuregulin; Neuregulin family
    PHA02887
    Location:278331
    PHA02887; EGF-like protein; Provisional
  4. XM_011539174.1XP_011537476.1  

    Conserved Domains (2) summary
    pfam02158
    Location:344692
    Neuregulin; Neuregulin family
    PHA02887
    Location:278331
    PHA02887; EGF-like protein; Provisional
  5. XM_005269444.3XP_005269501.1  

    See identical proteins and their annotated locations for XP_005269501.1

    UniProtKB/Swiss-Prot
    P56975
    UniProtKB/TrEMBL
    D9ZHP6
    Related
    ENSP00000384796, OTTHUMP00000245407, ENST00000404547, OTTHUMT00000412262
    Conserved Domains (2) summary
    pfam02158
    Location:353700
    Neuregulin; Neuregulin family
    PHA02887
    Location:278331
    PHA02887; EGF-like protein; Provisional
  6. XM_011539177.1XP_011537479.1  

    Related
    ENSP00000451376, OTTHUMP00000245410, ENST00000556918, OTTHUMT00000412265
    Conserved Domains (2) summary
    pfam02158
    Location:93416
    Neuregulin; Neuregulin family
    PHA02887
    Location:1171
    PHA02887; EGF-like protein; Provisional
  7. XM_011539176.1XP_011537478.1  

    Conserved Domains (2) summary
    pfam02158
    Location:93441
    Neuregulin; Neuregulin family
    PHA02887
    Location:1171
    PHA02887; EGF-like protein; Provisional
  8. XM_011539179.1XP_011537481.1  

    Related
    ENSP00000441201, ENST00000545131
    Conserved Domains (1) summary
    pfam02158
    Location:3351
    Neuregulin; Neuregulin family
  9. XM_011539178.1XP_011537480.1  

    Conserved Domains (1) summary
    pfam02158
    Location:10358
    Neuregulin; Neuregulin family

Alternate CHM1_1.1

Genomic

  1. NC_018921.2 Alternate CHM1_1.1

    Range
    83917602..85028760
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)