This gene encodes a novel member of the neuregulin family of growth and differentiation factors. Through interaction with the ERBB family of receptors, this protein induces the growth and differentiation of epithelial, neuronal, glial, and other types of cells. The gene consists of 12 exons and the genomic structure is similar to that of neuregulin 1, another member of the neur... See more...

Aliases for NRG2 Gene

Aliases for NRG2 Gene

  • Neuregulin 2 2 3 5
  • Neural- And Thymus-Derived Activator For ErbB Kinases 2 3
  • Pro-Neuregulin-2, Membrane-Bound Isoform 3 4
  • Divergent Of Neuregulin-1 2 3
  • Pro-NRG2 3 4
  • NTAK 3 4
  • DON1 3
  • HRG2 3

External Ids for NRG2 Gene

Previous GeneCards Identifiers for NRG2 Gene

  • GC05M139049
  • GC05M139210
  • GC05M139255
  • GC05M139207
  • GC05M134369

Summaries for NRG2 Gene

Entrez Gene Summary for NRG2 Gene

  • This gene encodes a novel member of the neuregulin family of growth and differentiation factors. Through interaction with the ERBB family of receptors, this protein induces the growth and differentiation of epithelial, neuronal, glial, and other types of cells. The gene consists of 12 exons and the genomic structure is similar to that of neuregulin 1, another member of the neuregulin family of ligands. The products of these genes mediate distinct biological processes by acting at different sites in tissues and eliciting different biological responses in cells. This gene is located close to the region for demyelinating Charcot-Marie-Tooth disease locus, but is not responsible for this disease. Alternative transcript variants encoding distinct isoforms have been described. [provided by RefSeq, May 2010]

GeneCards Summary for NRG2 Gene

NRG2 (Neuregulin 2) is a Protein Coding gene. Diseases associated with NRG2 include Dysbaric Osteonecrosis and Endometrial Adenosquamous Carcinoma. Among its related pathways are RET signaling and Downstream signaling events of B Cell Receptor (BCR). Gene Ontology (GO) annotations related to this gene include signaling receptor binding and growth factor activity. An important paralog of this gene is NRG1.

UniProtKB/Swiss-Prot Summary for NRG2 Gene

  • Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. May also promote the heterodimerization with the EGF receptor.

Gene Wiki entry for NRG2 Gene

Additional gene information for NRG2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NRG2 Gene

Genomics for NRG2 Gene

GeneHancer (GH) Regulatory Elements for NRG2 Gene

Promoters and enhancers for NRG2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NRG2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NRG2

Top Transcription factor binding sites by QIAGEN in the NRG2 gene promoter:
  • CREB
  • Egr-1
  • Egr-4
  • HEN1
  • Nkx2-5
  • Pax-5
  • SRF
  • SRF (504 AA)
  • USF-1
  • USF1

Genomic Locations for NRG2 Gene

Genomic Locations for NRG2 Gene
chr5:139,846,779-140,043,437
(GRCh38/hg38)
Size:
196,659 bases
Orientation:
Minus strand
chr5:139,226,364-139,422,884
(GRCh37/hg19)
Size:
196,521 bases
Orientation:
Minus strand

Genomic View for NRG2 Gene

Genes around NRG2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NRG2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NRG2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NRG2 Gene

Proteins for NRG2 Gene

  • Protein details for NRG2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14511-NRG2_HUMAN
    Recommended name:
    Pro-neuregulin-2, membrane-bound isoform
    Protein Accession:
    O14511

    Protein attributes for NRG2 Gene

    Size:
    850 amino acids
    Molecular mass:
    91679 Da
    Quaternary structure:
    • Interacts with ERBB3 and ERBB4.
    Miscellaneous:
    • [Isoform 5]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Alternative splice isoforms for NRG2 Gene

neXtProt entry for NRG2 Gene

Post-translational modifications for NRG2 Gene

  • Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.
  • Extensive glycosylation precedes the proteolytic cleavage.
  • Glycosylation at Asn278, Asn52, Asn53, Thr333, Thr334, Asn346, and Asn147
  • Modification sites at PhosphoSitePlus

Protein Products

  • Abcam proteins for NRG2

No data available for DME Specific Peptides for NRG2 Gene

Domains & Families for NRG2 Gene

Gene Families for NRG2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for NRG2 Gene

Blocks:
  • Immunoglobulin C-2 type
  • Type I EGF
  • Neuregulin family signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NRG2 Gene

GenScript: Design optimal peptide antigens:
  • Pro-neuregulin-2, membrane-bound isoform (NRG2_HUMAN)
  • NRG2 protein (Q3MI86_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O14511

UniProtKB/Swiss-Prot:

NRG2_HUMAN :
  • The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity).
  • Belongs to the neuregulin family.
Domain:
  • The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity).
  • ERBB receptor binding is elicited entirely by the EGF-like domain.
Family:
  • Belongs to the neuregulin family.
genes like me logo Genes that share domains with NRG2: view

Function for NRG2 Gene

Molecular function for NRG2 Gene

UniProtKB/Swiss-Prot Function:
Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. May also promote the heterodimerization with the EGF receptor.
GENATLAS Biochemistry:
neuregulin 2 multipotent epidermal growth factor-like factor with several splice variants,expressed in adult brain and developing heart,binding ERBB3 and ERBB4,involved in growth and differentiation of epithelial,neuronal,glial and other cell types

Phenotypes From GWAS Catalog for NRG2 Gene

Gene Ontology (GO) - Molecular Function for NRG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding IBA,IEA 21873635
GO:0008083 growth factor activity IEA --
genes like me logo Genes that share ontologies with NRG2: view
genes like me logo Genes that share phenotypes with NRG2: view

Animal Models for NRG2 Gene

MGI Knock Outs for NRG2:

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NRG2 Gene

Localization for NRG2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NRG2 Gene

[Pro-neuregulin-2, membrane-bound isoform]: Cell membrane; Single-pass type I membrane protein. Note=Does not seem to be active. {ECO:0000250}.
[Neuregulin-2]: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NRG2 gene
Compartment Confidence
plasma membrane 4
extracellular 4
nucleus 3
cytosol 2
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoli (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NRG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA 21873635
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with NRG2: view

Pathways & Interactions for NRG2 Gene

PathCards logo

SuperPathways for NRG2 Gene

SuperPathway Contained pathways
1 RET signaling
2 Apoptotic Pathways in Synovial Fibroblasts
.85
.85
.84
.84
.74
.72
.66
.65
.64
.62
.61
.60
.57
.57
3 Signaling by ERBB2
4 GAB1 signalosome
5 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
genes like me logo Genes that share pathways with NRG2: view

Pathways by source for NRG2 Gene

1 GeneGo (Thomson Reuters) pathway for NRG2 Gene
  • Development ERBB-family signaling
58 Qiagen pathways for NRG2 Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin-Based Motility by Rho Family GTPases
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR

SIGNOR curated interactions for NRG2 Gene

Activates:

Gene Ontology (GO) - Biological Process for NRG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0007165 signal transduction TAS 9168114
GO:0007399 nervous system development IEA --
GO:0035556 intracellular signal transduction IBA 21873635
GO:0038128 ERBB2 signaling pathway TAS --
genes like me logo Genes that share ontologies with NRG2: view

Drugs & Compounds for NRG2 Gene

(2) Drugs for NRG2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with NRG2: view

Transcripts for NRG2 Gene

mRNA/cDNA for NRG2 Gene

7 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NRG2 Gene

No ASD Table

Relevant External Links for NRG2 Gene

GeneLoc Exon Structure for
NRG2

Expression for NRG2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NRG2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NRG2 Gene

This gene is overexpressed in Brain - Cerebellum (x4.5) and Brain - Cerebellar Hemisphere (x4.3).

Protein differential expression in normal tissues from HIPED for NRG2 Gene

This gene is overexpressed in Lung (40.3) and Liver, secretome (23.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NRG2 Gene



Protein tissue co-expression partners for NRG2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NRG2

SOURCE GeneReport for Unigene cluster for NRG2 Gene:

Hs.408515

mRNA Expression by UniProt/SwissProt for NRG2 Gene:

O14511-NRG2_HUMAN
Tissue specificity: Restricted to the cerebellum in the adult.

Evidence on tissue expression from TISSUES for NRG2 Gene

  • Nervous system(4.3)
  • Lung(4.1)
genes like me logo Genes that share expression patterns with NRG2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for NRG2 Gene

Orthologs for NRG2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NRG2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NRG2 31 30
  • 98.48 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Nrg2 17 31 30
  • 91.01 (n)
rat
(Rattus norvegicus)
Mammalia Nrg2 30
  • 90.94 (n)
dog
(Canis familiaris)
Mammalia NRG2 31 30
  • 90.79 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NRG2 31 30
  • 90.41 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NRG2 31
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NRG2 31
  • 72 (a)
OneToOne
chicken
(Gallus gallus)
Aves NRG2 31 30
  • 73.48 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NRG2 31
  • 72 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii nrg2a 31 30
  • 66.83 (n)
OneToMany
nrg2b 31
  • 54 (a)
OneToMany
Species where no ortholog for NRG2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NRG2 Gene

ENSEMBL:
Gene Tree for NRG2 (if available)
TreeFam:
Gene Tree for NRG2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NRG2: view image

Paralogs for NRG2 Gene

Paralogs for NRG2 Gene

(3) SIMAP similar genes for NRG2 Gene using alignment to 4 proteins:

  • NRG2_HUMAN
  • F5GZS7_HUMAN
  • F5H0N2_HUMAN
  • Q3MI86_HUMAN
genes like me logo Genes that share paralogs with NRG2: view

Variants for NRG2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NRG2 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
713423 Likely Benign: not provided 140,043,017(-) C/T MISSENSE_VARIANT
737609 Likely Benign: not provided 140,042,646(-) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for NRG2 Gene

Structural Variations from Database of Genomic Variants (DGV) for NRG2 Gene

Variant ID Type Subtype PubMed ID
dgv10091n54 CNV loss 21841781
esv1004341 CNV deletion 20482838
esv2667289 CNV deletion 23128226
esv26674 CNV loss 19812545
esv2674763 CNV deletion 23128226
esv3303578 CNV mobile element insertion 20981092
esv3308333 CNV mobile element insertion 20981092
esv3327934 CNV insertion 20981092
esv3330122 CNV duplication 20981092
esv3347369 CNV duplication 20981092
esv3360693 CNV insertion 20981092
esv3566717 CNV deletion 23714750
esv3606944 CNV loss 21293372
esv3606946 CNV loss 21293372
nsv1074332 CNV deletion 25765185
nsv471051 CNV gain 18288195
nsv526406 CNV gain 19592680
nsv599821 CNV loss 21841781
nsv830506 CNV loss 17160897

Variation tolerance for NRG2 Gene

Residual Variation Intolerance Score: 23.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.01; 60.23% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NRG2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NRG2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NRG2 Gene

Disorders for NRG2 Gene

MalaCards: The human disease database

(4) MalaCards diseases for NRG2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
dysbaric osteonecrosis
  • caisson disease of bone
endometrial adenosquamous carcinoma
  • adenosquamous carcinoma of endometrium
charcot-marie-tooth disease
  • peroneal muscular atrophy
tooth disease
  • tooth disorders
- elite association - COSMIC cancer census association via MalaCards
Search NRG2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NRG2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NRG2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NRG2 Gene

Publications for NRG2 Gene

  1. Fine mapping of new glaucoma locus GLC1M and exclusion of neuregulin 2 as the causative gene. (PMID: 17563728) Fan BJ … Pang CP (Molecular vision 2007) 3 23 41 54
  2. The human neuregulin-2 (NRG2) gene: cloning, mapping and evaluation as a candidate for the autosomal recessive form of Charcot-Marie-Tooth disease linked to 5q. (PMID: 10369162) Ring HZ … Francke U (Human genetics 1999) 3 4 23 54
  3. Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases. (PMID: 9168115) Carraway KL … Lai C (Nature 1997) 2 3 23 54
  4. Characterization of a neuregulin-related gene, Don-1, that is highly expressed in restricted regions of the cerebellum and hippocampus. (PMID: 9199335) Busfield SJ … Gearing DP (Molecular and cellular biology 1997) 3 4 23 54
  5. A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4. (PMID: 9348101) Higashiyama S … Ishiguro H (Journal of biochemistry 1997) 3 4 23 54

Products for NRG2 Gene

Sources for NRG2 Gene