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Aliases for NRG2 Gene

Aliases for NRG2 Gene

  • Neuregulin 2 2 3 5
  • Neural- And Thymus-Derived Activator For ErbB Kinases 2 3
  • Divergent Of Neuregulin-1 2 3
  • Pro-NRG2 3 4
  • NTAK 3 4
  • Pro-Neuregulin-2, Membrane-Bound Isoform 3
  • 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 Charcot-Marie-Tooth Disease. Among its related pathways are ERK Signaling and Akt Signaling. 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 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 , fRNAdb sequence ontologies and piRNA Summary for NRG2 Gene

Genomics for NRG2 Gene

GeneHancer (GH) Regulatory Elements for NRG2 Gene

Promoters and enhancers for NRG2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05J140036 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE 654.2 +3.0 2951 7 SIN3A ZNF2 IRF4 YY1 ZNF207 ZNF143 FOS KLF13 SP3 SP5 NRG2 PCDHA2 PCDHA3 PCDHA7 PURA PCDHA6 PCDHA10 DNAJC18 PFDN1 MATR3
GH05J139438 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 10.7 +604.0 604045 1.8 HDGF PKNOX1 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 SLC30A9 ZNF766 DNAJC18 MATR3 NRG2 PURA GC05P139409 GC05P139410 GC05P138946
GH05J139984 Enhancer 1.1 Ensembl ENCODE 10.8 +57.9 57853 2 ATF1 TCF12 GLIS2 FOS RUNX3 MEF2D SMARCA4 GLIS1 HMBOX1 WT1 NRG2 GC05P139956 GC05P140021
GH05J139131 Enhancer 1 Ensembl ENCODE dbSUPER 10.7 +911.0 910955 2.7 ZNF521 ZNF398 ZIC2 ZNF335 ZFHX2 ZBTB48 ZNF341 PRDM10 PRDM1 EGR2 MATR3 LOC105379194 NRG2 SIL1 GC05P139103 GC05P139104 GC05P139105 GC05P139106 GC05P139102 GC05P139163
GH05J140010 Enhancer 0.9 ENCODE 11.6 +32.0 32030 1.4 PKNOX1 ATF1 CLOCK STAT5A BATF KLF5 IRF4 ZNF335 ATF7 FOS NRG2 PSD2 GC05P140021 GC05P139956
- 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

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

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.

    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 isoforms=2, 3, 4, 5, 6, 7, 8346, Thr333, Asn278, isoforms=2, 3, 4, 5, 6147, isoforms=2, 3, 4, 5, 653, and Asn52
  • Modification sites at PhosphoSitePlus

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

Suggested Antigen Peptide Sequences for NRG2 Gene

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:0004713 protein tyrosine kinase activity TAS --
GO:0005088 Ras guanyl-nucleotide exchange factor activity TAS --
GO:0005102 signaling receptor binding TAS 9168114
GO:0008083 growth factor activity IEA --
GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity TAS --
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:

Animal Model Products

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
extracellular 5
plasma membrane 4
nucleus 3
cytosol 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoli (3)
  • Nucleus (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 --
GO:0005622 intracellular IEA --
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with NRG2: view

Pathways & Interactions for NRG2 Gene

SuperPathway Contained pathways
1 RET signaling
2 Apoptotic Pathways in Synovial Fibroblasts
3 Signaling by ERBB2
4 PI3K/AKT activation
5 GPCR Pathway
genes like me logo Genes that share pathways with NRG2: view

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:0010469 regulation of signaling receptor activity IEA --
GO:0018108 peptidyl-tyrosine phosphorylation IEA --
GO:0035556 intracellular signal transduction IBA --
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

Unigene Clusters for NRG2 Gene

Neuregulin 2:
Representative Sequences:

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
ECgene alternative splicing isoforms for
NRG2

Expression for NRG2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP 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

NURSA nuclear receptor signaling pathways regulating expression of NRG2 Gene:

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 34 33
  • 98.48 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Nrg2 16 34 33
  • 91.01 (n)
rat
(Rattus norvegicus)
Mammalia Nrg2 33
  • 90.94 (n)
dog
(Canis familiaris)
Mammalia NRG2 34 33
  • 90.79 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NRG2 34 33
  • 90.41 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NRG2 34
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NRG2 34
  • 72 (a)
OneToOne
chicken
(Gallus gallus)
Aves NRG2 34 33
  • 73.48 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NRG2 34
  • 72 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii nrg2a 34 33
  • 66.83 (n)
OneToMany
nrg2b 34
  • 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 from dbSNP and Humsavar for NRG2 Gene

SNP ID Clin Chr 05 pos Variation AA Info Type
rs1000013397 -- 139,973,057(-) T/C genic_upstream_transcript_variant, intron_variant
rs1000016829 -- 139,992,881(-) C/G genic_upstream_transcript_variant, intron_variant
rs1000022435 -- 139,947,282(-) A/G genic_upstream_transcript_variant, intron_variant
rs1000025322 -- 140,019,077(-) A/G genic_upstream_transcript_variant, intron_variant
rs1000059033 -- 139,878,941(-) G/A intron_variant

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

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

Disorder Aliases PubMed IDs
charcot-marie-tooth disease
  • charcot marie tooth muscular atrophy
- 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 22 44 58
  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 22 58
  3. Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases. (PMID: 9168115) Carraway KL … Lai C (Nature 1997) 2 3 22 58
  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 22 58
  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 22 58

Products for NRG2 Gene

Sources for NRG2 Gene

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