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NRG2 neuregulin 2 [ Homo sapiens (human) ]

Gene ID: 9542, updated on 5-Mar-2024

Summary

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Official Symbol
NRG2provided by HGNC
Official Full Name
neuregulin 2provided by HGNC
Primary source
HGNC:HGNC:7998
See related
Ensembl:ENSG00000158458 MIM:603818; AllianceGenome:HGNC:7998
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
DON1; HRG2; NTAK
Summary
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]
Expression
Broad expression in ovary (RPKM 1.6), fat (RPKM 0.8) and 16 other tissues See more
Orthologs
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Genomic context

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Location:
5q31.2
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (139846781..140043299, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (140371883..140568402, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (139226366..139422884, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901085 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139104350-139104850 Neighboring gene RNA, U6 small nuclear 236, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139117735-139118662 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139121544-139122093 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139122094-139122642 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:139123561-139124154 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139125678-139126325 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23253 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16429 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:139128271-139128918 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:139131846-139131997 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16430 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139137793-139138691 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139138692-139139589 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139141892-139142555 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139142556-139143218 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:139143219-139143882 Neighboring gene PSD2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16431 Neighboring gene pleckstrin and Sec7 domain containing 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16432 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139169627-139170127 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:139174912-139175111 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139194145-139194646 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16433 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16434 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16435 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:139259501-139260264 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16436 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23254 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16437 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23255 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:139364881-139366080 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23256 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23257 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23258 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139422349-139423018 Neighboring gene uncharacterized LOC124900193 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23259 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16440 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16441 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16442 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:139487907-139488408 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16443 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16444 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23260 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:139494224-139494861 Neighboring gene mitosis associated long intergenic non-coding RNA 1 Neighboring gene purine rich element binding protein A

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. [Neuregulin 2 is highly expressed in glioma tissues to regulate glial fibrillary acidic protein expression via Akt signaling]. Zhao W, et al. Nan Fang Yi Ke Da Xue Xue Bao, 2021 Aug 20. PMID 34549707, Free PMC Article
  2. Neuregulin 2 (NRG2) is expressed in gliomas and promotes migration of human glioma cells. Zhao WJ, et al. Folia Neuropathol, 2021. PMID 34284546
  3. Identification of Neuregulin-2 as a novel stress granule component. Kim JA, et al. BMB Rep, 2016 Aug. PMID 27345716, Free PMC Article
  4. Stimulation of acetylcholine receptor transcription by neuregulin-2 requires an N-box response element and is regulated by alternative splicing. Ponomareva ON, et al. Neuroscience, 2005. PMID 15961242
  5. The N-terminal region of NTAK/neuregulin-2 isoforms has an inhibitory activity on angiogenesis. Nakano N, et al. J Biol Chem, 2004 Mar 19. PMID 14722120

See all (26) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The relevance of EGFR, ErbB receptors and neuregulins in human adipocytes and adipose tissue in obesity.
    Title: The relevance of EGFR, ErbB receptors and neuregulins in human adipocytes and adipose tissue in obesity.
  2. NRG1 and NRG2 fusion positive solid tumor malignancies: a paradigm of ligand-fusion oncogenesis.
    Title: NRG1 and NRG2 fusion positive solid tumor malignancies: a paradigm of ligand-fusion oncogenesis.
  3. Neuregulin 2 (NRG2) is expressed in gliomas and promotes migration of human glioma cells.
    Title: Neuregulin 2 (NRG2) is expressed in gliomas and promotes migration of human glioma cells.
  4. [Neuregulin 2 is highly expressed in glioma tissues to regulate glial fibrillary acidic protein expression via Akt signaling].
    Title: [Neuregulin 2 is highly expressed in glioma tissues to regulate glial fibrillary acidic protein expression via Akt signaling].
  5. Development and application of high-throughput screens for the discovery of compounds that disrupt ErbB4 signaling: Candidate cancer therapeutics.
    Title: Development and application of high-throughput screens for the discovery of compounds that disrupt ErbB4 signaling: Candidate cancer therapeutics.
  6. reduced expression of NRG2 led to marginal increase in cell survival under arsenite-induced stress.
    Title: Identification of Neuregulin-2 as a novel stress granule component.
  7. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
    Title: Interactions among genes in the ErbB-Neuregulin signalling network are associated with increased susceptibility to schizophrenia.
  8. Observational study of gene-disease association. (HuGE Navigator)
    Title: Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.
  9. NRG2 was positive in almost all breast cancers studied. High expression is related to the biological aggressiveness of breast cancer.
    Title: ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis.
  10. Gln43 of NRG2beta is both necessary and sufficient for NRG2 stimulation of ErbB4 coupling to IL3 independence.
    Title: Inter-conversion of neuregulin2 full and partial agonists for ErbB4.
Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables growth factor activity IEA
Inferred from Electronic Annotation
more info
  
enables signaling receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in animal organ development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in nervous system development IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
pro-neuregulin-2, membrane-bound isoform
Names
divergent of neuregulin-1
neural- and thymus-derived activator for ErbB kinases
pro-NRG2

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

  1. NM_001184935.2 → NP_001171864.1  pro-neuregulin-2, membrane-bound isoform isoform 7

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) lacks two in-frame exons in the central coding region, compared to variant 1, resulting in an isoform (7, also known as delta) that is shorter than isoform 1. This variant is supported by data in PMID:10974560.
    Source sequence(s)
    AB005060, AC008667, AI271427, DA090538
    Consensus CDS
    CCDS54910.1
    UniProtKB/TrEMBL
    F5GZS7
    Related
    ENSP00000444235.1, ENST00000541337.5
    Conserved Domains (3) summary
    cd05750
    Location:253 → 326
    Ig_Pro_neuregulin; Immunoglobulin (Ig)-like domain in neuregulins (NRGs)
    pfam07679
    Location:239 → 328
    I-set; Immunoglobulin I-set domain
    pfam02158
    Location:332 → 771
    Neuregulin; Neuregulin family

  2. NM_001410780.1 → NP_001397709.1  pro-neuregulin-2, membrane-bound isoform isoform 8

    Status: REVIEWED

    Source sequence(s)
    AC008523, AC008667
    Consensus CDS
    CCDS93793.1
    Related
    ENSP00000342660.3, ENST00000340391.8

  3. NM_004883.3 → NP_004874.1  pro-neuregulin-2, membrane-bound isoform isoform 1

    See identical proteins and their annotated locations for NP_004874.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1, which is also known as isoform alpha or alpha2. This variant is supported by data in PMID:10369162.
    Source sequence(s)
    AB005060, AC008667, AI271427, DA090538
    Consensus CDS
    CCDS4217.1
    UniProtKB/Swiss-Prot
    O14511
    Related
    ENSP00000354910.1, ENST00000361474.6
    Conserved Domains (4) summary
    cd05750
    Location:253 → 326
    Ig_Pro_neuregulin; Immunoglobulin (Ig)-like domain in neuregulins (NRGs)
    PHA02887
    Location:343 → 383
    PHA02887; EGF-like protein; Provisional
    pfam07679
    Location:239 → 328
    I-set; Immunoglobulin I-set domain
    pfam02158
    Location:398 → 837
    Neuregulin; Neuregulin family

  4. NM_013981.4 → NP_053584.1  pro-neuregulin-2, membrane-bound isoform isoform 2

    See identical proteins and their annotated locations for NP_053584.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon but includes a different in-frame exon in the central coding region, compared to variant 1. The encoded isoform (2, also known as beta or beta1) is shorter than isoform 1. This variant is supported by data in PMID:10369162.
    Source sequence(s)
    AB005060, AC008667, AI271427, DA090538
    UniProtKB/Swiss-Prot
    O14511
    Related
    ENSP00000289409.4, ENST00000289409.8
    Conserved Domains (4) summary
    cd05750
    Location:253 → 326
    Ig_Pro_neuregulin; Immunoglobulin (Ig)-like domain in neuregulins (NRGs)
    PHA03099
    Location:329 → 417
    PHA03099; epidermal growth factor-like protein (EGF-like protein); Provisional
    pfam07679
    Location:239 → 328
    I-set; Immunoglobulin I-set domain
    pfam02158
    Location:392 → 831
    Neuregulin; Neuregulin family

  5. NM_013982.3 → NP_053585.1  pro-neuregulin-2, membrane-bound isoform isoform 3

    See identical proteins and their annotated locations for NP_053585.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) includes an additional in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (3, also known as alphav or alpha1) that is longer than isoform 1. This variant is supported by data in PMID:10369162.
    Source sequence(s)
    AB005060, AC008667, AI271427, DA090538
    UniProtKB/Swiss-Prot
    O14511
    Related
    ENSP00000289422.7, ENST00000289422.11
    Conserved Domains (4) summary
    cd05750
    Location:253 → 326
    Ig_Pro_neuregulin; Immunoglobulin (Ig)-like domain in neuregulins (NRGs)
    PHA02887
    Location:343 → 383
    PHA02887; EGF-like protein; Provisional
    pfam07679
    Location:239 → 328
    I-set; Immunoglobulin I-set domain
    pfam02158
    Location:406 → 845
    Neuregulin; Neuregulin family

  6. NM_013983.3 → NP_053586.1  pro-neuregulin-2, membrane-bound isoform isoform 4

    See identical proteins and their annotated locations for NP_053586.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an alternate in-frame exon but includes two different in-frame exons in the central coding region, compared to variant 1. The encoded isoform (4, also known as betav) is longer than isoform 1. This variant is supported by data in PMID:10369162.
    Source sequence(s)
    AB005060, AC008667, AI271427, DA090538
    UniProtKB/Swiss-Prot
    O14511
    Related
    ENSP00000351323.3, ENST00000358522.7
    Conserved Domains (4) summary
    cd05750
    Location:253 → 326
    Ig_Pro_neuregulin; Immunoglobulin (Ig)-like domain in neuregulins (NRGs)
    PHA02887
    Location:343 → 386
    PHA02887; EGF-like protein; Provisional
    pfam07679
    Location:239 → 328
    I-set; Immunoglobulin I-set domain
    pfam02158
    Location:400 → 839
    Neuregulin; Neuregulin family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    139846781..140043299 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005268533.5 → XP_005268590.1  pro-neuregulin-2, membrane-bound isoform isoform X3

    Conserved Domains (1) summary
    pfam02158
    Location:7 → 446
    Neuregulin; Neuregulin family

  2. XM_047417897.1 → XP_047273853.1  pro-neuregulin-2, membrane-bound isoform isoform X2

  3. XM_006714810.4 → XP_006714873.1  pro-neuregulin-2, membrane-bound isoform isoform X4

    See identical proteins and their annotated locations for XP_006714873.1

    UniProtKB/Swiss-Prot
    O14511
    Related
    ENSP00000367483.4, ENST00000378238.5
    Conserved Domains (3) summary
    cd05750
    Location:253 → 326
    Ig_Pro_neuregulin; Immunoglobulin (Ig)-like domain in neuregulins (NRGs)
    PHA02887
    Location:343 → 383
    PHA02887; EGF-like protein; Provisional
    pfam07679
    Location:239 → 328
    I-set; Immunoglobulin I-set domain

  4. XM_011537713.3 → XP_011536015.1  pro-neuregulin-2, membrane-bound isoform isoform X1

    Conserved Domains (2) summary
    cd05750
    Location:253 → 326
    Ig_Pro_neuregulin; Immunoglobulin (Ig)-like domain in neuregulins (NRGs)
    pfam07679
    Location:239 → 328
    I-set; Immunoglobulin I-set domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    140371883..140568402 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054353831.1 → XP_054209806.1  pro-neuregulin-2, membrane-bound isoform isoform X3

  2. XM_054353830.1 → XP_054209805.1  pro-neuregulin-2, membrane-bound isoform isoform X2

  3. XM_054353832.1 → XP_054209807.1  pro-neuregulin-2, membrane-bound isoform isoform X4

  4. XM_054353829.1 → XP_054209804.1  pro-neuregulin-2, membrane-bound isoform isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_013984.1: Suppressed sequence

    Description
    NM_013984.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

  2. NM_013985.1: Suppressed sequence

    Description
    NM_013985.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O14511.1 GenPept UniProtKB/Swiss-Prot:O14511

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