Human Gene NRG2 (ENST00000358522.7) from GENCODE V44
  Description: Homo sapiens neuregulin 2 (NRG2), transcript variant 4, mRNA. (from RefSeq NM_013983)
RefSeq Summary (NM_013983): 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].
Gencode Transcript: ENST00000358522.7
Gencode Gene: ENSG00000158458.21
Transcript (Including UTRs)
   Position: hg38 chr5:139,847,917-140,043,069 Size: 195,153 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg38 chr5:139,847,917-140,043,069 Size: 195,153 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:139,847,917-140,043,069)mRNA (may differ from genome)Protein (852 aa)
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HGNCLynxMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: NRG2_HUMAN
DESCRIPTION: RecName: Full=Pro-neuregulin-2, membrane-bound isoform; Short=Pro-NRG2; Contains: RecName: Full=Neuregulin-2; Short=NRG-2; AltName: Full=Divergent of neuregulin-1; Short=DON-1; AltName: Full=Neural- and thymus-derived activator for ERBB kinases; Short=NTAK; Flags: Precursor;
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.
SUBUNIT: Interacts with ERBB3 and ERBB4.
SUBCELLULAR LOCATION: Pro-neuregulin-2, membrane-bound isoform: Cell membrane; Single-pass type I membrane protein (By similarity). Note=Does not seem to be active (By similarity).
SUBCELLULAR LOCATION: Neuregulin-2: Secreted (By similarity).
TISSUE SPECIFICITY: Restricted to the cerebellum in the adult.
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).
DOMAIN: ERBB receptor binding is elicited entirely by the EGF-like domain (By similarity).
PTM: Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form (By similarity).
PTM: Extensive glycosylation precedes the proteolytic cleavage (By similarity).
SIMILARITY: Belongs to the neuregulin family.
SIMILARITY: Contains 1 EGF-like domain.
SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: NRG2
Diseases sorted by gene-association score: charcot-marie-tooth disease (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 8.30 RPKM in Brain - Cerebellum
Total median expression: 75.80 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000742 - EG-like_dom
IPR013032 - EGF-like_CS
IPR007110 - Ig-like
IPR013783 - Ig-like_fold
IPR013098 - Ig_I-set
IPR003598 - Ig_sub2
IPR002154 - Neuregulin_1_C

Pfam Domains:
PF07679 - Immunoglobulin I-set domain
PF02158 - Neuregulin family

ModBase Predicted Comparative 3D Structure on O14511
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004713 protein tyrosine kinase activity
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0005102 receptor binding
GO:0008083 growth factor activity
GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Biological Process:
GO:0000165 MAPK cascade
GO:0007165 signal transduction
GO:0010469 regulation of receptor activity
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0035556 intracellular signal transduction
GO:0038128 ERBB2 signaling pathway
GO:0046854 phosphatidylinositol phosphorylation
GO:0048513 animal organ development
GO:0051897 positive regulation of protein kinase B signaling
GO:2000145 regulation of cell motility

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane


-  Descriptions from all associated GenBank mRNAs
  LF211010 - JP 2014500723-A/18513: Polycomb-Associated Non-Coding RNAs.
MA446587 - JP 2018138019-A/18513: Polycomb-Associated Non-Coding RNAs.
AB005060 - Homo sapiens mRNA for NTAK, complete cds.
BC166615 - Synthetic construct Homo sapiens clone IMAGE:100066341, MGC:195478 neuregulin 2 (NRG2) mRNA, encodes complete protein.
AK124504 - Homo sapiens cDNA FLJ42513 fis, clone BRACE2046295, highly similar to Pro-neuregulin-2, membrane-bound isoform precursor.
BC103983 - Homo sapiens neuregulin 2, mRNA (cDNA clone IMAGE:40016925), complete cds.
BC103984 - Homo sapiens neuregulin 2, mRNA (cDNA clone IMAGE:40016926), complete cds.
BC114333 - Homo sapiens neuregulin 2, mRNA (cDNA clone IMAGE:40016927), complete cds.
BC114334 - Homo sapiens neuregulin 2, mRNA (cDNA clone IMAGE:40016929), complete cds.
U92987 - Homo sapiens clone DT1P1C12 mRNA, CAG repeat region.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04012 - ErbB signaling pathway

BioCarta from NCI Cancer Genome Anatomy Project
h_erbB4pathway - g-Secretase mediated ErbB4 Signaling Pathway
h_agrPathway - Agrin in Postsynaptic Differentiation

Reactome (by CSHL, EBI, and GO)

Protein O14511 (Reactome details) participates in the following event(s):

R-HSA-1247497 ERBB3 binds neuregulins
R-HSA-1977958 ERBB4 forms heterodimers with ERBB3
R-HSA-1236398 ERBB4 binds NRGs or EGF-like ligands
R-HSA-1963589 ERBB2 forms heterodimers with ligand-activated ERBB receptors: EGFR, ERBB3 and ERBB4
R-HSA-1963582 Trans-autophosphorylation of ERBB2 heterodimers
R-HSA-1963586 SRC family kinases phosphorylate ERBB2
R-HSA-1963581 Trans-autophosphorylation of p-Y877-ERBB2 heterodimers
R-NUL-1248753 Shc1 binds phosphorylated ERBB2:ERBB3 heterodimers
R-HSA-1250189 Binding of PI3K to ERBB2:P-ERBB3 heterodimer
R-HSA-1306953 GRB7 binds phosphorylated heterodimer of ERBB2 and ERBB3
R-HSA-1358798 RNF41 binds neuregulin-activated ERBB3
R-NUL-1251988 Cleavage of P-ERBB4jmA isoforms by Adam17
R-HSA-1250220 Homodimerization of ERBB4
R-HSA-1977959 ERBB4 forms heterodimers with EGFR
R-HSA-1963563 MATK (CSK homologous kinase) binds phosphorylated ERBB2
R-HSA-1963578 SHC1 binds phosphorylated ERBB2 heterodimers
R-HSA-6785636 Phosphorylated ERBB2 heterodimers bind MEMO1
R-HSA-8847995 Activated ERBB2 binds PTK6 (BRK)
R-HSA-8863804 PTPN12 dephosphorylates ERBB2 on tyrosine Y1248
R-HSA-8848005 ERBB2 promotes PTK6 autophosphorylation
R-HSA-1358792 RNF41 ubiquitinates activated ERBB3
R-HSA-1250346 Binding of PI3K to p-ERBB2:p-ERBB4 CYT-1 heterodimers
R-HSA-1250357 SHC1 binds P-ERBB4 isoform dimers
R-HSA-1250315 Trans-autophosphorylation of ERBB4 homodimers
R-HSA-1251992 Cleavage of P-ERBB4jmA isoforms by ADAM17
R-HSA-1250353 Binding of p85 subunit of PI3K (PIK3R1) to p-ERBB4cyt1 homodimers
R-HSA-1250195 SHC1 phosphorylation by ERBB2 heterodimers
R-HSA-1250486 Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 heterodimers
R-HSA-6785648 MEMO1 binds RHOA:GTP:DIAPH1
R-HSA-1306969 GRB2:SOS1 complex binds phosphorylated ERBB4:ERBB2 heterodimers
R-HSA-1250380 Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers
R-HSA-1250348 Phosphorylation of SHC1 by ERBB4 homodimers
R-HSA-1250372 Recruitment of PI3K subunit p110 (PIK3CA) to PI3K subunit p85 (PIK3R1) bound to p-ERBB4cyt1 homodimers
R-HSA-1250462 PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB3
R-HSA-1306979 PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB4 CYT1
R-HSA-1250463 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers
R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity
R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3
R-HSA-1306972 RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers
R-HSA-1250383 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4
R-HSA-1250370 Conversion of PIP2 into PIP3 by PI3K bound to p-ERBB4cyt1 homodimers
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-1227986 Signaling by ERBB2
R-HSA-1236394 Signaling by ERBB4
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-162582 Signal Transduction
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-1306955 GRB7 events in ERBB2 signaling
R-HSA-1358803 Downregulation of ERBB2:ERBB3 signaling
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-6785631 ERBB2 Regulates Cell Motility
R-HSA-8847993 ERBB2 Activates PTK6 Signaling
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-1250342 PI3K events in ERBB4 signaling
R-HSA-8848021 Signaling by PTK6
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-199418 Negative regulation of the PI3K/AKT network
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-5663202 Diseases of signal transduction
R-HSA-5683057 MAPK family signaling cascades
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000358522.1, ENST00000358522.2, ENST00000358522.3, ENST00000358522.4, ENST00000358522.5, ENST00000358522.6, NM_013983, NRG2_HUMAN, NTAK, O14511, uc003lew.1, uc003lew.2, uc003lew.3
UCSC ID: ENST00000358522.7
RefSeq Accession: NM_013983
Protein: O14511 (aka NRG2_HUMAN)
CCDS: CCDS4217.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.