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  6. Pro-neuregulin-4, membrane-bound isoform

Tbio Pro-neuregulin-4, membrane-bound isoform

Low affinity ligand for the ERBB4 tyrosine kinase receptor. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors (By similarity).

The neuregulins, including NRG4, activate type-1 growth factor receptors (see EGFR; MIM 131550) to initiating cell-to-cell signaling through tyrosine phosphorylation (Harari et al., 1999 [PubMed 10348342]).[supplied by OMIM, Mar 2008]

 Comments

Property Summary

NCBI Gene PubMed Count 19
PubMed Score 16.76
PubTator Score 15.01

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (2)

Disease Target Count P-value
osteosarcoma 7933 3.0e-07
mucosa-associated lymphoid tissue lymphoma 480 6.4e-03
gastric carcinoma 832 8.2e-03
Disease Target Count Z-score Confidence
Peripheral vascular disease 90 0.0 2.0

Expression

  Differential Expression (3)

Disease log2 FC p
osteosarcoma -1.427 3.0e-07
gastric carcinoma -1.100 8.2e-03
mucosa-associated lymphoid tissue lympho... -1.363 6.4e-03

Synonym

Accession Q8WWG1 A6NIE8 Pro-NRG4
Symbols HRG4

Gene

NRG4

PANTHER Protein Class (3)

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (11)

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 GO Function (4)

 GO Component (5)

 GO Process (7)

 Compartment GO Term (12)

 MGI Phenotype (1)

 GWAS Trait (2)

 HCA RNA Cell Line (31)

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Pathway (83)

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Protein-protein Interaction (89)

PIK3CD   GFRA2   PIK3R2   SOCS3   RASGRF2   PIP5K1B   SPTBN2   PDPK1   FRS3   LAT   PIP5K1C   PSPN   RASGRP1   NRAS   HRAS   KRAS   PDGFB   SPTA1   PDGFA   NTRK1   RET   MET   PDGFRB   SPTB   FGFR1   CDK4   SRC   VAV1   PDGFRA   PTPN1   PTPRA   PLCG1   KITLG   FGFR2   FGFR3   CCND1   PIK3R1   SHC1   PIK3CA   PIK3CB   CDKN1B   PIP4K2A   PXN   PSEN2   PTEN   RHOA   PIP4K2B   SHC2   SPTBN1   NRG1   TEK   PTPN12   PTPN11   SOS1   GAB1   SPTAN1   PTK6   RASGRF1   ERBB4   CDC37   ARTN   TRAT1   PIK3AP1   KLB   RASGRP3   RASGEF1A   PIP4K2C   RASGRP4   FRS2   APH1B   SHC3   NCSTN   APH1A   ARAP1   ERBIN   RANBP9   NRTN   PIP5K1A   PTPN18   GFRA4   SPTBN4   RNF41   SPTBN5   ARHGAP35   PSENEN   KL   STAP2   RAPGEF2   ICOS  

Gene RIF (11)

PMID Text
26476959 Nrg4 might have a protective role in the development of Non-alcoholic fatty liver disease (NAFLD).
25401691 results establish Nrg4 as a brown fat-enriched endocrine factor with therapeutic potential for the treatment of obesity-associated disorders, including type 2 diabetes and nonalcoholic fatty liver disease (NAFLD).
25216938 NRG4 and its receptor ErbB4 are present in human breast milk and developing human intestine, respectively. Thus, NRG4-ErbB4 signaling may be a novel pathway for therapeutic intervention or prevention in NEC.
23033483 Pharmacological inhibition of PI3K/Akt signaling reversed the anti-apoptotic effects of NRG4, confirming the role of this cascade in NRG4-induced cell survival
21805036 The recombinant neuregulin 4 induced the tyrosine phosphorylation of HER4.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
17962208 NRG4 was positive in almost all breast cancers studied.
17684490 describes a novel splice variant of the NRG4 gene, NRG4A2, which encodes a C-terminal region containing a predicted type I PDZ-binding peptide
17545517 NRG4 overexpression is associated with advanced-stage prostate cancer
15583696 Neuregulin-4 expression is downregulated during urinary bladder cancer progression

AA Sequence 

MPTDHEEPCGPSHKSFCLNGGLCYVIPTIPSPFCRCVENYTGARCEEVFLPGSSIQTKSNLFEAFVALAV      1 - 70
LVTLIIGAFYFLCRKGHFQRASSVQYDINLVETSSTSAHHSHEQH                              71 - 115
//

Text Mined References (20)

PMID Year Title
26476959 2015 A case-control study: Association between serum neuregulin 4 level and non-alcoholic fatty liver disease.
25416956 2014 A proteome-scale map of the human interactome network.
25401691 2014 The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis.
25216938 2014 The ErbB4 ligand neuregulin-4 protects against experimental necrotizing enterocolitis.
23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
23222517 2012 Seventy-five genetic loci influencing the human red blood cell.
23033483 2012 Neuregulin-4 is a survival factor for colon epithelial cells both in culture and in vivo.
21805036 The role of neuregulin4 and HER4 in gastrointestinal malignant lymphoma.
21516116 2011 Next-generation sequencing to generate interactome datasets.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
17962208 2008 ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis.
17684490 2008 Characterization of the cell membrane-associated products of the Neuregulin 4 gene.
17545517 2007 Identification and characterization of novel spliced variants of neuregulin 4 in prostate cancer.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
16572171 2006 Analysis of the DNA sequence and duplication history of human chromosome 15.
15583696 2004 Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
10348342 1999 Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase.