Neuregulin 4

NRG4
Identifiers
Aliases	NRG4, HRG4, neuregulin 4
External IDs	OMIM: 610894; MGI: 1933833; HomoloGene: 12921; GeneCards: NRG4; OMA:NRG4 - orthologs
Gene location (Human)
Chr.	Chromosome 15 (human)
End	76,059,795 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	55,234,128 bp
RNA expression pattern
	Top expressed in
	body of pancreas; ; right uterine tube; ; cerebellar hemisphere; ; right hemisphere of cerebellum; ; secondary oocyte; ; left testis; ; olfactory zone of nasal mucosa; ; right testis; ; testicle; ; muscle of thigh;
	Top expressed in
	zygote; ; brown adipose tissue; ; secondary oocyte; ; Glandular part of endometrium; ; white adipose tissue; ; tunica adventitia of aorta; ; subcutaneous adipose tissue; ; intercostal muscle; ; mammary gland; ; primary oocyte;
	More reference expression data
	n/a
Gene ontology
Molecular function	protein binding; growth factor activity; protein tyrosine kinase activity; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; signaling receptor binding;
Cellular component	integral component of membrane; membrane; plasma membrane; extracellular region; intracellular anatomical structure; extracellular space;
Biological process	MAPK cascade; ERBB2 signaling pathway; phosphatidylinositol phosphate biosynthetic process; peptidyl-tyrosine phosphorylation; regulation of cell motility; intracellular signal transduction; animal organ development; regulation of signaling receptor activity; positive regulation of protein kinase B signaling; nervous system development;
	Sources:Amigo / QuickGO
Orthologs
	145957
	83961
	ENSG00000169752
	ENSMUSG00000032311
	Q8WWG1
	Q9WTX4
	NM_138573
	NM_032002
	NP_612640
	NP_114391
	Wikidata
View/Edit Human	View/Edit Mouse

Neuregulin 4 also known as NRG4 is a member of the neuregulin protein family which in humans is encoded by the NRG4 gene.^[5]^[6]^[7]

Function

The neuregulins, including NRG4, activate erb-b2 receptor tyrosine kinase 4 (ERBB4) to initiating cell signaling through cytosolic tyrosine phosphorylation.^[7]

Clinical significance

Loss of expression of NRG4 is frequently seen in advanced bladder cancer while increased NRG4 expression correlates to better survival.^[8]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000169752 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000032311 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: NRG4 neuregulin 4".
^ Strausberg RL, Feingold EA, Grouse LH, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
^ ^a ^b Harari D, Tzahar E, Romano J, Shelly M, Pierce JH, Andrews GC, Yarden Y (April 1999). "Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase". Oncogene. 18 (17): 2681–9. doi:10.1038/sj.onc.1202631. PMID 10348342.
^ Memon AA, Sorensen BS, Melgard P, Fokdal L, Thykjaer T, Nexo E (December 2004). "Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients". Br. J. Cancer. 91 (12): 2034–41. doi:10.1038/sj.bjc.6602251. PMC 2409781. PMID 15583696.

Révillion F, Lhotellier V, Hornez L, Bonneterre J, Peyrat JP (January 2008). "ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis". Ann. Oncol. 19 (1): 73–80. doi:10.1093/annonc/mdm431. PMID 17962208.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Hayes NV, Newsam RJ, Baines AJ, Gullick WJ (2008). "Characterization of the cell membrane-associated products of the Neuregulin 4 gene". Oncogene. 27 (5): 715–20. doi:10.1038/sj.onc.1210689. PMID 17684490.
Hayes NV, Blackburn E, Smart LV, et al. (2007). "Identification and characterization of novel spliced variants of neuregulin 4 in prostate cancer". Clin. Cancer Res. 13 (11): 3147–55. doi:10.1158/1078-0432.CCR-06-2237. PMID 17545517.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000169752 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000032311 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: NRG4 neuregulin 4".

[pmid12477932-6] Strausberg RL, Feingold EA, Grouse LH, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.

[pmid10348342-7] Harari D, Tzahar E, Romano J, Shelly M, Pierce JH, Andrews GC, Yarden Y (April 1999). "Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase". Oncogene. 18 (17): 2681–9. doi:10.1038/sj.onc.1202631. PMID 10348342.

[pmid15583696-8] Memon AA, Sorensen BS, Melgard P, Fokdal L, Thykjaer T, Nexo E (December 2004). "Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients". Br. J. Cancer. 91 (12): 2034–41. doi:10.1038/sj.bjc.6602251. PMC 2409781. PMID 15583696.

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v t e Cell signaling: Nervous tissue: Neurotrophic factors
Neurotrophins	NGF BDNF NT-3 NT-4
GDNF family	GDNF Artemin Neurturin Persephin
Ephrins	A1 A2 A3 A4 A5 B1 B2 B3
CNTF family	CNTF LIF IL-6
Other	GMF IGF-1 Neuregulins 1 2 3 4 PACAP VEGF

Neuregulin 4

Function

Clinical significance

References

Further reading