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Neuregulin 4

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(Redirected fromNRG4)

Protein-coding gene in the species Homo sapiens

"NRG4" redirects here. For the cannabinoid drug, seeRCS-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)^[1]

Band	15q24.2	Start	75,935,969bp^[1]
Band	15q24.2	End	76,059,795bp^[1]

Gene location (Mouse)

Chr.	Chromosome 9 (mouse)^[2]

Band	9\|9 B	Start	55,127,506bp^[2]
Band	9\|9 B	End	55,234,128bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

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

BioGPS

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

Species

Human

Mouse

Entrez


145957


83961

Ensembl


ENSG00000169752


ENSMUSG00000032311

UniProt


Q8WWG1


Q9WTX4

RefSeq (mRNA)


NM_138573


NM_032002

RefSeq (protein)


NP_612640


NP_114391

Location (UCSC)

Chr 15: 75.94 – 76.06 Mb

Chr 9: 55.13 – 55.23 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Neuregulin 4 also known asNRG4 is a member of theneuregulin protein family which in humans is encoded by theNRG4gene.^[5]^[6]^[7]

Function

[edit]

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

Clinical significance

[edit]

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

References

[edit]

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000169752 –Ensembl, May 2017
^^a ^b ^cGRCm38: 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 ^bHarari 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.

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

Growth factor receptor modulators

Angiopoietin

Agonists:Angiopoietin 1
Angiopoietin 4

Antagonists:Angiopoietin 2
Angiopoietin 3

Kinase inhibitors:Altiratinib
CE-245677
Rebastinib

Antibodies:Evinacumab (against angiopoietin 3)
Nesvacumab (against angiopoietin 2)

CNTF

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists:Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors:Afatinib Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies:Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab
ErbB2/HER2	Agonists:Unknown/none Antibodies:Ertumaxomab Pertuzumab Trastuzumab Trastuzumab deruxtecan Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors:Afatinib Lapatinib Mubritinib Neratinib Tucatinib
ErbB3/HER3	Agonists:Neuregulins (heregulins) (1,2,6 (neuroglycan C)) Antibodies:Duligotumab Patritumab Seribantumab
ErbB4/HER4	Agonists:Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1,2,3,4,5 (tomoregulin, TMEFF))

FGF

FGFR1	Agonists:Ersofermin FGF (1,2 (bFGF),3,4,5,6,8,10 (KGF2),20) Repifermin Selpercatinib Trafermin Velafermin
FGFR2	Agonists:Ersofermin FGF (1,2 (bFGF),3,4,5,6,7 (KGF),8,9,10 (KGF2),17,18,22) Palifermin Repifermin Selpercatinib Sprifermin Trafermin Antibodies:Aprutumab Aprutumab ixadotin Kinase inhibitors:Infigratinib
FGFR3	Agonists:Ersofermin FGF (1,2 (bFGF),4,8,9,18,23) Selpercatinib Sprifermin Trafermin Antibodies:Burosumab (against FGF23)
FGFR4	Agonists:Ersofermin FGF (1,2 (bFGF),4,6,8,9,19) Trafermin
Unsorted	Agonists:FGF15/19

HGF (c-Met)

Agonists:Fosgonimeton
Hepatocyte growth factor

Potentiators:Dihexa (PNB-0408)

IGF

IGF-1	Agonists:des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors:BMS-754807 Linsitinib NVP-ADW742 NVP-AEW541 OSl-906 Antibodies:AVE-1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab (against IGF-1 and IGF-2)
IGF-2	Agonists:Insulin-like growth factor-2 (somatomedin A) Antibodies:Dusigitumab Xentuzumab (against IGF-1 and IGF-2)
Others	Binding proteins:IGFBP (1,2,3,4,5,6,7) Cleavage products/derivatives with unknown target:Glypromate (GPE, (1-3)IGF-1) Trofinetide

LNGF (p75^NTR)

Antibodies:Against NGF:ABT-110 (PG110)
ASP-6294
Fasinumab
Frunevetmab
Fulranumab
MEDI-578
Ranevetmab
Tanezumab

Aptamers:Against NGF:RBM-004

Decoy receptors:LEVI-04 (p75^NTR-Fc)

PDGF

Agonists:Becaplermin
Platelet-derived growth factor (A,B,C,D)

RET (GFL)

GFRα1	Agonists:Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors:Vandetanib
GFRα2	Agonists:Neurturin (NRTN) Kinase inhibitors:Vandetanib
GFRα3	Agonists:Artemin (ARTN) Kinase inhibitors:Vandetanib
GFRα4	Agonists:Persephin (PSPN) Kinase inhibitors:Vandetanib
Unsorted	Kinase inhibitors:Agerafenib

SCF (c-Kit)

Agonists:Ancestim
Stem cell factor

TGFβ

Seehere instead.

Trk

TrkA	Agonists:Amitriptyline BNN-20 BNN-27 Cenegermin DHEA DHEA-S Gambogic amide NGF Tavilermide Antagonists:ALE-0540 Dexamethasone FX007 Testosterone Negative allosteric modulators:VM-902A Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib Milciclib ONO-4474 ONO-5390556 PLX-7486 Rebastinib SNA-120 (pegylated K252a)) Antibodies:Against TrkA:GBR-900;Against NGF:ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers:Against NGF:RBM-004 Decoy receptors:ReN-1820 (TrkAd5)
TrkB	Agonists:3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 Antagonists:ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Ligands:DHEA Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486
TrkC	Agonists:BNN-20 DHEA NT-3 Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486