Epiregulin

EREG
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1K36, 1K37, 5E8D
Identifiers
Aliases	EREG , EPR, ER, Ep, epiregulin
External IDs	OMIM: 602061 MGI: 107508 HomoloGene: 1097 GeneCards: EREG
Gene location (Human)
Chr.	Chromosome 4 (human)
End	74,388,749 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	91,093,646 bp
Gene ontology
Molecular function	• epidermal growth factor receptor binding ; • GO:0001948 protein binding ; • growth factor activity ; • protein tyrosine kinase activity ; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity ;
Cellular component	• integral component of membrane ; • membrane ; • plasma membrane ; • integral component of plasma membrane ; • extracellular region ; • intracellular anatomical structure ; • extracellular space ; • clathrin-coated vesicle membrane ;
Biological process	• luteinizing hormone signaling pathway ; • positive regulation of epidermal growth factor-activated receptor activity ; • cell differentiation ; • ovarian cumulus expansion ; • negative regulation of smooth muscle cell differentiation ; • positive regulation of cytokine production ; • cytokine-mediated signaling pathway ; • positive regulation of fibroblast proliferation ; • cell-cell signaling ; • anatomical structure morphogenesis ; • response to peptide hormone ; • wound healing ; • mRNA transcription ; • female meiotic nuclear division ; • primary follicle stage ; • keratinocyte differentiation ; • MAPK cascade ; • multicellular organism development ; • positive regulation of DNA replication ; • keratinocyte proliferation ; • oocyte maturation ; • angiogenesis ; • positive regulation of cell population proliferation ; • positive regulation of innate immune response ; • negative regulation of epithelial cell proliferation ; • animal organ morphogenesis ; • positive regulation of phosphorylation ; • negative regulation of transcription, DNA-templated ; • positive regulation of mitotic nuclear division ; • ovulation ; • positive regulation of cell division ; • negative regulation of cell population proliferation ; • positive regulation of smooth muscle cell proliferation ; • positive regulation of protein kinase activity ; • ERBB2 signaling pathway ; • regulation of cell motility ; • epidermal growth factor receptor signaling pathway ; • peptidyl-tyrosine phosphorylation ; • phosphatidylinositol phosphate biosynthetic process ; • positive regulation of protein kinase B signaling ; • signal transduction ; • negative regulation of epidermal growth factor receptor signaling pathway ; • membrane organization ;
	Sources:Amigo / QuickGO
Orthologs
	2069
	13874
	ENSG00000124882
	ENSMUSG00000029377
	O14944
	Q61521
	NM_001432
	NM_007950
	NP_001423
	NP_031976
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated February 13, 2022

Epiregulin (EPR) is a protein that in humans is encoded by the EREG gene.^[5]^[6]

Structure

Epiregulin consists of 46 amino acid residues. Its secondary structure contains approximately 30 percent of β-sheet in the strand.^[7] Some of the residues form loops and turns due to the hydrogen bonding.^[7] The percentage of β-sheet in epiregulin depends on the domain and the secondary structures that they occupy. The polymeric molecules of epiregulin has the formula weight of 5280.1 g/mol with a polypeptide(L), a polymer type.^[7]

Structural motifs in most proteins have typical connections in an all β motif. Meaning that the polypeptide chains do not make a crossover connection or in so far as this type of connection has not been observed. Epiregulin is one of the proteins that occupies a typical connection in all β motif. Furthermore, as the structure of epiregulin forms a chain in an all β motif, it also forms β hairpin structural motif. A β hairpin is when the two adjacent anti-parallel β strands connected by a β-turn.

Function

Epiregulin is a member of the epidermal growth factor family. Epiregulin can function as a ligand of epidermal growth factor receptor (EGFR), as well as a ligand of most members of the ERBB (v-erb-b2 oncogene homolog) family of tyrosine-kinase receptors.^[6] The secondary structure at the C-terminus epiregulin is different from other epidermal growth factor family ligands because of the lack of hydrogen bonds. The structural difference at the C-terminus may provide an explanation for the reduced binding affinity of epiregulin to the ERBB receptors.^[7]

Related Research Articles

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References

1 2 3 GRCh38: Ensembl release 89: ENSG00000124882 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029377 - 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.
↑ Toyoda H, Komurasaki T, Uchida D, Morimoto S (August 1997). "Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family". Biochem. J. 326 (1): 69–75. doi:10.1042/bj3260069. PMC 1218638 . PMID 9337852.
1 2 "Entrez Gene: epiregulin".
1 2 3 4 Sato K, Nakamura T, Mizuguchi M, Miura K, Tada M, Aizawa T, Gomi T, Miyamoto K, Kawano K (October 2003). "Solution structure of epiregulin and the effect of its C-terminal domain for receptor binding affinity". FEBS Lett. 553 (3): 232–8. doi: 10.1016/s0014-5793(03)01005-6 . PMID 14572630. S2CID 24761378.

Yamamoto T, Akisue T, Marui T, et al. (2004). "Expression of betacellulin, heparin-binding epidermal growth factor and epiregulin in human malignant fibrous histiocytoma". Anticancer Res. 24 (3b): 2007–10. PMID 15274392.
Li S, Takeuchi F, Wang JA, et al. (2008). "Mesenchymal-epithelial interactions involving epiregulin in tuberous sclerosis complex hamartomas". Proc. Natl. Acad. Sci. U.S.A. 105 (9): 3539–44. Bibcode:2008PNAS..105.3539L. doi: 10.1073/pnas.0712397105 . PMC 2265180 . PMID 18292222.
Cho MC, Choi HS, Lee S, et al. (2008). "Epiregulin expression by Ets-1 and ERK signaling pathway in Ki-ras-transformed cells". Biochem. Biophys. Res. Commun. 377 (3): 832–7. doi:10.1016/j.bbrc.2008.10.053. PMID 18948081.
Lindvall C, Hou M, Komurasaki T, et al. (2003). "Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene". Cancer Res. 63 (8): 1743–7. PMID 12702554.
Morita S, Shirakata Y, Shiraishi A, et al. (2007). "Human corneal epithelial cell proliferation by epiregulin and its cross-induction by other EGF family members". Mol. Vis. 13: 2119–28. PMID 18079685.
Freimann S, Ben-Ami I, Dantes A, et al. (2004). "EGF-like factor epiregulin and amphiregulin expression is regulated by gonadotropins/cAMP in human ovarian follicular cells". Biochem. Biophys. Res. Commun. 324 (2): 829–34. doi:10.1016/j.bbrc.2004.09.129. PMID 15474502.
Ben-Ami I, Armon L, Freimann S, et al. (2009). "EGF-like growth factors as LH mediators in the human corpus luteum". Hum. Reprod. 24 (1): 176–84. doi: 10.1093/humrep/den359 . PMID 18835871.
Shigeishi H, Higashikawa K, Hiraoka M, et al. (2008). "Expression of epiregulin, a novel epidermal growth factor ligand associated with prognosis in human oral squamous cell carcinomas". Oncol. Rep. 19 (6): 1557–64. doi: 10.3892/or.19.6.1557 . PMID 18497965.
Taylor DS, Cheng X, Pawlowski JE, et al. (1999). "Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin". Proc. Natl. Acad. Sci. U.S.A. 96 (4): 1633–8. Bibcode:1999PNAS...96.1633T. doi: 10.1073/pnas.96.4.1633 . PMC 15542 . PMID 9990076.
Zhang J, Iwanaga K, Choi KC, et al. (2008). "Intratumoral epiregulin is a marker of advanced disease in non-small cell lung cancer patients and confers invasive properties on EGFR-mutant cells". Cancer Prev Res (Phila). 1 (3): 201–7. doi:10.1158/1940-6207.CAPR-08-0014. PMC 3375599 . PMID 19138957.
Draper BK, Komurasaki T, Davidson MK, Nanney LB (2003). "Epiregulin is more potent than EGF or TGFalpha in promoting in vitro wound closure due to enhanced ERK/MAPK activation". J. Cell. Biochem. 89 (6): 1126–37. doi:10.1002/jcb.10584. PMID 12898511. S2CID 24643892.
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.
Ben-Ami I, Freimann S, Armon L, et al. (2006). "PGE2 up-regulates EGF-like growth factor biosynthesis in human granulosa cells: new insights into the coordination between PGE2 and LH in ovulation". Mol. Hum. Reprod. 12 (10): 593–9. doi: 10.1093/molehr/gal068 . PMID 16888076.
Takahashi M, Hayashi K, Yoshida K, et al. (2003). "Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells". Circulation. 108 (20): 2524–9. doi: 10.1161/01.CIR.0000096482.02567.8C . PMID 14581411.
Lasky-Su J, Neale BM, Franke B, et al. (2008). "Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations". Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B (8): 1345–54. doi:10.1002/ajmg.b.30867. PMID 18821565. S2CID 9493672.
Gupta GP, Nguyen DX, Chiang AC, et al. (2007). "Mediators of vascular remodelling co-opted for sequential steps in lung metastasis". Nature. 446 (7137): 765–70. Bibcode:2007Natur.446..765G. doi:10.1038/nature05760. PMID 17429393. S2CID 4420038.
Shirakata Y, Komurasaki T, Toyoda H, et al. (2000). "Epiregulin, a novel member of the epidermal growth factor family, is an autocrine growth factor in normal human keratinocytes". J. Biol. Chem. 275 (8): 5748–53. doi: 10.1074/jbc.275.8.5748 . PMID 10681561.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000124882 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029377 - 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.

[pmid9337852-5] Toyoda H, Komurasaki T, Uchida D, Morimoto S (August 1997). "Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family". Biochem. J. 326 (1): 69–75. doi:10.1042/bj3260069. PMC 1218638 . PMID 9337852.

[entrez-6] 1 2 "Entrez Gene: epiregulin".

[pmid14572630-7] 1 2 3 4 Sato K, Nakamura T, Mizuguchi M, Miura K, Tada M, Aizawa T, Gomi T, Miyamoto K, Kawano K (October 2003). "Solution structure of epiregulin and the effect of its C-terminal domain for receptor binding affinity". FEBS Lett. 553 (3): 232–8. doi: 10.1016/s0014-5793(03)01005-6 . PMID 14572630. S2CID 24761378.

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Epiregulin

Contents

Structure

Function

Related Research Articles

References

Further reading